Clinical characteristics and risk factors of non-mild outcomes in patients with Omicron variant COVID-19 in Shanghai, China

Zhu et al., The Journal of Infection in Developing Countries, doi:10.3855/jidc.18138

Jan 2024

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Retrospective 311 COVID-19 patients in China showing significantly slower viral clearance with paxlovid in multivariable analysis.

Resistance. Variants may be resistant to paxlovid1-3. Use may promote the emergence of variants that weaken host immunity and potentially contribute to long COVID4.

Confounding by contraindication. Hoertel et al. find that over 50% of patients that died had a contraindication for the use of Paxlovid5. 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"6.

AKI. Kamo et al. show significantly increased risk of acute kidney injury.

Important missing comments or errors? Let us know.

risk of no viral clearance, 78.6% higher, OR 1.79, p < 0.001, treatment 138, control 155, adjusted per study, inverted to make OR<1 favor treatment, multivariable, RR approximated with OR.

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

1. Zhou et al., Nirmatrelvir-resistant SARS-CoV-2 variants with high fitness in an infectious cell culture system, Science Advances, doi:10.1126/sciadv.add7197.science.org, doi.org.

2. Jochmans et al., The Substitutions L50F, E166A, and L167F in SARS-CoV-2 3CLpro Are Selected by a Protease Inhibitor In Vitro and Confer Resistance To Nirmatrelvir, mBio, doi:10.1128/mbio.02815-22.asm.org, doi.org.

3. Lopez et al., SARS-CoV-2 Resistance to Small Molecule Inhibitors, Current Clinical Microbiology Reports, doi:10.1007/s40588-024-00229-6.springer.com, doi.org.

4. Thomas et al., Nirmatrelvir-Resistant Mutations in SARS-CoV-2 Mpro Enhance Host Immune Evasion via Cleavage of NF-κB Essential Modulator, bioRxiv, doi:10.1101/2024.10.18.619137.biorxiv.org, doi.org.

5. 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.

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

7. Kamo et al., Association of Antiviral Drugs for the Treatment of COVID-19 With Acute Renal Failure, In Vivo, doi:10.21873/invivo.13637.iiarjournals.org, doi.org.

Zhu et al., 31 Jan 2024, retrospective, China, peer-reviewed, median age 76.0, 5 authors, study period 26 April, 2022 - 21 May, 2022.

This Paper Paxlovid All

Clinical characteristics and risk factors of non-mild outcomes in patients with Omicron variant COVID-19 in Shanghai, China

Wen Zhu, Haowei Wang, Hai Zhou, PhD Lei Cheng, Chao Weng

The Journal of Infection in Developing Countries, doi:10.3855/jidc.18138

Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant rapidly appeared in Shanghai, China in early March 2022. Although a few studies have analyzed the risk factors of the severe type, identifying risk factors for non-mild COVID-19 outcomes (general/severe/critical type) which occur with radiographic evidence of pneumonia is lacking. Methodology: The COVID-19 patients admitted to a district-level designated hospital from April 26 to May 21 were enrolled in this retrospective study. The clinical manifestations and laboratory examinations were analyzed. Logistic regression was employed to evaluate risk factors for non-mild outcomes. Results: Of the 311 patients, 196 (63.0%) were mild and 115 (37.0%) were non-mild. Among them, 215 cases (69.1%) were unvaccinated. Male, ≥ 60 years age, and chronic kidney disease were risk factors of progressing to non-mild. Patients with more than two comorbidities were more likely to become non-mild, whereas two/booster doses vaccinated patients had a lower risk of developing to non-mild. The median negative conversion days (NCDs) were 12 days. Non-mild, > 2 comorbidities, delayed admission (> 3 days), and Paxlovid (Pfizer, Freiburg, Germany) treatment significantly lengthened the NCDs. Conclusions: Our results call for special concern for full and booster vaccination of the elderly, which will effectively protect from progression of COVID-19 to non-mild state. In the meantime, symptomatic COVID-19 patients should be treated as soon as possible.

Conflict of interests: No conflict of interests is declared. Supplementary Figure 1 . Differential indicators from laboratory results among mild, general, severe/critical patients. Annex -Supplementary Items Supplementary The indicators include lymphocyte count, A/G ratio, myoglobin, troponin T, D-dimer, and inflammatory markers (CRP, IL-6, and IL-10).

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