January 4, 2023
Oral Antiviral Therapy for COVID-19 in Hospitalized, Nonhypoxic Patients Improves OutcomesBy Erica Kaufman West, MD
Two oral antivirals, molnupiravir and ritonavir-boosted nirmatrelvir, received emergency use authorization from the Food and Drug Administration for treatment of individuals with mild-to-moderate COVID-19 not requiring hospitalization, who are at risk for progression to severe disease. A retrospective cohort study in Lancet Infectious Diseases looked to answer questions still outstanding, such as whether oral antivirals were beneficial in hospitalized but nonhypoxic patients with COVID-19.
During the Omicron BA.2 wave in Hong Kong, hospitalized, nonhypoxic adult patients with PCR- or rapid-antigen-confirmed COVID-19 infection received one of the two oral antivirals. All patients were within three days of testing positive. Patients were excluded if they received oral anti-SARS-CoV-2 meds prior to admission, had contraindications to nirmatrelvir-ritonavir, or had severe renal or liver impairment. Primary outcomes were all-cause mortality, and secondary outcomes were a composite outcome of disease progression (all-cause mortality, initiation of invasive mechanical ventilation [IMV], intensive care unit admission, or need for oxygen therapy, with each of these also evaluated individually). In addition, they looked at length of stay and time to achieve low viral burden, as defined by a cycle threshold (Ct) value of 30 or higher on an RT-PCR assay.
The study included 1,856 molnupiravir patients with matched controls and 890 nirmatrelvir-ritonavir patients with matched controls. In both treatment groups, median duration from symptom onset to drug initiation was one day. Compared to controls, both groups individually had significantly lower risks of all-cause mortality and the composite disease progression outcome, along with a reduced need for oxygen therapy. There was no difference in initiation of IMV; length of stay was significantly shorter in the molnupiravir arm but not the nirmatrelvir-ritonavir arm (10.82 days vs. 11.50 days for molnupiravir vs. control). Notably, time to achieving low viral burden (Ct ≥ 30) was significantly shorter among oral antiviral recipients than controls. The average increase in Ct value between days 5 and 7 was 6.67 in the molnupiravir arm, 7.25 in the nirmatrelvir-ritonavir arm, and 3.57 in the control arm.
In looking at subgroup analysis, the differences in all-cause mortality, composite disease progression, and need for oxygen was lost in all except the group of patients older than age 65 years and in those who were not vaccinated. This study helps answer the question of whether patients hospitalized with mild-to-moderate COVID-19, without the baseline need for oxygen, will benefit from antivirals. Prioritization to those over 65 years of age and those unvaccinated seems reasonable, especially if supplies are limited.
