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Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a severe pandemic of the current century. The vicious tentacles of the disease have been disseminated worldwide with unknown complications and repercussions. Advanced COVID-19 syndrome is...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145892/ https://www.ncbi.nlm.nih.gov/pubmed/33946736 http://dx.doi.org/10.3390/vaccines9050436 |
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author | Rabaan, Ali A. Al-Ahmed, Shamsah H. Muhammad, Javed Khan, Amjad Sule, Anupam A Tirupathi, Raghavendra Mutair, Abbas Al Alhumaid, Saad Al-Omari, Awad Dhawan, Manish Tiwari, Ruchi Sharun, Khan Mohapatra, Ranjan K. Mitra, Saikat Bilal, Muhammad Alyami, Salem A. Emran, Talha Bin Moni, Mohammad Ali Dhama, Kuldeep |
author_facet | Rabaan, Ali A. Al-Ahmed, Shamsah H. Muhammad, Javed Khan, Amjad Sule, Anupam A Tirupathi, Raghavendra Mutair, Abbas Al Alhumaid, Saad Al-Omari, Awad Dhawan, Manish Tiwari, Ruchi Sharun, Khan Mohapatra, Ranjan K. Mitra, Saikat Bilal, Muhammad Alyami, Salem A. Emran, Talha Bin Moni, Mohammad Ali Dhama, Kuldeep |
author_sort | Rabaan, Ali A. |
collection | PubMed |
description | Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a severe pandemic of the current century. The vicious tentacles of the disease have been disseminated worldwide with unknown complications and repercussions. Advanced COVID-19 syndrome is characterized by the uncontrolled and elevated release of pro-inflammatory cytokines and suppressed immunity, leading to the cytokine storm. The uncontrolled and dysregulated secretion of inflammatory and pro-inflammatory cytokines is positively associated with the severity of the viral infection and mortality rate. The secretion of various pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6 leads to a hyperinflammatory response by recruiting macrophages, T and B cells in the lung alveolar cells. Moreover, it has been hypothesized that immune cells such as macrophages recruit inflammatory monocytes in the alveolar cells and allow the production of large amounts of cytokines in the alveoli, leading to a hyperinflammatory response in severely ill patients with COVID-19. This cascade of events may lead to multiple organ failure, acute respiratory distress, or pneumonia. Although the disease has a higher survival rate than other chronic diseases, the incidence of complications in the geriatric population are considerably high, with more systemic complications. This review sheds light on the pivotal roles played by various inflammatory markers in COVID-19-related complications. Different molecular pathways, such as the activation of JAK and JAK/STAT signaling are crucial in the progression of cytokine storm; hence, various mechanisms, immunological pathways, and functions of cytokines and other inflammatory markers have been discussed. A thorough understanding of cytokines’ molecular pathways and their activation procedures will add more insight into understanding immunopathology and designing appropriate drugs, therapies, and control measures to counter COVID-19. Recently, anti-inflammatory drugs and several antiviral drugs have been reported as effective therapeutic drug candidates to control hypercytokinemia or cytokine storm. Hence, the present review also discussed prospective anti-inflammatory and relevant immunomodulatory drugs currently in various trial phases and their possible implications. |
format | Online Article Text |
id | pubmed-8145892 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81458922021-05-26 Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm Rabaan, Ali A. Al-Ahmed, Shamsah H. Muhammad, Javed Khan, Amjad Sule, Anupam A Tirupathi, Raghavendra Mutair, Abbas Al Alhumaid, Saad Al-Omari, Awad Dhawan, Manish Tiwari, Ruchi Sharun, Khan Mohapatra, Ranjan K. Mitra, Saikat Bilal, Muhammad Alyami, Salem A. Emran, Talha Bin Moni, Mohammad Ali Dhama, Kuldeep Vaccines (Basel) Review Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a severe pandemic of the current century. The vicious tentacles of the disease have been disseminated worldwide with unknown complications and repercussions. Advanced COVID-19 syndrome is characterized by the uncontrolled and elevated release of pro-inflammatory cytokines and suppressed immunity, leading to the cytokine storm. The uncontrolled and dysregulated secretion of inflammatory and pro-inflammatory cytokines is positively associated with the severity of the viral infection and mortality rate. The secretion of various pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6 leads to a hyperinflammatory response by recruiting macrophages, T and B cells in the lung alveolar cells. Moreover, it has been hypothesized that immune cells such as macrophages recruit inflammatory monocytes in the alveolar cells and allow the production of large amounts of cytokines in the alveoli, leading to a hyperinflammatory response in severely ill patients with COVID-19. This cascade of events may lead to multiple organ failure, acute respiratory distress, or pneumonia. Although the disease has a higher survival rate than other chronic diseases, the incidence of complications in the geriatric population are considerably high, with more systemic complications. This review sheds light on the pivotal roles played by various inflammatory markers in COVID-19-related complications. Different molecular pathways, such as the activation of JAK and JAK/STAT signaling are crucial in the progression of cytokine storm; hence, various mechanisms, immunological pathways, and functions of cytokines and other inflammatory markers have been discussed. A thorough understanding of cytokines’ molecular pathways and their activation procedures will add more insight into understanding immunopathology and designing appropriate drugs, therapies, and control measures to counter COVID-19. Recently, anti-inflammatory drugs and several antiviral drugs have been reported as effective therapeutic drug candidates to control hypercytokinemia or cytokine storm. Hence, the present review also discussed prospective anti-inflammatory and relevant immunomodulatory drugs currently in various trial phases and their possible implications. MDPI 2021-04-29 /pmc/articles/PMC8145892/ /pubmed/33946736 http://dx.doi.org/10.3390/vaccines9050436 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Rabaan, Ali A. Al-Ahmed, Shamsah H. Muhammad, Javed Khan, Amjad Sule, Anupam A Tirupathi, Raghavendra Mutair, Abbas Al Alhumaid, Saad Al-Omari, Awad Dhawan, Manish Tiwari, Ruchi Sharun, Khan Mohapatra, Ranjan K. Mitra, Saikat Bilal, Muhammad Alyami, Salem A. Emran, Talha Bin Moni, Mohammad Ali Dhama, Kuldeep Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm |
title | Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm |
title_full | Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm |
title_fullStr | Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm |
title_full_unstemmed | Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm |
title_short | Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm |
title_sort | role of inflammatory cytokines in covid-19 patients: a review on molecular mechanisms, immune functions, immunopathology and immunomodulatory drugs to counter cytokine storm |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145892/ https://www.ncbi.nlm.nih.gov/pubmed/33946736 http://dx.doi.org/10.3390/vaccines9050436 |
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