Early molnupiravir and nirmatrelvir-ritonavir show substantial clinical benefits in local hospitalized COVID-19 patients

In a local retrospective cohort study analyzing data during Hong Kong’s omicron BA.2 wave, molnupiravir and nirmatrelvir-ritonavir were found to be effective in reducing the risks of all-cause mortality and disease progression, as well as the need for oxygen therapy among hospitalized patients due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without supplemental oxygen requirement.1 The study revealed the substantial clinical benefits of oral antivirals, serving as evidence to support their early use among Coronavirus disease 2019 (COVID-19) patients in Hong Kong.1

Currently, molnupiravir and nirmatrelvir-ritonavir are 2 treatment options that have gained approval by the United States (US) Food and Drug Administration (FDA) for the treatment of patients with symptomatic COVID-19 and at high risk for progression to severe disease.2 In the MOVe-OUT trial, early treatment with molnupiravir was associated with a 31% lower risk of hospitalization or death vs. placebo among non-hospitalized patients (HR=0.69; 95% CI: 0.48-1.01).4 In the EPIC-HR trial, the combination of nirmatrelvir-ritonavir also showed a high efficacy of 89% relative risk reduction of progression to severe COVID-19 vs. placebo among non-hospitalized patients in the EPIC-HR Trial (p<0.001).5 Despite the positive trial results, real-world evidence is needed to reveal their effectiveness in a real-life local clinical setting amid the omicron-predominant period.1

Then, a retrospective study was performed to evaluate the efficacy of the oral antivirals molnupiravir and nirmatrelvir-ritonavir among hospitalized COVID-19 patients during the omicron BA.2 outbreak in Hong Kong.1 The study identified 40,776 adult patients hospitalized during the study period, comprising a total of 1,856 molnupiravir recipients and 890 nirmatrelvir-ritonavir recipients with a 1:1 propensity-score matching.1

The study results showed that molnupiravir and nirmatrelvir-ritonavir significantly reduced the risk of all-cause mortality by 52% (HR=0.48; 95% CI: 0.40-0.59; p<0.0001) and by 66% (HR=0.34; 95% CI: 0.23-0.50; p<0.0001) when compared with matched controls, respectively.1 Molnupiravir and nirmatrelvir-ritonavir also lowered the risk of progression to severe disease by 40% (HR=0.60; 95% CI: 0.52-0.69; p<0.0001) and by 43% (HR=0.57; 95% CI: 0.45-0.72; p<0.0001) vs. matched controls, respectively.1 Moreover, the need for supplemental oxygen therapy was significantly lower for patients who had received the oral antivirals (p<0.05).1 The use of these oral antivirals was also associated with a significantly shorter time to achieve a low viral burden (molnupiravir, HR=1.38, 95% CI: 1.15-1.64, p=0·0005; nirmatrelvir-ritonavir, HR=1.38; 95% CI: 1.07-1.79; p=0.013).1

Overall, during the omicron BA.2 wave in Hong Kong, early treatment with the oral antivirals molnupiravir and nirmatrelvir-ritonavir demonstrated significant clinical benefits in local hospitalized COVID-19 patients who did not require oxygen therapy, in terms of all-cause mortality, disease progression, the need for oxygen therapy, and the time to achieve a low viral burden.1 These findings supported the use of oral antivirals in the local population.1

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