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      Pentoxifylline or theophylline use in hospitalized COVID‐19 patients requiring oxygen support

      brief-report

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          Abstract

          Introduction

          The phosphodiesterase inhibitors theophylline and pentoxifylline have anti‐inflammatory properties that may make them useful in COVID‐19 pneumonia. We conducted a retrospective review of hospitalized COVID‐19 patients requiring oxygen who received these drugs.

          Objectives

          To examine the potential efficacy and safety of theophylline and pentoxifylline in COVID‐19 pneumonia patients.

          Methods

          Adults with a positive test for SARS‐COV2 and were hospitalized due to pneumonia requiring either high flow nasal cannula or mechanical ventilation were included. Patients with a history of asthma or chronic obstructive pulmonary disease were preferentially given theophylline. All other patients received pentoxifylline 400 mg orally TID. A group of hospitalized COVID‐19 patients receiving standard of care acted as a comparison group. The coprimary outcomes were a change in C‐reactive protein (CRP) and ROX score between groups from day 1 to day 4 of therapy.

          Results

          Two hundred and nine inpatients were reviewed. Fifty‐eight patients received pentoxifylline/theophylline, with 151 patients serving as the comparison group. Active therapy was associated with an increase in the ROX score (mean: 2.9 (95% CI: 0.6, 5.1)) and decrease in CRP (mean: −0.7 (95% CI: −4.7, 3.2). Mortality rates were theophylline/pentoxifylline 24% and comparison group had a 26%, respectively.

          Conclusion

          In this retrospective study, theophylline and pentoxifylline were associated with an increase in ROX score and nominal decreases in CRP and mortality. Treatment was safe with few adverse reactions documented. We believe that this study could the basis for randomized‐controlled trials to further explore these drugs’ role in COVID‐19.

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          Most cited references9

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          Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

          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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            Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?

            The emergent outbreak of coronavirus disease 2019 (COVID-19) has caused a global pandemic. Acute respiratory distress syndrome (ARDS) and multiorgan dysfunction are among the leading causes of death in critically ill patients with COVID-19. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome (CRS), may play a major role in the pathology of COVID-19. However, the efficacy of corticosteroids, commonly utilized antiinflammatory agents, to treat COVID-19-induced CRS is controversial. There is an urgent need for novel therapies to treat COVID-19-induced CRS. Here, we discuss the pathogenesis of severe acute respiratory syndrome (SARS)-induced CRS, compare the CRS in COVID-19 with that in SARS and Middle East respiratory syndrome (MERS), and summarize the existing therapies for CRS. We propose to utilize interleukin-6 (IL-6) blockade to manage COVID-19-induced CRS and discuss several factors that should be taken into consideration for its clinical application.
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              Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome.

              Because it has no unique clinical, biologic, or histologic features, reactive hemophagocytic syndrome may be difficult to distinguish from other diseases such as severe sepsis or hematologic malignancies. This study was undertaken to develop and validate a diagnostic score for reactive hemophagocytic syndrome.
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                Author and article information

                Contributors
                geoff.wall@drake.edu
                Journal
                Clin Respir J
                Clin Respir J
                10.1111/(ISSN)1752-699X
                CRJ
                The Clinical Respiratory Journal
                John Wiley and Sons Inc. (Hoboken )
                1752-6981
                1752-699X
                28 March 2021
                : 10.1111/crj.13363
                Affiliations
                [ 1 ] Drake University College of Pharmacy and Health Sciences Des Moines IA USA
                [ 2 ] Department of Medical Education, UnityPoint Health – Des Moines Iowa Methodist Medical Center Des Moines IA USA
                [ 3 ] Division of Pulmonary and Critical Care Medicine The Iowa Clinic, PC Des Moines IA USA
                Author notes
                [*] [* ] Correspondence

                Geoffrey C. Wall, Department of Pharmacy, Iowa Methodist Medical Center, 1200 Pleasant Street, Des Moines, IA, USA.

                Email: geoff.wall@ 123456drake.edu

                Author information
                https://orcid.org/0000-0002-8668-9966
                Article
                CRJ13363
                10.1111/crj.13363
                8250682
                33735520
                d674ed34-7fa1-4a8a-9559-32cb965aadc4
                © 2021 John Wiley & Sons Ltd

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 22 September 2020
                : 22 September 2020
                : 11 March 2021
                Page count
                Figures: 1, Tables: 1, Pages: 4, Words: 3096
                Categories
                Brief Report
                Brief Reports
                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.4 mode:remove_FC converted:02.07.2021

                Respiratory medicine
                covid‐19,pentoxifylline,pneumonia,theophylline
                Respiratory medicine
                covid‐19, pentoxifylline, pneumonia, theophylline

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