Composite interventions on outcomes of severely and critically ill patients with COVID-19 in Shanghai, China

Abstract Background. The sixty-day effects of initial composite interventions for the treatment of severely and critically ill patients with COVID-19 are not fully assessed. Methods. Using a bayesian piecewise exponential model, we analyzed the 60-day mortality, health-related quality of life (HRQoL) and disability in 1082 severely and critically patients with COVID-19 between December 8, 2022 and February 9, 2023 in Shanghai, China. The final 60-day follow-up was completed on April 10, 2023. Results. Among 1082 patients (mean age, 78.0 years), 421 [38.9%] women), 139 patients (12.9%) died within 60 days. Azvudine had a 99.8% probability of improving 2-month survival (adjusted HR, 0.44 [95% credible interval 1, 0.24-0.79]) and Paxlovid had a 91.9% probability of improving 2-month survival (adjusted HR, 0.71 [95% credible interval 1, 0.44-1.14]) compared with the control. IL-6 receptor antagonist, Baricitinib, and a-thymosin each had a high probability of benefit (99.5%, 99.4%, and 97.5%, respectively) compared to their controls, while the probability of trail-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.8%; HR, 1.64 [95% CrI, 1.06-2.50]), glucocorticoid (91.4%; HR, 1.20 [95% CrI, 0.71-2.16]). Conclusions. Among severely and critically ill patients with COVID-19 who received 1 or more therapeutic interventions, treatment with Azvudine had high probability of improved 60-day mortality compared with the control, indicating its potential in resource-limited scenario. Treatment with IL-6 receptor antagonist, Baricitinib, and a-thymosin also had high probabilities of benefit of improving 2-month survival, among which a-thymosin could improve HRQoL. Keyword. COVID-19; Azvudine; Paxlovid; Interleukin-6 receptor antagonist; Baricitinib, α-thymosin, Intravenous immunoglobulin ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The study was funded by research grants from The National Natural Science Foundation of China (Grant No. 82127807), Shanghai Key Laboratory of Molecular Imaging (18DZ2260400), Shanghai University of Medicine and Health Sciences Clinical Research Centre for Metabolic Vascular Diseases Project (20MC2020004), Science and Technology Commission of Jiading District (Grant No. JDKW-2021-0022) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Ethics Committee of Jiading District Central Hospital affiliated to Shanghai University of Medicine and Health Sciences (Approval code 2023K15) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors