Impact of the Use of Oral Antiviral Agents on the Risk of Hospitalisation in Community COVID-19 Patients

Abstract

Background We examined the effectiveness of molnupiravir and nirmatrelvir/ritonavir in reducing hospitalisation and deaths in a real-world cohort of non-hospitalised COVID-19 patients.

Methods This was a territory-wide retrospective cohort study in Hong Kong. Non-hospitalised COVID-19 patients who attended designated outpatient clinics between 16 February and 31 March 2021 were identified. Patients who were hospitalised on the day of the first appointment at clinic or used both oral antivirals were excluded. The primary endpoint was hospitalisation. The secondary endpoint was a composite of intensive care unit admission, invasive mechanical ventilation use, and/or death. Patients’ clinical characteristics were balanced using propensity score weighting.

Findings Of 93,883 patients, 83,154 (88·6%), 5,808 (6·2%), and 4,921 (5·2%) were oral antiviral non-users, molnupiravir users, and nirmatrelvir/ritonavir users respectively. Compared to non-users, oral antiviral users were older and had more comorbidities, lower complete vaccination rate, and more hospitalisations in the previous year. Molnupiravir users were older, and had more comorbidities, lower complete vaccination rate, and more hospitalisations in the previous year than nirmatrelvir/ritonavir users. At a median follow-up of 30 days, 1,931 (2·1%) patients were admitted to hospital and 225 (0·2%) patients developed the secondary endpoint. After propensity score weighting, nirmatrelvir/ritonavir use (weighted hazard ratio 0·79, 95% CI 0·65-0·95, P =0·011) but not molnupiravir use (weighted hazard ratio 1·17, 95% CI 0·99-1·39, P =0·062) was associated with a reduced risk of hospitalisation than non-users. The use of molnupiravir or nirmatrelvir/ritonavir was not associated with a lower risk of the secondary endpoint as compared to non-users. In the subgroup of patients aged ≥60 years or aged <60 years with comorbidities, nirmatrelvir/ritonavir use but not molnupiravir use was associated with a reduced risk of hospitalisation than non-users.

Interpretation The use of nirmatrelvir/ritonavir but not molnupiravir was associated with a reduced risk of hospitalisation in real-world non-hospitalised COVID-19 patients.

Funding: None declared.

Declaration of Interest: Terry Yip has served as an advisory committee member and a speaker for Gilead Sciences. Grace Lui has served as an advisory committee member for Gilead, Merck and GSK, speaker for Merck and Gilead, and received research grant from Gilead, Merck and GSK. Vincent Wong has served as a consultant or advisory committee member for AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Merck, Novo Nordisk, Pfizer, ProSciento, Sagimet Biosciences and TARGET PharmaSolutions; and a speaker for Abbott, AbbVie, Echosens, Gilead Sciences and Novo Nordisk. He has received a research grant from Gilead Sciences, and is a cofounder of Illuminatio Medical Technology Limited. Henry Chan has served as an Independent Non-Executive Director for Shanghai Henlius Biotech Inc; as an advisory board member for Aligos, Aptorum, Arbutus, Hepion, Janssen, Gilead, Glaxo-Smith-Kline, Roche, Vaccitech, Virion Therapeutics, and Vir Biotechnology; and as a speaker for Gilead, Roche, and Viatris. Grace Wong has served as an advisory committee member for Gilead Sciences and Janssen, and as a speaker for Abbott, Abbvie, Ascletis, Bristol-Myers Squibb, Echosens, Gilead Sciences, Janssen and Roche. She has also received a research grant from Gilead Sciences. The other authors declare that they have no competing interests.

Ethical Approval: study protocol was approved by the Joint Chinese University of Hong Kong - New Territories East Cluster Clinical Research Ethics Committee (Reference number: 2021·239).

Keywords: SARS-CoV-2, hospital admission, death, molnupiravir, nirmatrelvir/ritonavir