Oral Antivirals Can Benefit Hospitalized COVID-19 Patients

Oral antiviral agents, that were granted emergency use authorization (EUA) by the FDA to reduce requirement for hospitalization by patients with mild to moderate symptoms of COVID-19 and risk for disease progression, were found beneficial even when started after hospital admission, in a "real world" study of a population affected by the omicron BA.2 subvariant.

The investigators claim that these are the first published data on both molnupiravir and nirmatrelvir/ritonavir in a real-word, inpatient setting during a spike in infections withomicron BA.2; and which demonstrate both improved outcomes in that setting and shorter times to reduction in viral burden.

"Although these oral antivirals are now indicated for non-hospitalized patients with COVID-19 who are at high risk of disease progression, the current analysis focuses on their effectiveness in hospitalized patients with COVID-19 who do not initially require any oxygen therapy on admission," explained Carlos Wong, PhD, Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China, and colleagues.

In accompanying invited commentary, Dorota Zarebska-Michaluk, MD, PhD, Department of Infectious Diseases, Jan Kochanowski University, Kielce, Poland and Rober Filisiak, MD, PhD, Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland emphasize that the study results demonstrate utility of the antiviral agents for COVID-19 patients whose symptom severity corresponds to the EUA indication, irrespective of the setting.

"(Results) support the early use of oral antiviral drugs in patients with mild to moderate COVID-19 who are at high risk, regardless of whether they are in outpatient or inpatient care," Zarebska-Michaluk and Filisiak indicate.

Wong and colleagues identified the population for this retrospective cohort study from over 40,000 patients hospitalized with COVID-19 in Hong Kong between February 26 and April 26, 2022, from the Hospital Authority, the Department of Health, and the Hong Kong Death Registry. The study cohort comprised 1856 molnupiravir recipients and 890 nirmatrelvir/ritonavir recipients admitted with mild to moderate symptoms within 3 days before or after confirmed COVID-19 diagnosis. Propensity score matched controls were drawn on a 1:1 ratio from the hospitalized patients admitted for COVID-19 without oxygen therapy who did not receive an oral antiviral.

The primary outcome was all-cause mortality, and a secondary measure was a composite outcome of disease progression; including time to reach a low viral burden, defined as a cycle threshold (Ct) value of 30 or higher on an RT-PCR assay for SARS-SoV-2.Length of hospital stay was among the secondary measures, for patients who survived until discharge.The investigators note that the study was not designed for head-to-head comparison of the agents.

Wong and colleagues reporteda lower risk of all-cause mortality with either agent than matched controls.Crude incidence rate per day with molnupiravir was 19.8 events per 10,000 person-days with molnupiravir compared to 38.07 events in matched controls; and 10.28 with nirmatrelvir/ritonavir compared to26.47 in matched controls.In addition, a significantly larger proportion of patients receiving the antivirals exhibited low viral outcome(Ct ≥30) within 5-7 days than matched controls.

The anti-viral agents were also associated with lower risks of the composite disease progression outcome, which included need for oxygen therapy; although the differences in initiation of invasive mechanical ventilation or admission to ICU were not statistically significant.

Zarebska-Michaluk and Flisiak point out that the study by Wong and colleagues added to the available data on the value of the oral antivirals by having included in the cohort a number of older adults with multiple pre-existing comorbidities who were not fully vaccinated."A group with a high risk of fatal disease progression," they pointed out.

Wong and colleagues caution on generalizing from this retrospective study; and note that while they find that their data support use of these antivirals in patients hospitalized with mild to moderate COVID-19, this was not the healthcare setting of the prospective trials which supported the EUA. "Ongoing research will inform the safety and effectiveness of oral antivirals in specific patient populations, drug combinations, and health-care settings," they suggest.