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expert reaction to study looking at vaccination, breakthrough infections, COVID disease and long COVID, from the ZOE COVID Symptom Study app

A study published in the Lancet Infectious Diseases looks at risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app.


Prof Penny Ward, Independent Pharmaceutical Physician, Visiting Professor in Pharmaceutical Medicine at King’s College London, said:

Is this robust data; what are the strengths and limitations?

“This report is one of the first to provide information on breakthrough cases of COVID detected post vaccination drawn from the 4.5million respondents that provide daily data using the ZOE app.  This app is a self reporting tool, and as shown in the data provided not all participants report daily and there is a relative excess of female participants, so it is not as completely representative of the UK population as a purist may like.  However this does not detract from the usefulness of the information provided, and we know from past experience that information provided by this group (for example the linkage between anosmia/dysgeusia and later testing positive for SARs CoV2) can be very helpful in providing early insight into public health policies.  In this case, the information provided is helpful in understanding the potential need for booster vaccinations in a proportion of the frail elderly as we approach winter.

What does the data show; are there caveats?

“The data are broadly reassuring in confirming that illness associated with breakthrough infection tends to be less severe than illness occurring in unvaccinated people, and in particular that the risk of needing to be hospitalised following breakthrough infection is reduced overall by ~two thirds (from 10-9 to 3.6% after the first dose and from 7.4 to 2.2% after two jabs) compared to age and risk matched unvaccinated controls, with greatest benefit among older people (>60) in whom double vaccination is ~80% effective in protecting against the need to be hospitalised.  In addition the proportion without symptoms ranged from ~1:4 to 1:8 (with more asymptomatic cases among older people) among the vaccinated compared to ~1:10 among the unvaccinated cases.  Persistent symptoms lasting >28 days were not much affected in cases occurring after a single dose of vaccine, but the incidence was halved (from 11.4 to 5.2%) among the double vaccinated, suggesting for the first time that vaccination can protect against Long COVID both by preventing infection and then ameliorating illness experienced following breakthrough infection.  Regrettably the study did not contain information on illness associated with different variants, and the duration of the study (Dec 2020 to early July 2021) covered the alpha and early delta variant waves in the UK.

Is the data on long COVID robust – is it just because vaccines reduce the risk of getting COVID in the first place or is there evidence here that there is more protection against long COVID than just that?

“Long COVID is explored in this study by assessing the proportion of cases with symptoms persisting for more than 28 days.  However long COVID is still poorly understood and the persistence of symptoms post infection, and their severity, remains to be explored.  It is however encouraging that the overall proportion of cases with persistent symptoms is reduced in patients that were previously fully vaccinated, which taken together with the milder overall illness and reduction in need for hospital care demonstrates the additional worth of vaccination in reducing severity of illness for individuals and reducing the burden on the NHS by lowering the number of people needing hospital care.

Can the study methods allow robust conclusions to be drawn like “fully vaccinated people are almost twice as likely to have no symptoms than unvaccinated if they catch COVID-19”?

“That is what the data suggest but the population using the App are not entirely representative of the whole population, so the information might merit some greater detail e.g. ‘About 1:5 people catching COVID after vaccination reported that they had no symptoms while only 1:10 people who had not been vaccinated reported having no symptoms‘.”



‘Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study’ by Michela Antonelli et al. was published in the Lancet Infectious Diseases at 23:30 UK time on Wednesday 1 September 2021.

DOI: 10.1016/S1473-3099



All our previous output on this subject can be seen at this weblink:



Declared interests

Dr Penny Ward: “No COIs. I am semi-retired, but I am owner/Director of PWG Consulting (Biopharma) Ltd a consulting firm advising companies on drug and device development.  Until July 2019 I was Chief Medical Officer of Virion Biotherapeutics, which was a company developing broad spectrum RNA therapy for the treatment/prevention of respiratory virus infections.  Between December 2016 and July 2019 I served as Chief Medical Officer of Virion Biotherapeutics Ltd, a company developing antiviral treatments for respiratory viral diseases.  Previous employee of Roche, makers of tocilizumab (anti IL6 antibody) and CMO of Novimmune, makers of empalumab (anti IFN gamma antibody).”

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