A systematic review of immune pathogenesis of SARS-COV-2 infection

Shabarini Srikumar, Shridharan Perumal


The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a pandemic by the world health organization on March 11, 2020. The host immune response to SARS-CoV-2 appears to play a critical role in disease pathogenesis and clinical manifestations. SARS-CoV-2 causes direct activation of anti-viral immune responses and leads to the release of uncontrolled inflammatory mediators. These SARS-CoV-2-induced immune responses may lead to various other abnormalities like lymphopenia, thrombocytopenia and granulocyte and monocyte dysfunction, making the patient more prone to secondary infections by microorganisms, which may result in further further serious complications like septic shock, severe multiple organ dysfunction and eventually death. Therefore, mechanisms underlying immune abnormalities in patients with COVID-19 disease must be elucidated to guide clinical management of the disease. Rational management in combating the disease includes enhancing anti-viral immunity and inhibiting systemic inflammation, which is key to successful treatment.


SARS-CoV-2, Immune response, Pathogenesis

Full Text:



Vabret N, Britton GJ, Gruber C, Hegde S, Kim J, Kuksin M, et al. Immunology of COVID-19: Current State of the Science. Immunity. 2020;52(6):910-41.

Cohen PA, Hall LE, John JN, Rapoport AB. The early natural history of SARS-CoV-2 infection: clinical observations from an urban, ambulatory COVID-19 clinic. Mayo Clin Proc. 2020;95(6):1124-6.

Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and prevention. JAMA. 2020;323(13):1239-42.

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229): 1054-62.

Cummings MJ, Baldwin MR, Abrams D, Jacobson SD, Meyer BJ, Balough EM, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020;395(10239):1763-70.

Jacob CO. On the genetics and immunopathogenesis of COVID-19. Clin Immunol. 2020;220:108591.

Zumla A, Chan JF, Azhar EI, Hui DS, Yuen KY. Coronaviruses—drug discovery and therapeutic options. Nature Rev Drug Disc. 2016;15(5):327-47.

Organization W. Clinical management of COVID-19: interim guidance, 27 May 2020. Available at: Accessed on 20 March 2021.

van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2020; 382(16):1564-1567.

Bourouiba L. Turbulent gas clouds and respiratory pathogen emissions: potential implications for reducing transmission of COVID-19. JAMA. 2020; 323(18):1837-8.

Barnkob MB, Pottegård A, Støvring H, Haunstrup TM, Homburg K, Larsen R, et al. Reduced prevalence of SARS-CoV-2 infection in ABO blood group O. Blood Adv. 2020;4(20):4990-3.

Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020; 181(2):281-92.

Bhandari S, Singh A, Sharma R, Rankawat G, Banerjee S, Gupta V, et al. Characteristics, treatment outcomes and role of hydroxychloroquine among 522 COVID-19 hospitalized patients in Jaipur City: An Epidemio-Clinical Study. J Assoc Physicians India. 2020:13-9.

Sanche S, Lin YT, Xu C, Romero-Severson E, Hengartner N, Ke R. High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus 2. Emerg Infect Dis. 2020;26(7):1470-7.

Bouhaddou M, Memon D, Meyer B, White KM, Rezelj V. The global phosphorylation landscape of SARS-CoV-2 infection. Cell. 2020;182:685-712.

Blanco-Melo D, Nilsson-Payant BE, Liu WC, Uhl S, Hoagland D, Møller R, et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020;181(5):1036-45.

Channappanavar R, Fehr AR, Zheng J, Wohlford-Lenane C, Abrahante JE. IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes. J Clin Invest. 2019;130:3625-39.

Zhou Z, Len R, Zhang L, Zhong J, Xiao Y. Heightened innate immune responses in the respiratory tract of COVID-19 patients. Cell Host Microbe. 2020;27(6):883-90.

Xiong Y, Liu Y, Cao L, Wang D, Guo M. Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients. Emerg Microbes Infect. 2020;9(1):761-70.

Sharma D, Dayama A, Banerjee S, Bhandhari S, Chatterjee A, Chatterjee D. To study the role of absolute lymphocyte count and RDW in COVID 19 patients and their association with appearance of symptoms and severity. J Assoc Physicians India. 2020;68(8):39-42.

Stephens DS, McElrath MJ. COVID-19 and the path to immunity. JAMA. 2020;324(13):1279-81.

Schulert GS, Zhang M, Fall N, Husami A, Kissell D, Hanosh A, et al. Whole-exome sequencing reveals mutations in genes linked to hemophagocytic lymphohistiocytosis and macrophage activation syndrome in fatal cases of H1N1 influenza. The Journal of infectious diseases. 2016;213(7):1180-8.

Crayne CB, Albeituni S, Nichols KE, Cron RQ. The immunology of macrophage activation syndrome. Front Immunol. 2019;10:119.

Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. New Eng J Med. 2020;383(2):120-8.

Carsana L, Sonzogni A, Nasr A, Rossi RS, Pellegrinelli A, Zerbi P, et al. Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study. Lancet Infect Dis. 2020;20(10):1135-40.

Mangalmurti N, Hunter CA. Cytokine Storms: understanding COVID-19. Immunity 2020;53:19-25.

Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-9.

Divani AA, Andalib S, Di Napoli M, Lattanzi S, Hussain MS, Biller J, et al. Coronavirus disease 2019 and stroke: clinical manifestations and pathophysiological insights. J Stroke Cerebrovasc Dis. 2020;20:104941.

Folco EJ, Mawson TL, Vromman A, Bernardes-Souza B, Franck G. Neutrophil extracellular traps induce endothelial cell activation and tissue factor production through interleukin-1alpha and cathepsin G. Arterioscler Thromb Vasc Biol. 2018;38(8):1910-12.

Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M. Neutrophil extracellular traps in COVID-19. JCI Insight. 2020;5(11):138999.

Yeager CL, Ashmun RA, Williams RK, Cardellichio CB, Shapiro LH, Look AT, Holmes KV. Human aminopeptidase N is a receptor for human coronavirus 229E. Nature. 1992;357(6377):420-2.

XuP, ZhouQ, XuJ. Mechanism of thrombocytopenia in COVID-19 patients. Ann Hematol. 2020;99(6): 1205-8.

Song Y, Liu P, Shi XL, Chu YL, Zhang J, Xia J, et al. SARS-CoV-2 induced diarrhoea as onset symptom in patient with COVID-19. Gut. 2020; 69(6):1143-4.

Chai X, Hu L, Zhang Y, Han W, Lu Z, Ke A, et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection. Biorxiv. 2020.

Zampino R, Mele F, Florio LL, Bertolino L, Andini R, Galdo M, De Rosa R, Corcione A, Durante-Mangoni E. Liver injury in remdesivir-treated COVID-19 patients. Hepatol Int. 2020;14(5):881-3.

Boettler T, Newsome PN, Mondelli MU, Maticic M, Cordero E, Cornberg M, et al. Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper. JHEP. 2020;2(3): 100113.

Driggin E, Madhavan MV, Bikdeli B, Chuich T, Laracy J, Biondi-Zoccai G, et al. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 Pandemic. J Am Coll Cardiol. 2020;75(18):2352-71.

Fan Ye MD, Hatahet M, Youniss MA, Toklu HZ, Mazza JJ, Yale S. The clinical significance of relative bradycardia. Address Dispar Improve Care. 2018;73:45-9.

Jiang K. How COVID-19 Causes loss of smell. Available at: Our%20findings%20indicate%20that%20the,the%20Blavatnik%20Institute%20at%20HMS. Accessed om 20 February 2021.

Chodosh J. COVID-19 background primer for ophthalmologists. Available at: headline/covid-19-background-primer-ophthalmologists. Accessed om 20 February 2021.

Garg D, Srivastava AK, Dhamija RK. Beyond fever, cough and dyspnea: The neurology of COVID-19. J Assoc Physicians India. 2020;68(9):62-6.

Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms. ACS Chem Neurosci. 2020;11:995-98.

Thomas T, Stefanoni D, Reisz JA, Nemkov T, Bertolone L, Francis RO, et al. COVID-19 infection alters kynurenine and fatty acid metabolism, correlating with IL-6 levels and renal status. JCI insight. 2020;5(14):59-65.

Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease. Nature Rev Dis Prim. 2017;3(1):1-21.

Nesbitt H. American society of nephrology. Available from: Accessed om 20 February 2021.

Landa N, Mendieta-Eckert M, Fonda-Pascual P, Aguirre T. Chilblain-like lesions on feet and hands during the COVID-19 pandemic. Int J Dermatol. 2020;59(6):739-43.

Abrams J, Godfred-Cato S, Oster M, Chow E, Koumans E, Bryant B, et al. multisystem inflammatory syndrome in children associated with severe acute respiratory syndrome coronavirus 2: A systematic review. J Pediatr. 2020;226:45-54.

Morris SB, Schwartz NG, Patel P, Abbo L, Beauchamps L, Balan S, et al. Case series of multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection-United Kingdom and United States, March-August 2020. Morbid Mortal Weekly Rep. 2020;69(40):1450.