Impact of the Use of Oral Antiviral Agents on the Risk of Hospitalization in Community Coronavirus Disease 2019 Patients (COVID-19)

Abstract

Background We examined the effectiveness of molnupiravir and nirmatrelvir/ritonavir in reducing hospitalization and deaths in a real-world cohort of non-hospitalized COVID-19 patients. Methods This was a territory-wide retrospective cohort study in Hong Kong. Non-hospitalized COVID-19 patients who attended designated outpatient clinics between 16 February and 31 March 2022 were identified. Patients hospitalized on the day of the first clinic appointment or used both oral antivirals were excluded. The primary endpoint was hospitalization. The secondary endpoint was a composite of intensive care unit admission, invasive mechanical ventilation use, and/or death. Results 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 hospitalizations in the previous year. Molnupiravir users were older, and had more comorbidities, lower complete vaccination rate, and more hospitalizations in the previous year than nirmatrelvir/ritonavir users. At a median follow-up of 30 days, 1,931 (2.1%) patients were hospitalized 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 hospitalization 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. Conclusion Use of nirmatrelvir/ritonavir but not molnupiravir was associated with a reduced risk of hospitalization in real-world non-hospitalized COVID-19 patients.

Real-Life Experience of Molnupiravir in Hospitalized Patients Who Developed SARS-CoV2-Infection: Preliminary Results from CORACLE Registry

“…We have confirmed these favourable findings also in the non-vaccinated population and in patients with two doses of anti-SARS-CoV-2 vaccine. Favourable outcomes in our results are in line with real-life data published by other centres [ 10 , 11 , 17 , 18 ], despite that most of the patients considered in other studies were treated from the beginning as outpatients. Patients’ characteristics who died in the study populations were reported in Table 5 : we found high comorbid patients, with high Charlson comorbidity index who died for complications other than COVID-19.…”

Molnupiravir Use and Severe Covid-19 Outcomes During the Omicron Surge

“…Another study of the real-world effectiveness of molnupiravir from Hong Kong with a comparable population size also reported an interaction between the age group (above or below 65) and molnupiravir treatment. Moreover, this study reported a signi cantly higher risk of hospitalization among younger patients and no bene t in older patients (11).…”

Effectiveness of nirmatrelvir-ritonavir against hospital admission or death: a cohort study in a large US healthcare system

“…Several studies have aimed to assess effectiveness of nirmatrelvir-ritonavir under real-world conditions of use in Israel, Hong Kong, and the United States, each yielding lower effectiveness estimates than those observed in the EPIC-HR trial. [7][8][9][10][11][12] Because the perceived risk for a patient to progress to severe disease endpoints likely factors into clinical decision-making around nirmatrelvir-ritonavir prescribing and patients' adherence to treatment, controlling for potential differences in clinical status among patients who receive or do not receive treatment is of key importance to causal inference. However, symptoms data were lacking in prior observational studies from all [7][8][9][10][11] or most 12 patients analyzed, hindering the possibility to control for differences in patients' clinical stage or disease severity potentially associated with treatment receipt.…”

“…[7][8][9][10][11][12] Because the perceived risk for a patient to progress to severe disease endpoints likely factors into clinical decision-making around nirmatrelvir-ritonavir prescribing and patients' adherence to treatment, controlling for potential differences in clinical status among patients who receive or do not receive treatment is of key importance to causal inference. However, symptoms data were lacking in prior observational studies from all [7][8][9][10][11] or most 12 patients analyzed, hindering the possibility to control for differences in patients' clinical stage or disease severity potentially associated with treatment receipt. Our sensitivity analyses allowing for relaxed matches with respect to patients' symptomatic status identified progressively lower estimates of treatment effectiveness with looser matching on time from symptoms to testing, and without matching on presence or timing of symptoms.…”

“…In recent observational studies, nirmatrelvirritonavir was estimated to confer 21-79% reductions in risk of COVID-19 related hospital admission or other severe endpoints, with the strongest evidence of clinical benefit found among high-risk subgroups including older adult patients, obese patients, and patients not known to have immunity to SARS-CoV-2 from prior infection or vaccination. [7][8][9][10][11][12] However, these studies have lacked sufficient statistical power to demonstrate effectiveness in other subpopulations that are at relatively low risk of severe illness; have been undertaken in contexts where access to treatment is relatively limited; and have lacked data describing patients' clinical status, including time from symptom onset, which may inform clinical decision-making around prescribing nirmatrelvir-ritonavir. 13 While data from the United States have identified that COVID-19 related emergency department (ED) presentations and hospital admissions are infrequent among patients receiving nirmatrelvir-ritonavir in ambulatory care settings, 14,15 systematic assessments of effectiveness are lacking.…”