3219 hospitalised patients with COVID-19 in Southeast Michigan: a retrospective case cohort study

Mulhem et al., BMJ Open, doi:10.1136/bmjopen-2020-042042, Apr 2021

https://c19early.org/mulhems.html

Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.

Gérard, Zhou, Wu, Kamo, Choi, Kim show increased risk of acute kidney injury with remdesivir. Leo, Briciu, Muntean, Petrov show increased risk of liver injury with remdesivir.

Standard of Care (SOC) for COVID-19 in the study country, the USA, is very poor with very low average efficacy for approved treatments11. Only expensive, high-profit treatments were approved. Low-cost treatments were excluded, reducing the probability of treatment—especially early—due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.

This study is excluded in the after exclusion results of meta analysis: substantial unadjusted confounding by indication likely; substantial confounding by time possible due to significant changes in SOC and treatment propensity during the study period.

Important missing comments or errors? Let us know.

Study covers aspirin, zinc, vitamin C, remdesivir, and HCQ.

risk of death, 85.7% higher, RR 1.86, p = 0.54, treatment 1 of 8 (12.5%), control 515 of 3,211 (16.0%), adjusted per study, odds ratio converted to relative risk, logistic regression.

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1. Gérard et al., Remdesivir and Acute Renal Failure: A Potential Safety Signal From Disproportionality Analysis of the WHO Safety Database, Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2145.wiley.com, doi.org.

2. Zhou et al., Acute Kidney Injury and Drugs Prescribed for COVID-19 in Diabetes Patients: A Real-World Disproportionality Analysis, Frontiers in Pharmacology, doi:10.3389/fphar.2022.833679.frontiersin.org, doi.org.

3. Wu et al., Acute Kidney Injury Associated With Remdesivir: A Comprehensive Pharmacovigilance Analysis of COVID-19 Reports in FAERS, Frontiers in Pharmacology, doi:10.3389/fphar.2022.692828.frontiersin.org, doi.org.

4. 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.

5. Choi et al., Comparative effectiveness of combination therapy with nirmatrelvir–ritonavir and remdesivir versus monotherapy with remdesivir or nirmatrelvir–ritonavir in patients hospitalised with COVID-19: a target trial emulation study, The Lancet Infectious Diseases, doi:10.1016/S1473-3099(24)00353-0.sciencedirect.com, doi.org.

6. Kim et al., Investigating the Safety Profile of Fast‐Track COVID‐19 Drugs Using the FDA Adverse Event Reporting System Database: A Comparative Observational Study, Pharmacoepidemiology and Drug Safety, doi:10.1002/pds.70043.wiley.com, doi.org.

7. Leo et al., Hepatocellular liver injury in hospitalized patients affected by COVID-19: Presence of different risk factors at different time points, Digestive and Liver Disease, doi:10.1016/j.dld.2021.12.014.sciencedirect.com, doi.org.

8. Briciu et al., Evolving Clinical Manifestations and Outcomes in COVID-19 Patients: A Comparative Analysis of SARS-CoV-2 Variant Waves in a Romanian Hospital Setting, Pathogens, doi:10.3390/pathogens12121453.mdpi.com, doi.org.

9. Muntean et al., Effects of COVID-19 on the Liver and Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta and Non-Delta Variants: An Analysis in a Single Centre, Pharmaceuticals, doi:10.3390/ph17010003.mdpi.com, doi.org.

10. Petrov et al., The Effect of Potentially Hepatotoxic Medicinal Products on Alanine Transaminase Levels in COVID-19 Patients: A Case–Control Study, Safety and Risk of Pharmacotherapy, doi:10.30895/2312-7821-2025-458.risksafety.ru, doi.org.

11. c19early.org, c19early.org/soc/usa.html.c19early.org/soc/usa.html.

Mulhem et al., 7 Apr 2021, retrospective, database analysis, USA, peer-reviewed, 3 authors.

This Paper Remdesivir All

3219 hospitalised patients with COVID-19 in Southeast Michigan: a retrospective case cohort study

Dr Elie Mulhem, Andrew Oleszkowicz, David Lick

BMJ Open, doi:10.1136/bmjopen-2020-042042

Objective To report the clinical characteristics of patients hospitalised with COVID-19 in Southeast Michigan. Design Retrospective cohort study. Setting Eight hospitals in Southeast Michigan. Participants 3219 hospitalised patients with a positive SARS-CoV-2 infection by nasopharyngeal PCR test from 13 March 2020 until 29 April 2020. Main outcomes measures Outcomes were discharge from the hospital or in-hospital death. Examined predictors included patient demographics, chronic diseases, home medications, mechanical ventilation, in-hospital medications and timeframe of hospital admission. Multivariable logistic regression was conducted to identify risk factors for in-hospital mortality. Results During the study period, 3219 (90.4%) patients were discharged or died in the hospital. The median age was 65.2 (IQR 52.6-77.2) years, the median length of stay in the hospital was 6.0 (IQR 3.2-10.1) days, and 51% were female. Hypertension was the most common chronic disease, occurring in 2386 (74.1%) patients. Overall mortality rate was 16.0%. Blacks represented 52.3% of patients and had a mortality rate of 13.5%. Mortality was highest at 18.5% in the prepeak hospital COVID-19 volume, decreasing to 15.3% during the peak period and to 10.8% in the postpeak period. Multivariable regression showed increasing odds of in-hospital death associated with older age (OR 1.04, 95% CI 1.03 to 1.05, p<0.001) for every increase in 1 year of age and being male (OR 1.47, 95% CI 1.21 to 1.81, p<0.001). Certain chronic diseases increased the odds of in-hospital mortality, especially chronic kidney disease. Administration of vitamin C, corticosteroids and therapeutic heparin in the hospital was associated with higher odds of death. Conclusion In-hospital mortality was highest in early admissions and improved as our experience in treating patients with COVID-19 increased. Blacks were more likely to get admitted to the hospital and to receive mechanical ventilation, but less likely to die in the hospital than whites. COVID-19 was first reported as an outbreak of pneumonia of unknown cause in Wuhan, China in December 2019. 1 The virus responsible was subsequently named SARS-CoV-2. The first confirmed case in the USA was reported on 31 January 2020, and the first case in Michigan was reported on 10 March 2020. 2 As of 1 June 2020, 57 532 cases have

Competing interests None declared. Patient consent for publication Not required. Ethics approval The study was approved by Beaumont IRB (study ID: 2020-161). Provenance and peer review Not commissioned; externally peer reviewed. Data availability statement Data available per reasonable request. Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise. Open access This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http:// creativecommons. org/ licenses/ by-nc/ 4. 0/. ..

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DOI record: { "DOI": "10.1136/bmjopen-2020-042042", "ISSN": [ "2044-6055", "2044-6055" ], "URL": "http://dx.doi.org/10.1136/bmjopen-2020-042042", "abstract": "ObjectiveTo report the clinical characteristics of patients hospitalised with COVID-19 in Southeast Michigan.DesignRetrospective cohort study.SettingEight hospitals in Southeast Michigan.Participants3219 hospitalised patients with a positive SARS-CoV-2 infection by nasopharyngeal PCR test from 13 March 2020 until 29 April 2020.Main outcomes measuresOutcomes were discharge from the hospital or in-hospital death. Examined predictors included patient demographics, chronic diseases, home medications, mechanical ventilation, in-hospital medications and timeframe of hospital admission. Multivariable logistic regression was conducted to identify risk factors for in-hospital mortality.ResultsDuring the study period, 3219 (90.4%) patients were discharged or died in the hospital. The median age was 65.2 (IQR 52.6–77.2) years, the median length of stay in the hospital was 6.0 (IQR 3.2–10.1) days, and 51% were female. Hypertension was the most common chronic disease, occurring in 2386 (74.1%) patients. Overall mortality rate was 16.0%. Blacks represented 52.3% of patients and had a mortality rate of 13.5%. Mortality was highest at 18.5% in the prepeak hospital COVID-19 volume, decreasing to 15.3% during the peak period and to 10.8% in the postpeak period. Multivariable regression showed increasing odds of in-hospital death associated with older age (OR 1.04, 95% CI 1.03 to 1.05, p<0.001) for every increase in 1 year of age and being male (OR 1.47, 95% CI 1.21 to 1.81, p<0.001). Certain chronic diseases increased the odds of in-hospital mortality, especially chronic kidney disease. Administration of vitamin C, corticosteroids and therapeutic heparin in the hospital was associated with higher odds of death.ConclusionIn-hospital mortality was highest in early admissions and improved as our experience in treating patients with COVID-19 increased. 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Late treatment
is less effective

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