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Review

Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm

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Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia
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Specialty Paediatric Medicine, Qatif Central Hospital, Qatif 32654, Saudi Arabia
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Department of Microbiology, The University of Haripur, Khyber Pakhtunkhwa 22620, Pakistan
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Department of Public Health/Nutrition, The University of Haripur, Khyber Pakhtunkhwa 22620, Pakistan
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Medical Director of Informatics and Outcomes, St Joseph Mercy Oakland, Pontiac, MI 48341, USA
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Department of Medicine Keystone Health, Penn State University School of Medicine, Hershey, PA 16801, USA
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Department of Medicine, Wellspan Chambersburg and Waynesboro (Pa.) Hospitals, Chambersburg, PA 16801, USA
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Research Center, Almoosa Specialist Hospital, Alahsa 36342, Saudi Arabia
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College of Nursing, Prince Nora University, Riyadh 11564, Saudi Arabia
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School of Nursing, Wollongong University, Wollongong, NSW 2522, Australia
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Administration of Pharmaceutical Care, Ministry of Health, Alahsa 31982, Saudi Arabia
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College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
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Dr. Sulaiman Al-Habib Medical Group, Critical Care and Infection Control Department, Research Centre, Riyadh 11372, Saudi Arabia
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Department of Microbiology, Punjab Agricultural University, Ludhiana 141027, Punjab, India
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The Trafford Group of Colleges, Manchester WA14 5PQ, UK
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Department of Veterinary Microbiology and Immunology, College of Veterinary Sciences, Uttar Pradesh; Pandit DeenDayal Upadhyaya PashuChikitsa Vigyan Vishwavidyalaya Evam Go AnusandhaSansthan (DUVASU), Mathura 281001, Uttar Pradesh, India
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Division of Surgery, ICAR-Indian Veterinary Research Institute, Mathura 281001, Uttar Pradesh, India
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Department of Chemistry, Government College of Engineering, Keonjhar 758002, Odisha, India
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Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh
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School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian 223003, China
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Department of Mathematics and Statistics, Imam Mohammad Ibn Saud Islamic University, Riyadh 11432, Saudi Arabia
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Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh
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WHO Collaborating Centre on eHealth, UNSW Digital Health, School of Public Health and Community Medicine, Faculty of Medicine, UNSW Sydney, NSW 2052, Australia
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Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India
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Authors to whom correspondence should be addressed.
Academic Editor: Hatem A. Elshabrawy
Vaccines 2021, 9(5), 436; https://doi.org/10.3390/vaccines9050436
Received: 14 March 2021 / Revised: 16 April 2021 / Accepted: 18 April 2021 / Published: 29 April 2021
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. View Full-Text
Keywords: COVID-19; inflammatory cytokines; cytokine storm; immunopathology; genomics; immunomodulatory drugs COVID-19; inflammatory cytokines; cytokine storm; immunopathology; genomics; immunomodulatory drugs
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MDPI and ACS Style

Rabaan, A.A.; Al-Ahmed, S.H.; Muhammad, J.; Khan, A.; Sule, A.A.; Tirupathi, R.; Mutair, A.A.; Alhumaid, S.; Al-Omari, A.; Dhawan, M.; Tiwari, R.; Sharun, K.; Mohapatra, R.K.; Mitra, S.; Bilal, M.; Alyami, S.A.; Emran, T.B.; Moni, M.A.; Dhama, K. Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm. Vaccines 2021, 9, 436. https://doi.org/10.3390/vaccines9050436

AMA Style

Rabaan AA, Al-Ahmed SH, Muhammad J, Khan A, Sule AA, Tirupathi R, Mutair AA, Alhumaid S, Al-Omari A, Dhawan M, Tiwari R, Sharun K, Mohapatra RK, Mitra S, Bilal M, Alyami SA, Emran TB, Moni MA, Dhama K. Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm. Vaccines. 2021; 9(5):436. https://doi.org/10.3390/vaccines9050436

Chicago/Turabian Style

Rabaan, Ali A., Shamsah H. Al-Ahmed, Javed Muhammad, Amjad Khan, Anupam A. Sule, Raghavendra Tirupathi, Abbas A. Mutair, Saad Alhumaid, Awad Al-Omari, Manish Dhawan, Ruchi Tiwari, Khan Sharun, Ranjan K. Mohapatra, Saikat Mitra, Muhammad Bilal, Salem A. Alyami, Talha B. Emran, Mohammad A. Moni, and Kuldeep Dhama. 2021. "Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm" Vaccines 9, no. 5: 436. https://doi.org/10.3390/vaccines9050436

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