Corticosteroids in SARS-COV2 infection: certainties and uncertainties in clinical practice

ABSTRACT Introduction The SARS-COV-2 pandemic is a worldwide public health problem due to the large medical burden and limited number of therapies available. Corticosteroids have a rather unclear efficacy in viral non-SARS-COV-2 pneumonias and therefore their use is not universally recommended. In SARS-COV-2 pneumonia however, it is expected that they can reduce the deleterious consequences of the virus-related systemic inflammation. Areas covered a MEDLINE search covering the period 1995–2020 was completed to identify relevant papers. SARS-COV-2 pathogenesis is very complex and is represented by the interplay of many cytokine-driven inflammation pathways. Its most severe form so called cytokine storm, is an exaggerate reaction of the host infected by the virus rapidly resulting in multiple organ dysfunction (MODS). Corticosteroids have the potential to blunt the inflammation response in such patients, but their efficacy is not the same for all patients. Further on the certainties and uncertainties regarding the efficacy of this therapy in SARS-COV-2 pneumonia are discussed Expert Opinion In patients with severe SARS-COV-2 pneumonia, corticosteroids can be efficacious, but it is still not clear if they can be safely used in patients with comorbid cardiovascular disease or how the optimal duration of therapy can be established.

[1]  T. Soumagne,et al.  Impact of late administration of corticosteroids in COVID-19 ARDS , 2020, Intensive Care Medicine.

[2]  M. Young,et al.  Endocrine aspects of ACE2 regulation: RAAS, steroid hormones and SARS-CoV-2. , 2020, The Journal of endocrinology.

[3]  Jeremy R. DeGrado,et al.  Inflammatory Biomarker Trends Predict Respiratory Decline in COVID-19 Patients , 2020, Cell Reports Medicine.

[4]  I. Tleyjeh,et al.  Association of corticosteroids use and outcomes in COVID-19 patients: A systematic review and meta-analysis , 2020, Journal of Infection and Public Health.

[5]  V. Nag,et al.  Pathophysiology and Potential Therapeutic Candidates for COVID-19: A Poorly Understood Arena , 2020, Frontiers in Pharmacology.

[6]  A. Burlacu,et al.  “A Chain Only as Strong as Its Weakest Link”: An Up-to-Date Literature Review on the Bidirectional Interaction of Pulmonary Fibrosis and COVID-19 , 2020, Journal of proteome research.

[7]  Christopher M. Horvat,et al.  Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. , 2020, JAMA.

[8]  W. Xu,et al.  Efficacy Evaluation of Early, Low-Dose, Short-Term Corticosteroids in Adults Hospitalized with Non-Severe COVID-19 Pneumonia: A Retrospective Cohort Study , 2020, Infectious Diseases and Therapy.

[9]  Á. Avezum,et al.  Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial. , 2020, JAMA.

[10]  A. Alam,et al.  Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past , 2020, Frontiers in Immunology.

[11]  O. Bakare,et al.  Understanding the epidemiology, pathophysiology, diagnosis and management of SARS-CoV-2 , 2020, The Journal of international medical research.

[12]  Z. Duan,et al.  Duration of SARS‐CoV‐2 RNA shedding and factors associated with prolonged viral shedding in patients with COVID‐19 , 2020, Journal of medical virology.

[13]  S. Tavangar,et al.  Pathologic features of COVID-19: A concise review , 2020, Pathology - Research and Practice.

[14]  Pratik Sinha,et al.  Is a "Cytokine Storm" Relevant to COVID-19? , 2020, JAMA internal medicine.

[15]  Jennifer L. Bell,et al.  Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report , 2020, medRxiv.

[16]  M. Montico,et al.  Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia , 2020, medRxiv.

[17]  Giuseppe Magro,et al.  COVID-19: Review on latest available drugs and therapies against SARS-CoV-2. Coagulation and inflammation cross-talking , 2020, Virus Research.

[18]  J. Riancho,et al.  GLUCOCOVID: A controlled trial of methylprednisolone in adults hospitalized with COVID-19 pneumonia , 2020, medRxiv.

[19]  B. François,et al.  Severe COVID-19 is associated with deep and sustained multifaceted cellular immunosuppression , 2020, Intensive Care Medicine.

[20]  S. Chevret,et al.  Clinical phenotypes of critically ill COVID-19 patients , 2020, Intensive Care Medicine.

[21]  B. Lipworth,et al.  Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19 , 2020, Journal of Allergy and Clinical Immunology.

[22]  P. van Wijngaarden,et al.  COVID-19–associated Pulmonary Aspergillosis , 2020, American journal of respiratory and critical care medicine.

[23]  G. Kai,et al.  COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons , 2020, Cytokine & Growth Factor Reviews.

[24]  Rachel M. Kenney,et al.  Early Short-Course Corticosteroids in Hospitalized Patients With COVID-19 , 2020, medRxiv.

[25]  P. Kavsak,et al.  Emerging key laboratory tests for patients with COVID-19 , 2020, Clinical Biochemistry.

[26]  C. Hedrich,et al.  COVID-19: Immunology and treatment options , 2020, Clinical Immunology.

[27]  M. Hallek,et al.  COVID‐19 associated pulmonary aspergillosis , 2020, Mycoses.

[28]  D. Halpin,et al.  Inhaled corticosteroids and COVID-19: a systematic review and clinical perspective , 2020, European Respiratory Journal.

[29]  Amber Dance What is a cytokine storm? , 2020 .

[30]  T. West,et al.  Covid-19 in Critically Ill Patients in the Seattle Region — Case Series , 2020, The New England journal of medicine.

[31]  Ling Yin,et al.  COVID-19 treatment: close to a cure? A rapid review of pharmacotherapies for the novel coronavirus (SARS-CoV-2) , 2020, International Journal of Antimicrobial Agents.

[32]  Yuntao Wu,et al.  Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools , 2020, Virologica Sinica.

[33]  P. Zhou,et al.  Analysis of 2019 novel coronavirus infection and clinical characteristics of outpatients: An epidemiological study from a fever clinic in Wuhan, China , 2020, Journal of medical virology.

[34]  M. Zhou,et al.  [Expert consensus on the use of corticosteroid in patients with 2019-nCoV pneumonia]. , 2020, Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases.

[35]  J. González-Martín,et al.  Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. , 2020, The Lancet. Respiratory medicine.

[36]  Yan Zhao,et al.  Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. , 2020, JAMA.

[37]  Y. Hu,et al.  On the use of corticosteroids for 2019-nCoV pneumonia , 2020, The Lancet.

[38]  Ming Yang Cell Pyroptosis, a Potential Pathogenic Mechanism of 2019-nCoV Infection , 2020 .

[39]  B. Wan,et al.  Effect of different doses and time-courses of corticosteroid treatment in patients with acute respiratory distress syndrome: A meta-analysis , 2019, Experimental and therapeutic medicine.

[40]  Rajaa Al-Raddadi,et al.  Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome , 2017, American journal of respiratory and critical care medicine.

[41]  Shigui Yang,et al.  Effect of low‐to‐moderate‐dose corticosteroids on mortality of hospitalized adolescents and adults with influenza A(H1N1)pdm09 viral pneumonia , 2017, Influenza and other respiratory viruses.

[42]  M. Rogers,et al.  Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study , 2017, British Medical Journal.

[43]  Malik Peiris,et al.  Middle East respiratory syndrome , 2015, The Lancet.

[44]  P. Ljungman Respiratory syncytial virus in hematopoietic cell transplant recipients: factors determining progression to lower respiratory tract disease. , 2014, The Journal of infectious diseases.

[45]  A. Osterhaus,et al.  Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. , 2012, The New England journal of medicine.

[46]  J. Rello,et al.  Corticosteroid therapy in patients with primary viral pneumonia due to pandemic (H1N1) 2009 influenza. , 2012, The Journal of infection.

[47]  L. Brochard,et al.  Early corticosteroids in severe influenza A/H1N1 pneumonia and acute respiratory distress syndrome. , 2011, American journal of respiratory and critical care medicine.

[48]  J. Chiche,et al.  Use of early corticosteroid therapy on ICU admission in patients affected by severe pandemic (H1N1)v influenza A infection , 2010, Intensive Care Medicine.

[49]  J. Chan,et al.  Corticosteroid treatment of severe acute respiratory syndrome in Hong Kong , 2006, Journal of Infection.

[50]  V. Wong,et al.  Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients , 2004, Journal of Clinical Virology.

[51]  V. Wong,et al.  Severe acute respiratory syndrome: report of treatment and outcome after a major outbreak , 2004, Thorax.

[52]  K. Kain,et al.  Severe Acute Respiratory Syndrome–associated Coronavirus in Lung Tissue , 2004, Emerging infectious diseases.

[53]  T. Welte,et al.  [SARS--Severe Acute Respiratory syndrome]. , 2003, Pneumologie.

[54]  G. Meduri,et al.  Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial. , 1998, JAMA.

[55]  C. Dolea,et al.  World Health Organization , 1949, International Organization.

[56]  Kaijin Xu,et al.  Factors Associated With Prolonged Viral RNA Shedding in Patients with Coronavirus Disease 2019 (COVID-19) , 2020 .