Effectiveness of XBB.1.5 vaccines and antiviral drugs against severe outcomes of omicron infection in the USA

In the fall of 2023, the US Food and Drug Administration (FDA) authorised the use of the updated Moderna (Sept 11), Pfizer-BioNTech (Sept 11), and Novavax (Oct 3) COVID-19 vaccines containing a monovalent component of the XBB.1.5 variant “to provide better protection against serious consequences of COVID-19, including hospitalization and death”, with neither the FDA nor the companies providing clinical evidence.1–2 The National Institutes of Health Guidelines prefer ritonavir-boosted nirmatrelvir to molnupiravir for outpatient treatment of symptomatic patients with COVID-19 at high risk of progressing to severe disease.3 In this Correspondence, we report data from a large cohort study on the effectiveness of the three XBB.1.5 vaccines and the two oral antiviral drugs, as well as their interaction, against admission to hospital and death from currently circulating SARS-CoV-2 variants. To estimate the effects of XBB.1.5 vaccines and antiviral drugs on progression to severe disease while adjusting for observed confounders, we fit a Cox proportional hazards model to the composite endpoint of admission to hospital and death (ie, time from SARS-CoV-2 infection to admission to hospital or death, whichever occurred first), with XBB.1.5 vaccination and antiviral treatment as exposure variables and with demographic factors, comorbidities, and previous infection or vaccination as covariates (appendix pp 2, 3). The hazard ratio (HR) for XBB.1.5 vaccination was estimated at 0·69 (95% CI 0·59–0·81), and the HR for antiviral treatment was 0·58 (0·52–0·65). Supplementary Material Supplementary appendix Total (N=27 194) Administered XBB.1.5 vaccines (N=3315) Not administered XBB.1.5 vaccines (N=23 879) Administered oral antiviral drugs (N=12 387) Not administered oral antiviral drugs (N=14 807) Admission to hospital (N=1637) Death (N=243) Age (years) Mean (SD) 57·5 (19·6) 67·3 (14·7) 56·2 (19·8) 62·6 (15·5) 53·3 (21·5) 65·9 (17·7) 76·8 (13·2) 12–49 8917 (33%) 428 (13%) 8489 (36%) 2423 (20%) 6494 (44%) 299 (18%) 9 (3·7%) 50– 64 6658 (24%) 621 (19%) 6037 (25%) 3644 (29%) 3014 (20%) 317 (19%) 31 (13%) 65–74 5782 (21%) 1169 (35%) 4613 (19%) 3436 (28%) 2346 (16%) 416 (25%) 50 (21%) 75–84 4210 (15%) 815 (25%) 3395 (14%) 2219 (18%) 1991 (13%) 414 (25%) 70 (29%) ≥85 1627 (6%) 282 (9%) 1345 (6%) 665 (5%) 962 (7%) 191 (12%) 83 (34%) Sex Male 10 328 (38%) 1366 (41%) 8962 (38%) 4819 (39%) 5509 (37%) 664 (41%) 136 (56%) Female 16 866 (62%) 1949 (59%) 14 917 (62%) 7568 (61%) 9298 (63%)