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Review

Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

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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 Community Medicine and Health Care for Pilgrims, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia
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Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
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Clinical Pharmacy Services Division, Pharmacy Services Department, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia
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Department 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, Al-Ahsa Health Cluster, Ministry of Health, Alahsa 31982, Saudi Arabia
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Department of Pathology, Faculty of Medicine, Al-Azhar University, Cairo 11884, Egypt
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Prince Mishari Bin Saud Hospital in Baljurashi, Ministry of Health, Baljurash 22888, Saudi Arabia
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Department of Microbiology, Punjab Agricultural University, Ludhiana 141004, 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 Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go Anusandha Sansthan (DUVASU), Mathura 281001, India
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Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, India
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Department of Chemistry, Government College of Engineering, Keonjhar 758002, India
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Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh
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Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh
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School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian 223003, China
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Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, India
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Department of Mathematics and Statistics, Imam Mohammad Ibn Saud Islamic University, Riyadh 11432, Saudi Arabia
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WHO Collaborating Centre on eHealth, UNSW Digital Health, School of Public Health and Community Medicine, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2052, Australia
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Authors to whom correspondence should be addressed.
Academic Editor: Theresa Chang
Pathogens 2021, 10(5), 565; https://doi.org/10.3390/pathogens10050565
Received: 29 March 2021 / Revised: 2 May 2021 / Accepted: 5 May 2021 / Published: 7 May 2021
(This article belongs to the Collection SARS-CoV Infections)
The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment methods are out on the market, a specific cure for the disease has not been discovered. Recent investigations and research studies primarily focus on the immunopathology of the disease. A healthy immune system responds immediately after viral entry, causing immediate viral annihilation and recovery. However, an impaired immune system causes extensive systemic damage due to an unregulated immune response characterized by the hypersecretion of chemokines and cytokines. The elevated levels of cytokine or hypercytokinemia leads to acute respiratory distress syndrome (ARDS) along with multiple organ damage. Moreover, the immune response against SARS-CoV-2 has been linked with race, gender, and age; hence, this viral infection’s outcome differs among the patients. Many therapeutic strategies focusing on immunomodulation have been tested out to assuage the cytokine storm in patients with severe COVID-19. A thorough understanding of the diverse signaling pathways triggered by the SARS-CoV-2 virus is essential before contemplating relief measures. This present review explains the interrelationships of hyperinflammatory response or cytokine storm with organ damage and the disease severity. Furthermore, we have thrown light on the diverse mechanisms and risk factors that influence pathogenesis and the molecular pathways that lead to severe SARS-CoV-2 infection and multiple organ damage. Recognition of altered pathways of a dysregulated immune system can be a loophole to identify potential target markers. Identifying biomarkers in the dysregulated pathway can aid in better clinical management for patients with severe COVID-19 disease. A special focus has also been given to potent inhibitors of proinflammatory cytokines, immunomodulatory and immunotherapeutic options to ameliorate cytokine storm and inflammatory responses in patients affected with COVID-19. View Full-Text
Keywords: COVID-19; SARS-CoV-2; cytokine storm; disease management; dysregulation of immune system; immunotherapy COVID-19; SARS-CoV-2; cytokine storm; disease management; dysregulation of immune system; immunotherapy
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MDPI and ACS Style

Rabaan, A.A.; Al-Ahmed, S.H.; Garout, M.A.; Al-Qaaneh, A.M.; Sule, A.A.; Tirupathi, R.; Mutair, A.A.; Alhumaid, S.; Hasan, A.; Dhawan, M.; Tiwari, R.; Sharun, K.; Mohapatra, R.K.; Mitra, S.; Emran, T.B.; Bilal, M.; Singh, R.; Alyami, S.A.; Moni, M.A.; Dhama, K. Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses. Pathogens 2021, 10, 565. https://doi.org/10.3390/pathogens10050565

AMA Style

Rabaan AA, Al-Ahmed SH, Garout MA, Al-Qaaneh AM, Sule AA, Tirupathi R, Mutair AA, Alhumaid S, Hasan A, Dhawan M, Tiwari R, Sharun K, Mohapatra RK, Mitra S, Emran TB, Bilal M, Singh R, Alyami SA, Moni MA, Dhama K. Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses. Pathogens. 2021; 10(5):565. https://doi.org/10.3390/pathogens10050565

Chicago/Turabian Style

Rabaan, Ali A., Shamsah H. Al-Ahmed, Mohammed A. Garout, Ayman M. Al-Qaaneh, Anupam A. Sule, Raghavendra Tirupathi, Abbas A. Mutair, Saad Alhumaid, Abdulkarim Hasan, Manish Dhawan, Ruchi Tiwari, Khan Sharun, Ranjan K. Mohapatra, Saikat Mitra, Talha B. Emran, Muhammad Bilal, Rajendra Singh, Salem A. Alyami, Mohammad A. Moni, and Kuldeep Dhama. 2021. "Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses" Pathogens 10, no. 5: 565. https://doi.org/10.3390/pathogens10050565

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