In the unlikely event of catching COVID-19 after being double vaccinated, the risk of long COVID was reduced by almost half, found a study, in The Lancet Infectious Diseases. There were also fewer hospitalisations (73% less likely) and lower burden of acute symptoms (31% less likely) among those fully vaccinated.
Researchers at King's College London analysed data from participants logging their symptoms, tests and vaccines on the UK ZOE COVID Symptom Study app between 8 December 2020 and 4 July 2021, including 1,240,009 (first dose) and 971,504 (second dose) vaccinated UK adults. The research team assessed a range of factors, including age, frailty and areas of deprivation and compared that with post-vaccination infection.
The study, published in The Lancet Infectious Diseases, found that in the unlikely event of catching COVID-19 after being double vaccinated, the risk of long COVID was reduced by almost half. There were also fewer hospitalisations (73% less likely) and lower burden of acute symptoms (31% less likely) among those fully vaccinated.
The most common symptoms were similar to unvaccinated adults – e.g. anosmia, (loss of smell) cough, fever, headaches, and fatigue. All of these symptoms were milder and less frequently reported by people who were vaccinated, and they were half as likely to get multiple symptoms in the first week of illness. Sneezing was the only symptom that was more commonly reported in vaccinated people with COVID-19.
However, people living in most deprived areas were at greater risk of infection after a single vaccination. While age on its own was not a risk factor, individuals who had health conditions that limited their independence, such as frailty, were up to two times more likely to contract COVID-19 infection after vaccination, and of getting sick.
The findings demonstrate the need to target at-risk groups. Frail adults have already been shown to be disproportionately affected by COVID-19. The research team suggests strategies such as a timely booster programme, targeted infection control measures and more research into the immune response to vaccination in this group could help address the issue.
Lead researcher Dr Claire Steves from King's College London said: “In terms of the burden of long COVID, it's good news that our research has found that having a double vaccination significantly reduces the risk of both catching the virus and if you do, developing long standing symptoms. However, among our frail, older adults and those living in deprived areas the risk is still significant and they should be urgently prioritised for second and booster vaccinations.”
Professor Tim Spector from King's College London and lead investigator of ZOE COVID Study said: “Vaccinations are massively reducing the chances of people getting Long COVID in two ways. First, by reducing the risk of any symptoms by eight to tenfold and then by halving the chances of any infection turning into Long COVID, if it does happen. Whatever the duration of symptoms, we are seeing that infections after two vaccinations are also much milder, so vaccines are really changing the disease and for the better. We are encouraging people to get their second jab as soon as they can.”
Study details
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
Michela Antonelli, Rose S Penfold, Jordi Merino, Carole H Sudre, Erika Molteni, Sarah Berry, Liane S Canas, Mark S Graham, Kerstin Klaser, Marc Modat, Benjamin Murray, Eric Kerfoot, Liyuan Chen, Jie Deng, Marc F Österdahl, Nathan J Cheetham, David A Drew, Long H Nguyen, Joan Capdevila Pujol, Christina Hu, Somesh Selvachandran, Lorenzo Polidori, Anna May, Jonathan Wolf, Andrew T Chan, Alexander Hammers, Emma L Duncan, Tim D Spector, Sebastien Ourselin, Claire J Steves.
Published in The Lancet on 1 September 2021
Summary
Background
COVID-19 vaccines show excellent efficacy in clinical trials and effectiveness in real-world data, but some people still become infected with SARS-CoV-2 after vaccination. This study aimed to identify risk factors for post-vaccination SARS-CoV-2 infection and describe the characteristics of post-vaccination illness.
Methods
This prospective, community-based, nested, case-control study used self-reported data (eg, on demographics, geographical location, health risk factors, and COVID-19 test results, symptoms, and vaccinations) from UK-based, adult (≥18 years) users of the COVID Symptom Study mobile phone app. For the risk factor analysis, cases had received a first or second dose of a COVID-19 vaccine between Dec 8, 2020, and July 4, 2021; had either a positive COVID-19 test at least 14 days after their first vaccination (but before their second; cases 1) or a positive test at least 7 days after their second vaccination (cases 2); and had no positive test before vaccination.
Two control groups were selected (who also had not tested positive for SARS-CoV-2 before vaccination): users reporting a negative test at least 14 days after their first vaccination but before their second (controls 1) and users reporting a negative test at least 7 days after their second vaccination (controls 2). Controls 1 and controls 2 were matched (1:1) with cases 1 and cases 2, respectively, by the date of the post-vaccination test, health-care worker status, and sex. In the disease profile analysis, we sub-selected participants from cases 1 and cases 2 who had used the app for at least 14 consecutive days after testing positive for SARS-CoV-2 (cases 3 and cases 4, respectively).
Controls 3 and controls 4 were unvaccinated participants reporting a positive SARS-CoV-2 test who had used the app for at least 14 consecutive days after the test, and were matched (1:1) with cases 3 and 4, respectively, by the date of the positive test, health-care worker status, sex, body-mass index (BMI), and age. We used univariate logistic regression models (adjusted for age, BMI, and sex) to analyse the associations between risk factors and post-vaccination infection, and the associations of individual symptoms, overall disease duration, and disease severity with vaccination status.
Findings
Between 8 December 2020, and 4 July 2021, 1 240 009 COVID Symptom Study app users reported a first vaccine dose, of whom 6030 (0·5%) subsequently tested positive for SARS-CoV-2 (cases 1), and 971 504 reported a second dose, of whom 2370 (0·2%) subsequently tested positive for SARS-CoV-2 (cases 2). In the risk factor analysis, frailty was associated with post-vaccination infection in older adults (≥60 years) after their first vaccine dose (odds ratio [OR] 1·93, 95% CI 1·50–2·48; p<0·0001), and individuals living in highly deprived areas had increased odds of post-vaccination infection following their first vaccine dose (OR 1·11, 95% CI 1·01–1·23; p=0·039). Individuals without obesity (BMI <30 kg/m2) had lower odds of infection following their first vaccine dose (OR 0·84, 95% CI 0·75–0·94; p=0·0030).
For the disease profile analysis, 3825 users from cases 1 were included in cases 3 and 906 users from cases 2 were included in cases 4. Vaccination (compared with no vaccination) was associated with reduced odds of hospitalisation or having more than five symptoms in the first week of illness following the first or second dose, and long-duration (≥28 days) symptoms following the second dose. Almost all symptoms were reported less frequently in infected vaccinated individuals than in infected unvaccinated individuals, and vaccinated participants were more likely to be completely asymptomatic, especially if they were 60 years or older.
Interpretation
To minimise SARS-CoV-2 infection, at-risk populations must be targeted in efforts to boost vaccine effectiveness and infection control measures. Our findings might support caution around relaxing physical distancing and other personal protective measures in the post-vaccination era, particularly around frail older adults and individuals living in more deprived areas, even if these individuals are vaccinated, and might have implications for strategies such as booster vaccinations.
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