Describing the population experiencing COVID-19 vaccine breakthrough following second vaccination in England: A cohort study from OpenSAFELY
Authors:   The OpenSAFELY Collaborative:, Green Amelia , Curtis Helen , Hulme William , Williamson Elizabeth , McDonald Helen , Bhaskaran Krishnan , Rentsch Christopher , Schultze Anna , MacKenna Brian , Mahalingasivam Viyaasan , Tomlinson Laurie , Walker Alex , Fisher Louis , Massey Jon , Andrews Colm , Hopcroft Lisa , Morton Caroline , Croker Richard , Morley Jessica , Mehrkar Amir , Bacon Seb , Evans David , Inglesby Peter , Hickman George , Ward Tom , Davy Simon , Mathur Rohini , Tazare John , Eggo Rosalind M , Wing Kevin , Wong Angel , Forbes Harriet , Bates Chris , Cockburn Jonathan , Parry John , Hester Frank , Harper Sam , Douglas Ian , Evans Stephen , Smeeth Liam , Goldacre Ben 
Published: November 2021

AbstractBackgroundWhile the vaccines against COVID-19 are considered to be highly effective, COVID-19 vaccine breakthrough is likely and a small number of people will still fall ill, be hospitalised, or die from COVID-19, despite being fully vaccinated. With the continued increase in numbers of positive SARS-CoV-2 tests, describing the characters of individuals who have experienced a COVID-19 vaccine breakthrough could be hugely important in helping to determine who may be at greatest risk.MethodWith the approval of NHS England we conducted a retrospective cohort study using routine clinical data from the OpenSAFELY TPP database of fully vaccinated individuals, linked to secondary care and death registry data, and described the characteristics of those experiencing a COVID-19 vaccine breakthrough.ResultsAs of 01st November 2021, a total of 15,436,455 individuals were identified as being fully vaccinated against COVID-19, with a median follow-up time of 149 days (IQR: 107-179). From within this population, a total of 577245 (<4%) individuals reported a positive SARS-CoV-2 test. For every 1000 years of patient follow-up time, the corresponding incidence rate was 98.02 (95% CI 97.9-98.15). There were 16,120 COVID-19-related hospital admissions, 1,100 COVID-19 critical care admission patients and 3,925 COVID-19-related deaths; corresponding incidence rates of 2.72 (95% C 2.7-2.74), 0.19 (95% C 0.18-0.19) and 0.66 (95% C 0.65-0.67), respectively. When broken down by the initial priority group, higher rates of hospitalisation and death were seen in those in care homes and those over 80 years of age. Comorbidities with the highest rates of breakthrough COVID-19 included chronic kidney disease, dialysis, transplant, haematological malignancy, and immunocompromised.ConclusionThe majority of COVID-19 vaccine breakthrough cases in England were mild with relatively few fully vaccinated individuals being hospitalised or dying as a result. However, some concerning differences in rates of breakthrough cases were identified in several clinical and demographic groups. While it is important to note that these findings are simply descriptive and cannot be used to answer why certain groups have higher rates of COVID-19 breakthrough than others, the emergence of the Omicron variant of COVID-19 coupled with the continued increase in numbers of positive SARS-CoV-2 tests are concerning. As numbers of fully vaccinated individuals increases and follow-up time lengthens, so too will the number of COVID-19 breakthrough cases. Additional analyses, aimed at identifying individuals at higher risk, are therefore required.