Post-vaccination SARS-CoV-2 infection: risk factors and illness profile in a prospective, observational community-based case-control study

BackgroundCOVID-19 vaccines show excellent efficacy in clinical trials and real-world data, but some people still contract SARS-CoV-2 despite vaccination. This study sought to identify risk factors associated with SARS-CoV-2 infection post-vaccination and describe characteristics of post-vaccination illness. MethodsAmongst 1,102,192 vaccinated UK adults from the COVID Symptom Study, 2394 (0.2%) cases of post-vaccination SARS-CoV-2 infection were identified between 8th December 2020 and 1st May 2021. Using a control group of vaccinated individuals testing negative, we assessed the associations of age, frailty, comorbidity, area-level deprivation and lifestyle factors with infection. Illness profile post-vaccination was assessed using a second control group of unvaccinated cases. FindingsOlder adults with frailty (OR=2.78, 95% CI=[1.98-3.89], p-value<0.0001) and individuals living in most deprived areas (OR=1.22 vs. intermediate group, CI[1.04-1.43], p-value=0.01) had increased odds of post-vaccination infection. Risk was lower in individuals without obesity (OR=0.6, CI[0.44-0.82], p-value=0.001) and those reporting healthier diet (OR=0.73, CI[0.62-0.86], p-value<0.0001). Vaccination was associated with reduced odds of hospitalisation (OR=0.36, CI[0.28-0.46], p-value<0.0001), and high acute-symptom burden (OR=0.51, CI[0.42-0.61], p-value<0.0001). In older adults, risk of [≥]28 days illness was lower following vaccination (OR=0.72, CI[0.51-1.00], p-value=0.05). Symptoms were reported less in positive-vaccinated vs. positive-unvaccinated individuals, except sneezing, which was more common post-vaccination (OR=1.24, CI[1.05-1.46], p-value=0.01). InterpretationOur findings suggest that older individuals with frailty and those living in most deprived areas are at increased risk of infection post-vaccination. We also showed reduced symptom burden and duration in those infected post-vaccination. Efforts to boost vaccine effectiveness in at-risk populations, and to targeted infection control measures, may still be appropriate to minimise SARS-CoV-2 infection. FundingThis work is supported by UK Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre (BRC) award to Guys & St Thomas NHS Foundation Trust in partnership with Kings College London and Kings College Hospital NHS Foundation Trust and via a grant to ZOE Global; the Wellcome Engineering and Physical Sciences Research Council (EPSRC) Centre for Medical Engineering at Kings College London (WT 203148/Z/16/Z). Investigators also received support from the Chronic Disease Research Foundation, the Medical Research Council (MRC), British Heart Foundation, the UK Research and Innovation London Medical Imaging & Artificial Intelligence Centre for Value Based Healthcare, the Wellcome Flagship Programme (WT213038/Z/18/Z and Alzheimers Society (AS-JF-17-011), and the Massachusetts Consortium on Pathogen Readiness (MassCPR). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSTo identify existing evidence for risk factors and characteristics of SARS-CoV-2 infection post-vaccination, we searched PubMed for peer-reviewed articles published between December 1, 2020 and May 18, 2021 using keywords ("COVID-19" OR "SARS-CoV-2") AND ("Vaccine" OR "vaccination") AND ("infection") AND ("risk factor*" OR "characteristic*"). We did not restrict our search by language or type of publication. Of 202 articles identified, we found no original studies on individual risk and protective factors for COVID-19 infection following vaccination nor on nature and duration of symptoms in vaccinated, community-based individuals. Previous studies in unvaccinated populations have shown that social and occupational factors influence risk of SARS-CoV-2infection, and that personal factors (age, male sex, multiple morbidities and frailty) increased risk for adverse outcomes in COVID-19. Phase III clinical trials have demonstrated good efficacy of BNT162b2 and ChAdOx1 vaccines against SARS-CoV-2 infection, confirmed in published real-world data, which additionally showed reduced risk of adverse outcomes including hospitalisation and death. Added value of this studyThis is the first observational study investigating characteristics of and factors associated with SARS-CoV-2 infection after COVID-19 vaccination. We found that vaccinated individuals with frailty had higher rates of infection after vaccination than those without. Adverse determinants of health such as increased social deprivation, obesity, or a less healthy diet were associated with higher likelihood of infection after vaccination. In comparison with unvaccinated individuals, those with post-vaccination infection had fewer symptoms of COVID-19, and more were entirely asymptomatic. Fewer vaccinated individuals experienced five or more symptoms, required hospitalisation, and, in the older adult group, fewer had prolonged illness duration (symptoms lasting longer than 28 days). Implications of all the available evidenceSome individuals still contract COVID-19 after vaccination and our data suggest that frail older adults and those living in more deprived areas are at higher risk. However, in most individuals illness appears less severe, with reduced need for hospitalisation and lower risk of prolonged illness duration. Our results are relevant for health policy post-vaccination and highlight the need to prioritise those most at risk, whilst also emphasising the balance between the importance of personal protective measures versus adverse effects from ongoing social restrictions. Strategies such as timely prioritisation of booster vaccination and optimised infection control could be considered for at-risk groups. Research is also needed on how to enhance the immune response to vaccination in those at higher risk.