- After two vaccines doses, the odds of hospitalisation were reduced by more than two-thirds and breakthrough infections were almost two times more likely to be completely asymptomatic.
- The odds of long COVID-19 (symptoms continuing for 28 days or more after testing positive) were also reduced by more than half for people who received two vaccine doses.
- People over age 60 who were frail or had underlying conditions had higher odds of a breakthrough infection, especially after only one dose.
- The findings could have implications for health policies around timing between vaccine doses, potential COVID-19 vaccine booster shots, and for continuing personal protective measures, including mask-wearing and social distancing.
People who tested positive for SARS-CoV-2 after one or two vaccine doses had significantly lower odds of severe disease or hospitalisation than unvaccinated people, according to a large-scale study investigating COVID-19 breakthrough infections published in The Lancet Infectious Diseases journal.
Researchers also found that the odds of experiencing long COVID (illness lasting 28 days or more after a positive test) were cut in half for people who received two vaccines doses.
People most vulnerable to a breakthrough infection after their first vaccine dose included frail older adults (60 years and older), and older adults living with underlying conditions such as obesity, heart disease, kidney disease, and lung disease. In all age groups, people living in deprived areas, such as densely populated urban settings, were more likely to experience a breakthrough infection. These factors were most significantly associated with a post-vaccination infection after receiving the first vaccine dose and before receiving a second dose.
“We are at a critical point in the pandemic as we see cases rising worldwide due to the delta variant. Breakthrough infections are expected and don’t diminish the fact that these vaccines are doing exactly what they were designed to do—save lives and prevent serious illness. Other research has shown a mortality rate as high as 27% for hospitalised COVID-19 patients. We can greatly reduce that number by keeping people out of the hospital in the first place through vaccination. Our findings highlight the crucial role vaccines play in larger efforts to prevent COVID-19 infections, which should still include other personal protective measures such as mask-wearing, frequent testing, and social distancing,” says study co-lead author Dr Claire Steves of King’s College London, UK. 
Using self-reported data from the UK COVID Symptom Study through the ZOE app from 8 December 2020 through 4 July 2021, researchers found that of more than 1.2 million adults who received at least one dose of either the BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCoV-19 (Oxford-AstraZeneca), or mRNA-1273 (Moderna) vaccine, fewer than 0.5% reported a breakthrough infection (6,030 positive cases after 1,240,009 first vaccine doses) more than 14 days after their first dose. Among adults who received two vaccine doses, fewer than 0.2% experienced a breakthrough infection (2,370 positive cases after 971,504 second vaccine doses) more than seven days after their second dose.
Among those who did experience a breakthrough infection, the odds of that infection being asymptomatic increased by 63% after one vaccine dose and by 94% after the second dose. Researchers also found that the odds of hospitalisation were reduced by approximately 70% after one or two doses, and that the odds of experiencing severe disease—defined as having five or more symptoms in the first week of illness—were lessened by approximately one-third. In addition, the odds of long COVID (having symptoms for 28 days or more after infection) were reduced by 50% after two doses.
For those who did experience symptoms after either one or two vaccine doses, such as fatigue, cough, fever, and loss of taste and smell, almost all symptoms were reported less frequently than in unvaccinated people.
In frail adults over the age of 60 years, the odds of a breakthrough infection after one vaccine dose were almost doubled, compared to healthy older adults. Additionally, in older adults who had received their first vaccine dose but not their second, kidney disease, heart disease, and lung disease were underlying conditions associated with a breakthrough infection.
The risk of a breakthrough infection was related to the place a person lived, with people living in areas with the highest deprivation having the highest odds of a breakthrough infection following their first vaccine dose. The authors note that this could be due to many underlying causes including closer living quarters and lower overall vaccination rates in those communities, making the virus more likely to be spread.
“The increased risks of breakthrough infections for frail, older adults—especially those living in care homes or who require frequent visits to health care facilities—and for other people living in deprived conditions reflect what we’ve seen throughout the pandemic. These groups are at a greater risk of exposure and are therefore more vulnerable to infection. Health policies designed to prevent infections, including policies around timing between the first and second dose and potential booster shots, should prioritize these groups,” says co-author Dr Rose Penfold of King’s College, London, UK. 
The authors note some limitations of the study. The research uses self-reported data and therefore the reported comorbidities, test results, and vaccination status could be inaccurate or incomplete, and individuals living in more deprived areas could be underrepresented. Furthermore, the authors note that these findings might not apply to all timepoints post-vaccination, to settings with different proportions of SARS-CoV-2 variants, or to countries with different vaccination schedules.
Peer-reviewed / Observational study / People
NOTES TO EDITORS
This study was funded ZOE Limited, the UK Government Department of Health and Social Care, the Wellcome Trust, the UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare, the UK National Institute for Health Research, the UK Medical Research Council, the British Heart Foundation, and the Alzheimer’s Society. It was conducted by researchers from King’s College London, Harvard Medical School, UCL, and ZOE.
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The Lancet Infectious Diseases
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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
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JW, AM, LP, CH, SS, and JCP report being employees of ZOE during the conduct of the study. JM reports grants from the European Commission and National Institutes of Health, and has served as a co-investigator on an unrelated nutrition trial sponsored by ZOE. ATC reports grants from the Massachusetts Consortium on Pathogen Readiness during the conduct of the study, and personal fees from Bayer Pharma, Pfizer, and Boehringer Ingelheim, outside the submitted work. DAD reports grants from the National Institutes of Health, the Massachusetts Consortium on Pathogen Readiness, and the American Gastroenterological Association during the conduct of the study, and has served as a co-investigator on an unrelated nutrition trial sponsored by ZOE. LHN reports grants from the National Institutes of Health, the American Gastroenterological Association, and the Crohn’s and Colitis Foundation. CHS reports grants from the Alzheimer’s Society during the conduct of the study. EM reports a grant from the Medical Research Council during the conduct of the study. CJS reports grants from the Chronic Disease Research Foundation, the Medical Research Council, the Wellcome Trust, and the National Institute for Health Research (NIHR) during the conduct of the study. SO reports grants from the Wellcome Trust, UK Research and Innovation, and the Chronic Disease Research Foundation during the conduct of the study. ELD reports receiving grants from the Chronic Disease Research Foundation during the conduct of the study. TDS reports being a consultant for ZOE during the conduct of the study. All other authors declare no competing interests.