Emergency use authorisations granted by the US Food and Drug Administration for three SARS-CoV-2 vaccines represent an important milestone in the response to the COVID-19 pandemic. Data presented from the VIVALDI study by Shrotri and colleagues1 and other phase 3 clinical trials2–4 have shown robust vaccine efficacies (> 85%) at preventing severe symptomatic disease. Although rare, emerging reports describe breakthrough SARS-CoV-2 infections in fully vaccinated individuals. 5 We describe the impact of vaccination on admission to hospital in patients with confirmed SARS-CoV-2 infection using real-world data collected by the Yale New Haven Health System. We did a systematic review of patients admitted to hospital with SARS-CoV-2 (confirmed by a positive PCR test at the time of admission) between March 23 and July 1, 2021. SARS-CoV-2 vaccination status was recorded, including the specific vaccine type (mRNA-1273 [elasomeran; Moderna], BNT162b2 [tozinameran; Pfizer–BioNTech], or Ad. 26. COV2. S [Janssen]) and vaccination dates. Patients were considered fully vaccinated if the final dose (either second dose of BNT162b2 or mRNA-1273, or first dose of Ad. 26. COV2. S) was administered at least 14 days before symptom onset or a positive PCR test for SARS-CoV-2. In total, we identified 969 patients who were admitted to a Yale New Haven Health System hospital with a confirmed positive PCR test for SARS-CoV-2. Severity of COVID-19 infection was determined on the basis of established guidelines. 6 172 (18%) of 969 patients had received at least one dose of a COVID-19 vaccine at the time of admission to hospital. Among these patients, 103 had received a partial vaccine course (one dose of BNT162b2 or mRNA-1273), 15 had received a complete course (two doses of BNT162b2 or mRNA-1273 or one dose of Ad. 26. COV2. S within 14 days before symptom onset or a positive PCR test), and 54 were fully vaccinated (appendix pp 1–2). Patients deemed to have a breakthrough SARS-CoV-2 infection—ie, the 54 patients who were fully vaccinated—were evaluated for illness severity. Among this cohort, we found that 25 (46%) patients were asymptomatic (admitted to hospital for a non-COVID-19-related diagnosis but with an incidental positive PCR test for

SARS-CoV-2), four (7%) had mild disease, 11 (20%) had moderate disease, and 14 (26%) had severe or critical illness. Among those with severe or critical illness, the median age was 80· 5 years (IQR 76· 5–85· 0); four of 14 patients required intensive care, one required mechanical ventilation, and three died. Pre-existing comorbidities in the 14 patients with severe or critical illness included overweight (body–mass index> 25 kg/m²; n= 9), cardiovascular disease (n= 12), lung disease (n= 7), malignancy (n= 4), type 2 diabetes (n= 7), and use of an immunosuppressive agent (n= 4; appendix pp 3). 13 of 14 patients had received BNT162b2 (appendix p 1–2). Vaccination for SARS-CoV-2 is highly effective against infection with SARS-CoV-2 or hospitalisation with COVID-19. In our real-world assessment of patients admitted to hospital with a positive SARS-CoV-2 PCR test, we found that nearly a fifth of patients had received at least one dose of the vaccine, and we observed that many patients had not completed the full vaccine course. The finding that more than a quarter of fully vaccinated patients admitted to hospital with SARS-CoV-2 were severely or critically ill with COVID-19 could be reflective of numerous factors, including the emergence of SARS-CoV-2 variants that might confer decreased vaccine effectiveness and an ineffective immune response mounted against …