Immunology and Pathophysiology of Covid-19 disease-A Review
Keywords:
COVID-19, Coronavirus, Innate immunity, Adaptive Immunity, Cytokine Storm, BiomarkersAbstract
Novel coronavirus (severe acute respiratory syndrome coronavirus-2 or SARS-CoV-2) is the causative agent of COVID-19. SARS-CoV-2 belongs to the β-coronavirus family and shares extensive genomic identity with bat coronavirus suggesting that bats are the natural host. SARS-CoV-2 uses the same receptor, angiotensin-converting enzyme 2 (ACE2), as that for SARS-CoV, the coronavirus associated with the SARS outbreak in 2003.Other receptors used by SARS-CoV-2 are CD147 and CD26. It mainly spreads through the respiratory tract with lymphopenia and cytokine storms occuring in the blood of subjects with severe disease. In severe cases this viral infection cause damage in the lungs, heart and kidney which ultimately leads to multiorgan failure and finally death. This suggests the existence of immunological dysregulation as an accompanying event during severe illness caused by this virus. The early recognition of this immunological phenotype could assist prompt recognition of patients who will progress to severe disease. This review summarizes the understanding of how immune dysregulation and altered cytokine networks contribute to the patho-physiology of COVID-19 patients. As pathological examination has confirmed the involvement of immune hyperactivation, cytokine storm and acute respiratory distress syndrome in fatal cases of COVID-19, several disease-modifying anti-rheumatic drugs (DMARDS), such as hydroxychloroquine and tocilizumab, have been proposed as potential therapies for the treatment of COVID-19. Further research on the immunological mechanisms associated with COVID-19 can lead to the development of newer drug targets and therapies against this deadly virus.
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References
Ahn JY, Sohn Y, Lee SH, et al. (2020). Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea. J Korean Med Sci, 35(14):e149.
Barnes BJ, Adrover JM, Baxter-Stoltzfus A, Borczuk A, Cools-Lartigue J, Crawford JM et al. (2020). Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med, 217(6):e20200652.
Bermejo-Martin JF, Almansa R, Menéndez R, Mendez R, Kelvin DJ and Torres A. (2020). Lymphopenic community acquired pneumonia as signature of severe COVID-19 infection. J Infect, 80(5):e23-e24.
Breedveld A and van Egmond M. (2019). IgA and FcαRI: Pathological Roles and Therapeutic Opportunities. Front Immunol. 10:553-553.
Casadevall A and Pirofski L-a. (2020). The convalescent sera option for containing COVID-19. J Clin Invest, 130(4):1545-1548.
Channappanavar R, Fehr AR, Vijay R, et al. (2016). Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice. Cell Host Microbe, 19(2):181-193.
Cui J, Li F and Shi ZL. (2019) Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol, 17(3):181-192.
Diao B, Wang C, Tan Y, Chen X, Liu Y, Ning L et al. (2020). Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19). Front Immunol, 11:827.
Diurno F, Numis FG, Porta G, et al. (2020). Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience. Eur Rev Med Pharmacol Sci, 24(7):4040-4047.
Finlay BB, McFadden G. (2006). Anti-immunology: evasion of the host immune system by bacterial and viral pathogens. Cell, 124(4):767-782.
Franceschi C, Garagnani P, Parini P, Giuliani C and Santoro A. (2018). Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. 14(10):576-590.
Hoffmann M, Kleine-Weber H, Schroeder S, et al. (2020). SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, 181(2):271-280.
Huang C, Wang Y and Li X. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 395(10223):496-496.
Iwasaki A and Yang Y. (2020). The potential danger of suboptimal antibody responses in COVID-19. Nat Rev Immunol, 20: 339–341.
Kindler E, Thiel V and Weber F. (2016). Interaction of SARS and MERS Coronaviruses with the Antiviral Interferon Response. Adv Virus Res, 96:219-243.
Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, Dequanter D et al. (2020). Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol, 277(8):2251-2261.
Lippi G and Favaloro EJ. (2020). D-dimer is Associated with Severity of Coronavirus Disease 2019: A Pooled Analysis. Thromb Haemost, 120(5):876-878.
Liu PP, Blet A, Smyth D and Li H. (2020). The Science Underlying COVID-19: Implications for the Cardiovascular System. Circulation, 142(1):68-78.
Liu Y, Sun W, Guo Y, Chen L, Zhang L, Zhao S et al. (2020). Association between platelet parameters and mortality in coronavirus disease 2019: Retrospective cohort study. Platelets, 31(4):490-496.
Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J et al. (2020). Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Transl Res, 220:1-13.
Magrone T, Magrone M and Jirillo E. (2020). Focus on Receptors for Coronaviruses with Special Reference to Angiotensin- Converting Enzyme 2 as a Potential Drug Target - A Perspective. Endocr Metab Immune Disord Drug Targets, 20(6):807-811.
McGonagle D, Sharif K, O'Regan A and Bridgewood C. (2020). The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease. Autoimmun Rev, 19(6):102537.
Menachery VD, Debbink K and Baric RS. (2014). Coronavirus non-structural protein 16: evasion, attenuation, and possible treatments. Virus Res, 194:191-199.
Monteil V, Kwon H, Prado P, Hagelkrüys A, Wimmer RA, Stahl M et al. (2020). Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2. Cell, 181(4):905-913.
Mortaz E, Tabarsi P, Varahram M, Folkerts G and Adcock IM. (2020).The Immune Response and Immunopathology of COVID-19. Front Immunol, 11:2037.
Nairz M, Theurl I, Swirski FK and Weiss G. (2017). "Pumping iron"-how macrophages handle iron at the systemic, microenvironmental, and cellular levels. Pflugers Arch, 469(3-4):397-418.
Netland J, Meyerholz DK, Moore S, Cassell M and Perlman S. (2008). Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol, 82(15):7264-7275.
Ng OW, Chia A, Tan AT, et al. (2016). Memory T cell responses targeting the SARS coronavirus persist up to 11 years post-infection. Vaccine, 34(17):2008-2014.
Nguyen LT and Ohashi PS. (2015). Clinical blockade of PD1 and LAG3--potential mechanisms of action. Nat Rev Immunol, 15(1):45-56.
Pan L, Mu M, Yang P, et al. (2020). Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study. Am J Gastroenterol, 115(5):766-773.
Park MD. (2020). Macrophages: a Trojan horse in COVID-19? Nat Rev Immunol, 20(6):351.
Perlman S, and Netland J. (2009). Coronaviruses post-SARS: update on replication and pathogenesis. Nat Rev Microbiol, 7:439–50.
Pfefferle S, Schopf J, Kogl M, et al. (2011). The SARS-coronavirus-host interactome: identification of cyclophilins as target for pan-coronavirus inhibitors. PLoS Pathog, 7(10):e1002331.
Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S and Griffith B. (2020). COVID-19-associated Acute Hemorrhagic Necrotizing Encephalopathy: Imaging Features. Radiology, 296(2):E119-E120.
Prokunina-Olsson L, Alphonse N, Dickenson RE, et al. (2020). COVID-19 and emerging viral infections: The case for interferon lambda. J Exp Med, 217(5).
Prompetchara E, Ketloy C and Palaga T. (2020). Immune responses in COVID-19 and potential vaccines:Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol, 38(1):1-9.
Qi F, Qian S, Zhang S and Zhang Z. (2020). Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun, 526(1):135-140.
Qu X, Wang C, Zhang J, Qie G and Zhou J. (2014). The roles of CD147 and/or cyclophilin A in kidney diseases. Mediators Inflamm, 2014:728673.
Ratajczak MZ and Kucia M. (2020). SARS-CoV-2 infection and overactivation of Nlrp3 inflammasome as a trigger of cytokine “storm” and risk factor for damage of hematopoietic stem cells. Leukemia, 34: 1726–1729.
Sallard E, Lescure FX, Yazdanpanah Y, Mentre F and Peiffer-Smadja N. (2020). Type 1 interferons as a potential treatment against COVID-19. Antiviral Res, 178:104791.
Shang J, Wan Y, Luo C, et al. (2020). Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci U S A, 117(21):11727-11734.
Sokolowska M, Lukasik ZM, Agache I, et al. (2020). Immunology of COVID-19: Mechanisms, clinical outcome, diagnostics, and perspectives-A report of the European Academy of Allergy and Clinical Immunology (EAACI). Allergy, 75(10):2445-2476.
Thevarajan I, Nguyen THO, Koutsakos M, et al. (2020). Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med, 26(4):453-455.
Tian S, Hu W, Niu L, Liu H, Xu H and Xiao SY. (2020). Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients with Lung Cancer. J Thorac Oncol, 15(5):700-704.
Tikellis C and Thomas MC. (2012). Angiotensin-converting enzyme 2 (ACE2) is a key modulator of the renin angiotensin system in health and disease. Int J Pept, 2012:256294.
Vardhana SA and Wolchok JD. (2020).The many faces of the anti-COVID immune response. J Exp Med, 217(6): e20200678.
Velavan TP and Meyer CG. (2020). Mild versus severe COVID-19: Laboratory markers. Int J Infect Dis, 95:304-307.
Versteeg GA, Bredenbeek PJ, van den Worm SH and Spaan WJ. (2007).Group 2 coronaviruses prevent immediate early interferon induction by protection of viral RNA from host cell recognition. Virology, 361(1):18-26.
Wambier CG and Goren A. (2020). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to be androgen mediated. J Am Acad Dermatol, 83(1):308-309.
Wang B, Li R, Lu Z and Huang Y. (2020). Does comorbidity increase the risk of patients with COVID-19: evidence from meta-analysis. Aging (Albany NY), 12(7):6049-6057.
Wit DE, Doremalen VN, Falzarano D and Munster JV. (2016). SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol, 14:523–34.
Wu A, Peng Y, Huang B, et al. (2020). Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China. Cell Host Microbe, 27(3):325-328.
Wu Y, Xu X, Chen Z, Duan J, Hashimoto K, Yang L et al. (2020). Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun, 87:18-22.
Xu Z, Shi L, Wang Y, et al. (2020). Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med, 8(4):420-422.
Zhang YZ and Holmes EC. (2020). A Genomic Perspective on the Origin and Emergence of SARS-CoV-2. Cell, 181(2):223-227.
Zhou B, She J, Wang Y and Ma X. (2020). A Case of Coronavirus Disease 2019 With Concomitant Acute Cerebral Infarction and Deep Vein Thrombosis. Front Neurol, 11:296.
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Copyright (c) 2021 Subha Bose Banerjee
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