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 , 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: July 2022

Abstract
Background
While the vaccines against COVID-19 are highly effective, COVID-19 vaccine breakthrough is possible despite being fully vaccinated. With SARS-CoV-2 variants still circulating, describing the characteristics of individuals who have experienced COVID-19 vaccine breakthroughs could be hugely important in helping to determine who may be at greatest risk.

Methods
With 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 COVID-19 vaccine breakthroughs.

Results
As of 1st November 2021, a total of 15,501,550 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 579,780 (<4%) individuals reported a positive SARS-CoV-2 test. For every 1000 years of patient follow-up time, the corresponding incidence rate (IR) was 98.06 (95% CI 97.93–98.19). There were 28,580 COVID-19-related hospital admissions, 1980 COVID-19-related critical care admissions and 6435 COVID-19-related deaths; corresponding IRs 4.77 (95% CI 4.74–4.80), 0.33 (95% CI 0.32–0.34) and 1.07 (95% CI 1.06–1.09), respectively. The highest rates of breakthrough COVID-19 were seen in those in care homes and in patients with chronic kidney disease, dialysis, transplant, haematological malignancy or who were immunocompromised.

Conclusions
While the majority of COVID-19 vaccine breakthrough cases in England were mild, some differences in rates of breakthrough cases have been identified in several clinical 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 number of positive SARS-CoV-2 tests still occurring is concerning and as numbers of fully vaccinated (and boosted) individuals increases and as follow-up time lengthens, so too will the number of COVID-19 breakthrough cases. Additional analyses, to assess vaccine waning and rates of breakthrough COVID-19 between different variants, aimed at identifying individuals at higher risk, are needed.