During the Omicron BA.2 wave, antivirals molnupiravir and nirmatrelvir-ritonavir (Paxlovid) appeared to have clinical benefit in hospitalized patients with mild-to-moderate COVID-19 who did not require oxygen therapy, a retrospective cohort study from Hong Kong showed.

For patients who were treated with the antivirals within 2 days of hospitalization, a 52% and 66% lower risk of all-cause mortality was observed with molnupiravir and nirmatrelvir-ritonavir, respectively, compared with a matched group of controls, reported Carlos Wong, PhD, of the University of Hong Kong and colleagues.

Recipients of the antivirals also had a 40-43% lower risk of disease progression, and a 27-31% lower risk when it came to need for oxygen, according to findings in Lancet Infectious Diseases.

Both antivirals were also associated with shortened viral burden compared to the controls, though there were no significant differences in initiation of intermittent mandatory ventilation and admission to the intensive care unit (ICU).

“As both oral antivirals are currently indicated for non-hospitalized patients with COVID-19 who are at high risk of disease progression, ongoing research will inform the safety and effectiveness of oral antivirals in specific patient populations, drug combinations, and healthcare settings,” Wong and team wrote.

The FDA authorized use of both antivirals in late December 2021, but data for this authorization were based on the randomized MOVe-OUT and EPIC-HR trials, which were conducted before the Omicron variant was dominant.

This is the first time these antivirals have been studied in a real-world setting during the Omicron variant, and while other in vitro studies have shown the drugs’ efficacy against this variant, “the added value of [this] study is the inclusion of a cohort consisting mainly of older adults with multiple pre-existing comorbidities who were not fully vaccinated — a group with a high risk of fatal disease progression,” noted Dorota Zarębska-Michaluk, MD, PhD, of Jan Kochanowski University in Kielce, Poland, and Robert Flisiak, MD, PhD, of Medical University of Białystok in Poland, in an accompanying comment.

The results of this study “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,” they concluded.

For this study, Wong and colleagues used data from electronic health records on 40,776 patients ages 65 and up hospitalized during the Omicron BA.2 wave in Hong Kong from Feb. 26 to April 26. After propensity-score matching, they paired 1,856 molnupiravir recipients with 1,856 controls, and 890 nirmatrelvir-ritonavir recipients with 890 controls.

Patients hospitalized more than 5 days after symptom onset, those younger than 18 years old, those with a history of oral antiviral use before admission, those who needed supplemental oxygen on admission, those who had drug-related contraindications to nirmatrelvir-ritonavir, and those who had severe renal or liver impairments were excluded.

On day 7 from the date of hospitalization, fewer molnupiravir recipients died in the hospital compared with controls (2.3% vs 5.3%), as did fewer nirmatrelvir-ritonavir recipients (1.3% vs 3.6%), and this difference persisted to day 28 (7.5% vs 14.9% and 3.5% vs 9.3%, respectively).

On day 28, more patients who received the antivirals were discharged alive compared with matched controls (molnupiravir: 84.4% vs 75.3%; nirmatrelvir-ritonavir: 89.6% vs 82.5%).

Lower risk of all-cause mortality was noted in those who received molnupiravir compared with matched controls (crude incidence rate of 19.98 vs 38.07 events per 10,000 person-days; HR 0.48, 95% CI 0.40-0.59, P<0.0001), and in those who received nirmatrelvir-ritonavir compared with matched controls (10.28 vs 26.47 events; HR 0.34, 95% CI 0.23-0.50, P<0.0001).

Recipients of molnupiravir had lower risks of the composite disease progression outcome (all-cause mortality, initiation of invasive mechanical ventilation, ICU admission, or need for oxygen) compared with the matched controls (HR 0.60, 95% CI 0.52-0.69, P<0.0001), as did nirmatrelvir-ritonavir recipients (HR 0.57, 95% CI 0.45-0.72, P<0.0001) compared with control patients.

The same was true for need for oxygen therapy (molnupiravir: HR 0.69, 95% CI 0.57-0.83, P=0.0001; nirmatrelvir-ritonavir: HR 0.73, 95% CI 0.54-0.97, P=0.032).

“Results of our subgroup analyses suggested a possible lack of significant benefit in younger patients (aged ≤65 years) and those who had been fully vaccinated, which would support prioritizing the prescription of oral antivirals to older people and those not adequately vaccinated, who are also likely to be at increased risk of progression to severe COVID-19,” Wong and team noted.

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