Jia Zeng,1,* Heping Xu,1,* Shuai Luo,1,* Xiaotian Zhou,2 Xishi Li,3 Yuwen Zeng,3 Yihan Wang,2 Haotian Jiang,3 Changfeng Lin,4 Chengfang Zheng,5 Jianwen Ruan,6 Weiling Yu,7 Jinjian Yao,1 Jiannong Zhao8 

1Emergency Department of Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China; 2Emergency Trauma College, Hainan Medical University, Haikou, Hainan, 571199, People’s Republic of China; 3Emergency Department, The second Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China; 4Department of Infectious Diseases, Sanya Central Hospital, SanYa, Hainan, 572000, People’s Republic of China; 5Department of Infectious Diseases, Hainan Western Central Hospital, Danzhou, Hainan, 813099, People’s Republic of China; 6Department of Infectious Diseases, Haikou City People’s Hospital, Haikou, Hainan, 570208, People’s Republic of China; 7Oncology Department, Haikou City People’s Hospital, Haikou, Hainan, 570208, People’s Republic of China; 8Department of Neurosurgery, Hainan General Hospital, Hainan Medical University, Haikou, Hainan, 571199, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jinjian Yao, Emergency Department of Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, 570311, People’s Republic of China, Email 114715854@qq.com Jiannong Zhao, Department of Neurosurgery, Hainan General Hospital, Hainan Medical University, Haikou, Hainan, 571199, People’s Republic of China, Email zhaojiannong@muhn.edu.cn

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.

Keywords: inactivated COVID-19 vaccine, comorbidities, viral clearance, antiviral drugs