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Vaccination against COVID-19 is highly successful at reducing severe illness and death in the population, but people still get infected after vaccination. New research also shows that frail older people, and those who live in deprived areas, are more at risk of infection after vaccination than other groups. The researchers urge family and friends to remain cautious around these vulnerable groups of people.

This research was based on data from the COVID-19 Symptom Study app (ZOE app), in which adults report their own symptoms. The study found that vaccination reduced the severity of disease. People who had been vaccinated had fewer symptoms, and were less likely to have symptoms that lasted 28 days or more. People who were fully vaccinated were more likely to have no symptoms at all when they got infected.

Even if they are vaccinated, frail adults and people living in deprived areas remain more vulnerable than others. The move in February 2022 to lift infection control measures (physical distancing, mask wearing, and so on) could have a bigger impact on them. These results suggest they will benefit from protective measures such as being prioritised in current and future booster campaigns.

What’s the issue?

Before COVID-19 vaccines became available, it was known that some groups faced higher risks from infection: healthcare professionals, people living in deprived areas, older people, and those who are frail or had other long-term conditions. Little was known about whether the vaccine would prevent infections, or whether it would reduce the severity of illness.

The COVID-19 Symptom Study is an ongoing online programme in which adults log their daily symptoms (or lack of them) using a mobile app. The app launched in March 2020 and millions of people signed up. Those who report symptoms are asked to take a COVID-19 test and report the results. Since the vaccination programme started, people also record their vaccines.

This study, based on data in the app, was set up to monitor infection rates among vaccinated and unvaccinated people in the UK. Researchers looked at reports logged between December 2020 (when the vaccination programme began), and July 2021, when most adults had received at least one dose. Many older adults had received second dose by then.

App users provide information on their age, health status and geographical area. In this study, people were defined as ‘frail’ if they scored above a certain level on a standard questionnaire that asks if they need help with everyday activities, have to limit their activities because of their health, and so on.

The study sought to find out which groups of people are most likely to become infected after receiving 1 or 2 vaccine doses, and to describe the symptoms and duration of COVID-19 illness after vaccination.  

What’s new?

The first part of the study looked at people’s chances of testing positive after vaccination. It included 6,030 (0.5%) people who reported a positive COVID-19 test on the app after their first vaccination but before their second.

After the first vaccination:

  • among people aged 60+, those who were frail were almost twice as likely (93% more likely) to test positive for COVID-19 than those who were not frail
  • people who lived in the most deprived areas had an 11% higher risk of testing positive than those in areas with average deprivation;  those living in the least deprived areas had a 9% lower risk than the average
  • people without obesity were less likely (16% less likely) to test positive than those with obesity.

The second part of the study included a further 2,370 (0.2%) people who reported a positive test after their second dose. It looked at the severity of illness, based on data on symptoms (and hospitalisations). Those who tested positive were compared to others using the app, who had not been infected.

People who tested positive after vaccination generally had less severe illness. Compared to unvaccinated people, those who had been vaccinated:

  • were more likely to be completely without symptoms
  • were less likely to be hospitalised with COVID-19
  • were less likely to have 5 symptoms or more during their first week of illness
  • were half as likely to have symptoms that lasted 28 days or more (49% less likely) if they’d had two vaccinations.

Why is this important?

People in this study reported their own test results, vaccination status and information about other conditions. This allowed many to participate, but their data was not checked by researchers. In addition, women were more likely than men to participate, and few people included data about their ethnicity. People from more deprived areas were underrepresented.

Despite these drawbacks, the results helped inform the UK’s vaccine booster programme – which prioritised older people – in Autumn 2021. The study demonstrates the effectiveness of the vaccine at reducing the severity of COVID-19, and at reducing the chances of long-term symptoms which can become long COVID.

The study also shows that frail older people remain at risk of catching COVID-19 after vaccination. These people may not be able to isolate because they need others to assist them in daily life. They tend also to have reduced immune function and are more likely to become ill when they encounter the virus.

This research was carried out before the Omicron variant, which is far more infectious, emerged. However, the researchers say the general lessons of who is most at risk – and the benefits of vaccination – still hold true.

What’s next?

The UK vaccine booster programme is continuing, and the researchers say that particular effort is needed to ensure that the most vulnerable groups – frail older people and those living in deprived areas – take up booster jabs.

Legal restrictions including social distancing, self-isolation and mask-wearing due to COVID-19 have now been lifted. The study results underline the need to continue to be cautious around the most vulnerable people, even if they have been vaccinated. These groups need to be prioritised in current and future booster campaigns.

Research is ongoing into the reasons why people from deprived areas are more likely to be vulnerable to infection with the coronavirus. Researchers are exploring whether long-term daily life stresses can impair people’s immune response.

You may be interested to read

This NIHR Alert is based on: Antonelli M, and others. 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. Lancet Infectious Diseases 2022;22:1

The study website: ZOE Covid Symptom Study.


Funding: This research was supported by the NIHR Comprehensive Biomedical Research Centre Award to Guy’s and St Thomas’ NHS Foundation Trust and a grant to ZOE, and by the Wellcome Trust.

Conflicts of Interest: None declared.

Disclaimer: NIHR Alerts are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that views expressed in NIHR Alerts are those of the author(s) and reviewer(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.


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Commentaries

Study author

We wanted to know who was most at risk of post-vaccination infection, to tell us whether some groups of people need to be more careful about being exposed to the virus. We shared the paper upfront with health policy makers and it was influential in bringing forth the booster vaccinations for older people.

Two things have changed. Most of the UK population has now had a third vaccine, which is great, and most have antibodies that help them to fight the virus. But that is not the case for the rest of the world. It’s important to get that message out.

The second thing is Omicron, and we are expecting there will be further variants. We have shown in another paper that Omicron is much more an upper respiratory tract infection and has milder symptoms over a generally shorter duration. But we don’t know what other variants are around the corner.

We weren’t sure whether vaccination would reduce long COVID and we are pleased to see that it did.

Claire Steves, Clinical Senior Lecturer, Department of Twin Research and Genetic Epidemiology, King’s College London 

Quality manager

This is a key message for NHS professionals and community leaders to give to the general public to persuade them to have the required vaccinations and to follow guidance. This will also give assurance to those who are sceptical and may help to boost numbers coming forwards. Leaders of local vaccination programmes may want to communicate to the specific populations described in the study, the potential impact of not being vaccinated.

All evidence will be invaluable as we continue to build up a picture of the impacts of COVID and how the different variants will affect our vaccination programmes alongside other risk factors.

Beverly Ryton, Quality Manager, Sheffield Clinical Commissioning Group

Nurse 

These findings support the case for a cautious approach in relaxing preventive measures (such as self-distancing and mask wearing) given the risk to older frail adults and those living in deprived areas. It offers evidence-based recommendations for policy on booster vaccination programmes.

The data is robust from a large range of ZOE app users. It should improve vaccine uptake among vulnerable groups.

This research informs healthcare professionals about how to interact with clinically vulnerable, older and frail adults in our care. It will help us plan and recommend vaccinations and boosters. It is also relevant on a personal level as it informs the precautionary measures one needs to take when interacting with older, frail adults and those who are clinically vulnerable.

Ayiecho Odembi, Registered Nurse, Birmingham 

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