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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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0 0.5 1 1.5 2+ Mortality 66% Improvement Relative Risk Ventilation 3% Combined death/ventilati.. 43% Hospitalization time 4% Ct<30 28% Paxlovid for COVID-19  Wong et al.  EARLY TREATMENT Is early treatment with paxlovid beneficial for COVID-19? PSM retrospective 1,780 patients in China (February - April 2022) Lower mortality (p<0.0001) and progression (p<0.0001) Wong et al., The Lancet Infectious Dis.., May 2022 Favors paxlovid Favors control
PSM retrospective 40,776 patients in Hong Kong, showing lower mortality and lower combined mortality, ventilation, ICU, and oxygen therapy with paxlovid treatment.
Confounding by contraindication. Hoertel et al. find that over 50% of patients that died had a contraindication for the use of Paxlovid1. Retrospective studies that do not exclude contraindicated patients may significantly overestimate efficacy.
Black box warning. The FDA notes that "severe, life-threatening, and/or fatal adverse reactions due to drug interactions have been reported in patients treated with paxlovid"2.
Study covers paxlovid and molnupiravir.
risk of death, 66.0% lower, HR 0.34, p < 0.001, treatment 890, control 890, propensity score matching.
risk of mechanical ventilation, 3.0% lower, HR 0.97, p = 0.96, treatment 890, control 890, propensity score matching.
combined death/ventilation/ICU/oxygen, 43.0% lower, HR 0.57, p < 0.001, treatment 890, control 890, propensity score matching.
hospitalization time, 4.3% lower, relative time 0.96, p = 0.32, treatment 890, control 890, propensity score matching.
Ct<30, 27.5% lower, HR 0.72, p = 0.01, treatment 890, control 890, inverted to make HR<1 favor treatment, propensity score matching.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Wong et al., 20 May 2022, retrospective, China, peer-reviewed, 6 authors, study period 26 February, 2022 - 26 April, 2022. Contact:,
This PaperPaxlovidAll
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'415', 'DOI': '10.1093/infdis/jiab247', 'article-title': 'β-d-N4-hydroxycytidine inhibits SARS-CoV-2 through lethal mutagenesis ' 'but is also mutagenic to mammalian cells', 'volume': '224', 'author': 'Zhou', 'year': '2021', 'journal-title': 'J Infect Dis'}, { 'key': '10.1016/S1473-3099(22)00507-2_bib49', 'doi-asserted-by': 'crossref', 'DOI': '10.3390/ijms23073507', 'article-title': 'Potential resistance of SARS-CoV-2 main protease (Mpro) against ' 'protease inhibitors: lessons learned from HIV-1 protease', 'volume': '23', 'author': 'Mótyán', 'year': '2022', 'journal-title': 'Int J Mol Sci'}], 'container-title': 'The Lancet Infectious Diseases', 'original-title': [], 'language': 'en', 'link': [ { 'URL': '', 'content-type': 'text/xml', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': '', 'content-type': 'text/plain', 'content-version': 'vor', 'intended-application': 'text-mining'}], 'deposited': { 'date-parts': [[2022, 8, 24]], 'date-time': 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