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Review on therapeutic targets for COVID-19: insights from cytokine storm
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  1. Mário Luciano de Mélo Silva Júnior1,2,
  2. Lívia Maria Alves de Souza1,
  3. Renata Ellen Maria Carvalho Dutra1,
  4. Ramon Gonçalves de Melo Valente1,
  5. Thayanara Silva Melo3
  1. 1 Medical School, Centro Universitário Maurício De Nassau, Recife, Brazil
  2. 2 Neurology Unit, Hospital da Restauração, Recife, Brazil
  3. 3 Dentistry post-graduation program, Universidade Federal De Pernambuco, Recife, Brazil
  1. Correspondence to Mário Luciano Mélo Silva Junior, 316 Jonathas De Vasconcelos Street, Boa Viagem, Recife, Pernambuco 51021-140, Brazil; mariomelosjr{at}gmail.com

Abstract

Introduction Severe 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’.

Objectives We 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.

Methods A narrative review of the literature was conducted using PubMed, SciELO, Bireme, Google Scholar and ClinicalTrials.

Results SARS-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).

Conclusions Understanding 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.

  • Virology
  • Tropical medicine
  • Pharmacology
  • General medicine (see Internal Medicine)
  • Basic sciences
  • Immunology
https://bmj.com/coronavirus/usage

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Footnotes

  • Contributors MLMSJ concepted and designed the study and reviewed critically this paper for intelectual content. LMAS and REMCD reviewed the literature, acquired data and wrote the first draft. RGMV designed figure 1 and helped in literature review. TSM reviewed critically this paper for intellectual content.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication It does not apply because it is a review.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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