Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app

A study published on 1 September attempted to identify risk factors for post-vaccination SARS-CoV-2 infection and describe the characteristics of post-vaccination illness. 

This prospective, community-based, nested, case-control study used self-reported data 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 8 Dec 2020 and 4 July 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, healthcare worker status, and sex. In the disease profile analysis, participants were sub-selected 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, healthcare worker status, sex, body-mass index (BMI), and age. 

Between 8 Dec 2020, and 4 July 2021, 1,240,009 COVID Symptom Study app users reported a first vaccine dose; of these, 6,030 (0.5%) subsequently tested positive for SARS-CoV-2 (cases 1), and 971,504 reported a second dose, with 2,370 (0.2%) subsequently testing 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 postvaccination 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, 3,825 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 hospitalization (OR 0.27, 95% CI 0.16 – 0.45; p = <0·001). and with having more than five symptoms in the first week of illness following the first or second dose (OR 0.69, 95% CI 0.51 – 0.94; p = <0·01), and long-duration (≥28 days) symptoms following the second dose (OR 0.51, 95% CI 0.32 – 0.82; p = <0·001).  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.

These 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. 

Source: Antonelli M, Penfold RS, Merino J. 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 Infect Dis 2021; Published online 1 September. doi.org/10.1016/S1473-3099(21)00460-6.