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 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, 0.71–2.16]). 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.

Antiviral effectiveness and survival correlation of azvudine and nirmatrelvir/ritonavir in elderly severe patients with COVID-19: a retrospective real-world study

“…Nirmatrelvir/ritonavir seems to have a lower probability of improving 2-month survival. 23 Another open-label, multicenter, randomized controlled trial indicated that nirmatrelvir/ritonavir showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS-CoV-2 RNA clearance in which hospitalized adult patients with severe comorbidities. 24 Therefore, patients' critical status may also be responsible for the early favorable antiviral trend and seemingly poor survival outcome of nirmatrelvir/ritonavir in this study.…”

Effectiveness and safety of azvudine in COVID-19: A systematic review and meta-analysis

“…The pooled estimate of nine studies [ 19 , 20 , 27 – 29 , 32 , 33 , 37 , 38 ] showed a significant difference in mortality rate between patients receiving azvudine and SOC (RR = 0.48, 95% CI: 0.40 to 0.57, P < 0.001, I 2 = 0%, GRADE certainty: moderate) ( Fig 2 ). According to the pooled estimate, seven studies [ 6 , 7 , 25 , 32 , 35 – 37 ] revealed a significant difference in mortality rate between the azvudine and nirmatrelvir-ritonavir groups (RR = 0.73, 95% CI: 0.58 to 0.92, P < 0.05, I 2 = 41%, GRADE certainty: moderate) ( Fig 3 ).…”

“…The effectiveness of azvudine in reducing COVID-19-related deaths has been the subject of conflicting evidence. While some real-world studies and RCTs have shown a lower risk of death in patients receiving azvudine compared to those receiving SOC/PBO [ 27 ] or nirmatrelvir–ritonavir [ 6 , 32 ], other studies [ 6 , 7 , 25 , 35 ] found no significant differences between azvudine and nirmatrelvir-ritonavir treatments in reducing mortality rates in COVID-19 patients. Conversely, strong evidence supports the effectiveness of nirmatrelvir-ritonavir in reducing the mortality rate related to COVID-19 [ 2 , 40 , 41 ].…”

Efficacy and Safety of Azvudine in Patients With COVID‐19 in China: A Meta‐Analysis of Observational Studies

“…These clinical studies were all conducted in China, with 22 published in English and 2 published in Chinese [28,29]. In terms of disease severity, the majority of the included patients in most studies had mild to moderate disease, with four studies including patients with severe to critical illness [14,23,32,33]. Among the analyzed population, one study focused on renal transplant recipients [28], one included individuals with a history of cancer [30], and one study included patients with concomitant cardiovascular disease [31].…”