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The multinational outbreak of Andes hantavirus (ANDV) linked to cruise ship travel in the South Atlantic should prompt urgent strengthening and harmonisation of respiratory protection guidance for healthcare workers, first responders, travellers, and close contacts. The outbreak has also exposed important tensions within current international guidance on transmission risk and respiratory precautions. More broadly, the outbreak highlights the need for WHO and other public health agencies to adopt a precaution-first approach for severe pathogens with respiratory transmission potential: begin with stringent airborne protections, then scale back if evidence later justifies doing so — rather than starting with minimal precautions and escalating only after transmission has occurred.

On 8 May 2026, WHO issued multiple documents related to the outbreak that reflected markedly different operational assumptions regarding respiratory transmission risk. A WHO Disease Outbreak News report acknowledged possible person-to-person transmission but continued largely to frame precautions around direct-deposition (droplet or spray) and contact transmission outside aerosol-generating procedures.[1] In contrast, contemporaneous WHO operational and contact-management guidance adopted substantially more precautionary measures.[2, 3] Although these WHO documents do not formally contradict one another, they reflect different conceptual and operational approaches to respiratory transmission risk.

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WHO’s interim guidance explicitly invokes the precautionary principle and recognises exposure risks associated with enclosed and shared spaces, transport settings, and prolonged indoor interactions.[2] It classifies all passengers and crew onboard the MV Hondius as high-risk contacts, recommends quarantine and active monitoring for 42 days, and advises use of FFP2/N95 respirators when social interactions are unavoidable.[2] That advice also states that the “highest risk of transmission” may occur during the prodromal phase and recommends identifying contacts beginning two days before symptom onset as a precautionary measure.[2] These changes represent a substantial evolution from earlier formulations focused primarily on direct contact and droplets.

WHO’s contemporaneous technical note for disembarkation and onward management of passengers and crew adopts an even more precautionary operational framework.[3] The document recommends universal respirator use (N95/FFP2) for all passengers and crew during disembarkation and screening procedures, explicitly describing this as a “precautionary source control measure.”[3] It also recommends respirators, eye protection, gowns, and gloves for healthcare workers providing direct care to suspected or confirmed cases; respirators for patients during transfer; outdoor or well-ventilated screening areas; and open-window ventilation during transport.[3] Operationally, these recommendations resemble precautionary guidance used for pathogens with suspected inhalation transmission, even though WHO guidance still stops short of explicitly characterising Andes virus transmission as airborne.

In contrast, updated CDC guidance recommends that patients with suspected or confirmed Andes virus infection be managed in airborne infection isolation rooms, with healthcare workers using “an N95 or higher-level respirator” together with gowns, gloves, and eye protection.[4] Rapid scientific advice issued by the European Centre for Disease Prevention and Control (ECDC) recommends respirators (FFP2/FFP3), transmission-based personal protective equipment, enhanced ventilation without air recirculation, masking during transport, and precautionary quarantine of all passengers onboard the ship.[5] Unlike ECDC guidance, WHO documents do not explicitly address avoidance of air recirculation or use of portable HEPA filtration.

The evidence supporting respiratory person-to-person transmission of ANDV is now substantial and comes from epidemiological, biological, and operational observations. It has been documented repeatedly for nearly 30 years.[6-10] The 2018–19 Epuyén outbreak in Argentina is especially instructive. Martínez and colleagues reconstructed transmission chains involving 34 confirmed infections and 11 deaths after a single zoonotic introduction.[9] Transmission was amplified by symptomatic individuals attending crowded social events, including a birthday gathering and a wake.

The supplementary outbreak reconstruction in Appendix 1 to reference 9 provides evidence difficult to reconcile with a purely contact-based model of transmission.[9] In the initial superspreading event, more than 100 people attended a birthday gathering at which secondary infections occurred among individuals seated up to approximately 2.5 metres from the index patient, who attended the event for 90 minutes. One infected attendee reportedly merely crossed paths with the index case en route to a restroom and had no physical contact with him (Appendix 1 to ref 9).^[9]

Airborne transmission is known to be an important factor in zoonotic transmission, especially of Sin Nombre virus (the principal cause of hantavirus pulmonary syndrome in North America), where infection is strongly associated with inhalation of aerosolised rodent excreta in enclosed spaces.^[11] Several transmission events in the Epuyén outbreak were considered consistent with inhalational exposure. Martínez et al reported that transmission may have occurred through “inhalation of droplets or aerosolized virions,” and in over half of reconstructed secondary cases, exposure occurred on the first day of fever in the index patient.[9] Prodromal symptoms frequently included fever, headache, abdominal pain, nausea, diarrhoea, and malaise before respiratory deterioration.^[9] WHO’s updated guidance now similarly acknowledges that transmission risk may be greatest during the prodromal phase, when symptoms are non-specific and potentially difficult to recognise.[2]

WHO guidance repeatedly emphasises “close contact” transmission.[1, 2] Yet “close contact” is not itself a mechanism of transmission but rather a description of circumstances under which exposure occurs. WHO now explicitly includes shared enclosed spaces, shared cabins, prolonged indoor interactions, and transport settings within its exposure definitions.[2] WHO’s own 2024 technical consultation on airborne pathogens recognised that close contact frequently represents exposure to concentrated aerosols from exhaled breath as well as larger droplets and contaminated surfaces.[12] Far from arguing against airborne spread, the repeated association with “close contact” is entirely consistent with respiratory aerosol transmission, since close proximity is precisely where exposure to concentrated infectious aerosols is greatest.[13, 14] Thus, repeated reports of transmission predominantly during “close contact” should raise concern for airborne inhalation risk, not lower it.

Biological plausibility for airborne-inhalation transmission is substantial. Andes virus RNA and antigen have been detected in saliva and respiratory-associated specimens, and infectious virus has been recovered from patient-derived materials.[15-17] Experimental evidence supports respiratory and salivary pathways of transmission.[17] Yet we are unaware of any research which has examined aerosol shedding dynamics or the timing of contagiousness relative to symptom onset.

This uncertainty is acknowledged by the International Hantavirus Society and leading hantavirus researchers in their recent statement regarding the current outbreak.[18] They note that “human-to-human transmission of ANDV should therefore no longer be regarded as hypothetical or unproven”, and they caution against “overly categorical statements that transmission can occur only after clear symptom onset.” [18]

Importantly, Epuyén outbreak investigators themselves adopted respiratory precautions substantially stronger than traditional droplet-based recommendations. Appendix 1 to reference 8 states that high-risk contacts were instructed to self-quarantine for 40 days and “were asked to wear N95 respirators in the presence of others.”[9] WHO’s updated interim guidance now similarly recommends respirators (FFP2 or N95) for high-risk contacts during unavoidable social interactions.[2] WHO’s technical note additionally recommends universal respirator use during disembarkation and screening procedures.[3] N95 respirators provide substantially greater source control than medical masks. In a randomised controlled trial, N95 respirators resulted in a 98% reduction in viral aerosol release from infected persons, significantly outperforming KN95s, surgical masks, and cloth masks.[19]

There is also strong evidence that respirators provide greater protection than surgical masks for healthcare workers against respiratory infections when worn continuously indoors. In a randomised clinical trial of 1669 healthcare workers, continuous N95 use resulted in significantly lower rates of clinical respiratory illness than either targeted N95 use or medical masks alone.^[20]

The setting of the present outbreak further strengthens the case for precaution. Cruise ships are highly conducive to respiratory spread because of prolonged indoor exposure, shared dining and social activities, variable ventilation, and extensive international travel, bringing opportunity for contact with novel pathogens. The current outbreak also involves subsequent commercial air travel, healthcare exposures across multiple countries, and incubation periods that may extend to 42 days.[1] Many of these circumstances are reminiscent of the introduction of SARS-CoV-1 into Canada and the United States.[21, 22]

Although efficient community transmission comparable to measles or SARS-CoV-2 has not been demonstrated, this is not justification for dismissing respiratory risk. The relevant public health question is not whether ANDV is highly transmissible, but whether substantial evidence consistent with infectious respiratory aerosol inhalation transmission of a pathogen with a current case fatality ratio which WHO itself estimates at 38%[1] warrants stronger respiratory protection. The answer should be yes in the face of uncertainty and following the precautionary principle.

This outbreak also has implications beyond ANDV itself. A rapidly evolving outbreak involving international travel, healthcare exposures, prolonged incubation periods, and possible respiratory transmission represents a test of global readiness for future severe respiratory pathogens. If a more efficiently transmissible pathogen with similar clinical severity emerged under comparable circumstances, delayed adoption of airborne precautions could have far greater consequences.

We therefore urge WHO and national public health agencies to continue strengthening precautionary respiratory protection strategies while transmission dynamics remain incompletely understood. Healthcare workers and first responders caring for suspected or confirmed cases should routinely use fit-tested respirators. Respirator use should also continue to be recommended for close contacts, exposed travellers, and others with prolonged shared indoor air exposure linked to the outbreak, particularly during travel and quarantine periods. Public health guidance should place greater emphasis on measures to reduce airborne transmission, including ventilation optimisation, avoidance of unfiltered air recirculation, and portable HEPA filtration — measures explicitly recommended by ECDC during transport, healthcare interactions, and environmental decontamination.[5]

The history of emerging infectious diseases repeatedly shows that delayed recognition of risk for airborne transmission leads to preventable infections among healthcare workers and the public;[23] this was certainly the case for COVID-19. [24] WHO’s contemporaneous guidance documents now implicitly acknowledge substantial uncertainty about respiratory transmission routes and the possibility of inhalation exposure.[2, 3] However, WHO’s conceptual framing of Andes virus transmission has not yet fully reconciled the operational implications of its own precautionary recommendations. In its 2024 framework, WHO stated that “airborne transmission/inhalation” can occur “when IRPs [infectious respiratory particles] have travelled either short or long distances from the infectious person”.[12]

WHO’s current guidance already incorporates many measures ordinarily associated with pathogens transmitted through inhalation, including universal respirator use, ventilation measures, patient masking during transfer, and respirators for healthcare workers providing routine care. Yet these measures coexist with conceptual language that continues to avoid explicit recognition of airborne respiratory transmission risk. This disconnect matters. Conceptual framing influences how risks are perceived, communicated, and operationalised by public health authorities, healthcare institutions, employers, and the public.

In the face of continuing uncertainty surrounding a potentially lethal pathogen with documented human-to-human spread, WHO should align its conceptual framing with the precautionary implications of its own operational guidance and explicitly recognise the plausibility of infectious respiratory aerosol inhalation transmission. Failure to do so risks perpetuating avoidable ambiguity at precisely the moment when clarity and precaution are most needed.

WHO’s default recommendations for severe pathogens with respiratory transmission potential should begin from a precautionary airborne-risk framework — including respirators, ventilation optimisation, and portable HEPA filtration — and only be relaxed if evidence later demonstrates that such measures are unnecessary. The costs of implementing these protections early are modest; the costs of delaying them during a high-consequence outbreak may be profound.

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References

1. World Health Organization: Hantavirus cluster linked to cruise ship travel, Multi-country. 8 May. Geneva: WHO. Accessed 9 May 2026 at https://www.who.int/emergencies/disease-outbreak-news/item/2026-DON600; 2026.

2. World Health Organization: Management of contacts of Andes virus (ANDV) cases from the MV Hondius cruise ship: Interim guidance 8 May. . Geneva: WHO. Accessed 10 May 2026 at https://www.who.int/publications/m/item/management-of-contacts-of-andes-virus-(andv)-cases-fromthe-mv-hondius-cruise-ship; 2026.

3. World Health Organization: Technical note for the disembarkation and onward management of passengers and crew in the context of an Andes virus-associated cluster, MV Hondius cruise ship: Interim guidance. 8 May. Geneva: WHO. Accessed 11 May at https://www.who.int/publications/m/item/who-technical-note-for-the-disembarkation-and-onward-management-of-passengers-and-crew-in-the-context-of-an-andes-virus-associated-cluster-mv-hondius-cruise-ship; 2026.

4. Centers for Disease Control and Prevention: Multi-country Hantavirus Cluster Linked to Cruise Ship. CDC Health Alert Network (CDCHAN-00528), 8 May. . Atlanta, GA: CDC. Accessed 9 May 2026 at https://www.cdc.gov/han/php/notices/han00528.html. ; 2026.

5. European Centre for Disease Prevention and Control: Rapid scientific advice on the management of passengers: in the context of the Andes virus outbreak on the cruise ship MV Hondius (9 May). Stockholm: ECDC. Accessed 9 May 2026 at https://www.ecdc.europa.eu/en/news-events/ecdc-publishes-guidance-management-passengers-linked-andes-hantavirus-outbreak-cruise; 2026.

6. Wells RM: An unusual hantavirus outbreak in Southern Argentina: person-to-person transmission? Emerg Infect Dis 1997, 3:171-174.

7. Martinez VP, Bellomo C, San Juan J, Pinna D, Forlenza R, Elder M, Padula PJ: Person-to-person transmission of Andes virus. Emerging infectious diseases 2005, 11(12):1848.

8. Alonso DO, Pérez-Sautu U, Bellomo CM, Prieto K, Iglesias A, Coelho R, Periolo N, Domenech I, Talmon G, Hansen R: Person-to-person transmission of Andes virus in hantavirus pulmonary syndrome, Argentina, 2014. Emerging infectious diseases 2020, 26(4):756.

9. Martínez VP, Di Paola N, Alonso DO, Pérez-Sautu U, Bellomo CM, Iglesias AA, Coelho RM, López B, Periolo N, Larson PA: “Super-spreaders” and person-to-person transmission of Andes virus in Argentina. New England Journal of Medicine 2020, 383(23):2230-2241.

10. Ferrés M, Vial P, Marco C, Yanez L, Godoy P, Castillo C, Hjelle B, Delgado I, Lee S-J, Mertz GJ: Prospective evaluation of household contacts of persons with hantavirus cardiopulmonary syndrome in Chile. The Journal of infectious diseases 2007,195(11):1563-1571.

11. Duchin JS, Koster FT, Peters C, Simpson GL, Tempest B, Zaki SR, Ksiazek TG, Rollin PE, Nichol S, Umland ET: Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease. New England Journal of Medicine 1994, 330(14):949-955.

12. World Health Organisation: Global technical consultation report on proposed terminology for pathogens that transmit through the air. Geneva: WHO. Accessed 9 May 2026 at https://www.who.int/publications/m/item/global-technical-consultation-report-on-proposed-terminology-for-pathogens-that-transmit-through-the-air; 2024.

13. Chen W, Zhang N, Wei J, Yen H-L, Li Y: Short-range airborne route dominates exposure of respiratory infection during close contact. Building and Environment 2020, 176:106859.

14. Jones NR, Qureshi ZU, Temple RJ, Larwood JP, Greenhalgh T, Bourouiba L: Two metres or one: what is the evidence for physical distancing in covid-19? bmj 2020, 370.

15. Ferrés M, Martínez-Valdebenito C, Henriquez C, Marco C, Angulo J, Barrera A, Palma C, Pinto GB, Cuiza A, Ferreira L: Viral shedding and viraemia of Andes virus during acute hantavirus infection: a prospective study. The Lancet Infectious Diseases 2024, 24(7):775-782.

16. Godoy P, Marsac D, Stefas E, Ferrer P, Tischler ND, Pino K, Ramdohr P, Vial P, Valenzuela PD, Ferrés M: Andes virus antigens are shed in urine of patients with acute hantavirus cardiopulmonary syndrome. Journal of virology 2009, 83(10):5046-5055.

17. Pizarro E, Navarrete M, Mendez C, Zaror L, Mansilla C, Tapia M, Carrasco C, Salazar P, Murua R, Padula P: Immunocytochemical and ultrastructural evidence supporting that Andes hantavirus (ANDV) is transmitted person-to-person through the respiratory and/or salivary pathways. Frontiers in microbiology 2020, 10:2992.

18. International Hantavirus Society: Statement regarding the current Andes virus outbreak investigation (8 May). . Santiago, Chile: International Hantavirus Society. Accessed 9 May 2026 at https://zenodo.org/records/20075274; 2026.

19. Lai J, Coleman KK, Tai SHS, German J, Hong F, Albert B, Esparza Y, Rastogi D, Srikakulapu A, Kalliomäki P et al: Relative efficacy of masks and respirators as source control for viral aerosol shedding from people infected with SARS-CoV-2: a controlled human exhaled breath aerosol experimental study. eBioMedicine 2024, 104.

20. MacIntyre C, Wang Q, Seale H, Yang P, Shi W, Gao Z, Rahman B, Zhang Y, Wang X, Newall AT: A randomized clinical trial of three options for N95 respirators and medical masks in health workers. American journal of respiratory and critical care medicine 2013, 187(9):960-966.

21. Oberholtzer K, Sivitz L, Mack A, Lemon S, Mahmoud A, Knobler S: Learning from SARS: preparing for the next disease outbreak: workshop summary. 2004.

22. Olsen SJ, Chang H-L, Cheung TY-Y, Tang AF-Y, Fisk TL, Ooi SP-L, Kuo H-W, Jiang DD-S, Chen K-T, Lando J: Transmission of the severe acute respiratory syndrome on aircraft. New england journal of medicine 2003, 349(25):2416-2422.

23. Jimenez JL, Marr LC, Randall K, Ewing ET, Tufekci Z, Greenhalgh T, Tellier R, Tang J, Li Y, Morawska L et al: What Were the Historical Reasons for the Resistance to Recognizing Airborne Transmission during the COVID-19 Pandemic? Indoor Air 2022, 32:e13070.

24. Morawska L, Bahnfleth W, Bluyssen PM, Boerstra A, Buonanno G, Dancer SJ, Floto A, Franchimon F, Haworth C, Hogeling J: Coronavirus Disease 2019 and Airborne Transmission: Science Rejected, Lives Lost. Can Society Do Better? Clinical infectious diseases 2023, 76(10):1854-1859.

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Covid Hospitalisations

Well it was nice while it lasted. We had an unprecedented 10 months of low and stable Covid levels in England - but this is now over. We are seeing a definite, significant wave of Covid infections across England. The below chart of Covid hospitalisations in England since September 2023 shows this clearly. The last time we had more recorded Covid hospitalisations was two years ago, and this wave isn’t over yet.

I’m sure most people now know someone in bed with Covid. If someone says they are in bed with flu, it’s almost certainly Covid, given that the number of people admitted to hospital for Covid last week was 50 times higher than the number admitted for flu! Flu is seasonal - last year we had a massive flu spike, concentrated within a few weeks around New Year, and this year’s season has barely started.

Covid simply is not seasonal yet (although winter behaviours such as mixing indoors help it spread). Even the low and stable Covid hospitalisation levels we saw between November 2024 and last month are substantially higher than the effectively zero flu and RSV hospital admissions, as is clear from the chart of hospitalisations for all three diseases below.

Wastewater indicators

England (stupidly) isn’t doing Covid wasterwater analysis. The good thing about wastewater testing is that measured virus amounts are not reliant on people getting tested or having symptoms, so it gives a pretty good idea of levels of infection in the community. That said, it’s not a precise estimate of number of people infected because there’s variation between individuals, and between variants, on how much virus is excreted.

Scotland is still measuring wastwater and interestingly it is not showing much at the moment (a modest increase compared to a few months ago).

BUT Scotland also isn’t experiencing a as big a spike in Covid hospital admissions as England, so it’s possible that the wave England is experiencing will hit Scotland a bit later (it has hit Wales already). Many countries in Europe are however seeing Covid waves reflected in their wastewater measurements as shown in this chart by Bob Hawkins.

Variants

We are not having a wave because there’s a new Covid variant. The latest variant picture from UKHSA shows that Omicron variant XFG is firmly dominant here and has been since July. I did think it would cause a summer wave as it took over quite rapidly in May and June, but it didn’t. This suggests that the current wave is driven more by people’s waning immunity (especially given no big waves for almost a year) and more indoor mixing, from changing weather and return to work and education after summer.

Boosters

The autumn vaccine booster campaign has only just started and so far about 14% of over-75s and 8% of eligible clinically vulnerable people have had it. The eligibilty criteria keep narrowing - this round the following groups can get a free NHS vaccine.

I urge anyone eligible to get boosted! If you can afford the vaccine (currently almost £100 at Boots!!), then it might be worth doing. Personally, I am planning to buy a booster in November, to get maximum protection in December and over Christmas and New Year. Sandy Laping pointed me to a recent peer-reviewed paper looking at timing of booster vaccinations. It suggested a booster is most effective from 6 months since your last Covid infection (i.e. when immunity from your last infection has started to wane), so that’s also worth bearing in mind.

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How is the NHS faring?

As we head into another winter, let’s take stock of how the NHS is doing. Has it has recovered after the last few winters? No.

Ambulance response times are at their ‘summer’ baseline, but that baseline is notably higher than its pre-pandemic baseline. Before 2020, even the winter peak ambulance response time was below the current summer baseline.

Long waits in A&E tell an even worse story. Before 2021, it was almost unheard of to wait more than 12 hours on a trolley before being admitted. Now, tens of thousands of people do every month. The number falls every summer, but year on year that summer baseline has grown higher and we are already seeing a sharp increase in September.

What this means is that we head into winter with a stretched NHS, and which is getting more stretched every year. Labour has put resources into reducing waits and getting the backlog down but all they’ve done is stop the increase. Yes,numbers are trending better, but if the waiting list keeps reducing by only 160,000 people a year, it will be 2040 before it’s at April 2020 levels and 2050 before it’s back to 2010 levels. With government finances so stretched, not enough staff and increasing restrictions on immigration, I am not hopeful that we’ll see noticeable improvements any time soon.

Summary

We are definitely in another significant Covid wave. Neither flu nor RSV have kicked in yet this season, so if you feel grotty and with a fever, it’s most likely to be Covid. Try to avoid mixing with others while infectious, especially anyone who might be more vulnerable to getting seriously ill from Covid (e.g. elderly parents or grandparents, especially those who’ve not been boosted). In fact, if you feel grotty with anything infectious, best to reduce indoor mixing. Your friends, colleagues and family won’t thank you for passing it to them, whether it’s Covid, flu or even a cold!

If you are eligible for a free NHS booster, I’d encourage you to get one. If not, and you can afford to, you might want to invest in a private Covid booster. Oh, and get your flu jab too.

Last summer we had a large Covid wave in the UK, followed by another wave in the autumn but then things have been as quiet as they’ve been since the start of the pandemic since November 2024. Lasting six months so far, this has been a very welcome respite but it looks as if this might be coming to an end in the coming months.

A new variant called NB.1.8.1 has emerged which has quickly become dominant in China, and is taking over in Singapore, Hong Kong, Taiwan and Australia. All these countries are reporting significant increases in reported cases and hospital visits. The apparent growth advantage of NB.1.8.1 over current strains prompted the World Health Organization (WHO) to designate it a “variant under monitoring” three days ago.

It remains rare in Europe but is increasing - the WHO report that its share has grown from 1% to 6% in the most recent 4 weeks of monitoring, representing an approximate doubling of just under two weeks. Since the UK and Europe have seen low Covid activity for 6 months, and most people haven’t had a Covid booster in years, our population immunity to infection (if not necessarily severe illness) is also probably lower than it’s been for a while. This combined with the significant growth means that it’s quite possible we will see a large wave of infection here in two months or so once it becomes dominant.

That said, there is no evidence that this variant causes more severe disease and because it is an offshoot of last summer’s JN.1 strain, which is the strain used for the most recent vaccines, hopefully anyone boosted in the last 12 months will be well protected from severe illness. Thus, we might see many people getting ill, but hopefully a much lower relative increase in the number needing hospital.

Newer kid on the block: XFG

There is an even newer variant popping up which has got some Covid experts’ attention. The main worry with XFG is that it is an offshoot of a much older Coronavirus strain and has added a lot of new mutations, raising concerns that it could more easily evade our immune responses. That said, a new pre-print (research that is not yet peer-reviewed) reported that while XFG is much more immune-evasive than other current variants it is less good at attaching to and entering human cells which could limit its spread and impact. We’ve seen previous variants that have found good immune evasion nevertheless die off because they were not as good as infecting humans as other circulating variants. Ma et al, in a 2023 Nature paper, found that the ability to enter cells (via “ACE2 binding”) was if anything more important than extent of immune evasion in determining virus spread, and so I’m not too worried about this variant unless it finds a way around this problem. However, XFG shows that there are still plenty of mutational spaces for the virus to explore and a new significant variant is definitely possible.

Covid is not yet in any way seasonal

As well as the likelihood of a summer wave, I want to highlight - again - that Covid is not in any way a winter virus. It is not like RSV and Flu and its waves are not predictable. There is a desire to believe that Covid is now just another ‘winter virus’, but doing so risks leaving us unprepared when the facts are very different.

Vaccine development has had a huge impact on our health and longevity. In the last 50 years its estimated vaccines have saved over 150 million lives. Vaccine design has changed enormously since the early days of Jenner and Pasteur; becoming increasingly more sophisticated as our understanding of immunology and infections has become more advanced.

However, the pace of scientific development does not necessarily equate to wider public understanding. This mismatch can lead to confusion and even vaccine hesitancy among the public. Vaccine hesitancy and confusion about vaccines can be further fuelled by misinformation (misunderstanding) and disinformation (deliberate spreading of incorrect information). This issue of mis-and dis-information has been especially acute and severe with regards to the “messenger RNA” (mRNA) vaccines. This is perhaps because this type of vaccine uses a technology that will be unfamiliar for many people, despite having been in use for decades. To this end, we at Independent SAGE have put together a document that hopes to address common queries, demystify the technology as well as debunking common myths.

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What is an mRNA vaccine?

First of all I just want to clarify what mRNA is - in simple terms mRNA is a recipe for how to make a specific protein. It is a fundamental component of all life on our planet which conveys the information (DNA) from our genes to enable us to make the specific proteins we need to survive. As such, mRNA vaccines contain the genetic “recipe” corresponding to part of the pathogen or disease they target.

What does this mean in practice? When the mRNA vaccine is administered, cells at the site of injection take up the mRNA and follow the instructions to make the target protein-this is exactly what happens when cells get infected with a pathogen. Our immune cells can detect the change in the cell and then react accordingly to start mounting a protective immune response. However, UNLIKE a pathogen the vaccine mRNA instructions to make the protein are temporary. The mRNA from the vaccine is short-lived, like all mRNA is. We have special enzymes that recognise and chop up mRNA- these enzymes are called RNAses.

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Were mRNA vaccines that were used during the peak of the pandemic new technology?

Whilst mRNA vaccines may have seemed like the new kid on the block when the mRNA vaccines for COVID were rolled out in 2020 in fact that was not the case at all! The SARS-CoV-2 mRNA vaccines for COVID were made possible by years of research and clinical development into mRNA vaccine technology as well as research into SARS and MERS (diseases caused by coronaviruses related to SARS-CoV-2).

The first human clinical trial for an mRNA vaccine was against rabies virus and took place in 2013. A trial for an influenza vaccine followed in 2015. Multiple other vaccines targeting other infections and cancers were in human clinical trials before the peak of the COVID-19 pandemic. All had shown promising results and no major safety concerns. Given how flexible mRNA vaccine technology is, it was inevitable it would be investigated and of interest to address the desperate need for a global COVID-19 vaccine. In fact, compared to more traditional vaccine approaches tested (such as whole, inactivated virus), the mRNA vaccines by far outperformed the other vaccines that were used in 2020/21. This was true both for lab measurements of immunity and for real-world efficacy, i.e. stopping the majority of people developing severe COVID-19 or dying.

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Why are mRNA vaccines under threat?

There has been a lot of misinformation and disinformation about vaccines and especially mRNA vaccines. This has become particularly politicised in the United States. For example, Joseph Ladapo, Florida’s surgeon general, has been an outspoken critic of vaccines. In January 2024, he called for a halt in the distribution and use of mRNA Covid boosters claiming that the vaccines could integrate into our genome. This is NOT TRUE nor is it even remotely possible. The mRNA delivered by the vaccine cannot enter the cell nucleus, where your DNA is stored, and will in fact degrade naturally within our cells within a few hours. The vaccines have NONE of the machinery that is needed to even incorporate into DNA. Ladapo has also suggested the vaccines cause cancer despite there being NO scientific evidence linking the vaccines to cancer. In fact, his misleading claims about mRNA vaccines have been regularly debunked. His actions led him to be shown to violate his university’s rules against careless, irregular, or contentious research practices. However, his is not the only prominent voice making spurious claims about mRNA vaccines.

Several (predominantly Republican) states in the US are now considering bills to limit or ban the use of messenger RNA vaccines. Bills introduced in Texas propose to ban the administration, manufacture or sale of mRNA vaccines there. Legislation in Kentucky would prevent the use of mRNA vaccines in kids under the age of 18 and in Idaho a Republican state senator has proposed a 10-year moratorium on mRNA vaccine administration. A bill introduced by Republicans in Minnesota state legislature goes several steps further calling mRNA vaccines "weapons of mass destruction" - and if this bill is passed would carry punishment of up to 20 years in prison for possessing or administering them. Whilst several of these state measures are unlikely to pass into law, the rampant disinformation that is being spread is extremely concerning as is the sentiments they express.

Changes in law are not the only way that access to mRNA vaccines in the States may be curbed. The new head of the NIH Bhattacharya said he would support pulling the regulatory authorization for the marketing of the Covid mRNA vaccines in a post on X in June 2024. Furthermore, the lead for health policy in the US - Robert Kennedy Jr is a known long-standing vaccine sceptic who has previously criticized the mRNA COVID-19 vaccines. Since the new administration has come into power it is notable that contracts with Moderna for mRNA vaccines are being reviewed for example for bird flu and flu. Research grants researching the technology are amongst the vast swathes of grants that are being paused whilst the NIH, NHF and DOGE re-assesses them and scientists warned to avoid submitting research using mRNA vaccine technology.

Why does it matter if research and access to mRNA vaccines is reduced?

mRNA vaccines have several advantages over other vaccine platforms including their flexibility in the targets they are developed to. This means that the list of applications for mRNA vaccines are growing and include not just infectious disease but also cancers. This not to say other vaccine platforms are not important- they very much are and there is a place for a variety of vaccine platform types especially in the context of infectious disease.

However for cancer, mRNA vaccines have the potential to change the landscape for treatment of some types of cancer that been so resistant to standard immunotherapies such as pancreatic cancer. The fact that the mRNA vaccine platform is so flexible means that it can be tailored to enable the development of personalised cancer vaccines. These vaccines train the immune system to recognise and attack a patient’s own cancer cells, thereby helping to prevent the disease from coming back. Here the goal is to use mRNA vaccines to teach the immune system to fight cancer by targeting proteins called “neoantigens”, which are unique to a person’s cancer cells. This has the potential to revolutionise cancer care, especially with cancers that are difficult to target with targeted chemotherapies, radiotherapy, or immunotherapy. Trials for several cancer vaccines are well under way. Measures that hinder research and or access to mRNA vaccines therefore has grave implications for the future of cancer treatment - something that is not being made clear by those attacking the vaccines.

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We believe it’s important and timely to provide some clarity about mRNA vaccines. To this end, we have assembled some reliable information about how vaccines work and specifically what mRNA vaccines are. We hope that this will help people to understand these products better and so make informed decisions about vaccination.

Whether you choose to receive a vaccine, or to access one for your children, is a personal choice, but we want to make it easier for that decision to be an informed one.

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This is the reasoning behind the introduction of physician associates (PAs) in the UK (and in a handful of other countries, although differences in training and roles mean that they cannot easily be compared).¹ A PA is someone with an undergraduate degree, usually but not always in a science of some sort, who has done an additional two years’ training (compared to doctors, whose basic training is 4-6 years, followed by a similar number of years of postgraduate training). PAs are a great idea in theory. But the experiment appears to have largely failed, for reasons we explain below.

The UK’s PA experiment began in 2006, when just 15 US-trained PAs, recruited by open advertisement, were placed in Scottish hospitals and general practices for short periods, mainly in remote under-doctored settings.² An independent research team conducted interviews with the PAs, staff who had worked with them and patients who had been managed by them. The results of this pilot exercise were described very briefly and in almost exclusively positive terms in an academic paper. Two PAs who had been placed in intermediate care settings, for example, were described as “confident, flexible and autonomous”, “reported capable of working at level of a staff grade doctor” and “perceived to have a positive impact on patient throughput”. Patients were reported as “satisfied” with care delivered by PAs. Two “minor” safety incidents were documented—one “mix-up” with patient notes and one in which a PA advised a patient to change their drug regimen without consulting their GP (the authors did not report which drugs or anything about the context). Nothing was measured quantitatively. Nobody checked the clinical decisions made by the PAs.

Put another way, 15 self-selecting Americans, who had had longer and more intensive training than was (or is) offered in the UK, were well-received in remote areas of Scotland that had struggled to retain doctors. This led to an assumption that all PAs were safe, were clinically effective and cost-effective, and could be deployed in place of doctors in many, if not all, clinical tasks. Several UK universities began to offer two-year Physician Associate courses, and policymakers created incentives for NHS organisations to hire graduates from these courses instead of (or, sometimes, as well as) doctors in training. This combination of push and pull led to a rapid increase in numbers. As the Financial Times reported recently, the NHS employed only 120 PAs in 2015 but this rose to 3200 by 2023, half of them in primary care.

2023 was also the year when the NHS published its Long Term Workforce Plan,³ against a background of worsening crises. Doctors were on strike (always a sign of a health system in trouble)⁴ or were emigrating; many posts remained unfilled, and hospitals were spending vast sums on locums hired through extorting agencies.⁵ The plan was ambitious: it promised major reforms designed to grow the workforce, retain staff, and reform working practices. It seemed authoritative, backed up with detailed modelling and extensively referenced. Yet of the 270 references cited, most related to other policy documents or internal reports. Only six were research studies published in peer-reviewed journals and none of these related to PAs. In this context, the proposal to create a workforce of 10,000 PAs by 2036 seemed plucked out of the sky. Other elements of the Long Term Workforce Plan, such as a proposed expansion of medical schools, had not been thought through.⁶ Some, such as a proposal to create medical apprenticeships, have already been abandoned.

One of the shortcomings of the Long Term Workforce Plan was lack of clarity on what problem PAs were meant to solve.⁷ They had initially been called physician assistants, suggesting that they were to assist doctors by relieving them of some basic tasks. But in 2013 they were renamed physician associates. A Faculty of Physician Associates was created within the Royal College of Physicians of London. The government, with enthusiastic support from the General Medical Council (but to the alarm of some doctors), took forward legislation to regulate them.⁸ Proponents of the PA experiment labeled them as “medical professionals”, ignoring the extensive literature on what constitutes a profession,⁹ and described their training as “following the medical model”, a term that seemed authoritative but was never actually defined.¹⁰ Hospitals and general practices facing difficulties in recruiting doctors began to employ PAs as doctor substitutes, sometimes on the same rotas as doctors.

The expansion of PA numbers and the extension of their scope, reflected in their new title, were accompanied by growing concerns. Were PAs really as clinically effective as doctors, even in “low complexity” cases? Were they as cost-effective? Patients were, understandably, confused and many assumed that the person they were seeing was a doctor. Above all, were PAs as safe as policymakers were now assuming? The answer to all these questions is certainly not an unqualified “yes”, and there is growing evidence that it may be a firm “no”.

It's hard to measure whether one health professional is as “clinically effective” or “cost-effective” as another. Let’s say you attend your GP’s surgery for a routine blood pressure check. The healthcare assistant (HCA, someone with minimal training, hired on a low wage to perform very routine tasks) takes your blood pressure very competently. It’s 155/90. They record this on your electronic record. This takes them about 8 minutes, but their hourly rate is cheap. It’s now someone else’s job to become concerned about that blood pressure level and ask you to come in to discuss it.

Alternatively, you might see the PA. They check your blood pressure, explain that 155/90 is just outside the recommended range for someone of your age, and (following a guideline) advise you to start taking your own blood pressure at home and bring the readings in for checking. Or perhaps the PA, knowing that this reading is out of range but unsure of the next step, knocks on the GP’s door and asks their advice. All this might take them 15 minutes (at a higher hourly rate than the HCA, but they’ve achieved a lot more). The GP’s time (90 seconds or so) advising the PA would also need to be factored into the costs.

If you went directly to a GP for your blood pressure check-up, they would follow the same guideline as the PA and give you the same advice, but, on average, they’d do so more quickly (taking perhaps 9 minutes rather than 15). This result would be achieved at a cost marginally more than the cost of the PA (since the PA is both slower and cheaper than the GP), but approximately the same cost if the 90-second input of the advising GP is factored in. However, if your GP was operating at the top of his or her game, they might also notice that you smelt faintly of alcohol even though it was only 11.30 am. In the context of a long-term doctor-patient relationship, they might mention this and ask if things are OK at home. You might then disclose domestic violence—a complex problem that the GP could get started on within the same consultation, thus achieving highly effective and cost-effective care. Less dramatically, your GP might check your blood pressure opportunistically whenever you attended for another reason, which would save you a special trip to either the HCA or the PA.

Unfortunately, the only UK-based study which attempted to compare the cost-effectiveness of PAs and GPs in general practice measured neither the time of the supervising GP (including any delays as the PA and GP found a slot when both were free – with neither hanging around waiting for the other to finish their consultation) nor any of the myriad of subtle things an experienced GP does in a consultation over and above dealing with the problem the patient has made the appointment for.¹¹ That study is often interpreted, erroneously, to mean that PAs can do GPs’ jobs more cheaply than the GPs themselves. In reality, the study showed nothing of the sort.

Here's another example. You twist your ankle while out walking and decide to go and get checked out in the emergency department. You’re in luck – you see the consultant, who quickly and skilfully examines your ankle. She assures you that nothing’s broken and that you don’t need an X-ray. You’re fine with this as she’s clearly an expert. If you’re less lucky, you’ll see a junior doctor or a PA and spend a lot longer in the ED before you depart with reassurance. It may be that the consultant, despite her expensive hourly rate, is the most cost-effective (and safest) of the three. Broadly speaking, the less training someone has had, the longer they take to see patients and the more trigger-happy they are with the prescription pad and the investigation request form. In one study in the emergency department, PAs were 2.7 times as likely to send patients for X-rays as junior doctors, after adjusting for case mix.¹²

Does this mean that PAs are never effective or cost-effective? Not quite. As we showed in a recent systematic review of the UK evidence published in the British Medical Journal,¹³ the evidence isn’t that definitive yet. But it’s pointing to the conclusion that if they are effective it is only in very limited circumstances. Furthermore, they are rarely cost-effective when working autonomously, partly because of the double-handling needed to oversee and check their work and partly because of the additional costs of the unnecessary tests they order. The circumstances where they might be effective is when working as part of a team. One study of PAs working on hospital wards, for example, suggested that they were useful and valued when doing “clinically related” tasks (such as finding test results, taking blood or writing discharge summaries) that contributed to the smooth running of the team (one doctor described them as “not the engine, but the oil in the engine”).¹⁴ That study set out to measure cost-effectiveness but found that the costs (and hence the value) of PAs could not be meaningfully disaggregated from that of the team as a whole. The question then arises: could these same “oil in the engine” tasks be performed by a cheaper member of staff, such as a clerk, a phlebotomist or a nurse? Inexplicably, such a study, which would involve attending to an entire workforce rather than simply hiring one staff group and trying to measure its impact, has not been done.

Finally, let’s talk about safety. While it may seem intuitive that recruiting additional staff would make things safer, the empirical evidence does not support this. There is now extensive evidence that adding nursing associates to nursing teams, even when keeping the numbers of nurses the same, leads to worse outcomes.¹⁵ The reasons are unclear, but one explanation is that tasks are inappropriately delegated to less well-trained staff.

Deaths linked to decisions by PAs seem to be very rare, but several have occurred in the UK. Emily Chesterton, 30, developed calf pain, palpitations and breathlessness (classic symptoms of a life-threatening thrombosis) four weeks after a bout of COVID-19 (which can, rarely, cause thrombosis). A PA working semi-autonomously in a GP surgery diagnosed a muscle sprain and anxiety. After Emily returned a second time in the same week, complaining of worsening symptoms, they recommended a beta-blocker to slow the heart. Emily died soon afterwards of a thrombosis, having not seen a doctor at all during her final illness.

Pamela Marking, 77, developed severe abdominal pain and brought up blood through her nose; she attended the emergency department and was diagnosed with a “nosebleed” by a PA. She died later at home from internal bleeding. In a Prevention of Future Deaths Report, the coroner expressed concern at the PA’s lack of understanding of the significance of abdominal pain in a patient who was losing blood. She noted that both Mrs Markham and her son had assumed that she had been seen by a qualified doctor, and said that “the term ‘Physician Associate’ is misleading to the public”.

Susan Pollitt, 77, was admitted to hospital with a broken arm and found to have some other conditions including fluid on the abdomen. On the advice of a junior doctor, but without consulting the consultant in charge, a PA inserted a tube to drain off the excess fluid. He ordered that the tube be clamped, and it remained so for several hours. Mrs Pollitt died of septicaemia a few days later. The coroner’s report commented that there had been no clinical indication Mrs Pollitt to have the tube inserted in the first place, that the tube should not have remained clamped, and that the prolonged clamping likely increased the risk of infection.

Ben Peters, an apparently healthy 25-year-old, developed sudden onset chest pains, breathlessness and aching arms (classic symptoms of aortic dissection, a life-threatening emergency). He attended the emergency department and was sent for a chest X-ray, ECG and a blood test for troponin (a test for heart attack), which were all reported as normal. He was then seen by a PA who, after discussing his case briefly with a consultant, discharged him with a diagnosis of panic attack. Ben died later that day, having not been assessed by a doctor.

Safety incidents should never be blamed on one person’s individual failings. We should ask “what system issues have contributed to the incident, and how does the system need to change to prevent a similar incident in the future?”. The coroner’s report on Mrs Pollitt’s death, for example, noted the low staffing levels in the hospital at the time of her death.

There are many additional system issues identifiable from these four cases. One is that all might reasonably been classified as “low complexity” at the stage of initial triage. A young woman with (in her own words) a “muscle strain”, someone with a “nosebleed”, someone with a “broken arm” and an apparently fit young man with chest pain but in whom tests have shown no heart attack.

The idea that patients can be straightforwardly and proactively divided into “complex” (to be seen by doctors) and “non-complex” (safe to be seen by PAs) is dangerously incorrect. Rather, some life-threatening illnesses begin in ways that are indistinguishable from simple, self-limiting conditions. An early cancerous breast lump may feel just like a benign lumpy breast. An ectopic pregnancy (which, if untreated, can kill both the foetus and the mother) may first show itself with some mild “spotting” (a common symptom in normal pregnancies). Sepsis (blood poisoning) can start with symptoms that mimic flu. The rash of meningococcal disease looks similar (but not identical) to that of many benign viral illnesses.

Doctors acquire their clinical knowledge in two broad ways. First, from detailed training in the human body, how it works, why it goes wrong and how particular treatments work—in other words, anatomy, physiology, pathology and pharmacology. Second, from “scripts”—the accumulated stories of the hundreds of patients they have seen personally, and also those that they have discussed with other doctors. In their two years of training, PAs can only cover the basic medical sciences extremely superficially, something confirmed by inspection of their curricula. An undergraduate degree in, say, physics, is no substitute. And they also lack exposure to the scripts. With two years exposure focused on patients who have been deemed “low complexity” means that it could take them a lifetime to accumulate sufficient complex cases to hone their clinical instincts sufficiently to practise safely.

All this points to the conclusion that PAs should never be seeing what are known as “undifferentiated” patients—that is, patients whose problems have not yet been sorted by severity or risk. While undifferentiated patients in general practice and in the “minors” queue in the emergency department are, statistically speaking, likely to have mundane and easily diagnosable problems, it is also the case that some patients with as-yet undiagnosed serious and even life-threatening conditions will be in the same queue.

Another system problem, illustrated by Mrs Pollitt’s case, is the danger of “taskification”—uncoupling a medical procedure from the knowledge and professional attitudes needed to perform that task safely and appropriately (and know when not to perform it). Anecdotal examples of unnecessary procedures performed by PAs are not hard to find on a Google search, though in many of these, key medical details are lacking or impossible to verify. In our systematic review, we found no studies of the clinical indications and safety of interventional procedures performed by PAs (mainly because the literature relates largely to PAs working to a narrower scope of practice and under much closer supervision than is now often the case in the UK).

The safety incidents described above also raise the question of what we mean by “supervision”. In each of the above cases, a doctor would have been technically overseeing the PA’s decisions. In reality, the doctor must either repeat the history-taking and examination themselves or take the PA’s word for some or all of the assessment. If the former, the arrangement cannot possibly be cost-effective. If the latter, they become at least partly accountable if anything goes wrong.

In November 2024, Wes Streeting, the Secretary of State for Health and Social Care, commissioned public health doctor Gillian Leng to conduct a review of PAs and the related group anaesthetic associates (AAs). Specifically, she was asked whether their roles are safe and whether they are effective “as members of a multidisciplinary team, across all tasks, roles and settings?”. She has been asked to look comprehensively at the roles and settings in which PAs and AAs work, including internationally, and covering a range of potential activities.

These are very important questions and our review of research in the British Medical Journal sought answers to some of them. As we have noted above, despite searching assiduously and systematically, we have been unable to find evidence that either PAs or AAs are as safe and effective as doctors in the settings in which they are deployed. We found no evidence that they are cost effective and have strong grounds to believe that, given current salary scales, there is no model of care that would enable them to be cost effective undertaking their current roles. We are also aware, as described above, of serious concerns about their safety and, while any things can go wrong with any type of health worker, we cannot ignore the warnings issued by coroners who do not make such reports unless they have evidence of real concern about the wider context.

The Leng Review has been asked to look at international evidence. This is welcome, given how often health policy in the UK ignores lessons from elsewhere. However, this must be undertaken with particular caution here given the evidence that these roles are so very different in the very few countries where they exist in more than tiny numbers.

In this light, it is perhaps regrettable that the Leng Review is not charged with asking a more fundamental question. If the PA role did not already exist, would there be any reason to create it? PAs came about as a new role in the NHS without any clear assessment of need. Had this been done, it is likely that the result would have been very different. Doctors do often need assistance, but not usually with their clinical work. Rather, they seek solutions that reduce the time they spend entering data onto computer systems, arranging tests and referrals, and a myriad of administrative tasks. This is the role that has been created, much less controversially, in France. Instead, the UK now seems to be faced with a solution in search of a problem. A wider remit would have allowed the Leng Review to ask what is needed to make the work of doctors more efficient, cost-effective and fulfilling (and thus encourage more of them to stay in the NHS)?

The current situation is one that satisfies no-one. It is increasingly being seen as a serious policy failure. The question then becomes how to resolve it while doing the least damage. PAs and AAs have already invested considerable personal and financial resources in their career. They have been let down by those in authority, who now have a responsibility to support them through any future transition to other roles. Hopefully, the Leng Review can inform this process.

1. Showstark M, Smith J, Honda T. Understanding the scope of practice of physician associate/physician associate comparable professions using the World Health Organization global competency and outcomes framework for universal health coverage. Hum Resour Health 2023;21(1):50. doi: 10.1186/s12960-023-00828-2 [published Online First: 20230623]

2. Farmer J, Currie M, Hyman J, et al. Evaluation of physician assistants in National Health Service Scotland. Scott Med J 2011;56(3):130-4. doi: 10.1258/smj.2011.011109

3. NHS England. NHS Long Term Workforce Plan. London: NHS England. Accessed 29th February 2024 at https://www.england.nhs.uk/publication/nhs-long-term-workforce-plan/ 2023.

4. Weil LG, Nun GB, McKee M. Recent physician strike in Israel: a health system under stress? Isr J Health Policy Res 2013;2(1):33. doi: 10.1186/2045-4015-2-33 [published Online First: 20130815]

5. Weil LG, Nun GB, McKee M. Recent physician strike in Israel: a health system under stress? Israel journal of health policy research 2013;2:1-11.

6. Geary U, McKee M, Petty-Saphon K. Mind the implementation gap: a systems analysis of the NHS Long Term Workforce Plan to increase the number of doctors trained in the UK raises many questions. Br Med Bull 2024;150(1):1-10. doi: 10.1093/bmb/ldae002

7. Vaughan L, McKee M. Sorting out scope of practice of physician associates in the UK: the clock is ticking. Bmj 2024;387:q2445. doi: 10.1136/bmj.q2445 [published Online First: 20241114]

8. Rimmer A. Physician associates: Doctors raise alarm over legislation to allow GMC regulation. BMJ: British Medical Journal (Online) 2024;384:q156.

9. Freidson E. Theory and the Professions. Ind LJ 1988;64:423.

10. Salisbury H. Helen Salisbury: Training in the medical model. Bmj 2023;383:2793. doi: 10.1136/bmj.p2793 [published Online First: 20231128]

11. Drennan VM, Halter M, Joly L, et al. Physician associates and GPs in primary care: a comparison. British Journal of General Practice 2015;65(634):e344-e50.

12. Halter M, Drennan V, Wang C, et al. Comparing physician associates and foundation year two doctors-in-training undertaking emergency medicine consultations in England: a mixed-methods study of processes and outcomes. BMJ Open 2020;10(9):e037557. doi: 10.1136/bmjopen-2020-037557 [published Online First: 20200901]

13. Greenhalgh T, McKee M. Physician Associates and Anaesthetic Associates in the UK: A rapid systematic review of recent UK-based research to inform the Leng review. BMJ 2025;388:e084613.

14. Drennan VM, Halter M, Wheeler C, et al. The role of physician associates in secondary care: the PA-SCER mixed-methods study. Health services and delivery research 2019;7(19):1-158.

15. Greenley R, McKee M. How will expansion of physician associates affect patient safety? Bmj 2024;386:q1377. doi: 10.1136/bmj.q1377 [published Online First: 20240705]

Vaccines have transformed health expectancy and health outcomes.

Vaccines have been an incredible success: from the earliest vaccines developed by pioneers including Edward Jenner for small pox in 1796 and Louis Pasteur for rabies in 1885. Most recently, innovations in vaccine technology by Katalin Karikó and Drew Weissman lead to the development implementation of mRNA vaccines that underpinned the development of vaccines targeting Covid-19 and even some cancers. Thanks to vaccination, elimination, meaning no sustained community transmission of a pathogen, has been achieved for multiple infections in the USA, UK and other countries. However, vaccination has also become a victim of its own success. Diseases such as whooping cough and measles that were once common killers in the early 20^th centuries are now so much rarer that most people—including many clinicians—have never seen a case. Mis- and dis-information about adverse effects of vaccines, whether true or false, are now also ubiquitously amplified on social media.

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Childhood immunisation rates have been falling for several years with the WHO estimating that 3 in 4 infants live in countries or counties where low vaccine coverage is driving measles outbreaks. This is perhaps epitomised by the growing numbers of cases and states affected with measles in the USA. The report by Independent SAGE discusses some once common diseases that can or have been controlled by vaccines including Measles, Tetanus, Whooping Cough, Diphtheria, Chickenpox, Hepatitis B, Polio, Mumps, Meningococcal Disease, Rubella (German Measles), Haemophilus Influenza B (Hib), and Human Papilloma Virus (HPV).

Images of vaccine preventable infections or the symptoms they can cause. All images Creative Commons Attribution-Share Alike 2.0 Generic license

What is vaccination and how does it work?

Individual immunity

When we get infected with a pathogen our white blood cells- immune cells- quickly detect and try to deal with the threat. However, if this the first infection with that pathogen, it takes a little time for the body to generate the specific white blood cells and antibodies that are tailored for that pathogen. This lag creates a window of opportunity for the pathogen take advantage which can making you very sick or can even be fatal. Once our immune cells have learned about a specific pathogen they have “memory” of that meaning they can respond much more quickly should you encounter the pathogen again. A second infection may not occur at all or may be milder than the first.

A vaccine helps develop immune memory without having to risk the infection which is a LOT safer. Vaccines are usually a safe weakened (‘attenuated’) or killed form of a specific pathogen, or part(s) of the pathogen in isolation that can be delivered using a variety of vaccine types. Some vaccines require several doses initially to ensure you get the best possible immune response- an example is the MMR vaccine and the protection it confers is not optimal unless the full course of vaccines is taken. Some vaccines for diseases such as flu, require annual boosters due to a combination of changes in the virus structure and waning immunity.

Vaccine campaigns are often targeted to the most vulnerable people such as young babies and the elderly who are most at risk of severe infection. Some vaccines will make you immune to ever contracting the infection- this is known as “sterilising immunity” whereas others (such as COVID) still partially prevent infection and dramatically reduce the chances of severe illness or death.

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Population immunity

As well as protecting the individual, vaccines benefit the community. The more people that are vaccinated, the better because that means fewer people are likely to become infection hosts and “Typhoid Mary’s” spreading the infection to others. If more people are vaccinated the pathogen has nowhere to go and its numbers will start to decline also known as “population immunity”. Population immunity has been transformational in reducing many formerly common diseases to very low levels in many countries (e.g. polio or measles).

The name “Typhoid Mary” refers to a cook who is believed to have unintentionally infected between 50-122 people with typhoid fever. She was an asymptomatic carrier of the pathogenic bacterium Salmonella typhi. The term is now a colloquial term for anyone who spreads disease or something else undesirable. Image used using Creative Commons Attribution-Share Alike 2.0 Generic license.

How a disease spreads is determined by both how infectious it is, as well as how many people in the population are susceptible to infection. A person who has never met the pathogen is susceptible whereas someone who has had the disease or been vaccinated will often be immune. For a disease to spread, each infected person must, on average, give the disease to more than one other susceptible person. But if an infected person passes the pathogen to fewer than one other person on average, then the number of infections in the population starts to fall. This “basic reproduction number”, or “R₀”, is an estimate of how many people, on average, an infected person passes the pathogen to. The higher the R₀, the higher the percentage of the population will need to be vaccinated to prevent an outbreak spreading. Measles has a high R₀ - around 18- so 92-95% of the population must be protected to prevent (or curtail) an outbreak. Historically, this level of population immunity has only ever been achieved through concerted vaccination programmes. If fewer people take up the vaccines on offer though, the pathogens can exploit this gap in population immunity resulting in abrupt rises in cases. For example at least 378 cases have been reported in 17 states of the USA typically in un- or under-vaccinated children and two unvaccinated individuals have tragically died.

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Why is vaccine uptake falling?

One reason for the reduction in vaccine uptake is the rise in vaccine hesitancy which has led the WHO to declare it as one of the ten biggest risks to human health. Vaccine hesitancy refers to a delay in acceptance or refusal of vaccination despite availability of vaccination services. However, vaccine hesitancy does not fully account for the reduction in vaccine uptake with a combination of factors influencing the likelihood vaccines uptake including how accessible vaccines or information about vaccines is, prior negative health-care experiences and mistrust of organisations or advocacy of alternative healthcare all being factors.

The ‘5 Cs’—Confidence, Complacency, Convenience, Communication and Context ar often used to explain reduced vaccine uptake. ‘Confidence’ considers fears around the safety and efficacy of vaccination and the possibility of side effects versus the risk of the actual diseases. Like any medicine, vaccines can have very rare side effects which is discussed more fully in this report. Confidence is also linked with ‘Complacency’ about the severity of eliminated or seasonal diseases has become more common as fewer people have experience of these diseases. Misunderstanding of the risks of a disease versus the risk of being vaccinated against that disease plays into this. Complacency is also linked to ‘Convenience.’ Vaccines may not be easy to access- for example appointments are in work hours, or vaccine centres are far away and inaccessible by public transport or their be a fee for the vaccine- all of which can dissuade people from being vaccinated. This factor likely impacts those from more socio-economically deprived backgrounds further compounding pre-existing health inequalities.

‘Communication’ about vaccines is critical - how accessible and clear the information is regarding vaccines, including where and when it is available locally. Good communication can have a positive influence on confidence. Barriers to communication are evidenced by the recent announcement by the Louisiana surgeon general for its staff to stop engaging in media campaigns and encouraging vaccines even though vaccines will still be available. ‘Context’ is also important- considering cultural sensitivities and needs—for example, informing people if vaccines are halal or suitable for vegans.

Misinformation (that is, information that is incorrect, whether intentional or not) and disinformation (information deliberately put out to mislead), especially on social media, add to vaccine hesitancy by sowing confusion and fuelling uncertainty and breed vaccine hesitancy. For example, an alleged link between the combined measles, mumps and rubella (MMR) vaccine and autism spectrum disorder has been widely circulated despite this alleged link been thoroughly debunked in multiple studies. For example, recent statements by the US secretary for health RFK Jr, who has a history of spreading vaccine disinformation, have cast doubts on the severity of measles and the risks of vaccination.

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Vaccines should be celebrated as a global success story

Despite the success of vaccines, we are facing a crisis of public confidence in the efficacy and safety of vaccines. Vaccines have transformed our life expectancy so that fewer people should have to face the horrors of seeing a loved one suffer or even die of diseases such as measles. The author Roald Dahl, who watched his daughter Olivia tragically die of measles, said:

“I should think there would be more chance of your child choking to death on a chocolate bar than of becoming seriously ill from a measles immunization. So what on earth are you worrying about? It really is almost a crime to allow your child to go unimmunized”

I hope you will find our report from Independent SAGE helpful and do also look to trusted organisations such as The British Society for Immunology who published this pamphlet tackling common questions about childhood vaccines.

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The main page now is essentially a short overview of what Indie SAGE is and a search bar that lets you search for content in the description of our output (e.g. “Testing” or “Guests”).

You may wish to go directly to the pages for types of output: Reports; Short Statements; and Weekly Briefings. Reports and Short Statements let you filter by topic category (e.g. Contact tracing; Education; or Behavioural Science). Each report can be allocated to more than category. New output from this year has its own category of “2025 onwards”. At the moment this is just our new DEI in Science report, but we are planning more reports/output at the moment.

For Weekly Briefings, you can filter by Data Topics covered in the regular numbers updates.

You can also do a comprehensive filter process on the All Posts page where you can filter by categories (Reports/Short Statements) and Content Type (including Q&A and Media Highlights).

Finally, information about membership and FAQs about us are given on our About page.

We wanted to just let our subscribers know that this resource now exists and we hope that you find it useful! New content will also be signposted via this Substack.

A shorter version of the report is here, but please do go and read the full three page report.

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A diverse and inclusive science community is not just morally right, it improves the quality of science. Companies and scientific research teams and institutions that prioritise diversity perform better financially and scientifically. Our definition of science includes the physical, health, medical and social sciences.

How Diversity Strengthens Science

Science thrives on innovation, collaboration, and problem-solving. Scientific ability is not restricted to one sex, ethnicity, religion or to the able bodied. Embracing diversity has the simple advantage of widening the pool of talent from which scientists are drawn. But, over and above that, diversity enriches the scientific process by fostering different ways of thinking and problem-solving. Research has shown that diverse teams are more innovative, produce higher-impact work, and are better at tackling complex problems.

1. Improved Creativity and Innovation: Diversity fuels innovation, as different viewpoints challenge conventional thinking and encourage creative solutions. For instance, one study found that while authors on a scientific paper were of the same ethnicity more often than you would expect by chance, in fact it was scientific papers authored by more ethnically diverse teams that received more citations, indicating broader impact and influence. However, when compared to comparable innovations by scientists from majority groups, scientific innovations by minority scientists have been shown to lead to poorer careers.

2. Enhanced Problem-Solving Ability: Homogenous groups may suffer from similar perspectives and life experiences that can limit creative problem-solving. By contrast, both modelling and observational research suggests that diverse teams consider more alternatives and make better decisions. This is particularly important in scientific fields that require interdisciplinary, global, approaches, such as climate science, biomedical research, and artificial intelligence – fields crucial to humanity’s continued ability to thrive.

3. Better Representation of global challenges and possible solutions: Many scientific challenges—such as disease outbreaks, climate change, poor infrastructure (e.g. housing, transport), service provision (e.g. access to health care), and resource management—disproportionately affect certain populations. Scientists from diverse backgrounds are more likely to ask research questions that address these disparities. For instance, research of Sickle Cell disease (which affects mostly black communities) was neglected until activism from black groups in the 1970s repeatedly brought the issue to medical and popular attention, eventually resulting in more research funding for treatments. The first gene therapy for Sickle Cell disease was finally established in 2019. Meanwhile lack of research attention to issues of both gender and ethnicity, meant that it was only in 2018 that it became widely known that black and Asian women were much more likely to die in pregnancy or childbirth than white women.

4. Diversity in Research Design: Medical sciences have long suffered from a lack of diversity in research design, leading to findings that do not apply to all populations. For example, clinical trials have tended to test treatments mainly on men, leading to poorer health outcomes for women. Ensuring diverse participant recruitment in clinical trials and inclusive data collection (including in international genome studies) improves scientific validity, societal impact and supports more equitable outcomes from medical treatment.

Equity and Inclusion in Science: rebalancing the playing field

Equity is not only about ensuring that scientists, regardless of backgrounds, have the same opportunities, but also about recognising that not everyone starts from the same place: there is no level playing field. Inclusion is not only about scientists from different walks of life feeling that they belong and that their voices are being heard; it is also about ensuring that we produce better science which takes account of everybody's lived experiences. Without equity and inclusion, calls for diversity in science will never achieve meaningful change while historically excluded groups, including women, those from ethnic minorities and those with disabilities, remain disadvantaged. Addressing inequities requires systemic changes in science policy and institutional structures.

1. Reducing Bias and Discrimination: Bias affects hiring, funding decisions, and publication rates. Women and minorities face additional barriers to career progression, with female scientists receiving less credit for their work. DEI initiatives, such as blind peer review and bias-awareness training, are crucial to mitigate these disparities.

2. Equitable Access to Funding and Resources: Scientific funding has historically excluded researchers from minoritised ethnic groups and women, and continues to favour white male researchers from prestigious institutions. Structural biases in grant allocation require reform, such as implementing transparent evaluation criteria, double-blind peer review and increasing funding for minority-led research projects.

3. Workplace Flexibility and Support Systems: Policies that support work-life balance, such as parental leave, flexible working arrangements, adjustments in the workplace and anti-harassment measures, help create equitable work environments. Institutions that implement these policies see higher retention rates among women and minority researchers. Additionally, more diverse workplaces are associated with attracting and retaining more diverse staff, not least by providing role models – creating a positive feedback loop

4. Increasing trust in science: As well as improving the science itself, a diversity amongst scientists also improves the willingness of marginalised communities to trust, engage with and accept scientific developments. For instance, recent research has shown that where there are black researchers, black people are more likely to participate in a clinical trial – and this in turn is critical for acceptance of the findings as relevant for the black community. This was a major issue during Covid where distrust of the medical establishment led to far lower rates of vaccine take-up amongst black communities.

Conclusion

Diversity, equity and inclusion in science are not “nice to have” or about “wokeness”. They are essential for scientific excellence. Silencing minoritised voices restricts the pool of talent, leads to knowledge gaps, and exacerbates inequalities in society. US scientists already feel they need to self-censor because of the administration’s aggressive stance.

By fostering diverse, inclusive, and equitable research environments, science can produce more innovative solutions, improve societal outcomes, increase trust in science, and address the most pressing global challenges. We cannot afford to let the political and ideological motivations of the Trump administration taint and undermine robust, rigorous and inclusive science. Now is the time to stand up – loudly – for diversity, equity and inclusion in science.

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Both hospital and wastewater measurements agree that we’ve had a very quiet winter in terms of Covid infection levels. Hospital admissions have been stable and low since the beginning of November 2024 - so that’s four months now. We’ve not seen such a long stable period since the start of the pandemic.

This probably saved the NHS this winter given the large 2024/25 flu wave - you can see very clearly how both Covid and Flu rose together in the winters of 2022/23 and 2023/24.

Of course, hospital data is limited by reduced testing since 2023 and only people sick enough to be in hospital being tested. That’s where wastewater testing is useful, because it doesn’t depend on testing behaviour (or symptoms) and so gives a fair representations of levels of Covid in the community.

England (stupidly in my opinion) stopped wastewater testing in March 2022, but Scotland still does it. The latest data from there shows exactly the same picture as hospitalisations - very low levels for the last several months.

Several European countries monitor wastewater as well - and show the same picture, including Ireland, Austria, Netherlands, Finland and Belgium. I’ve shown Belgium below where you can see a very similar pattern to the hospital admissions in England - a drop and then steady low state since November 2024.

There is simply no evidence of high Covid levels in the UK since November, and we should be thankful for that.

A couple of variants to watch out for

That said, there are a few things happening now in the variant space that are worth keeping an eye on. In England there are two closely related variants on the rise: LP.8.1 (darker blue) and LP.8.1.1 (lighter blue). They emerged towards the end of last year and now comprise about a third of newly sequenced cases. It is possible that they will become dominant but not be immune evasive enough to cause a significant wave, especially with the advent of warmer weather where people spend more time outside or with the windows open. But if a new Covid wave starts in England soon, it will come from these variants and it’s something I will keep an eye on over the coming weeks.

The second thing to watch out for is the re-emergence of Omicron BA.3 in South Africa after three years of nothing (!). It faded pretty quickly back in the winter of 2022 because it could not compete with BA.1, BA.2 and BA.5 which caused massive UK waves in January, March and July 2022 repsectively. However, it seems that it has been evolving quietly and significantly in someone with a chronic Covid infection (likely immunocompromised) and that recently it has started spreading to other people. Note that we don’t know where it emerged - just that it has been spotted in South Africa first.

It is still lacking some key mutations that might help it spread more easily, but if it picks them up it could cause the next big global wave. It’s very early days and could still easily just fade away but this is also something I’ll be keeping an eye on over the coming months. Also worth nothing that LP.8.1 is growing rapidly in South Africa at the moment, just as it is here.

To summarise, we’ve had by far the quietest Covid winter since the start of the pandemic but there are signs that activity might rise again over the spring and summer.

This is adapted from a susbtack that was published by Sheena Cruickshank at the weekend.

The CDC has announced it plans to launch a study into exploring possible links with MMR and autism spectrum disorder (ASD). This makes no sense considering the research has already been done robustly multiple times before with consistent results as they all showed NO link between ASD and MMR vaccines. I thought it may be helpful to review these studies and frame why this announcement is particularly ill-timed.

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Why would there have been so many MMR and Autism spectrum disorder studies?

A putative link with ASD and MMR was raised in the 90s by a then clinician called Andrew Wakefield. The results were misleading, couldn’t be reproduced, the research unethical (for example highly invasive unnecessary procedures were performed on children with ASD) and there was a clear conflict of interest regarding Mr Wakefield’s funding. Wakefield was subsequently struck off as a clinician and the data he published retracted. Unfortunately, this episode did impact vaccine confidence with devastating effects. in response, multiple studies have been conducted to debunk one man’s fraud.

There is extensive evidence of there being no link between the MMR vaccine and ASD.

In 1999, Taylor and colleagues assessed the clinical records of 498 children to see if there was a hint of a link between ASD and MMR administration. They found no such association: the percentage of children who were vaccinated and unvaccinated had the same incidence of ASD. Furthermore, there was no difference in the age of diagnosis of ASD in vaccinated and unvaccinated children.

An even bigger study of 537,303 children was then conducted- of which 82% had received the MMR vaccine. The risk of ASD in the group of vaccinated children was THE SAME as that in the unvaccinated children. In other words there was NO link between ASD and MMR again.

A further study asked what about people who had a history of ASD in their family (ASD has a strong genetic component)- might there be a link there? So they looked at 100,000 people with a family history of ASD and again found no increased risk of developing ASD if vaccinated.

Studies evaluating MMR and ASD have been repeated multiple times in different countries. Studies have even asked is there were impacts of trace ingredients found in the vaccine- there was not. The results have ALWAYS been the same. Just to emphasise this further- a meta-study reviewed multiple studies including five cohort studies involving 1,256,407 children and five case-control studies involving 9,920 children. Guess what they found- NO enhanced risk of ASD from the MMR vaccine. The National Academy of Medicine even performed 3 additional evaluations and again found no risk!!

MMR Vaccines are NOT associated with ASD and a great deal of time, effort and money has been spent debunking a study that was shown to be fraudulent. So why are CDC announcing they want to repeat all this work all over again? Well- we don’t know for sure. However, the CDC are now under the directorship of RFK Jr, Trump’s pick to lead the department of health. RFK Jr has been notorious for years for seeding vaccine doubts including stating that vaccines cause ASD as recently as 2023.

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Measles is a very serious and life threatening disease.

Currently, the USA has multiple cases of measles with the incidence highest in parts of the country with lower vaccine rates including parts of Texas and New Mexico. Tragically two people have died as a result- a child and an adult. Both were unvaccinated. At least 20 people are hospitalised and the situation is extremely concerning.

In response to the growing health crisis Kennedy agreed to have 2000 vaccines sent to Texas. Reports are emerging the state is facing shortages of the vaccine so more may be needed. Kennedy wrote an Op-Ed that highlighted the importance of vaccines. However, Kennedy did NOT recommend vaccination- rather he framed vaccines as personal choices and pushed a healthy diet and particularly vitamin A supplementation. Furthermore, he downplayed the severity of measles and wrote about people dying in the 19th century. He has since gone one step further, whilst downplaying the severity of the virus he implied that the vaccine was more risky than the virus itself- this is not true- the vaccine is known to be very safe. Given his position as health secretary, his narrative is irresponsible to say the least. Equally shocking are reports of a Texas pastor bragging about how few people are vaccinated in their school. This is not a bragging matter.

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Here’s the thing. Measles is extremely infectious and it’s a nasty airborne virus so easy to catch- especially if unvaccinated. The vaccine, if a full course is taken, can prevent 97% -99% of cases. People without the vaccine are not only more likely to catch the virus, they are highly susceptible to the infection which can cause pneumonia, meningitis and encephalitis. Approximately 1 in 5 unvaccinated people who get measles need to be hospitalised and roughly the same proportion of children develop pneumonia. As is that were not bad enough, the virus can also cause the immune system to forget prior infections - a kind of immune amnesia- making people much more likely to get sick from infections after recovering from measles.

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Sadly, I know only too well how serious measles can be. My brother contracted measles before he could be vaccinated and was incredibly sick. He spent months in hospital far from our home. I was not born yet but my parents, extended relatives and my brother (who survived measles thank goodness) used to talk about how frightening it was, how alone he and they felt and the hallucinations he endured whilst feverish. It left a scar on my family and I am devastated that measles is resurging when it can be prevented by a safe vaccine.

There are many reasons why people may be hesitant about the vaccine so how we discuss the vaccine really matters. Dismissing the seriousness of measles, promoting diet above vaccines and announcing a needless research study into vaccine safety at this time is irresponsible and reprehensible.

I really fear that the narrative from Kennedy is fuelling the concerns of the vaccine hesitant. We should be promoting vaccines especially at a time when people are dying of measles.

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Vaccines against SARS-CoV2 have prevented million of deaths from COVID-19, dramatically reducing the risk of both severe acute illness and long-COVID. Estimates of the number of lives saved range upwards from 20 million in just the first year (2021), with an approximate reduction of potential deaths by 59% over the course of the pandemic. Notably, these were the first ever successful vaccines targeting a Coronavirus, whether in man or in animals. We were fortunate.

These vaccines have clearly been an enormous success story but, like all medicines, side effects are possible. This is especially important to understand as vaccines, unlike most medicines, deliberately engage our immune response to achieve their protective effects. As immunity is defined by our genes, a planet of seven billion genetically diverse human beings will inevitably include rare outcomes.

Predictably, with billions of doses administered since 2021, this has been the case for COVID-19 vaccines too. A very small fraction of the population have reported a chronic condition following immunisation – which has also been dubbed as post-vaccination syndrome (PVS). Critically, PVS is largely unrecognised by healthcare systems, leaving patients with limited options in terms of support and/or treatment.

What is PVS?

The incidence of PVS is low, even compared to other rare adverse vaccine reactions, which has made it difficult to study. For example, one study assessed just 3 patients with other reports involving single case studies. As such, the mechanisms underpinning why some responses lead to PVS are not well understood. There does, however, seem to be many similarities between the self-reported symptoms of long COVID and PVS. This may include, for example, clusters of symptoms spanning extreme fatigue, breathlessness, brain fog, neurological problems, cardiovascular issues, and joint pain, persisting for 12 weeks, or more. Logically, given that both infection and vaccination “programme” our immunity in similar ways, this may not be as surprising as it first sounds.

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People with PVS had distinct immune signatures

A new pre-print yet to be peer-reviewed from the Yale LISTEN Study compared 42 participants with PVS with no pre-existing comorbidities and 22 control subjects; 42 counts as the largest PVS study to date, illustrating how scarce PVS is. This low number also means there must caution to over-interpreting the data based on relatively low numbers. PVS was defined akin to the criteria used to define Long Covid i.e. a change in health status that began after the vaccine was administered and had not resolved within 12 weeks. The groups were further split into 4 groups, depending on whether the researchers could establish a prior history of infection using an antibody test (I) before the vaccination (this couldn’t be conclusively shown in everyone).

The researchers looked at what sort of immune cells (white blood cells) were present in the blood of these patients, how they were behaving, and which antibodies had been made. Similarly, they looked at what genes may have been switched on or off in these patients to understand the mechanisms at play. They also looked at how other infections, including other viruses, were behaving in people with PVS.

Overall, the picture was complex with the condition manifesting as multiple subgroups rather than a one-size-fits-all disease. Again, this is reminiscent (yet distinct in many ways) of long COVID. PVS groups predictably reported increased ill-health compared with controls, and were understandably less likely to have completed full COVID vaccine/booster courses and these were naturally further in the past. The number of vaccines correlated with the levels of anti-spike protein antibodies, and so were lower in PVS patients.

PVS groups showed differences in both their innate (non-specific) and adaptive (antigen-targeted) white blood cell responses. Monocytes, a type of innate white blood cell, were higher in PVS patients, likely indicating ongoing inflammation. By contrast, another innate cell type, conventional dendritic cells (cDC), were much lower, as were a type of adaptive cell called an effector memory CD4 T-cells (CD4em). This can indicate a “misfire” of the adaptive response, as cDC and CD4em cells help coordinate immune responses against specific targets of the virus. Accordingly, a type of T-cell that are needed to kill virally infected cells and viruses, cytotoxic T cells or CD8 T-cells, showed evidence of being “exhausted” - making them less effective at viral killing. This overall shows an immune response that has gone awry and is not working as it should. A hallmark of a less effective immune response is that so-called latent infections can re-emerge and this is exactly what was seen.

The researchers looked at Epstein Barr virus (EBV), a herpes virus that causes Glandular Fever. EBV is never fully cleared from our body and persists at low levels for life following infection held in check by our immunity. In several of the PVS patients, the EBV had been reawakened. This was indicated by increased production of antibodies that can target EBV. In addition, some of the PVS cohort had some evidence of antibodies reacting against their own bodies, so-called autoantibodies. Collectively this data paints a picture of an immune system that is misfiring.

Finally, PVS patients were more likely to have detectable, yet miniscule (a million-billionths up to 10 billionths of a gram per mL of blood), levels of spike protein along with their reduced levels of anti-spike antibodies. Interestingly, higher circulating Spike levels appeared to be positively linked with having previously experienced an infection.

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PVS data had clear correlations with Long COVID immune features.

Interestingly, much of this data overlaps results from studies assessing Long COVID, which also show distinct immune signatures. For example changes in monocytes, adaptive cells (T and B cells), T cell exhaustion, reactivation of latent viruses such as EBV and persistent viral antigen are also evident in many people with Long COVID. It was also notable that somewhat more of the people with PVS in this study were women. Data has shown that Long Covid is more likely if you are female. Severity of infection is also a factor in likelihood of developing long COVID, but this was not assessed in this study.

One important distinction with Long Covid studies is that people with co-morbidities were excluded from the LISTEN study, whereas this is a key predisposition towards developing Long Covid. The small group sizes for PVS make such data difficult to interpret though. Hence, although there may be similarities in the groups of people that are susceptible to both Long Covid and PVS we can’t really speculate if this is due to the same susceptibility factors and/or common mechanisms.

The observation of persistent, albeit low level, spike protein in PVS patients without prior infection is perhaps surprising to some; similarly low levels of spike protein are observed in some long COVID sufferers. However, the lower levels of spike-reactive antibodies in PVS again suggests that the immune response may have misfired, being unable to clear the protein generated by the cells, including monocytes (raised in this study), whose job it is to “present” the spike protein to the adaptive immune system. Another possibility is that all the individuals had had a prior infection. Previous infection was established by looking for the presence of antibodies to parts of the virus which is not completely unequivocal - as some people will not have a good antibody response so the possibility that all participants had prior infection cannot be excluded.

Another possibility is given the small sample size is that some of these features observed are down to chance. More studies are needed to confirm findings and look for mechanisms and consequences. Given the rarity of PVS this is challenging but cooperation across the world bringing together data sets may help.

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What should we take away from this study?

First and foremost, this is to date the most comprehensive analysis of PVS and its incredibly important we look at this study and do not ignore it. Whilst the study is yet to pass peer review, people suffering with this albeit rare condition have been overlooked and deserve to have better treatments. PVS, much like long COVID and other conditions such as ME/CFS are complex consequences of how our immune responses behave. Our immune system is incredibly powerful but it does sometimes misfire, so the more we understand it, the better we can counteract its impacts when it goes awry. There is already greater focus and progress on these issues as we continue to learn from the pandemic, and this study further informs scientists on this mission.

However, this analysis should neither derail vaccine development, nor be weaponised to support anti-vaccine disinformation campaigns. We must remember that rare individual adverse reactions are balanced against the population-scale benefits that vaccines bring. It is not correct or rational to simply compare outcomes with/without a vaccine, but to the impact of a disease being allowed to run rampant, unchecked. COVID vaccines have broken the link between infection and severe disease for the majority of the population, something that really ought not to be taken for granted.

Improved understanding of PVS and other conditions should lead both to new ways of tailoring how we give medicines to avoid people developing severe reactions, as well as to develop treatments for those who do. This is only realistically possible for rare events when vaccines or other medicines are given at scale, such that enough rare cases can be compared and action can be taken to avoid problems in the future. Examples include the tragic but rare cerebral blood clots caused by the AZ vaccine, or reactions to the immunosuppressive drug, azathioprine, understanding of which led to a newly available test to determine its suitability for patients.

Ultimately, any medicine is an intervention and it’s critical to monitor safety both during development as well as through ongoing clinical use to ensure that benefits outstrip potential harms. Public health must act both in the interests of the population as well as to support the individual, and this can only be achieved through scientific rigour and honest interpretation of an ever-evolving wealth of data.

The vaccines for Covid19 saved millions of lives and reduced the risks of severe disease and long Covid and this must not be forgotten. These vaccines continue to be an invaluable tool to help tackle Covid19 which continues to evolve and is ever pervasive. PVS is incredibly rare and affecting a tiny minute fraction of the millions of those who have been vaccinated. Nonetheless the more we understand about PVS, the more we can help people who have it and the more we can try ways to prevent it in future. This is why it’s important to study it BUT bad faith people are misrepresenting the study. Don’t listen to them.

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Within a few hours of RFKJr being sworn in as Trump’s health secretary, Trump ordered an end to funding for schools and colleges that require Covid vaccines. But, what will these changes mean for infection prevention?

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What are Vaccine Mandates?

Vaccine mandates are a way to try and make people get vaccinations by for example fining those who refuse or excluding them from certain roles or places such as educational institutions. Mandates have been used in a number of countries to try and tackle a variety of infections - often to try to increase the level and/or speed of vaccination programs in response to a health crisis or need. For example, the US was amongst the countries bringing in vaccine mandates for Covid19 in schools, colleges and some professions like the army or healthcare. In 2020, Germany made measles vaccines mandatory for schools and childcare attendance following serious measles outbreaks.

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Do Vaccine Mandates work?

Data does suggest that vaccine mandates do work to increase vaccine access and coverage. However, another study found no correlation between mandates and rates of childhood vaccination. Arguments for mandates are generally strongest in countries where vaccine confidence is lower or when countries are facing a surge in infections and significant pressure on healthcare provision. Arguments against mandates often centre on vaccines being forced, removing freedom of choice and creating antagonistic attitudes to vaccines. The reality is that often there are many exemptions from vaccines whether it be for religious reasons or medical reasons. For example, some people are allergic to egg components that are used in some flu vaccines. In the USA, some states even allow exemption based on personal reasons. As such, mandatory vaccines are not necessarily ALL that mandatory. Removal of vaccines mandates also doesn’t necessarily mean vaccines are not advised or available so the change in policy in the States may not be as frightening as it first seems. I personally have quite mixed feelings about mandates- I am very much pro-vaccine but I do worry about the mistrust that mandates may unintentionally incur as a result of mandates.

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Vaccine Trust

This takes us back to what is happening in the States right now. Vaccine mistrust is increasing across the globe, fuelled in large part by misinformation and disinformation. A notable study made by the Center for Countering Digital Hate found that just 12 individuals -also known as the Disinformation Dozen- were responsible for 65% of Covid-19 misinformation circulating on social media. Guess who one of the most active spreaders of disinformation was? If you look at the table taken from the study I have highlighted the second name from the top-RFKJr - Trump’s recently appointed health secretary.

Not only has RFK Jr sown extensive vaccine disinformation, he has made a profit from doing so! He made over $20,000 per week as chairman of his Children’s Health Defense “non-profit” in 2023. He also stood to make vast sums from his role in the court case that aims to sue Merck for the vaccine against HPV known as Gardasil. It is alleged that he took action beyond just sowing doubt about the safety and efficacy of the vaccine and helped build a case. HPV is tightly linked with the development of cervical cancer and the vaccine has resulted in a dramatic decline in cervical cancer mortality. Whether he continues to be a part of the team pursuing this case now is not clear.

We know that rhetoric regarding vaccines really matters for vaccine uptake. I worry that a man who has sown such extensive mistrust and has NO scientific OR medical qualifications is now in charge of health decisions for an entire nation. The fact that the likes of Musk and his social media site also spread vaccine disinformation adds to my disquiet.

My nervousness regarding vaccine access and trust has not been assuaged as within a few hours of Kennedy’s role being formalised, Louisiana announced it was ending mass vaccinations campaigns. The Louisiana surgeon general has ordered its staff to stop engaging in media campaigns and encouraging vaccines. To be clear you can still get vaccines there but there will be NO large drives such as winter flu campaigns or information circulated. This essentially will make it hard to find out anything about vaccines. This is despite the state having had a lot of flu this winter and being the state to report human death from bird flu.

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I really fear that the actions of Louisiana may be the first of several such measures and the continued rhetoric around vaccines will cause more and more distrust and a further fall in vaccine confidence. That American scientists are being muzzled at a time and science roles and budgets slashed when they are so needed is also very worrying. Despite RFK Jr’s prior rhetoric on vaccines, he stated during the hearing for his post that “I support vaccines. I support the vaccine schedule. I support good science" . However subsequently now he is IN post, he appears to be rolling back on this and is now demanding there are investigations into "whether the timing of childhood vaccinations” are possible factors in development of chronic diseases. To be clear there is NO such evidence but this type of statement chimes with his prior disinformation campaigns.

Another concern is that RFK Jr is in charge now of the independent advisory committee to the Centers for Disease Control and Prevention (AICP) -this organisation plays a key role in setting US vaccine policy. Since, being sworn in, RFK Jr has stated in a interview of Fox news interview that it was his view that ACIP members are rife with conflicts of interest. There is nothing to stop him from changing who is in this committee and, if he does, vaccine policies WILL be impacted. His rhetoric and past statements do not give me any confidence in this regard.

So what can we do? For those seeking accurate science information, I urge you to consider the reliability of the sources and whether the people involved stand to make money out of their actions (many proponents of disinformation and woo woo health practices do). We will do our best to keep posting up dates of course. If you do have questions about vaccines then there are good sources such as the British Society for Immunology who have made accessible resources.

Take care !

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This week several hospitals declared criticial incidents due to winter pressures. The pressure in December was mainly due a very large flu wave, which has - thankfully - just peaked. While there might be a second peak (as there was last year), hopefully there will now be a rapid decline in flu infections, although hospital capacity will remain under severe pressure for a few weeks yet.

Today also saw the release of December’s NHS performance indicators and pretty much everything got worse in December compared to November. Ambulance response times increased - going up to 47 minutes for category 2 calls (vs an 18 minute target) although they did not reach the extreme delays we saw in December 2022. Hospital A&E’s remained overloaded, with tens of thousands of sick patients waiting more than 12 hours to be admitted. Most of these patients will have received ‘corridor care’, described as “unsafe and undignified” this week by the Royal College of Physicians.

What is also abundantly clear is the degradation in NHS ability to cope with winter since 2019. This degradation has consequences. While it certainly makes it harder to deliver routine care in the NHS and damages staff morale and retention, its most important impact is on those who desperately need emergency care. This week The Guardian reported an analysis suggesting that over 1000 patients a day in 2024 might have been harmed by delays in ambulance handovers. Last year, the Royal College of Emergency Medicine estimated that 14,000 people died in 2023 because of waits over 12 hours for a hospital bed.

I feel like I sound like a broken record, simply highlighting over and over each winter how bad things get. But this is because the NHS is a broken system and stutters over and over each winter. While the Labour government has promised action and has started various initiatives for the NHS, many of these will take years to have impact even if they are successful, not least because lack of experienced staff is a key issue and staff don’t grow on trees. So, unfortunately, I am not that hopeful about next winter. I do hope that the least we could do is to relearn the lessons on infection control within hospitals and GPs - cleaner indoor air and high quality (FFP2, not the blue surgical ones!) mask wearing for staff and visitors during peak winter months at the very least.

Nevertheless, “normality” prevails so powerfully that we accept NHS winter (now perennial) pressures, despite knowing we CAN mitigate respiratory diseases. The previous Government pushed individual responsibility through staying alert and common sense to restore freedom. Yet this illusory policy leaves us at risk, whether “vulnerable” or “healthy” (yes, quotations are deliberate).

Public health should act at the population level, yet only the Green Party has a substantive COVID/respiratory infection policy. We must “mitigate, vaccinate, and communicate”.

1. Mitigate

The previous Government’s pendulum-like response created a false binary of “lockdown” vs. freedom. Delay and dithering as cases skyrocketed ultimately led to much harsher and longer restrictions, whilst unlocking too quickly drove yo-yoing prevalence and far higher deaths and hospitalisations than countries that controlled COVID, like South Korea.

Figure 1. Weekly deaths with COVID-19 on the death certificate by date of registration (Source UKHSA Dashboard).

Find, Test, Trace, Support, and Isolate (FTTIS) underpins infection control, depriving the virus of hosts within environments refractory to transmission, expertly practiced in Southeast Asia. Critically, FTTIS needn’t restrict freedoms, unlike initial UK COVID measures that eliminated seasonal influenza during 2020/21.

Knowledge is power, so testing is critical. PCR is costly, yet essential during the acute phase or healthcare settings, whereas LFDs provide excellent community insights. Wastewater surveillance provides near real-time prevalence, comparable genetic epidemiology to PCR, and is amenable to tracking multiple pathogens. However, UKHSA halted this in England during 2022.

Since 2010, the damage done to the NHS and dramatically worsening health inequalities have in turn affected how we are affected by the pandemic. This has been compounded by the abandonment of infection control in favour of futile drives to improve school and NHS staff attendances. Unsurprisingly, nosocomial SARS-CoV2 and other infections continue to blight hospitals and care settings. Means to combat airborne transmission of SARS-CoV2 and other viruses have been abandoned, including the wearing of well-fitted respirator masks, placing vulnerable patients at risk along with a lack of testing.

“Infection resilient” environments provide an excellent public health solution to these problems, removing the onus from individuals whilst reducing infection AND pollution. Improving indoor air quality by ventilation, filtration, sterilisation etc. would save £8bn annually, rising to £23bn during a pandemic according to the Royal College of Engineering. The CLASS-ACT trial showed that air filtration reduced overall absence from school by 20%, and a similar approach eliminated SARS-CoV2 and other pathogens from Addenbrookes Hospital. However, an absence of nationwide investment restricts best practice to venues such as the Davos WEF summit.

If the Sanitary act of 1866 was introduced after ~6000 died of cholera, surely losing almost fifty times that number to COVID since 2020 (>10K in the last 12-months) should motivate us to add clean air as a basic human right.

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2. Vaccinate

A vaccines plus strategy fits the “Swiss Cheese” pandemic mitigation model for COVID or other infections. The notion that you should get infected to become immune to what just infected you is madness when effective vaccines are available.

This was finally recognised by JCVI recommendations for childhood chicken pox vaccines, although this is yet to materialise. Juvenile vaccinations are down across the board and targeted vaccination doesn’t protect enough people to prevent inevitable winter waves. Whilst the initial and booster COVID programmes succeeded in older adults, uptake was much lower in under 40s, and almost non-existent in young children due to delayed, confused and lacklustre messaging (Figure 2). I remain dumbfounded that we vaccinate kids for influenza, but not SARS-CoV2, despite prolific acute hospitalisations and 10s of 1000s of kids suffering from long COVID in the UK.

UK COVID booster offers are now highly limited after stringent narrowing of eligibility, set to preclude pregnant women from spring 2025. Targeted vaccination continues to mystify, and not just for COVID. Delayed kids chicken pox vaccines are compounded by bizarre older age eligibility, whilst new RSV jabs are confined to pregnant women and over 75’s, but not over 80s or babies, unlike the USA. Even resurgent seasonal influenza in 2022 and a larger UK susceptible pool wasn’t enough to expand or accelerate seasonal vaccine programmes. Damaging concomitant waves of COVID, influenza and RSV ensued.

Unlike endemic viruses, balancing the rapid evolution of SARS-CoV2 with population immunity will require both reduced transmission and improved vaccines, involving invariant targets and longer-lasting protection. Alongside relentlessly evolving subvariants, “saltatory” evolutionary jumps emerge periodically from chronic patients, resetting the immunological clock. Crowbarring COVID into an influenza mould doesn’t work it evolves far more quickly; hence, “current” COVID immunisations are based upon JN.1 from Christmas 2023…imagine doing this for influenza vaccines!

Figure 2. Coverage of English initial and booster vaccine campaigns by age group until Nov 2023. Source: Independent SAGE, courtesy of Bob Hawkins and Prof Christina Pagel (UK Government data).

3. Communicate

Despite understandable pressures during a crisis, confused messaging was a constant feature of the previous Government’s COVID response. For example, the pervasive subject of supposedly accruing herd immunity by infection made a huge impact in the media, not helped by the now infamous quote from Boris Johnson that that the UK should take COVID “on the chin”. Despite this being taken somewhat out of context and “herd immunity never being the official UK strategy, confirmed by Sir Chris Whitty speaking to the COVID inquiry, the lack of nuance in public debate, and the favouring of such a strategy by some in Government, resulted in a major mismanagement of public communications.

Tragically, this concept was taken to the extreme by those advocating for the virus to “let rip” to obtain herd immunity, despite this never occurring historically without vaccination. Whilst fundamentally flawed, this appealed to some in Government, and fringe advisors were drafted in to argue against SAGE guidance as cases rose again in autumn 2020, before vaccines. The ensuing wave and the drive to save Christmas was itself highly damaging despite last minute restrictions, and provided fertile ground (R>1) for the emergence of the Alpha VoC. The handling of this resurgence led to widespread public distrust of the government response.

Whilst the availability of vaccines then prompted a roadmap out of restrictions based upon four key criteria, the precise data and thresholds used to guide decision making were never clarified. Ultimately, dates became more important than data, culminating in “freedom” day, which went ahead despite soaring cases of the Delta VoC and an attempt by Boris Johnson and Rishi Sunak to avoid self-isolation guidance. Naturally, this represented the opposite of freedom for many. A delayed tokenistic response to the Omicron variant later that year continued the “rollercoaster” series of reactive, rather than proactive responses to the virus. Trust was further undermined by high profile government figures contravening their own COVID guidance and revelations around a widespread “party culture” at Number 10.

In addition to policy, failures to communicate how SARS-CoV2 is transmitted have had important consequences for how COVID has been managed. Airborne transmission (Figure 3) has featured consistently at the inquiry, supported by experts. Yet, the healthcare Infection Prevention Control (IPC) cell continues to dismiss airborne transmission, doubling down on droplet transmission and insisting that fluid resistant surgical masks (FRSM) are sufficient protection for staff versus FFP2/3 respiratory protective equipment (RPE). Unsurprisingly, we continue to experience unacceptable levels of NHS staff illness as well as patient endangerment. Why does NHS policy appear beholden to the politicisation of mask wearing, rather than scientific evidence and WHO guidance?

Figure 3. Illustration highlighting how improved indoor air quality can mitigate infection risks, generated using ChatGPT.

The new Labour government faces tough logistic and financial challenges to repair the damage done to the NHS since 2010, but our pandemic strategy simply must adopt a more preventative approach. Since 2020, Independent SAGE has sought to fill a gap in science communication around pandemic policy, and to provide a forum where scientists communicate with the public. This has led to demonstrable impact, including organisations pledging to improve indoor air quality and other measures. The Government must communicate that urgent change is needed, with long-term investment in surveillance, vaccines, therapeutics, and a paradigm shift towards cleaner indoor air, reducing the need for draconian measures during the inevitable next pandemic.

What is a flu pandemic?

We are all familiar with the annual winter flu season. Even though circulating flu viruses mutate from year to year, existing population immunity from previous infection and vaccination limits the size of the annual wave and the severity of infections. Nonetheless, seasonal flu remains a significant problem. In Europe, about 10% of the population is infected every year and between 15,000 and 70,000 people die. Global estimates are about 400,000 annual deaths from seasonal flu. The elderly, the very young and those with other health conditions are most at risk of severe illness.

Sometimes a strain of flu arises that is so different to previous strains that most people have little pre-existing immunity to it, and, as long as it can transmit between people, the conditions are set for a flu pandemic. A pandemic flu strain is often due to spillover from flu strains circulating in animals. For instance in 2009’s swine flu H1N1 pandemic, it was a mix of pig, bird and human flu viruses that likely developed in pigs (which can be infected by all three) before jumping over to humans. The 1957 H2N2 pandemic arose from a mix of bird and human virus. Because far fewer people have any immunity to pandemic strains, attack rates are much higher - anywhere from 15% - 40% of the population can be infected by the time the pandemic is over. This means that even if the severity is not necessarily higher than seasonal flu, the population impact is much higher simply because so many more people get sick. This is what happened for instance in 1957, where a million people are estimated to have died. When the pandemic strain is more severe as well as infecting many more people, the consequences can be devastating as in the 1918 flu pandemic, where an estimated 50-100 million people died worldwide.

Flu pandemics can disproportionately affect younger adults and children, simply because older adults have been exposed to more strains of flu in their lifetimes. This means they might have some protection from severe disease if they were infected with a related strain years before. This is exactly what happened in the 1918 and 2009 flu pandemics.

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Why did people worry about bird flu (H5N1)?

Because flu viruses continue to circulate in animals, evolve relatively rapidly and can jump between species, flu pandemics in humans will continue to occur at sporadic intervals for the forseeable future - we just can’t know exactly when they will hit. Scientists around the world have been worried about a new bird flu (H5N1) pandemic for years - partly because it was circulating in wild bird populations, particularly in Asia, and partly because in rare cases when people were infected the reported case fatality rates were really high (as high as 50%). While this case fatality rate is a significant overestimate since non-serious infections are generally unlikely to be caught, it is still frightening because even a mortality rate of a few percent can lead to horrific consequences. The mortality rate of the devastating 1918 flu was somewhere between 1-2%.

So, before Covid hit in 2020, the state of play was that scientists knew that there would be a new flu pandemic at some point and were most worried about the potential for one arising from wild bird populations first infecting poultry and then finding a route to humans. However, outbreaks in domestic bird populations were still sporadic, geographically concentrated in Asia, with very little spillover to other species, and, in the rare case a person was infected (normally through contact with infected poultry), little or no human-to-human transmission.

Global spread of bird flu (H5N1) in animals since 2020

In 2021, a new strain of H5N1 emerged in wild birds which spread rapidly around the world, helped by migratory wild birds. Some wild bird populations might never recover. By 2022, domestic poultry flocks were infected around the world, leading to the culling or death from infection of over 130 million domestic birds across the US, Europe, Asia and Africa.

Since 2022, H5N1 has infected over 50 species of mammals - mostly through eating infected wild birds, although some mass death events in seals and sea lions have raised worries that it might also be spreading from mammal to mammal. This matters because the most likely way H5N1 adapts to humans is by finding relevant evolutionary jumps in other mammals first. However, at least people were not in regular contact with these wild mammals and so human spillover events were rare. But that was about to change.

By the end of 2022, there was a big outbreak in farmed mink in Spain, with some evidence of mink-to-mink transmission. The mink got pretty sick and all of them were culled. Then, in early 2024, H5N1 popped up in dairy herds in two US states. The concerning thing is how quickly it then spread - confirmed in over 500 dairy herds across 15 states by mid November 2024.

The virus’s move into high volume animal farming, particularly cows, is concerning for two reasons: firstly, it means the virus comes into contact far more often with humans (mainly farm workers) and secondly, large cow herds mean it has a greater opportunity to adapt to mammals and develop mammal-to-mammal transmission.

Worryingly, the virus has been detected in 1 in 5 samples of milk for sale in the US. This means that it is likely more widespread in herds than confirmed testing has shown. We do know that pasteurisation of milk inactivates the virus. However, raw milk might be problematic. While it’s not known whether humans could catch flu by drinking infected raw milk, studies had shown that cats and mice definitely can.

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Are humans getting infected?

The short answer is yes, but not in great numbers. There were a handful of infections confirmed in humans across various countries in 2022 and 2023 - all from exposure to infected birds (mainly poultry). In 2024, almost all cases have been in the US with 58 confirmed infections in people. 56 of these were in farm workers at either poultry (21) or cattle farms (35), with zero evidence of human-to-human transmission and all 56 farm-related cases were mild infections.

The concern is that two recent US confirmed infections were in people with no known exposure to infected animals (one a child in California, the other a man in Missouri who was ill enough to need hospital). It has been confirmed this week that the California child’s strain was closely related to the strain circulating in US cattle. Alongside that, Canada recently reported a severe case in a child, also with no known exposure to infected animals. The Canadian child’s strain is genetically distinct from that infecting US cattle, so that is not a possible route of transmission.

What does this all mean?

It looks as if people infected through direct contact with infected animals are primarily infected through their eyes - this leads to distinctive conjunctivitis symptoms and might also explain the mildness of the disease (it mostly isn’t - thankfully - getting into their lungs).

It is also worrying to have three recent cases with no known source of exposure. This certainly doesn’t mean that human-to-human transmission has occurred, but as Prof Alan McNally says, unexplained transmission of any non-seasonal (i.e. new or unusual) virus is worrying.

The other worrying thing is the strain infecting the severely ill Canadian child because it has picked up a key new mutation that might help the virus attack the lungs - and make it easier to spread between people (because being in the lungs makes it more likely to spread through exhaled air). Essentially, there a few necessary mutational steps the virus needs to take to become pandemic, and this is one of them. Thankfully, the virus is still not good at transmitting between people (no one else in contact with the child has been infected) - and so hopefully this particular strain is a dead end. However, it is not good news that the virus has found mutations in this direction and might do so again.

Finally, recent research has shown that a single mutation in the US cattle H5N1 strain is enough to switch it to be more specific to humans than to birds. The good news is that this mutation has not yet been found in any of the sequenced cases, and, on its own, this mutation is not sufficient for rapid human-to-human spread. But it has been found in a mouse H5N1 sequence and it does mean that the number of mutational steps the virus needs to become a pandemic threat are perhaps fewer than hoped.

What about H5N1 vaccines?

There are already vaccines for H5 type flu, but very few are tailored to the circulating H5N1 strains (a new vaccine based on the latest strain is being produced now in the US). Of course, a strain that takes off in humans will be genetically different to current strains and will likely need an updated vaccine to be fully effective.

We know a lot about flu viruses and vaccines, and should be able to make an excellent vaccine quickly. But this is not a get out of jail free card - manufacturing, and then administering, tens or hundreds of millions of doses nationally and globally will take months, during which many millions could get infected.

What next?

Essentially, it’s a numbers game. The more mammals - and people - are infected, the higher the chance that the H5N1 virus will take the mutational steps it needs to spread easily between people. The conditions are as conducive to an emerging H5N1 pandemic as they’ve ever been. As Seema Lakdawala, a flu researcher, told Science Magazine “If H5 is ever going to be a pandemic, it’s going to be now”.

This means that surveillance and preparedness are crucial. Canada is testing its cattle farms, restricting livestock imports from the US and monitoring its wastewater for bird flu strains. The UK is actively testing poultry farms and culling birds where there are outbreaks (as there have been this week). There have been no confirmed infections in any UK cattle so far. The UK is also buying access to existing H5 vaccines in case a pandemic takes off, although these are a stopgap measure for use while pandemic specific vaccines are developed and deployed.

Given where the virus spreading, surveillance and action are particularly crucial in the US. The Centers for Disease Control (CDC) is testing cattle herds, people with suspected bird flu, waste water, and doing genetic testing as part of its routine annual flu surveillance. However, many have criticised the US response for slowness and a lack of transparency. For instance, mandatory nationwide testing of raw milk is only starting this month despite months of infections in dairy herds. Vanity Fair reported that private enterprise is conflicting with public health, delaying a coordinated response. When Donald Trump takes office in January 2025, we can expect reduced funding and power for the CDC, and infectious disease research in general, perhaps at the worst possible time.

Summary and Further Reading

Essentially, we can’t say how close a bird flu pandemic is because there is simply a lot of chance and unpredictability involved. At the moment, there is no evidence that the virus is spreading between people and the virus still has some genetic hoops to jump through to get to that stage. However, we can say that we are a lot closer to one than we have been in decades - uncomfortably close. In a world of rising vaccine scepticism, disinformation and populism, how confident can we be in an effective, coordinated, response?

Finally here are some useful and accesssible articles about the current situation if you want to read more.

Why hasn’t the bird flu pandemic started?, Kai Kupferschmidt, Science Magazine, 5 Dec 2024

Under certain conditions, a single H5N1 flu virus mutation could lead to spread among people, University of Minnesota, 6 December 2024.

H5N1 influenza: some troubling preliminary signals, Adam Kucharski, 27 Nov 2024

Why a teenager’s bird-flu infection is ringing alarm bells for scientists, Heidi Ledford, Nature, 20 November 2024

A Bird Flu Vaccine Might Come Too Late to Save Us from H5N1, Maggie Fox, Scientific American, 30 October 2024

What is the best way to stop a pandemic? Adam Kucharski, 22 July 2024

How fatal is H5N1 influenza? Adam Kucharski, 24 June 2024

This weekly Covid Situation report was originally posted on my substack ‘Seeing the Forest for the Trees’ where I publish articles on Covid and other topics. You can access my substack at the following link.

Seeing the Forest for the Trees

This weeks report includes the most recent weekly test positivity rates and hospital admissions data for England. It also incorporates daily case rates from the UKHSA Covid dashboard, alongside the latest data for Scotland, Wales and Northern Ireland. The report also reviews the progress of the Autumn 2024 Covid booster campaign across the Home Nations. Finally, there is an update on the latest data on Covid variants.

Summary.

This week continues to bring positive news, with data showing low levels of Covid across England, Scotland, Wales, and Northern Ireland. However, there are some early signs of levels increasing in Wales.

Contrastingly, there has been a significant rise in Flu and RSV, making it more likely for those with Covid-like symptoms to actually be suffering from Flu or RSV rather than Covid.

In England, the Covid test positivity rate, hospital admissions and case rates remained stable, and are at low levels well below those of the other respiratory viruses.

Concerningly, Flu test positivity and hospital admissions increased significantly and at a rate similar to the severe 2022/23 season that led to extreme pressures on the NHS.

In Scotland, Covid levels also remained low across all measures, including admissions to hospital and wastewater monitoring.

For the second week, Covid hospital admissions in Wales have increased but remain relatively low.

In Northern Ireland, Covid indicators have remained at low levels and are currently significantly lower than those of other major respiratory viruses.

The prevalence of the XEC variant is falling as the FLiRT variant KP.3.1.1 regains dominance in England.

Vaccination remains a powerful way to minimise the risk of Covid and, although the Autumn 2024 booster campaign is starting to slow down, over half of the targeted demographic aged 65 years and older have been vaccinated in England. However, coverage for those at clinical risk and amongst health care workers is worryingly low.

As a reminder, the Autumn 2024 booster campaign which started on October 3, 2024 will close earlier than previous years on Friday, December 20. Eligibility can be established and bookings made at the following link.

Book Covid Vaccination

As always, it’s important to remember that the risk of hospitalisation from Covid infection increases significantly with age and for those immunocompromised. Also Long Covid remains a risk for all as shown by the recent ONS report. Therefore, it is prudent to take appropriate measures such as self-isolating when experiencing Covid symptoms and enhancing ventilation or wearing masks whenever possible.

Status of main respiratory diseases in England.

This section starts with the latest available data on positivity rates for primary respiratory infections in England. It is important to understand that positivity differs from prevalence, which refers to the overall percentage of COVID-19 in the general population. Appendix 1 provides a more detailed explanation of the difference and why positivity rates are a useful indicator of trends in Covid infection levels.

The chart below displays the test positivity rates for the main respiratory illnesses in England, covering Flu, Covid, RSV, and Rhinovirus.

The Covid positivity rate has remained stable and at low level this week, and once again is lower than that other respiratory viruses. Worryingly, RSV rates are rising fast, particularly amongst those under five years old, and remain significantly higher than for Covid. Flu rates are also rising fast and are now much higher than Covid. Rhinovirus rates are falling slowly but remain relatively high.

The following chart in this section shows weekly hospital admissions per 100,000 people in England for the main respiratory diseases.

Over the past week, weekly hospital admission rates for Covid have stabilised at relatively low levels and are below those of the other respiratory viruses. Meanwhile, admission rates for RSV continued to increase and, worryingly, there was a significant increase in admissions for Flu this week.

The chart below illustrates hospital admissions for flu per 100,000 people, comparing the years before Covid, represented by dashed lines, with the years following Covid, indicated by dotted lines. The current year is marked with a solid red line. For clarity, the years during which Covid was active and there was no flu season have been excluded.

It is noteworthy that post-Covid, the flu season has generally begun earlier compared to the pre-Covid years. The 2022/23 flu season was especially harsh and occurred simultaneously with a surge in Covid admissions, placing severe pressure on the NHS. While it is unlikely that Covid levels will reach the heights of previous winters, current trends indicate that Flu admissions may be as severe as they were in 2022/23, placing significant pressure on the NHS.

Covid case rates in England

The UKHSA Covid dashboard continues to publish daily case rates for England on a weekly basis. As the majority of testing now occurs in hospitals or under medical supervision, these rates should closely align with hospital admissions. However, a comparison of daily case rates and daily admissions shows that this is not the case.

Appendix 2 indicates that although Covid case rates typically reflect the pattern of hospital admissions, there is a notable discrepancy in the magnitude of changes, with admissions experiencing a more pronounced fluctuation than case rates. Therefore, while case rates are helpful in signalling the general trend of Covid within the population, they do not precisely represent the degree of change.

The following chart shows daily case rate per 100,000 individuals.

The chart shows that Covid case rates have remained stable this week, reaching their lowest point in more than a year. Although it is important to note, as detailed above and in Appendix 2, that comparisons with the peak in Winter 2023 are not recommended.

Scotland weekly hospital admissions and bed occupancy

Scotland continues to publish weekly data on hospital admissions and bed occupancy for Covid as well as wastewater monitoring data. The dashboard for Scotland’s data can be accessed here.

The following panel chart shows the most recent data for weekly Covid hospital admissions depicted in blue, together with the number of beds occupied by Covid patients, shown in orange. The number of occupied beds represent patients being treated for Covid as well as those being treated with Covid.

The charts shows that the recent 'summer' Covid wave in Scotland led to more hospital admissions and a greater number of beds occupied by Covid patients compared to the 'winter' wave. This contrasts with England, where 'summer' hospital admissions did not surpass those seen in 'winter'.

This week Covid admissions and bed occupancy remained broadly unchanged staying at the lower levels seen earlier in the year.

Scotland remains the only home nation that is monitoring Covid levels using wastewater sampling. Recently reporting was paused as responsibility for laboratory Covid water samples testing transferred from the Scottish Environment Protection Agency (EPA) to NHS Lothian but has now been resumed.

The wastewater sampling data indicates that the high Covid levels observed at the start of August have significantly decreased and, by the end of November, have dropped to low levels.

Wales Covid cases and hospital admissions.

Public Health Wales recently updated the published data on respiratory viruses, resulting in the currently available data being limited.

The following chart provides the trend for weekly hospital admissions in Wales.

Hospital admissions for Covid in Wales rose slightly again this week but remained at comparable levels to the same period last year.

Northern Ireland hospital admissions

Recently Public Health Northern Ireland began issuing a combined surveillance report on influenza, respiratory syncytial virus (RSV), and COVID-19 to offer a comprehensive view of the epidemiology of these infections within Northern Ireland. The new report, published every Thursday, can be accessed here.

The first chart in this section shows the test positivity rates in Northern Ireland for the main respiratory illnesses — Flu, RSV, and Covid.

The chart indicates that Covid levels, shown in purple, have stopped falling this week but are still much lower than the summer peak. They also remain lower than the rates of the other major respiratory viruses which are increasing at a faster rate.

The chart below presents the weekly count of hospital admissions for the main respiratory illnesses where the infection was contracted in the community, thereby excluding patients who contracted Covid while in hospital. It is important to note that the hospital admissions data for other home nations include patients who contracted infections in the hospital, making them not directly comparable to the data from Northern Ireland.

The chart shows that for most of 2024, the bulk of hospital admissions for respiratory infections stemmed from Covid. In recent weeks, hospital admissions for Covid, indicated in purple, have remained stable and are now at their lowest in a year.

Meanwhile, hospital admissions for Flu and RSV have continued to increase and currently exceed those for Covid.

Covid vaccination coverage across the home nations

The Autumn 2024 Covid booster campaign started started on October 3 and will close on December 20. Similar to previous booster campaigns, eligibility is restricted to those at the highest risk of hospitalisation and death. Those eligible are older people in care homes, individuals 65 years and older, the immunosuppressed. Eligibility can be checked and boosters booked at this link. In addition, health and care workers will be offered boosters through their employers.

This year's Autumn vaccination campaign is set to end earlier than in previous years, with the majority of vaccinations scheduled to be completed by Friday, 20 December 2024. However, outreach efforts to administer vaccines in underserved communities will continue until 31 January 2025.

The following chart shows the number of Covid vaccinations given by week for each of the booster campaigns in England.

The number of booster doses administered in the week ending December 1 fell to 227,794 from 300,633 the previous week, resulting in a total of just under 9.3 million doses given in the first nine weeks of the campaign. This means that progress is now behind that achieved in the two previous Autumn booster campaigns.

The next chart in this section displays the booster coverage for individuals aged 65 and over across each of the Home Nations. It is important to note that the most recent published data is used, and there are varying dates for the nations, which are indicated in brackets.

The weekly change in booster coverage is slowing down, and while the data for Wales may not be as current, its coverage is lagging in comparison to the other Home Nations.

The final chart in this section shows the latest booster coverage for those aged under 65 years old who are clinically at risk for the Home Nations that publish this information.

Booster coverage for the clinically at risk across the Home Nations varies, but all have significantly lower rates and slower progress compared to the population aged 65 and over.

Finally, it was recently reported that UKHSA are urging healthcare professionals to come forward for their flu jab and Covid booster, amid ‘lower than expected’ uptake.

In all, 24% of NHS workers have received their flu vaccine and 14% have received their Covid vaccine. GPs have a slightly higher uptake than other healthcare professionals but it was still only 42% for flu and 23.6% for Covid.

Variants update

The XEC variant has received considerable attention due to its reported higher growth advantage over other variants and this section provides a brief update on it’s progress.

The chart below illustrates the prevalence of variants in sequenced cases up to the week ending Nov 17, 2024. For clarity, the various JN and FLiRT (KP) variants have been grouped into 'families'.

The chart indicates that the FLiRT family of variants was dominant in September, while the XEC variant was quickly emerging. Nevertheless, the latest data reveals that XEC did not surpass FLiRT in prevalence, and the FLiRT KP.3.1.1 variant has re-established its dominance, accounting for the majority of all sequenced cases in England. However, it’s important to acknowledge that the most recent data may contain a high degree of uncertainty due to the low levels of Covid currently in circulation.

In conclusion

Although the amount of data currently being published has decreased, the information available for England show that Covid levels are at relatively low levels and much lower than Flu or RSV.

Recent data indicates that Scotland and Wales, unlike England, experienced higher Covid-19 infection levels during the 'summer' wave compared to the 'winter' wave. Following a peak in the summer, infection levels have been on a downward trend and are currently at relatively low levels in Scotland. However, levels in Wales may be starting to rise. Northern Ireland Covid levels remain low.

As always, if you have any comments on this Covid Situation Report or suggestions for topics to cover, please post a message below.

Appendix 1. Test positivity rates and prevalence

Positivity rates are derived from the results of hospital laboratory tests conducted on patients exhibiting symptoms of respiratory diseases. Test positivity is the percentage of patients who test positive for Covid of the total number of patients tested. Since the individuals tested for this measure are not a representative sample of the general population it differs from prevalence, which is derived from a representative sample of the population.

Test positivity rates, while not directly estimating the number of Covid infections in the general population, can be a valuable indicator of the infection trend. The panel chart below compares the weekly test positivity rate among hospital patients with respiratory symptoms to the prevalence of Covid in the general population, as reported in the Winter Infection Survey.

The chart shows that the weekly test positivity rates for patients with symptoms of respiratory infections follows the same pattern as the prevalence for Covid reported by the Winter Infection Survey. Since the Winter Infection Survey is based on a representative sample of the general population this supports using test positivity as a useful proxy for infection trends.

Appendix 2. How reliable are Daily Covid Case Rates?

The UKHSA Covid dashboard continues to publish daily case rates for England on a weekly basis. As the majority of testing now occurs in hospitals or under medical supervision, these rates should be closely aligned with hospital admissions and the positivity rate of tests.

The first panel chart in this section tests that assumption by comparing the daily case rate per 100,000 individuals, shown in red, with daily hospital admissions for Covid reported by NHS England, depicted in blue.

The chart shows that while Covid case rates generally mirror the pattern of Covid hospital admissions, there is a significant disparity in the scale of changes. The grey shaded areas on each chart highlights the difference between the peak of the winter wave and the recent peak in June. Case rates experienced a 64% decrease, whereas hospital admissions saw a reduction of only 32% between the winter and June peaks.

In conclusion, although case rates are useful for indicating the overall trend of Covid in the population, they do not accurately reflect the extent of change. The likely reason for this is that testing levels have decreased by about a half since January.

State of emergency services

Last week, the Guardian ran a story warning of a massive winter crisis in A&E. A huge 94% of surveyed medics feared that patients are coming to harm because of delays in access emergency care.

The key performance indicators (KPIs) for the NHS are published retrospectively every month, so at the moment we only have data up to October. The Nuffield Trust has started a dashboard tracking these and certainly the signals aren’t pretty.

Ambulance times for category 2 calls (urgent but not life threatening) were at an average of 42 minutes - much higher than the 18 minute target, which has not been achieved since 2021. These times are about the same as October 2023, but better than we saw in both 2021 and 2022. Waiting times for admission to hospital are looking pretty bad though - the number of people waiting more than 12 hours from the decision to admit is almost as high as it was in the last two winters and this is only October.

How bad this winter will get is largely down to how likely it is that we see a spike in all three main respiratory diseases (Covid, RSV, Flu) at once. If we do, like we did in 2022/23, winter is likely to be dreadful but if we see waves peaking at different times, we will be ‘lucky’ and only get a more ordinary bad winter, like 2023/2024.

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Trends in respiratory diseases

At the moment, the signs are that we are on course to be lucky. RSV peaked this week last year. The most recent data puts RSV levels near last year’s peak and with luck we will start to see RSV hospital admissions trending down from early December. Flu is increasing but the main flu peak hasn’t hit yet and is likely to come a few weeks after RSV has died down which will help. Of course, if it’s a very bad flu year then it can cause plenty of problems all on its own.

Meanwhile, there is good news on the Covid front. The October peak is still coming down and while it might take off again this winter, its peak would likely be after both RSV and Flu, relieving potential NHS pressure.

But that said, there is no particular sign of a new Covid wave on its way. Wastewater monitoring from Scotland shows the enormous summer wave and smaller autumn ones, but relatively low and flat levels for the past few weeks. This is mirrored in wastewater monitoring from other nearby countries such as Ireland, The Netherlands, and Denmark. There are also no new variants that I’m aware of causing imminent concern. XEC is growing but only slowly and I don’t expect to be a major issue. So - fingers crossed - the NHS might escape with a ‘normal’ winter this year.

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Vaccines

Meanwhile, we’ve been trying to vaccinate vulnerable groups against Covid, Flu and RSV this autumn, although confusingly the elgibility for each of these vaccines is quite different (flu is the most broadly available). Covid vaccine uptake (from UKHSA weekly report) shows reasonable uptake in the oldest age groups, but worryingly low uptake in the younger clinically vulnerable groups.

Flu vaccine uptake is higher than that for the Covid vaccine, but lower than this time last year for all groups except for pregnant women and toddlers. The more we can encourage vaccination each autumn, the better we can protect our population and the NHS each winter.

Summary

At the moment then, things are not looking terrible for this winter. But I’ll be keeping an eye out for the November NHS stats (due out in December) and what the three respiratory diseases do over the next few weeks.

And once again, I want to point out how crazy it is that we leave the winter NHS crisis - the single most predictable NHS crisis - down to luck every year, instead of actually planning to be resilient to whatever nature throws at us.

Paul Mainwood, in his substack (which I recommend) put it best a couple of weeks ago:

A couple of years ago I wrote an article in The Conversation about the quiet removal of the offer to vaccinate primary age children to protect them against COVID-19 in England. The decision was that any child who turned five after August 2022 would not be eligible to receive a COVID vaccine until they are 12, unless they are in a higher-risk group. Vaccines for children under the age of 4 (from the age of 6 months), whilst approved for use on the UK, are not, nor have been, provided. This is very different to other countries including the USA which do offer vaccines to children from 6 months of age. What I want to do this with article is talk through some recent studies on paediatric infection and consider the potential implications of that, if any, on vaccine policy.

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Why are most children not offered COVID-19 vaccines in the UK?

The reason for this is the idea that COVID is a less serious infection in young children than it is in adult. Whilst this can be true for many children, some do experience worse infections and a recent paper has looked at data in the UK regarding hospitalisations for COVID-19 across age groups. I also encourage you to read Christina Pagel’s excellent substack summarising the findings here.

The research analysis summarised in Professor Pagel’s substack showed that over 40% of all admissions in children between 2020 and 23  (under the age of 18) were in infants under the age of 1.

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Vaccines and pregnancy.

Young infants are exceptionally vulnerable to COVID 19. The reason for this is that infants’ immune systems are still developing which makes them particularly vulnerable to any infection including COVID-19. The good news is that babies can be protected from COVID-19 in the first six months of life if the mum has been recently vaccinated. This is because if the mum is vaccinated she can pass on protective antibodies to the developing baby whilst pregnant. These will wane over time but if the mum is then able to breastfeed she can then top up the baby’s antibodies further by passing on antibodies that are found in breast milk.

Covid vaccines in pregnancy are recommended in the UK. These vaccines are recommended as the severity of COVID-19 is higher in unvaccinated than vaccinated women. Although the risk in the post-omicron era is lower, there is still a greater risk to the mum and baby from COVID-19. However, takeup of COVID-19 vaccines has not been great in pregnant women. For example, a study showed that only 1 in 3 pregnant women would have the COVID-19 vaccine during pregnancy. Younger women and people from socially economically deprived backgrounds were least likely to be vaccinated. Much more targeted work must be done to work with pregnant women and explain why these vaccines are both safe and important. Dr Viki Male maintains an excellent and up-to-date list of research on vaccines and COVID-19 in pregnancy so do look at her google document if you have further questions.

What are the risks of COVID-19 for older children?

Whilst I would personally advocate that infants and children would benefit from the offer of a vaccine between 6 months to 4 years of age to help develop their immunity so their first encounter with COVID-19 is helped and shaped by vaccine induced immunity, its unlikely the policy in the UK will change.

The current rationale influencing UK policy is that most children will be exposed to infection via school or nursery and that the risks of severe impacts of COVID are low. This is because most children with COVID-19 remain asymptomatic or develop mild disease, often with upper respiratory symptoms. The proportion of children over the age of 1 who get severe disease is still rare. Of those children that do get severe disease, it has been suggested that many children who require hospitalised with Covid have underlying health conditions. This thinking then influences the policy decisions. However, in older children (over the age of 1) this is true for around half of all hospitalisations though so that reasoning doesn’t quite chime. However, it is true that overall deaths from COVID in children DO remain rare which is very good news. The green book (which publishes data and recommendations for vaccines) cites a 2022 study which showed an infection fatality ratio of less than 1 in 100,000 infections in 0-19 year-olds. The risk is therefore considered low and decision makers have been concerned this risk is outweighed by the possible risk of acute resolving myocarditis from the vaccine in adolescent boys.

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However, infection is NOT risk-free and some children do develop Long Covid (symptoms that last more than 4 weeks). We still do not understand why this happens and how we can better identify children who are most at risk. This is important so we can establish who falls into the more vulnerable groups that are currently eligible for vaccines. A recent scoping review was published investigating Long Covid in 659,286 children and adolescents under the age 21. A scoping review looks at the published literature and tries to build a consensus of what the research is telling us. The incidence of Long Covid was really variable in children so we need to better understand the true incidence- one study for example suggested 3.7% children developed Long Covid symptoms. Surprisingly, 80% of the cases of long Covid started with a mild infection. This suggests that severity might not be the best indicator of vaccine eligibility and must be followed up. Symptoms very hugely variable but many children described how this affected their day- to day lives a lot (see below). This must be absolutely devastating and we must understand why some children get Long Covid symptoms.

Many of the children identified in the scoping study had pre-existing conditions including a spectrum of allergic conditions (asthma, allergy, allergic rhinitis) and/or obesity. These are not necessarily all groups considered at risk and eligible for childhood vaccines in the UK. Of these criteria, only children with severe asthma that is poorly controlled are currently eligible. This scoping study needs following up but, as vaccination reduces the likelihood of developing post-Covid complications, it could suggest we may need to revise eligibility for the vaccines in children to further reduce the risk of Long Covid in children.

Other risks of infection should be evaluated. A recent paper showed the growing incidence of juvenile type II diabetes within 6 months of the diagnosis of COVID 19 in children between 10 and 19 years of age. Studies like this show the need to continue to assess the impacts of the infection in the un-vaccinated.

It is vital that we understand the scale of the risks, and who are most at risk so that if can ensure that decisions regarding vaccinating children are made in the light of all the most up to date evidence. Much more work is needed too to enhance vaccine information, address vaccine hesitancy and take-up in pregnant women so that babies can be best protected from COVID-19.

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This phrase, clearly aimed at normalising pandemic harms, effectively benchmarks flu, which causes 1000s of UK deaths annually, as “normal”. This is despite available vaccines, drugs, and hard-earned population immunity against the flu virus. Sadly, familiarity breeds contempt, or in this case, complacency.

The UK “living with” COVID response relies entirely on this premise of flu as a “normal” illness, crowbarring a COVID peg into an influenza-shaped hole. The result: an overstretched NHS enduring additional health burden with little extra resource.

SARS-CoV2 has made “winter pressures” perennial (Figure 1). As a result, more people are dying, hundreds of thousands more people are unable to work, and support for Long Covid patients is dwindling. This “new normal” is NOT befitting of a country with (historically) advanced health and social care.

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We are comparing two different chalks with two different cheeses…

We sometimes hear discussion of SARS-CoV2 “settling down”, becoming “endemic”, and – my personal favourite – behaving like “any other respiratory virus”.

This is disingenuous on at least two levels. First, it really hasn’t settled, and it shows no sign of doing so (Figure 2). Second, and perhaps most troubling, is the implication that SARS-CoV2, influenza, or other viruses, cause so little harm that they shouldn’t affect our lives.

What’s actually being discussed is predictability, with the implication that predictable means benign. However, virus transmission and disease depend upon the balance between virus and host, namely the capacity of the virus to evolve and transmit, versus immunity and our environment.

Figure 2. Prevalence of SARS-CoV-2 lineages amongst available sequenced cases for England from 2 October 2023 to 22 September 2024. Source: UKHSA flu/COVID surveillance report 2024, week 41.

The “R value”, familiar from Government COVID briefings, shows infections increasing when R (the Reproduction rate, or how many people an infected person infects on average) is above 1, or decreasing when R is below 1. When R is about 1, things remain stable, predictable, yet infections still occur if the baseline prevalence (infections over time) is high. Endemic flu and Coronaviruses have a low baseline with one, sometimes two, waves each year caused by newly susceptible kids, waning immunity, and behaviour/environment temporarily pushing R over 1, usually in winter.

Seasonality is more complicated than “people spending more time indoors”, I heartily recommend this review by Prof Akiko Iwasaki.

Even hardened sceptics would struggle arguing that SARS-CoV2 fits this pattern, given it is causing multiple waves annually since emerging in 2019. The balance still favours its fast-paced evolution outmanoeuvring immunity; any support from public health mitigations is now all but extinct.

The SARS-CoV2 evolutionary rate is 3-4 times that of the fastest seasonal influenza, H3N2. This is more to do with the virus tolerating change rather than mutating quickly, with the spike protein adapting for transmissibility and antibody evasiveness, seemingly without limits.

Essentially, this slippery virus successively creates new pools of susceptible hosts, driving new waves. Even now in 2024, we see concomitant epidemic waves across multiple countries; this, incidentally, is the definition of a pandemic. Virus evolution also “jumps” when highly mutated lineages emerge from immunocompromised hosts. This “saltatory” evolution occurred most recently for BA2.86, the forebear of JN.1 and the class of 2024. Once labelled “Variants of Concern” (VoC), this practice has now stalled, despite jumping immense evolutionary distances.

Whilst an emergent “pandemic” influenza would also tip the balance very much in its favour, influenza pandemics have historically caused one, two, or sometimes three large waves prior to establishing predictable, “endemic” behaviour. SARS-CoV2, the first Coronavirus pandemic of the modern era, simply doesn’t fit the influenza mould.

Even confronted with this, sceptics still retort: “doesn’t matter because COVID is mild”. I despair…

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Viruses do NOT “just evolve to become mild”!

Misguided Australian rabbit folklore aside, this fallacy refers to disease, not viruses themselves, and is often false. Once again, the virus-host balance matters most. However, as individuals, each infection is a race and, if you run enough races, you can still lose, even with a head start from immunity.

Mercifully, we no longer see COVID hospitalisations and deaths on the scale of 2020/21, largely because vaccines accelerated our progress towards, and I mean towards, balance. Infection-induced immunity plays its part but is accompanied by far greater risk of harm and inherent survivorship bias. Depressingly, labelling this as “natural immunity”, like something from a health food shop, has led to profoundly misleading, tabloid-fuelled concepts like “immunity debt”. Please, just stop.

Nevertheless, the diminished individual risk of severe acute COVID is countered by uncontrolled prevalence at the population level. In addition to antibody evasive variants, our immunity vs. severe disease also wanes, but can be restored using well-matched boosters.

Boosters are critical for millions of erstwhile shielders and clinically vulnerable people, who usually mount poorer vaccine responses and are more likely to develop severe disease should they get infected. Whilst multiple boosters can help protect some patients, this is confounded by the high level of exposure due to now-skeletal vaccine programmes and poor mitigations. Hence, the trivialisation of COVID and other infectious diseases remains unjustifiable.

Shockingly, some proponents of “natural immunity” dubbed the ancestral Omicron variants of concern as “nature’s vaccine” in 2022, due mainly to their preference for the upper over the lower airway. While BA.1 and BA.2 were less acutely pathogenic in animal models, they caused the largest COVID waves of all time and did profound harm. Hospitalisations exceeded the pre-vaccine November 2020 peak and were double that of the Delta variant. England saw ~33K certificated COVID deaths during 2022, despite vaccines, and inherent virulence was clear from a devastating outbreak of BA.2 in poorly vaccinated populations of Hong Kong. Over time, Omicron subvariants have adjusted to both innate and adaptive immunity, with some regaining lower lung preferences and animal model pathogenicity. This appears to be happening again for BA.2.86/JN.1 derived lineages. Thus, severe disease is mainly countered by immunity, NOT viral attenuation.

So, the only way to slow a pandemic is to either improve immune longevity or slow down the virus, ideally both! For influenza, so far, we caught up relatively quickly, thankfully limiting the 1918 H1N1 “Spanish” influenza to just two waves, albeit at the cost of over 50 million lives. This is difficult to compare with prevalence-adjusted death estimates for COVID of 20-35M to date, due to duration, modern healthcare, vaccines, and therapeutics. Interestingly, the 2009 H1N1 “Swine flu” pandemic had comparatively lower impact due to cross-protective anti-H1N1 responses in older patients, derived against endemic offspring of Spanish influenza. Swine flu emerging just a decade later may have been far more devastating.

Despite familiar “winter pressures”, most of the public don’t take flu seriously enough. Over 10,000 deaths are attributed to influenza and pneumonia (ICD-10 codes J09-J18) annually. Consistent with good cross-protective immunity, only ~10% list seasonal influenza (J09 to J11) as underlying cause, compared with 50-70% for COVID; the main complication of influenza is secondary bacterial pneumonia, and this was also the case for Spanish influenza. Ultimately, despite the “with, not of”-ness throughout the pandemic, for anyone with a semblance of common sense the clinical impact of both viruses is a major issue. Years like 2018 when the flu vaccine match was poor were highly damaging, but again the pandemic balance tells; 1.4 million years of UK lives were lost to COVID in 2020 pre-vaccine, four to five times that for 2018 flu AND pneumonia.

Finally, whilst post-viral syndromes are not new, the sheer scale of long COVID is unprecedented (Figure 3). It is, by no means, “bollocks”. More than 2 million people in the UK alone continue to report suffering symptoms in 2024, including 10s of 1000s of children. Whilst acute severity increases risk, many cases follow mild infections. Sadly, many experience similar dismissive gaslighting encountered by ME/CFS patients over past decades. However, this is being countered by firm immunological and other markers of disease, although it’s recognised that long COVID has overlapping features with ME/CFS and some adverse vaccine reactions. Interestingly, for many people with Long Covid, ongoing symptoms appear linked to persistent SARS-CoV2 infection as well as reactivation of preexisting herpesviruses. Worryingly, other post-acute sequelae are now conclusively linked to SARS-CoV2, including cardiovascular, neurological, gastrointestinal, and metabolic diseases, including a worrying spike in juvenile onset type 1 diabetes.

Figure 3. Estimated global cumulative incidence of long COVID, based upon meta-regression estimates that pool together all available evidence. Source: Al-Aly, Z., Davis, H., McCorkell, L. et al. Long COVID science, research and policy. Nat Med 30, 2148–2164 (2024). https://doi.org/10.1038/s41591-024-03173-6

Recent vaccination reduces long COVID risk, plus some promising drug repurposing prospects exist. In fact, reinfection is associated with a cumulative higher risk of developing long COVID, because you can’t get Long Covid without getting Covid first. Sadly, despite recognised health, economic and societal impact, research and patient support in the UK has been downgraded. However, a clear lesson for future pandemics is to dovetail initial responses with mitigations against the long-term sequelae of infection.

As we continue to see warning shots from H5N1 influenza infecting birds, wild animals and currently US cattle, the frustration at this country’s continued inability to learn from mistakes and improve upon pandemic preparedness is tangible. We owe it to those who have been lost and continue to suffer to ensure that the same mistakes don’t happen again. This absolutely requires that we also reduce the harm done by existing endemic diseases whilst addressing health inequality across the UK. Back to normal simply isn’t good enough.

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The pandemic is as bad as it ever was for babies - in the year to August 2023, 6,300 babies under 1 were admitted to hospital wholly or partly because of Covid.

They are the only age group where admissions have not gone down over time.

Our study, published yesterday in the Journal of Pediatrics and led by Prof Kate Brown, looked at all hospitalisations in England in children with a Covid diagnosis or positive test from August 2020-August 2023.

We then excluded all admissions where a Covid diagnosis was incidental (ie not why they were in hospital), using a rigorous classification method that we developed and published in a previous BMJ paper.

Infants (babies under 1) are generally at higher risk from respiratory infections, plus they are the age group that, if infected, are overwhelmingly (>99%) meeting the virus for the first time. They are also not vaccinated.

Over the whole period of our study, Covid admissions in infants accounted for 43% of all admissions in children under 18 (19,700/45,900).

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As children over one year old gained some immunity from infection or were vaccinated (vaccination mostly in teens), their risk of needing hospital fell.

But this doesn't help infants in their first encounter with the virus. In the most recent 12 months of our data to August 2023, infants accounted for 64% of all covid child admissions.

We also checked for evidence of underlying health conditions considered high risk by JCVI. We found that by the most recent 12 months of data, 52% of Covid admissions in children over 1 had an underlying condition. But only 10% of infants did.

While most infants were in hospital for only a short time - about 2 days, a significant minority did need intensive care. For instance, in last 12 months about 5% needed intensive care and 8 babies died.

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We also found that children of ethnic minority background or in deprived areas were more at risk of Covid admission to hospital.

So what are the implications? There is a safe and effective covid vaccine for 6 month-4 yr olds. It's part of routine childhood immunisation in some countries like the US and Ireland. It's approved in UK, but JCVI has not recommended its use in otherwise healthy babies.

However, while personally I am in favour including the Covid vaccine in the standard childhood immunisation programme, it's not quite that simple.

Firstly, newborn babies are by far the most vulnerable and there is no available vaccine (anywhere) before 6 months old. US analysis has shown that Covid hospitalisations in babies under 6 months old are higher than any other age group apart from over 75s! Similar to adults aged 65-74! Almost 1 in 5 babies under 6 months in the US needed intensive care.

The most effective thing to protect newborns is for their mothers to be vaccinated during pregnancy (ideally in 3rd trimester). It's not perfect but far better than nothing and, most importantly, Covid vaccines in pregnancy are recommended in the UK.

Dr Viki Male curates a comprehensive google document answering all your questions on the covid vaccine in pregnancy! Please do check it out.

In fact, pregnant women can protect their newborns against all sorts of nasty respiratory viruses by being vaccinated in pregnancy. As well as Covid, there's flu, whooping cough, and - now - RSV!

The problem is that uptake of vaccines in pregnancy is quite low. About 40% for the Covid vaccine and 42% for flu vax in pregnancy. Uptake of whooping cough vaccine was only 60% last winter - 15% points lower than in 2017. This year has seen more babies died of whooping cough.

We also know that uptake of routine childhood vaccinations in childhood is declining in England, and we've seen not just whooping cough outbreaks this year, but several measles ones as well.

Given increasing vaccine hesitancy, perhaps the most important immediate effort is to tackle that across all existing childhood vaccines and uptake in pregnant women- esp whooping cough & RSV, two of the nastiest things for babies (worse than Covid). For instance, while average stay in hospital for babies with Covid is 2 days., it’s more than a week for babies with RSV.

We need to be vaccine champions! Decline in vaccine uptake, particularly in pregnant women, is risking babies’ lives.

Then, in the medium term, I believe we should offer infants and young children the covid vaccination, as part of routine immunisation. This is so that those not already infected can meet their first infection (e.g. on starting nursery) with good protection against severe disease.

In summary, our new paper shows clearly that for babies, the pandemic is as bad as it ever was. There are things we can do to protect them, and we should.