Composite Interventions on Outcomes of Severely and Critically Ill Patients with COVID-19 in Shanghai, China

Shao et al., Microorganisms, doi:10.3390/microorganisms11071859

Jul 2023

Retrospective 1,082 severely and critically ill COVID-19 patients in China showing lower 60 day mortality with azvudine. Mortality was also lower with paxlovid, but without statistical significance, and health related quality of life was significantly lower for paxlovid patients at 60 days.

Confounding by contraindication. Hoertel et al. find that over 50% of patients that died had a contraindication for the use of Paxlovid Hoertel. Retrospective studies that do not exclude contraindicated patients may significantly overestimate efficacy.

Black box warning. The FDA notes that "severe, life-threatening, and/or fatal adverse reactions due to drug interactions have been reported in patients treated with paxlovid" FDA.

1. FDA, Fact sheet for healthcare providers: emergency use authorization for paxlovid, www.fda.gov/media/155050/download.fda.gov.

2. Hoertel et al., Prevalence of Contraindications to Nirmatrelvir-Ritonavir Among Hospitalized Patients With COVID-19 at Risk for Progression to Severe Disease, JAMA Network Open, doi:10.1001/jamanetworkopen.2022.42140.jamanetwork.com, doi.org.

Important missing comments or errors? Let us know.

Study covers paxlovid and azvudine.

risk of death, 29.0% lower, HR 0.71, p = 0.16, treatment 280, control 509, adjusted per study, day 60.

relative HRQoL, 28.3% worse, RR 1.28, p < 0.001, treatment mean 0.46 (±0.42) n=237, control mean 0.59 (±0.41) n=456, day 60.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Shao et al., 23 Jul 2023, retrospective, China, peer-reviewed, 9 authors, study period 8 December, 2022 - 9 February, 2023. Contact: huanggang@sumhs.edu.cn (corresponding author), shaojiasheng@jdhospital.com, rfan1@tulane.edu, cnguo22@m.fudan.edu.cn, huangxuyuan@jdhospital.com, guorunsheng@jdhospital.com, zhangfengdi@126.com, hujianrong@jdhospital.com, caoliou@jdhospital.com.

This Paper Paxlovid All

Composite Interventions on Outcomes of Severely and Critically Ill Patients with COVID-19 in Shanghai, China

Jiasheng Shao, Rong Fan, Chengnan Guo, Xuyuan Huang, Runsheng Guo, Fengdi Zhang, Jianrong Hu, Gang Huang, Liou Cao

Microorganisms, doi:10.3390/microorganisms11071859

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 ill patients with COVID-19 between 8 December 2022 and 9 February 2023 in Shanghai, China. The final 60-day follow-up was completed on 10 April 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, 0.24-0.79]), and Paxlovid had a 91.9% probability of improving 2-month survival (adjusted HR, 0.71 [95% credible interval, 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]) and glucocorticoid (91.4%; HR, 1.20 [95% CrI,). Paxlovid, Azvudine, and therapeutic anticoagulation showed a significant reduction in disability (p < 0.05) Conclusions: Among severely and critically ill patients with COVID-19 who received 1 or more therapeutic interventions, treatment with Azvudine had a high probability of improved 60-day mortality compared with the control, indicating its potential in a resource-limited scenario. Treatment with an IL-6 receptor antagonist, baricitinib, and a-thymosin also had high probabilities of benefit in improving 2-month survival, among which a-thymosin could improve HRQoL. Treatment with Paxlovid, Azvudine, and therapeutic anticoagulation could significantly reduce disability at day 60.

Conflicts of Interest: The authors declare no conflict of interest.

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Late treatment
is less effective

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