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      Overweight and obesity are not associated with worse clinical outcomes in COVID-19 patients treated with fixed-dose 6 mg dexamethasone

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          Abstract

          Objective

          A fixed 6 mg dexamethasone dose for 10 days is the standard treatment for all hospitalised COVID-19 patients who require supplemental oxygen. Yet, the pharmacokinetic properties of dexamethasone can lead to diminishing systemic dexamethasone exposure with increasing body mass index (BMI). The present study examines whether this translates to overweight and obesity being associated with worse clinical outcomes, defined as ICU admission or in hospital death, in COVID-19 patients treated with fixed-dose dexamethasone.

          Methods

          We conducted a single centre retrospective cohort study in COVID-19 patients who were admitted to a non-ICU ward and were treated with dexamethasone (6 mg once daily for a maximum of ten days) between June 2020 and January 2021. Univariable and multivariable logistic regression analyses were conducted to assess the association between BMI-categories and an unfavourable clinical course (ICU admission and/or in hospital death). Analyses were adjusted for age, comorbidities, inflammatory status, and oxygen requirement at admission. For reference, similar analyses were repeated in a cohort of patients hospitalised before dexamethasone was introduced (March 2020 through May 2020).

          Results

          In patients treated with dexamethasone ( n = 385) an unfavourable clinical course was most prevalent in patients with normal weight (BMI < 25) compared to patients with overweight (BMI 25–30) and patients with obesity (BMI ≥ 30) with percentages of 33, 26 and 21% respectively. In multivariable analyses, there was no association between BMI-category and an unfavourable clinical course (respectively with aORs of 0.81 (0.43–1.53) and 0.61 (0.30–1.27) with normal weight as reference). In the reference cohort ( n = 249) the opposite was observed with an unfavourable clinical course being most prevalent in patients with overweight (39% vs 28%; aOR 2.17 (0.99–4.76)). In both cohorts, CRP level at admission was higher and lymphocyte count was lower in patients with normal weight compared to patients with obesity.

          Conclusions

          Overweight and obesity are not associated with an unfavourable clinical course in COVID-19 patients admitted to a non-ICU ward and treated with 6 mg dexamethasone once daily.

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          Most cited references26

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          Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

          Mark Peters (2020)
          Abstract Background Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death. Methods In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison. Results A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55). Conclusions In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.)
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            Remdesivir for the Treatment of Covid-19 — Final Report

            John H. Beigel, Kay Tomashek, Lori Dodd … (2022)
            Abstract Background Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. Methods We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. Results A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). Conclusions Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.)
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              Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data.

              Hude Quan, Vijaya Sundararajan, Patricia Halfon … (2005)
              Implementation of the International Statistical Classification of Disease and Related Health Problems, 10th Revision (ICD-10) coding system presents challenges for using administrative data. Recognizing this, we conducted a multistep process to develop ICD-10 coding algorithms to define Charlson and Elixhauser comorbidities in administrative data and assess the performance of the resulting algorithms. ICD-10 coding algorithms were developed by "translation" of the ICD-9-CM codes constituting Deyo's (for Charlson comorbidities) and Elixhauser's coding algorithms and by physicians' assessment of the face-validity of selected ICD-10 codes. The process of carefully developing ICD-10 algorithms also produced modified and enhanced ICD-9-CM coding algorithms for the Charlson and Elixhauser comorbidities. We then used data on in-patients aged 18 years and older in ICD-9-CM and ICD-10 administrative hospital discharge data from a Canadian health region to assess the comorbidity frequencies and mortality prediction achieved by the original ICD-9-CM algorithms, the enhanced ICD-9-CM algorithms, and the new ICD-10 coding algorithms. Among 56,585 patients in the ICD-9-CM data and 58,805 patients in the ICD-10 data, frequencies of the 17 Charlson comorbidities and the 30 Elixhauser comorbidities remained generally similar across algorithms. The new ICD-10 and enhanced ICD-9-CM coding algorithms either matched or outperformed the original Deyo and Elixhauser ICD-9-CM coding algorithms in predicting in-hospital mortality. The C-statistic was 0.842 for Deyo's ICD-9-CM coding algorithm, 0.860 for the ICD-10 coding algorithm, and 0.859 for the enhanced ICD-9-CM coding algorithm, 0.868 for the original Elixhauser ICD-9-CM coding algorithm, 0.870 for the ICD-10 coding algorithm and 0.878 for the enhanced ICD-9-CM coding algorithm. These newly developed ICD-10 and ICD-9-CM comorbidity coding algorithms produce similar estimates of comorbidity prevalence in administrative data, and may outperform existing ICD-9-CM coding algorithms.
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                Author and article information

                Contributors
                Esther Wittermans:
                ORCID: http://orcid.org/0000-0002-6035-2601
                e.wittermans@antoniusziekenhuis.nl
                Journal
                Journal ID (nlm-ta): Int J Obes (Lond)
                Journal ID (iso-abbrev): Int J Obes (Lond)
                Title: International Journal of Obesity (2005)
                Publisher: Nature Publishing Group UK (London )
                ISSN (Print): 0307-0565
                ISSN (Electronic): 1476-5497
                Publication date (Electronic): 19 August 2022
                Pages: 1-6
                Affiliations
                [1 ]GRID grid.415960.f, ISNI 0000 0004 0622 1269, Department of Internal Medicine, , St. Antonius Hospital, ; Utrecht/Nieuwegein, The Netherlands
                [2 ]GRID grid.10419.3d, ISNI 0000000089452978, Department of Internal Medicine, , Leiden University Medical Centre, ; Leiden, The Netherlands
                [3 ]GRID grid.415960.f, ISNI 0000 0004 0622 1269, Department of Pulmonology, , St. Antonius Hospital, ; Utrecht/Nieuwegein, The Netherlands
                [4 ]GRID grid.7692.a, ISNI 0000000090126352, Division of Heart and Lungs, , University Medical Centre Utrecht, ; Utrecht, The Netherlands
                [5 ]GRID grid.415960.f, ISNI 0000 0004 0622 1269, Department of Medical Microbiology and Immunology, , St. Antonius Hospital, ; Utrecht/Nieuwegein, The Netherlands
                [6 ]GRID grid.415960.f, ISNI 0000 0004 0622 1269, Department of Pharmacy, , St. Antonius Hospital, ; Utrecht/Nieuwegein, The Netherlands
                [7 ]GRID grid.5477.1, ISNI 0000000120346234, Division of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, , Utrecht University, ; Utrecht, The Netherlands
                Author information
                http://orcid.org/0000-0002-6035-2601
                http://orcid.org/0000-0002-1334-2144
                Article
                Publisher ID: 1204
                DOI: 10.1038/s41366-022-01204-1
                PMC ID: 9388353
                PubMed ID: 35982120
                SO-VID: 55944267-b6ab-43a6-9b45-284a8d7edb99
                Copyright © © The Author(s), under exclusive licence to Springer Nature Limited 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 27 January 2022
                Date revision received : 14 July 2022
                Date accepted : 2 August 2022
                Categories
                Subject: Article

                ScienceOpen disciplines: Nutrition & Dietetics
                Keywords: diseases,risk factors
                Data availability:
                ScienceOpen disciplines: Nutrition & Dietetics
                Keywords: diseases, risk factors

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