Azvudine versus Paxlovid for oral treatment of COVID-19 in Chinese patients with pre-existing comorbidities

Dian et al., Journal of Infection, doi:10.1016/j.jinf.2023.05.012, Aug 2023
Mortality -175% improvement lower risk ← → higher risk Ventilation -200% ICU admission 0% Composite outcome -94% Respiratory suport -80% Paxlovid for COVID-19  Dian et al.  LATE TREATMENT Is late treatment with paxlovid beneficial for COVID-19? PSM retrospective 2,118 patients in China (December 2022 - January 2023) Study compares with azvudine, results vs. placebo may differ Higher progression with paxlovid (p=0.03) c19early.org Dian et al., J. Infection, August 2023 0 0.5 1 1.5 2+ RR
Retrospective 2,118 hospitalized COVID-19 patients in China, showing improved results with azvudine vs. paxlovid.
Resistance. Variants may be resistant to paxlovid1-8. Use may promote the emergence of variants that weaken host immunity and potentially contribute to long COVID9.
Confounding by contraindication. Hoertel et al. find that over 50% of patients that died had a contraindication for the use of Paxlovid10. 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 paxlovid11.
Kidney and liver injury. Studies show significantly increased risk of acute kidney injury12 and liver injury13.
Standard of Care (SOC) for COVID-19 in the study country, China, is average with moderate efficacy for approved treatments14.
Important missing comments or errors? Let us know.
Study covers paxlovid and azvudine.
risk of death, 175.0% higher, RR 2.75, p = 0.11, treatment 11 of 228 (4.8%), control 4 of 228 (1.8%), propensity score matching.
risk of mechanical ventilation, 200.0% higher, RR 3.00, p = 0.28, treatment 6 of 228 (2.6%), control 2 of 228 (0.9%), propensity score matching.
risk of ICU admission, no change, RR 1.00, p = 1.00, treatment 1 of 228 (0.4%), control 1 of 228 (0.4%), propensity score matching.
composite outcome, 93.8% higher, RR 1.94, p = 0.03, treatment 31 of 228 (13.6%), control 16 of 228 (7.0%), non-invasive respiratory support, endotracheal intubation, ICU admission, all-cause death, propensity score matching.
respiratory suport, 80.0% higher, RR 1.80, p = 0.07, treatment 27 of 228 (11.8%), control 15 of 228 (6.6%), propensity score matching.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Dian et al., 31 Aug 2023, retrospective, China, peer-reviewed, 5 authors, study period 5 December, 2022 - 31 January, 2023, this trial compares with another treatment - results may be better when compared to placebo.
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org November 2025 China United Kingdom Russia USA Sudan Angola Colombia Kenya Mozambique Pakistan Argentina Vietnam Peru Philippines Spain Brazil Italy France Japan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Bosnia-Herzegovina Côte d'Ivoire Eritrea Bulgaria Greece Slovakia Singapore Iceland New Zealand Czechia Mongolia Israel Trinidad and Tobago Hong Kong North Macedonia Belarus Qatar Panama Serbia CAR China favored low-cost treatments.The average efficacy of treatments was moderate.Low-cost treatments improve early treatment, andprovide complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org November 2025 China United Kingdom Russia USA Sudan Angola Colombia Kenya Mozambique Pakistan Argentina Vietnam Peru Philippines Spain Brazil Italy France Japan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Côte d'Ivoire Eritrea Togo Bulgaria Greece Slovakia Singapore New Zealand Malawi Czechia Mongolia Israel Trinidad and Tobago North Macedonia Belarus Qatar Panama Serbia Syria China favored low-cost treatments.The average efficacy was moderate.Low-cost protocols improve early treatment,and add complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
Abstract: Journal of Infection 87 (2023) e24–e27 Contents lists available at ScienceDirect Journal of Infection journal homepage: www.elsevier.com/locate/jinf Letter to the Editor Azvudine versus Paxlovid for oral treatment of COVID-19 in Chinese patients with pre-existing comorbidities ]]]] ]] Dear Editor, Chinese guidelines grant the use of Azvudine and Paxlovid in COVID-19 patients, especially those with pre-existing comorbid­ ities.1,2 Recently, Gao Y et al. reported that Paxlovid appears to be superior to Azvudine in the virus clearance among general COVID-19 patients.3 However, a multicenter randomized controlled study de­ monstrated that Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of virus clearance in hospitalized adult COVID-19 patients with pre-existing co­ morbidities.4 Several studies demonstrated that Azvudine could re­ duce the duration of virus clearance and improve the clinical prognosis in COVID-19 patients including those with pre-existing comorbidities.5–8 Therefore, concerns arise about the clinical effec­ tiveness of Azvudine versus Paxlovid in COVID-19 patients with preexisting comorbidities on admission. Here, we conducted a single-center, retrospective cohort study during the outbreak caused by the omicron from December 5, 2022 to January 31, 2023 in Xiangya Hospital of Central South University. The study included hospitalized patients with preexisting comorbidities and confirmed diagnosis of SARS-CoV-2 infection who received Paxlovid or Azvudine. The patients with these conditions were excluded: 1) younger than 18 years; 2) re­ ceived oxygen support or mechanical ventilation on the date of the admission; 3) not received any antiviral agents; 4) received both Azvudine and Paxlovid. The study was approved by the in­ stitutional review board of Xiangya Hospital of Central South University, and all the patients were anonymous and no need for individual informed consent. The primary endpoint was a composite disease progression outcome which was defined as any of the following events: 1) noninvasive respiratory support; 2) initiation of endotracheal intuba­ tion; 3) intensive care unit admission; 4) all-cause death. The sec­ ondary endpoints were each of these individual disease progression outcomes. Patients were observed from the date of admission until discharge, occurrence of outcome event or death, whichever came first. We used propensity-score models conditional on baseline characteristics, and the probability of receiving Azvudine was esti­ mated in an approach of calliper matching without replacement, with a calliper width of 0.2. The baseline covariates included age, sex, time from symptom onset to hospitalization, COVID-19 vacci­ nation status, severity of COVID-19 on admission (severe cases were defined as having respiratory rate ≥30, or oxygen saturation ≤93%, or PaO2/FiO2 ≤300 mmHg, or lung infiltrates > 50%), and concomitant treatments initiated at admission (systemic steroid and antibiotics). The standard mean differences (SMDs) were used to assess the balance of each baseline covariates between the groups before and after propensity-score matching which less than 0.1 indicating covariate was balanced.9 The incidence rates of outcome events were calculated as the number of outcome events / (sum of person × hospital days). Univariate Cox regression model was used to estimate a hazard ratio (HR) with 95% confidence interval (CI) for each..
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Late treatment
is less effective
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