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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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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) c19early.org Wong et al., The Lancet Infectious Dis.., May 2022 Favorspaxlovid Favorscontrol 0 0.5 1 1.5 2+
PSM retrospective 40,776 patients in Hong Kong, showing lower mortality and lower combined mortality, ventilation, ICU, and oxygen therapy with paxlovid treatment.
Resistance. Variants may be resistant to paxlovid1-4. Use may promote the emergence of variants that weaken host immunity and potentially contribute to long COVID5.
Confounding by contraindication. Hoertel et al. find that over 50% of patients that died had a contraindication for the use of Paxlovid6. 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"7.
AKI. Kamo et al. show significantly increased risk of acute kidney injury.
Standard of Care (SOC): SOC for COVID-19 in the study country, China, is average with moderate average efficacy for approved treatments9.
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: carlosho@hku.hk, bcowling@hku.hk.
This PaperPaxlovidAll
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