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Adekunle Babajide Rowaiye,1 Okiemute Ajiroghene Okpalefe,2 Olukemi Onuh Adejoke,3 Joyce Oloaigbe Ogidigo,4 Oluwakemi Hannah Oladipo,5 Amoge Chidinma Ogu,3 Angus Nnamdi Oli,1 Samson Olofinase,2 Onyekachi Onyekwere,6 Abdullahi Rabiu Abubakar,7 Dilshad Jahan,8 Salequl Islam,9 Siddhartha Dutta,10 Mainul Haque11 1Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka, Anambra State, Nigeria; 2Department of Genetics, Genomics, Bioinformatics, National Biotechnology Development Agency, Abuja, Nigeria; 3Department of Medical Biotechnology, National Biotechnology Development Agency, Abuja, Nigeria; 4Bioresources Development Centre, Abuja, National Biotechnology Development Agency, Abuja, Nigeria; 5Bioresources Development Centre, Ilorin, National Biotechnology Development Agency, Kwara State, Nigeria; 6Bioresources Development Centre, Ubulu-Uku, National Biotechnology Development Agency, Delta State, Nigeria; 7Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Bayero University, Kano, 700233, Nigeria; 8Department of Hematology, Asgar Ali Hospital, Gandaria, Dhaka, 1204, Bangladesh; 9Department of Microbiology, Jahangirnagar University, Savar, Dhaka, 1342, Bangladesh; 10Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India; 11Unit of Pharmacology, Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kem Perdana Sungai Besi, Kuala Lumpur, 57000, MalaysiaCorrespondence: Mainul HaqueUnit of Pharmacology, Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kem Perdana Sungai Besi, Kuala Lumpur, 57000, MalaysiaTel +60109265543Email runurono@gmail.comAbstract: The COVID-19 pandemic constitutes an arduous global health challenge, and the increasing number of fatalities calls for the speedy pursuit of a remedy. This review emphasizes the changing aspects of the COVID-19 disease, featuring the cytokine storm’s pathological processes. Furthermore, we briefly reviewed potential therapeutic agents that may modulate and alleviate cytokine storms. The literature exploration was made using PubMed, Embase, MEDLINE, Google scholar, and China National Knowledge Infrastructure databases to retrieve the most recent literature on the etiology, diagnostic markers, and the possible prophylactic and therapeutic options for the management of cytokine storm in patients hospitalized with COVID-19 disease. The causative agent, severe acute respiratory coronavirus-2 (SARS-CoV-2), continually threatens the efficiency of the immune system of the infected individuals. As the first responder, the innate immune system provides primary protection against COVID-19, affecting the disease’s progression, clinical outcome, and prognosis. Evidence suggests that the fatalities associated with COVID-19 are primarily due to hyper-inflammation and an aberrant immune function. Accordingly, the magnitude of the release of pro-inflammatory cytokines such as interleukin (IL)-1, (IL-6), and tumor necrosis alpha (TNF-α) significantly differentiate between mild and severe cases of COVID-19. The early prediction of a cytokine storm is made possible by several serum chemistry and hematological markers. The prompt use of these markers for diagnosis and the aggressive prevention and management of a cytokine release syndrome is critical in determining the level of morbidity and fatality associated with COVID-19. The prophylaxis and the rapid treatment of cytokine storm by clinicians will significantly enhance the fight against the dreaded COVID-19 disease.Keywords: COVID-19, SARS-CoV-2, cytokine storm, hyper-inflammation, fatality