Early stage administration of Paxlovid has been shown to improve the prognosis of mild to moderate COVID-19 patients with high risk. However, few evidence was validated in severe COVID-19 patients with hypoxemia. It is also unclear whether delayed usage of Paxlovid affected prognosis in COVID-19 patients or not. In this multiple-centers prospective study, we collected the clinical data in hospitalized severe adult Omicron infection patients with hypoxemia. All patients were divided into two groups according to the time of Paxlovid usage after the symptom onset: early group (Paxlovid administration in 5 days after symptom onset) and delayed group (Paxlovid administration beyond 5 days after symptom onset). The 28-day composite outcomes were evaluated. Totally 198 hospitalized severe omicron-infected subjects with hypoxemia were enrolled. There was no difference between the two groups about the baseline characteristics and laboratory parameters, except for leukocytes (5.29 × 109 vs. 7.90 × 109/L, p = 0.01) and albumin levels (35 vs. 31 g/L, p = 0.04). The 28-day composite outcomes in early group were slightly lower than that in delayed group but with no difference (12.8% vs. 16.67%, p = 0.602). The viral clearance ratio at Day 7 after Paxlovid treatment in early group was higher than that in delayed group (79.48% vs. 58.33%, p = 0.029). The medium hospitalized duration in early group was shorter than that in delayed group (11.31 vs. 15.32 days, p = 0.005). Logistic analysis showed the independent risk factors of prognosis including underlying diseases ≥ 3 kinds (ORR = 1.72), d-dimer ≥ 2.0 μg/mL (ORR = 1.35), and MODS (ORR = 14.01). In Omicron-infected subjects with hypoxemia, early usage of Paxlovid received benefits in hospitalized time and viral clearance, but delayed usage did not result in a worse composite prognosis. This result might provide direct evidence of antiviral strategy in severe Omicron infection subjects with hypoxemia.
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