Factors Influencing COVID-19 Viral Clearance: Implications for Vaccination and Antiviral Therapy.

Background: Understanding the factors influencing viral clearance in hospitalized COVID-19 patients, including vaccination status and antiviral therapy, is critical for optimizing clinical management.

Methods: 1,424 hospitalized COVID-19 patients retrospectively included from four tertiary hospitals in Hainan Province between March and December 2022. Viral clearance was defined as the interval from hospital admission to the first of two consecutive RT-PCR tests with Ct values ≥35. Clinical data, vaccination history, and antiviral treatment were collected. A generalized linear mixed model and Robust regression were used to assess viral clearance dynamics and their predictors.

Results: Delayed viral clearance was independently associated with advanced age (p < 0.001), male sex (p = 0.006), hypertension (p < 0.001), coronary heart disease (p = 0.004), ICU admission (p < 0.001), and mechanical ventilation (p < 0.001).Patients receiving ≥2 inactivated vaccine doses had significantly higher baseline Ct values (median 29.75 vs 28.75, p = 0.014), shorter time to viral negativity (6.3 vs 7.4 days, p < 0.001), and reduced hospital stay (11.2 vs 12.7 days, p < 0.001). Among these, patients vaccinated ≥360 days prior had shortest negative conversion time (5.6 days) and shortest hospitalization (10.3 days).Antiviral therapy with Nirmatrelvir-ritonavir (N/R) accelerated viral clearance more effectively than Azvudine (2.29 vs 1.82 Ct/day, p = 0.045) and no antiviral treatment (1.88 Ct/day, p = 0.041), Although NAT-treated patients achieved viral negativity more rapidly (6.2 days, p = 0.013), N/R demonstrated superior clearance rate. Hospital stays were shorter with N/R than Azvudine (12.1 vs 13.5 days, p = 0.015).

Conclusion: Viral clearance dynamics in hospitalized COVID-19 patients are influenced by age, comorbidities, vaccination, and antiviral treatment. Administration of ≥2 inactivated vaccine doses-especially ≥360 days apart-and early N/R therapy may accelerate viral clearance and reduce hospital stay.