Abstract: Biomedicine & Pharmacotherapy 133 (2021) 110825 Contents lists available at ScienceDirect Biomedicine & Pharmacotherapy journal homepage: www.elsevier.com/locate/biopha Tocilizumab combined with favipiravir in the treatment of COVID-19: A multicenter trial in a small sample size Hong Zhao a, b, 1, Qi Zhu c, 1, Chi Zhang a, 1, Jiawen Li a, Ming Wei d, Yuhong Qin e, Guilin Chen c, Ke Wang d, Junhua Yu f, Zhao Wu a, Xianxiang Chen g, *, Guiqiang Wang a, b, ** a Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, China Peking University International Hospital, Beijing, China Department of Tuberculosis, Wuhan Pulmonary Hospital, Wuhan, 430030, China d Wuhan Jinyintan Hospital, No. 1 Yintan Road, Dongxihu District, Wuhan, 430040, China e Emergency Department of Peking University International Hospital, Life-Science Park, Changping District, Beijing, 102206, China f Ezhou Central Hospital, 9 Wenxing Road, Ezhou City, Hubei Province, 463000, China g Surgical Department, Wuhan Pulmonary Hospital, No. 28 Baofeng Road, Wuhan, 430030, China b c A R T I C L E I N F O A B S T R A C T Keywords: Tocilizumab Favipiravir Interleukin-6 COVID-19 SARS-CoV-2 Background: Since December 2019, COVID-19 has spread to almost every corner of the world. In theory, toci­ lizumab and favipiravir are considered to be reliable drugs for the treatment of COVID-19 with elevated IL-6. We aimed to assess the efficacy and safety of tocilizumab combined with favipiravir in patients with COVID-19. Methods: This was a multicenter trial in adults with COVID-19. Patients were randomly assigned (3:1:1) to a 14day combination of favipiravir combined with tocilizumab (combination group), favipiravir, and tocilizumab. The primary outcome was the cumulative lung lesion remission rate (lung CT examination indicated absorption of lung inflammation). Results: Between Feb 2 and March 15, 2020, 26 patients were recruited; 14 were randomly assigned to the combination group, 7 were assigned to the favipiravir group and 5 were assigned to the tocilizumab group. The cumulative lung lesion remission rate at day 14 was significantly higher in combination group as compared with favipiravir group (P = 0.019, HR 2.66 95 % CI [1.08–6.53]). And there was also a significant difference between tocilizumab and favipivavir (P = 0.034, HR 3.16, 95 % CI 0.62–16.10). In addition, there was no significant difference between the combination group and the tocilizumab group (P = 0.575, HR 1.28 95 %CI 0.39–4.23). Furthermore, combined therapy can also significantly relieve clinical symptoms and help blood routine to return to normal. No serious adverse events were reported. Conclusion: Tocilizumab combined with or without favipiravir can effectively improve the pulmonary inflam­ mation of COVID-19 patients and inhibit the deterioration of the disease.