Real-world effectiveness of early anti-SARS therapy in severely immunocompromised COVID-19 outpatients during the SARS-CoV-2 omicron variant era: a propensity score-adjusted retrospective cohort study.

Background: The effectiveness of the early treatment for antiviral agents in SARS-CoV-2 infection is closely related to patient comorbidities. Data on effectiveness in immunocompromised patients are limited, with reports involving highly heterogeneous and not well-defined populations. We aimed to assess the effectiveness of treatment in reducing hospitalizations in a real-world cohort of severely immunocompromised COVID-19 outpatients.

Patients and methods: We conducted a multicentre, retrospective, observational cohort study of immunocompromised outpatients attended in infectious diseases departments from 1 January to 31 December 2022. Propensity score matching (PSM) multivariable logistic regression models were used to estimate the adjusted odds ratio [(aOR, 95% confidence interval (CI)] for the association between antiviral prescription and outcome (COVID-19-related hospitalization up to Day 90).

Results: We identified 746 immunocompromised outpatients with confirmed SARS-CoV-2 infection. After eligibility criteria and PSM, a total of 410 patients were analysed: 205 receiving treatment (remdesivir, sotrovimab or nirmatrelvir/ritonavir) and 205 matched controls. Fifty-two patients required at least one COVID-19-related hospitalization 8 (3.9%) versus 44 (21.5%) in the antiviral and matched control cohorts, respectively. There were 13 deaths at 90 days, of which only 4 were COVID-19-related and none in the antiviral treatment group. After adjustment for residual confounders, the use of early therapy was associated with a protective effect on the risk of hospitalization [aOR 0.13 (0.05-0.29)], as was the use of biological immunomodulators [aOR 0.27 (0.10-0.74)], whereas chronic obstructive pulmonary disease [aOR 4.65 (1.09-19.69)] and anti-CD20 use [aOR 2.76 (1.31-5.81)] increased the odds.

Conclusions: Early antiviral treatment was associated with a reduced risk of COVID-19-related hospitalization in ambulatory severely immunocompromised COVID-19 patients.