Review on therapeutic targets for COVID-19: insights from cytokine storm

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been caused the greatest pandemic of our century. Many of the deaths related to it are due to a systemic inflammatory response, which has been called ‘cytokine storm’.ObjectivesWe developed a comprehensive review of the pat...

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Bibliographic Details
Published in:	Postgraduate medical journal Vol. 97; no. 1148; pp. 391 - 398
Main Authors:	Mélo Silva Júnior, Mário Luciano de, Souza, Lívia Maria Alves de, Dutra, Renata Ellen Maria Carvalho, Valente, Ramon Gonçalves de Melo, Melo, Thayanara Silva
Format:	Journal Article
Language:	English
Published:	England Oxford University Press 01-06-2021
Subjects:	Antiviral drugs Coronaviruses COVID-19 COVID-19 - complications COVID-19 - diagnosis COVID-19 - therapy COVID-19 Drug Treatment Cytokine Release Syndrome - diagnosis Cytokine Release Syndrome - therapy Cytokine Release Syndrome - virology Humans Kinases Review SARS-CoV-2 - physiology Tumor necrosis factor-TNF Viruses Tropical medicine Pharmacology Basic sciences Immunology General medicine (see Internal Medicine) Virology
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Summary:	IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been caused the greatest pandemic of our century. Many of the deaths related to it are due to a systemic inflammatory response, which has been called ‘cytokine storm’.ObjectivesWe developed a comprehensive review of the pathophysiology mechanisms of COVID-19 and of the rationale for drugs and therapeutics that have been tested in clinical trials.MethodsA narrative review of the literature was conducted using PubMed, SciELO, Bireme, Google Scholar and ClinicalTrials.ResultsSARS-CoV-2 has evolutive mechanisms that made it spread all around the globe, as a higher latency period and a lesser lethality than other coronaviruses. SARS-CoV-2 causes a delay in the innate immune response and it disarranges the immune system leading to an overwhelming inflammatory reaction (the ‘cytokine storm’). In this scenario, high levels of interleukins (IL), notably IL-6 and IL-1, create a positive feedback of chemokines and immune responses, and powers pulmonary and systemic tissue damage, leading to capillary leakage and SARS, the main cause of death in patients with COVID-19. On 17 July 2020, there were 1450 entries on ClinicalTrials.gov of ongoing studies on COVID-19. The mechanisms of the main therapeutic approaches were comprehensively reviewed throughout the text. Therapies focus on blocking viral entry (remdesivir, umifenovir, among others) and blocking of immune system for cytokine storm control (IL-1 and IL-6 inhibitors, glucocorticoids, convalescent plasma, among others).ConclusionsUnderstanding of action mechanisms of SARS-CoV-2 enables us to direct efforts on effective therapeutic targets. This comprehensive review helps to interpret the clinical results of the several trials ongoing.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1
ISSN:	0032-5473 1469-0756
DOI:	10.1136/postgradmedj-2020-138791