Inflammation, Immunity and Immunogenetics in COVID-19: A Narrative Review

Malavika Lingeswaran, Taru Goyal, Raghumoy Ghosh, Smriti Suri, Prasenjit Mitra, Sanjeev Misra, Praveen Sharma, Malavika Lingeswaran, Taru Goyal, Raghumoy Ghosh, Smriti Suri, Prasenjit Mitra, Sanjeev Misra, Praveen Sharma

Abstract

The novel Coronavirus Disease 2019 (COVID-19), that began in Wuhan Province, China was labelled as an International Public Health Emergency on January 30, 2020 and later was declared a pandemic by the World Health Organisation (WHO) on March 11, 2020. The causative agent, SARS-CoV-2 was the third coronavirus responsible for causing major disease outbreaks in human population after Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) caused by SARS-CoV and MERS-CoV respectively. The patients of COVID-19 present with a clinical feature resembling mild form of viral pneumonia which in certain cases progress to a severe form characterised by adult respiratory distress syndrome (ARDS) and/or multiorgan failure leading to death. The transition from mild to severe form of COVID-19 is affected by a lot of factors like age, co-morbidities etc. In the absence of an absolute cure, it is essential to explore the molecular pathogenesis of the disease to identify people at risk of developing severity so that alternative treatment modalities may be planned. The aim of this review is to provide an update on the general characteristics of SARS-CoV-2 and highlight the inflammatory changes and immune dysregulation that may help in identification of molecular predictors of disease severity.

Keywords: COVID-19; Cytokine storm; Immunity; Immunogenetics; Inflammation.

Conflict of interest statement

Conflict of InterestThe authors declare that they have no conflict of interest.

© Association of Clinical Biochemists of India 2020.

References

    1. COVID-19 situation reports [Internet]. . Accessed 9 May 2020
    1. Coronavirus in India: Latest Map and Case Count [Internet]. . Accessed 9 May 2020
    1. Mitra P, Misra S, Sharma P. COVID-19 Pandemic in India: what lies ahead. Indian J Clin Biochem. 2020;2020:1.
    1. Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal. 2020;10(2):102–108. doi: 10.1016/j.jpha.2020.03.001.
    1. Masters PS. The molecular biology of coronaviruses. In: Advances in virus research [Internet]. Elsevier; 2006, p. 193–292. Accessed 9 May 2020
    1. Knoops K, Kikkert M, Worm SHE van den, Zevenhoven-Dobbe JC, van der Meer Y, Koster AJ, et al SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum. Emerman M, editor. PLoS Biol. 2008; 6(9):e226.
    1. Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270–273. doi: 10.1038/s41586-020-2012-7.
    1. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450–454. doi: 10.1038/nature02145.
    1. Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, Villamizar-Peña R, Holguin-Rivera Y, Escalera-Antezana JP, et al. Clinical, laboratory and imaging features of COVID-19: a systematic review and meta-analysis. Travel Med Infect Dis. 2020;34:101623. doi: 10.1016/j.tmaid.2020.101623.
    1. Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis. 2020;94:91–95. doi: 10.1016/j.ijid.2020.03.017.
    1. Emami A, Javanmardi F, Pirbonyeh N, Akbari A. Prevalence of underlying diseases in hospitalized patients with COVID-19: a systematic review and meta-analysis. Arch Acad Emerg Med. 2020;8(1):e35.
    1. Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130(5):2620–2629. doi: 10.1172/JCI137244.
    1. Xiang J, Wen J, Yuan X, Xiong S, Zhou X, Liu C, et al. Potential biochemical markers to identify severe cases among COVID-19 patients [Internet]. Epidemiology; 2020. Accessed 9 May 2020
    1. Huang L, Shi Y, Gong B, Jiang L, Liu X, Yang J, et al. Blood single cell immune profiling reveals the interferon-MAPK pathway mediated adaptive immune response for COVID-19 [Internet]. Infectious Diseases (except HIV/AIDS); 2020. Accessed 9 May 2020
    1. Chousterman BG, Swirski FK, Weber GF. Cytokine storm and sepsis disease pathogenesis. Semin Immunopathol. 2017;39(5):517–528. doi: 10.1007/s00281-017-0639-8.
    1. Ye Q, Wang B, Mao J. The pathogenesis and treatment of the `Cytokine Storm’ in COVID-19. J Infect [Internet]. 2020 [ Accessed 9 May 2020
    1. Li G, Fan Y, Lai Y, Han T, Li Z, Zhou P, et al. Coronavirus infections and immune responses. J Med Virol. 2020;92(4):424–432. doi: 10.1002/jmv.25685.
    1. Channappanavar R, Fehr AR, Zheng J, Wohlford-Lenane C, Abrahante JE, Mack M, et al. IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes. J Clin Invest. 2019;129(9):3625–3639. doi: 10.1172/JCI126363.
    1. Channappanavar R, Fehr AR, Vijay R, Mack M, Zhao J, Meyerholz DK, et al. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe. 2016;19(2):181–193. doi: 10.1016/j.chom.2016.01.007.
    1. Herold S, Steinmueller M, von Wulffen W, Cakarova L, Pinto R, Pleschka S, et al. Lung epithelial apoptosis in influenza virus pneumonia: the role of macrophage-expressed TNF-related apoptosis-inducing ligand. J Exp Med. 2008;205(13):3065–3077. doi: 10.1084/jem.20080201.
    1. Högner K, Wolff T, Pleschka S, Plog S, Gruber AD, Kalinke U, et al. Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia. PLoS Pathog. 2013;9(2):e1003188. doi: 10.1371/journal.ppat.1003188.
    1. Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol. 2020;38(1):1–9.
    1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China The Lancet. 2020;395(10223):497–506. doi: 10.1016/S0140-6736(20)30183-5.
    1. Velazquez-Salinas L, Verdugo-Rodriguez A, Rodriguez LL, Borca MV. The role of interleukin 6 during viral infections. Front Microbiol. 2019;10(10):1057. doi: 10.3389/fmicb.2019.01057.
    1. Diao B, Wang C, Tan Y, Chen X, Liu Y, Ning L, et al. Reduction and functional exhaustion of t cells in patients with coronavirus disease 2019 (COVID-19) [Internet]. Infectious Diseases (except HIV/AIDS); 2020. Accessed 9 May 2020
    1. Wan S, Yi Q, Fan S, Lv J, Zhang X, Guo L, et al. Relationships among lymphocyte subsets, cytokines, and the pulmonary inflammation index in coronavirus (COVID-19) infected patients. Br J Haematol. 2020;189(3):428–437. doi: 10.1111/bjh.16659.
    1. Liu J, Li S, Liu J, Liang B, Wang X, Wang H, et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients [Internet]. Infectious Diseases (except HIV/AIDS); 2020. Accessed 9 May 2020
    1. Liu T, Zhang J, Yang Y, Ma H, Li Z, Zhang J, et al. The potential role of IL-6 in monitoring severe case of coronavirus disease 2019 [Internet]. Infectious Diseases (except HIV/AIDS); 2020. Accessed 9 May 2020
    1. Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med [Internet]. 2020. Accessed 9 May 2020
    1. Chen X, Zhao B, Qu Y, Chen Y, Xiong J, Feng Y, et al. Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely associated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients [Internet]. Infectious Diseases (except HIV/AIDS); 2020. Accessed 9 May 2020
    1. Liu F, Li L, Xu M, Wu J, Luo D, Zhu Y, et al. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J Clin Virol. 2020;127:104370. doi: 10.1016/j.jcv.2020.104370.
    1. Zhu Z, Cai T, Fan L, Lou K, Hua X, Huang Z, et al. Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019. Int J Infect Dis. 2020;95:332–339. doi: 10.1016/j.ijid.2020.04.041.
    1. Herold T, Jurinovic V, Arnreich C, Hellmuth JC, von Bergwelt-Baildon M, Klein M, et al. Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients [Internet]. Infectious Diseases (except HIV/AIDS); 2020. Accessed 9 May 2020
    1. 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):1054–1062. doi: 10.1016/S0140-6736(20)30566-3.
    1. Zhang B, Zhou X, Qiu Y, Feng F, Feng J, Jia Y, et al. Clinical characteristics of 82 death cases with COVID-19 [Internet]. Infectious Diseases (except HIV/AIDS); 2020. Accessed 9 May 2020
    1. Gupta S, Bi R, Kim C, Chiplunkar S, Yel L, Gollapudi S. Role of NF-κB signaling pathway in increased tumor necrosis factor-α-induced apoptosis of lymphocytes in aged humans. Cell Death Differ. 2005;12(2):177–183. doi: 10.1038/sj.cdd.4401557.
    1. He R, Lu Z, Zhang L, Fan T, Xiong R, Shen X, et al. The clinical course and its correlated immune status in COVID-19 pneumonia. J Clin Virol. 2020;127:104361. doi: 10.1016/j.jcv.2020.104361.
    1. Ouyang Y, Yin J, Wang W, Shi H, Shi Y, Xu B, et al. Down-regulated gene expression spectrum and immune responses changed during the disease progression in COVID-19 patients. Clin Infect Dis. 2020;ciaa462.
    1. Li Y, Hu Y, Yu J, Ma T. Retrospective analysis of laboratory testing in 54 patients with severe- or critical-type 2019 novel coronavirus pneumonia. Lab Invest [Internet]. 2020. Accessed 9 May 2020
    1. Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 2012;76(1):16–32. doi: 10.1128/MMBR.05015-11.
    1. Ong EZ, Chan YFZ, Leong WY, Lee NMY, Kalimuddin S, Haja Mohideen SM, et al. A Dynamic Immune Response Shapes COVID-19 Progression. Cell Host Microbe. 2020 Apr;S1931312820301852.
    1. Wu D, Yang XO. TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib. J Microbiol Immunol Infect [Internet]. 2020. Accessed 31 Mar 2020
    1. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39(5):529–539. doi: 10.1007/s00281-017-0629-x.
    1. Mahallawi WH, Khabour OF, Zhang Q, Makhdoum HM, Suliman BA. MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile. Cytokine. 2018;104:8–13. doi: 10.1016/j.cyto.2018.01.025.
    1. Wong CK, Lam CWK, Wu AKL, Ip WK, Lee NLS, Chan IHS, et al. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol. 2004;136(1):95–103. doi: 10.1111/j.1365-2249.2004.02415.x.
    1. Chien J-Y, Hsueh P-R, Cheng W-C, Yu C-J, Yang P-C. Temporal changes in cytokine/chemokine profiles and pulmonary involvement in severe acute respiratory syndrome. Respirology. 2006;11(6):715–722. doi: 10.1111/j.1440-1843.2006.00942.x.
    1. Wei L, Ming S, Zou B, Wu Y, Hong Z, Li Z, et al. Viral Invasion and Type I Interferon Response Characterize the Immunophenotypes during COVID-19 Infection. SSRN Electron J [Internet]. 2020. Accessed 9 May 2020
    1. Hindson J. COVID-19: faecal–oral transmission? Nat Rev Gastroenterol Hepatol. 2020;17(5):259–259. doi: 10.1038/s41575-020-0295-7.
    1. Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol [Internet]. 2020. Accessed 7 May 2020
    1. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271–280.e8. doi: 10.1016/j.cell.2020.02.052.
    1. Zhou Y, Fu B, Zheng X, Wang D, Zhao C, qi Y, et al. Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients. Natl Sci Rev [Internet]. 2020. Accessed 7 May 2020
    1. Liao M, Liu Y, Yuan J, Wen Y, Xu G, Zhao J, et al. The landscape of lung bronchoalveolar immune cells in COVID-19 revealed by single-cell RNA sequencing [Internet]. Allergy and Immunology; 2020 Accessed 7 May 2020
    1. Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A, Antonakos N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe. 2020;S1931312820302365.
    1. Hadjadj J, Yatim N, Barnabei L, Corneau A, Boussier J, Pere H, et al. Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients [Internet]. Infectious Diseases (except HIV/AIDS); 2020. Accessed 7 May 2020
    1. Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis [Internet]. 2020 Accessed 28 Mar 2020
    1. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–513. doi: 10.1016/S0140-6736(20)30211-7.
    1. Zhang J, Dong X, Cao Y, Yuan Y, Yang Y, Yan Y, et al. Clinical characteristics of 140 patients infected with SARS‐CoV‐2 in Wuhan, China. Allergy. 2020;all.14238.
    1. Wang Z, Yang B, Li Q, Wen L, Zhang R. Clinical Features of 69 Cases With Coronavirus Disease 2019 in Wuhan, China. Clin Infect Dis. 2020 Mar 16;ciaa272.
    1. Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020;ciaa248.
    1. Zhou Y, Zhang Z, Tian J, Xiong S. Risk factors associated with disease progression in a cohort of patients infected with the 2019 novel coronavirus. Ann Palliat Med. 2020;9(2):428–436. doi: 10.21037/apm.2020.03.26.
    1. Wang F, Nie J, Wang H, Zhao Q, Xiong Y, Deng L, et al. Characteristics of peripheral lymphocyte subset alteration in COVID-19 Pneumonia. J Infect Dis. 2020;jiaa150.
    1. Liu Y, Yan L-M, Wan L, Xiang T-X, Le A, Liu J-M, et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis [Internet]. 2020. Accessed 28 Mar 2020
    1. Zheng H-Y, Zhang M, Yang C-X, Zhang N, Wang X-C, Yang X-P, et al. Elevated exhaustion levels and reduced functional diversity of T cells in peripheral blood may predict severe progression in COVID-19 patients. Cell Mol Immunol [Internet]. 2020. Accessed 28 Mar 2020
    1. Wang F, Hou H, Luo Y, Tang G, Wu S, Huang M, et al. The laboratory tests and host immunity of COVID-19 patients with different severity of illness. JCI Insight [Internet]. 2020. Accessed 9 May 2020
    1. Sun D, Li H, Lu X-X, Xiao H, Ren J, Zhang F-R, et al. Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center’s observational study. World J Pediatr [Internet]. 2020. Accessed 9 May 2020
    1. Thevarajan I, Nguyen THO, Koutsakos M, Druce J, Caly L, van de Sandt CE, et al. Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med [Internet]. 2020. Accessed 31 Mar 2020
    1. Yang X, Dai T, Zhou X, Qian H, Guo R, Lei L, et al. Analysis of adaptive immune cell populations and phenotypes in the patients infected by SARS-CoV-2 [Internet]. Infectious Diseases (except HIV/AIDS); 2020. Accessed 31 Mar 2020
    1. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med [Internet]. 2020. Accessed 31 Mar 2020
    1. Baric R. Systems immunogenetics of emerging coronavirus infections in the collaborative cross. Accessed 9 May 2020
    1. Mcweeney S. Systems immunogenetics and bioinformatics. Accessed 9 May 2020
    1. Baric R, Heise M. Systems immunogenetics of biodefense and emerging pathogens in the collaborative cross. Accessed 9 May 2020
    1. Saghazadeh A, Rezaei N. Introductory Chapter. Immunogenetics [Internet]. 2019 Accessed 9 May 2020
    1. Nguyen A, David JK, Maden SK, Wood MA, Weeder BR, Nellore A, et al. Human leukocyte antigen susceptibility map for SARS-CoV-2. J Virol. 2020 Apr 17; JVI.00510-20, jvi;JVI.00510-20v1.
    1. MacDonald KS, Fowke KR, Kimani J, Dunand VA, Nagelkerke NJD, Ball TB, et al. Influence of HLA supertypes on susceptibility and resistance to human immunodeficiency virus type 1 infection. J Infect Dis. 2000;181(5):1581–1589. doi: 10.1086/315472.
    1. Stephens HAF, Klaythong R, Sirikong M, Vaughn DW, Green S, Kalayanarooj S, et al. HLA-A and -B allele associations with secondary dengue virus infections correlate with disease severity and the infecting viral serotype in ethnic Thais. Tissue Antigens. 2002;60(4):309–318. doi: 10.1034/j.1399-0039.2002.600405.x.
    1. Gerlach H. Agents to reduce cytokine storm. F1000Research. 2016;5:2909. doi: 10.12688/f1000research.9092.1.
    1. Zumla A, Hui DS, Azhar EI, Memish ZA, Maeurer M. Reducing mortality from 2019-nCoV: host-directed therapies should be an option. Lancet. 2020;395(10224):e35–e36. doi: 10.1016/S0140-6736(20)30305-6.

Source: PubMed

3
订阅