Although corticosteroids dampen the dysregulated immune system and sometimes are prescribed as an adjunctive treatment for pneumonia, their effectiveness in the treatment of coronavirus disease 2019 (COVID-19) remains controversial. In this issue of the JCI, Liu and Zhang et al. evaluated corticosteroid treatment in more than 400 patients with severe COVID-19. The authors assessed subjects retrospectively for cardiac and liver injury, shock, ventilation, mortality, and viral clearance. Corticosteroids in severe COVID-19–related acute respiratory distress syndrome (ARDS) were associated with increased mortality and delayed viral clearance. Here, we consider how to reconcile the negative effects of corticosteroids revealed by Liu and Zhang et al. with the favorable effects (reduced mortality) that were described in the RECOVERY trial. We posit that treatment timing, dosage, and COVID-19 severity determine immune response and viral outcome. Patients with moderate-to-severe COVID-19 pneumonia are likely to benefit from moderate-dose corticosteroid treatment when administered relatively late in the disease course.
Michael A. Matthay, Katherine D. Wick
Title and authors | Publication | Year |
---|---|---|
Assessment of Knowledge, Perception, Experience, and Phobia Toward Corticosteroids Among the General Public in Two Southeast Asian Countries
Barakat M, Abdulrazzaq SB, Alzaghari LF, Ramatillah D, Muhammad RF, Elnaem MH |
Inquiry: A Journal of Medical Care Organization, Provision and Financing | 2025 |
Time-Varying Effects of Glucocorticoid Treatment in Critically III Patients with Severe Fever with Thrombocytopenia Syndrome: An Inverse Probability of Treatment Weighting Analysis
Xia P, Liu Y, Wang J, Li H, Zhai Y, Wang B, Tong H, Ge W, Jiang C |
Journal of Inflammation Research | 2025 |
Ketoprofen Lysine Salt Versus Corticosteroids in Early Outpatient Management of Mild and Moderate COVID-19: A Retrospective Study.
Mariniello DF, Pagliaro R, D'Agnano V, Schiattarella A, Perrotta F, Bianco A |
Pharmacy (Basel, Switzerland) | 2025 |
Biological Effects of Corticosteroids on Pneumococcal Pneumonia in Mice and Humans
Taenaka H, Wick KD, Sarma A, Matsumoto S, Ghale R, Fang X, Maishan M, Gotts JE, Langelier CR, Calfee CS, Matthay MA |
Research square | 2024 |
Biological effects of corticosteroids on pneumococcal pneumonia in Mice-translational significance.
Taenaka H, Wick KD, Sarma A, Matsumoto S, Ghale R, Fang X, Maishan M, Gotts JE, Langelier CR, Calfee CS, Matthay MA |
Critical Care | 2024 |
Evaluation of High-dose versus Standard-dose of Dexamethasone on Mortality among the Mechanically Ventilated COVID-19 Patients.
Kale-Pradhan PB, Pacitto R, Giuliano CA, Johnson LB |
Current drug safety | 2024 |
Study on the clinical characteristics, treatment, and outcome influencing factors of severe pneumonia complicated with ARDS.
Zhang W, Xiao H, Tong X, He L, Xu X, Dong J |
Medicine | 2024 |
Non-Dexamethasone Corticosteroid Therapy’s Effect on COVID-19 Prognosis in Cancer Patients: A Retrospective Study
Souan L, Al-Khairy Z, Battah A, Sughayer MA |
Human vaccines | 2023 |
Growth hormone-releasing hormone antagonists protect against hydrochloric acid-induced endothelial injury in vitro.
Barabutis N, Kubra KT, Akhter MS |
Environmental Toxicology and Pharmacology | 2023 |
Corticosteroids in adults with acute respiratory distress syndrome and severe pneumonia
Jayasimhan D, Matthay MA |
2023 | |
Treatment of Cognitive Deficits and Behavioral Symptoms Following COVID-19-Associated Autoimmune Encephalitis With Intravenous Immunoglobulin: A Case Report and Review of the Literature.
Naeem S, Oros SM, Adams CS, Rakesh G |
Cureus | 2023 |
Growth hormone-releasing hormone antagonists counteract interferon-γ – induced barrier dysfunction in bovine and human endothelial cells
Fakir S, Barabutis N |
Cytokine | 2023 |
Hallmarks of Severe COVID-19 Pathogenesis: A Pas de Deux Between Viral and Host Factors
Rovito R, Augello M, Ben-Haim A, Bono V, d\u2019Arminio Monforte A, Marchetti G |
Frontiers in immunology | 2022 |
2‐Deoxy‐d‐glucose induces deglycosylation of proinflammatory cytokine receptors and strongly reduces immunological responses in mouse models of inflammation
Uehara I, Kajita M, Tanimura A, Hida S, Onda M, Naito Z, Taki S, Tanaka N |
Pharmacology Research & Perspectives | 2022 |
Matrix Metalloproteinases on Severe COVID-19 Lung Disease Pathogenesis: Cooperative Actions of MMP-8/MMP-2 Axis on Immune Response through HLA-G Shedding and Oxidative Stress
da Silva-Neto PV, do Valle VB, Fuzo CA, Fernandes TM, Toro DM, Fraga-Silva TF, Basile PA, de Carvalho JC, Pimentel VE, Pérez MM, Oliveira CN, Rodrigues LC, Bastos VA, Tella SO, Martins RB, Degiovani AM, Ostini FM, Feitosa MR, Parra RS, Vilar FC, Gaspar GG, da Rocha JJ, Feres O, Arruda E, Maruyama SR, Russo EM, Viana AL, Santos IK, Bonato VL, Cardoso CR, Tanus-Santos JE, Donadi EA, Faccioli LH, Dias-Baruffi M, Fernandes AP, Gerlach RF, Sorgi CA |
Biomolecules | 2022 |
The Spontaneous Course of Human Herpesvirus 6 DNA-Associated Myocarditis and the Effect of Immunosuppressive Intervention.
Elsanhoury A, Kühl U, Stautner B, Klein O, Krannich A, Morris D, Willner M, Jankowska E, Klingel K, Van Linthout S, Tschöpe C |
Viruses | 2022 |
Steroid therapy and antiviral treatment in SARSCoV-2 pneumonia: clinical contexts and indications
Torres A, Cilloniz C |
2022 | |
Home as the new frontier for the treatment of COVID-19: the case for anti-inflammatory agents
Perico N, Cortinovis M, Suter F, Remuzzi G |
The Lancet Infectious Diseases | 2022 |
A narrative review of COVID-19-related acute respiratory distress syndrome (CARDS): "typical" or "atypical" ARDS?
Pu D, Zhai X, Zhou Y, Xie Y, Tang L, Yin L, Liu H, Li L |
Annals of translational medicine | 2022 |
Coronavirus 2019 disease: Are corticosteroids the key treatment? A retrospective case-control study in Brazil
Rios SS, Chen AC, Chen JR, de Resende CN, Araujo Júnior E |
Annals of Medicine and Surgery | 2022 |
Respiratory viruses: their importance and lessons learned from COVID-19.
Cilloniz C, Luna CM, Hurtado JC, Marcos MÁ, Torres A |
European respiratory review : an official journal of the European Respiratory Society | 2022 |
Efficacy and safety profile of corticosteroids and non-steroidal anti-inflammatory drugs in COVID-19 management: A narrative review
Amponsah SK, Tagoe B, Adams I, Bugyei KA |
Frontiers in pharmacology | 2022 |
Challenges of using external data in clinical trials- an illustration in patients with COVID-19
Chevret S, Timsit JF, Biard L |
BMC medical research methodology | 2022 |
Strategies Tackling Viral Replication and Inflammatory Pathways as Early Pharmacological Treatment for SARS-CoV-2 Infection: Any Potential Role for Ketoprofen Lysine Salt?
Mariniello DF, Allocca V, D\u2019Agnano V, Villaro R, Lanata L, Bagnasco M, Aronne L, Bianco A, Perrotta F |
Molecules (Basel, Switzerland) | 2022 |
Raloxifene as a treatment option for viral infections
S Hong, JO Chang, K Jeong, W Lee |
The Journal of Microbiology | 2021 |
Pharmacologic Treatments for Acute Respiratory Distress Syndrome
N Qadir, SY Chang |
Critical Care Clinics | 2021 |
COVID-19-Associated Acute Respiratory Distress Syndrome (CARDS): Mechanistic Insights on Therapeutic Intervention and Emerging Trends
K Thapa, N Verma, TG Singh, AK Grewal, N Kanojia, L Rani |
International Immunopharmacology | 2021 |
Bridging animal and clinical research during SARS-CoV-2 pandemic: A new-old challenge
MS Winkler, T Skirecki, FM Brunkhorst, S Cajander, JM Cavaillon, R Ferrer, SB Flohé, A García-Salido, EJ Giamarellos-Bourboulis, M Girardis, M Kox, G Lachmann, I Martin-Loeches, MG Netea, T Spinetti, JC Schefold, A Torres, F Uhle, F Venet, S Weis, A Scherag, I Rubio, MF Osuchowski |
EBioMedicine | 2021 |
COVID-19, corticosteroids and public health: a reappraisal
M Fernandes, J Brábek |
Public Health | 2021 |
Dexamethasone in hospitalised coronavirus-19 patients not on intensive respiratory support
K Crothers, R DeFaccio, J Tate, P Alba, M Goetz, B Jones, J King, V Marconi, M Ohl, C Rentsch, M Rodriguez-Barradas, S Shahrir, A Justice, K Akgün |
The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology | 2021 |
Factores relacionados con la neumonía bacteriana en pacientes con COVID-19 en una unidad de cuidados intensivos de Barranquilla, Colombia
Algarín-Lara H, Guevara-Romero E, Osorio-Rodríguez E, Patiño-Patiño J, Flórez García V, Tuesca RD, Aldana-Roa M, Arciniegas-Vergel YS, Rodado-Villa R |
Acta Colombiana de Cuidado Intensivo | 2021 |
Corticosteroids treatment in severe patients with COVID-19: a propensity score matching study
Chen Q, Song Y, Wang L, Zhang Y, Han L, Liu J, Yang M, Ma J, Wang T |
Expert Review of Respiratory Medicine | 2021 |
Therapeutic implications of ongoing alveolar viral replication in COVID-19.
McGonagle D, Kearney MF, O'Regan A, O'Donnell JS, Quartuccio L, Watad A, Bridgewood C |
2021 | |
Prognosis of patients hospitalized with a diagnosis of COVID-19 pneumonia in a tertiary hospital in Turkey.
Birtay T, Bahadir S, Kabacaoglu E, Yetiz O, Demirci MF, Genctoy G |
Annals of Saudi medicine | 2021 |
Organ-specific genome diversity of replication-competent SARS-CoV-2
Van Cleemput J, van Snippenberg W, Lambrechts L, Dendooven A, D\u2019Onofrio V, Couck L, Trypsteen W, Vanrusselt J, Theuns S, Vereecke N, van den Bosch TP, Lammens M, Driessen A, Achten R, Bracke KR, Van den Broeck W, Von der Thüsen J, Nauwynck H, Van Dorpe J, Gerlo S, Maes P, Cox J, Vandekerckhove L |
Nature Communications | 2021 |
ADAM17/MMP inhibition prevents neutrophilia and lung injury in a mouse model of COVID‐19
Lartey NL, Valle\u2010Reyes S, Vargas\u2010Robles H, Jiménez\u2010Camacho KE, Guerrero\u2010Fonseca IM, Castellanos\u2010Martínez R, Montoya\u2010García A, García\u2010Cordero J, Cedillo\u2010Barrón L, Nava P, Filisola\u2010Villaseñor JG, Roa\u2010Velázquez D, Zavala\u2010Vargas DI, Morales\u2010Ríos E, Salinas\u2010Lara C, Vadillo E, Schnoor M |
Journal of leukocyte biology | 2021 |
Dexamethasone in hospitalised patients with COVID-19: addressing uncertainties
Matthay MA, Thompson BT |
The lancet. Respiratory medicine | 2020 |
Phenotypes and personalized medicine in the acute respiratory distress syndrome.
Matthay MA, Arabi YM, Siegel ER, Ware LB, Bos LDJ, Sinha P, Beitler JR, Wick KD, Curley MAQ, Constantin JM, Levitt JE, Calfee CS |
Intensive Care Medicine | 2020 |
Journal Club—Severe Acute Respiratory Syndrome Coronavirus-2: Impact on COPD Patients
Balkissoon R |
Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation | 2020 |
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd |
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 2009 |