Real-world effectiveness of early molnupiravir or nirmatrelvir–ritonavir in hospitalised patients with COVID-19 without supplemental oxygen requirement on admission during Hong Kong's omicron BA.2 wave: a retrospective cohort study

Wong et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(22)00507-2 (date from preprint)

May 2022

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PSM retrospective 40,776 patients in Hong Kong, showing lower mortality and lower combined mortality, ventilation, ICU, and oxygen therapy with molnupiravir treatment.

Potential risks of molnupiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity1-10. Multiple analyses have identified variants potentially created by molnupiravir11-15.

Important missing comments or errors? Let us know.

Study covers paxlovid and molnupiravir.

risk of death, 52.0% lower, HR 0.48, p < 0.001, treatment 1,856, control 1,856, propensity score matching.

risk of mechanical ventilation, 58.0% lower, HR 0.42, p = 0.06, treatment 1,856, control 1,856, propensity score matching.

combined death/ventilation/ICU/oxygen, 40.0% lower, HR 0.60, p < 0.001, treatment 1,856, control 1,856, propensity score matching.

hospitalization time, 5.9% lower, relative time 0.94, p = 0.03, treatment 1,856, control 1,856, propensity score matching.

Ct<30, 27.5% lower, HR 0.72, p < 0.001, treatment 1,856, control 1,856, inverted to make HR<1 favor treatment, propensity score matching.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

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Wong et al., 20 May 2022, retrospective, China, peer-reviewed, 6 authors, study period 26 February, 2022 - 26 April, 2022. Contact: carlosho@hku.hk, bcowling@hku.hk.

This Paper Molnupiravir All

Real-world effectiveness of early molnupiravir or nirmatrelvir–ritonavir in hospitalised patients with COVID-19 without supplemental oxygen requirement on admission during Hong Kong's omicron BA.2 wave: a retrospective cohort study

Dr Carlos K H Wong, Ivan C H Au, Kristy T K Lau, Eric H Y Lau, Prof Benjamin J Cowling, Prof Gabriel M Leung

The Lancet Infectious Diseases, doi:10.1016/s1473-3099(22)00507-2

Background Data on the effectiveness of oral antivirals in patients with mild-to-moderate COVID-19 are urgently needed. This retrospective cohort study aimed to evaluate the clinical and virological outcomes associated with molnupiravir or nirmatrelvir-ritonavir use in hospitalised patients with mild-to-moderate COVID-19 during a pandemic wave dominated by the omicron BA.2 subvariant. Methods We analysed data from a territory-wide retrospective cohort of patients in Hong Kong who were hospitalised with a confirmed diagnosis of SARS-CoV-2 infection between Feb 26 and April 26, 2022. Data were extracted from the Hospital Authority, the Department of Health, and the Hong Kong Death Registry. Patients were eligible for inclusion if their admission date was within 3 days before or after confirmation of their COVID-19 diagnosis. Those who were admitted to hospital more than 5 days after symptom onset, were younger than 18 years, had a history of oral antiviral use before admission, required supplemental oxygen on admission, had drug-related contraindications to nirmatrelvir-ritonavir use, or had severe renal or severe liver impairment were excluded. Patients who received the oral antivirals molnupiravir or nirmatrelvir-ritonavir were matched with controls using propensity-score matching in a ratio of 1:1. The primary outcome was all-cause mortality and secondary outcomes included a composite outcome of disease progression (all-cause mortality, initiation of invasive mechanical ventilation [IMV], intensive care unit [ICU] admission, or the need for oxygen therapy) and each of these individual disease progression outcomes, and time to reaching a low viral burden (RT-PCR cycle threshold value ≥30). For each event outcome, crude incidence rates were calculated and hazard ratios (HRs) estimated using Cox regression models. Findings We identified 40 776 patients hospitalised with SARS-CoV-2 infection during the study period, with a mean follow-up of 41•3 days (total 925 713 person-days). After exclusions and propensity-score matching, we included 1856 molnupiravir recipients and 1856 matched controls, and 890 nirmatrelvir-ritonavir recipients and 890 matched controls. A lower risk of all-cause mortality was observed in molnupiravir recipients (crude incidence rate per 10 000 person-days 19•98 events [95% CI 16•91-23•45]) versus matched controls (38•07 events [33•85-42•67]; HR 0•48 [95% CI 0•40-0•59], p<0•0001) and in nirmatrelvir-ritonavir recipients (10•28 events [7•03-14•51]) versus matched controls (26•47 events [21•34-32•46]; HR 0•34 [0•23-0•50], p<0•0001). Oral antiviral recipients also had lower risks of the composite disease progression outcome (molnupiravir HR 0•60 [95% CI 0•52-0•69], p<0•0001; nirmatrelvir-ritonavir 0•57 [0•45-0•72], p<0•0001) and need for oxygen therapy (molnupiravir 0•69 [0•57-0•83], p=0•0001; nirmatrelvir-ritonavir 0•73 [0•54-0•97], p=0•032) compared with controls. Time to achieving a low viral burden was..

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