SARS-CoV-2 associated pathogenesis, immune dysfunction and involvement of host factors: a comprehensive review

Infectious diseases, especially viral infections, have emerged as a major concern for public health in recent years. Recently emerged COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has been declared a pandemic by World Health Organization since March 2020. It was first identified in Wuhan, China, in December 2019 and has since claimed more than a million lives. Complicated symptoms are associated with rising incidence and fatality rates, while many of the vaccine candidates are in the final stages of clinical trials. This review encompasses a summary of existing literature on COVID-19, including the basics of the disease such as the causative agent's genome characterization. modes of transmission of the virus, pathogenesis, and clinical presentations like associated immune responses, neurological manifestations, the variety of host genetic factors influencing the disease and the vulnerability of different groups being affected by COVID-19.

[1]  Y. Waheed,et al.  Mapping the effect of drugs on ACE2 as a novel target site for COVID-19 therapy. , 2021, European review for medical and pharmacological sciences.

[2]  Sara Zandpazandi,et al.  Novel Coronavirus Characteristic Cerebrovasculopathic Effects , 2020, International Clinical Neuroscience Journal.

[3]  C. Wellington,et al.  Confronting the controversy: interleukin-6 and the COVID-19 cytokine storm syndrome , 2020, European Respiratory Journal.

[4]  Xiaodong Sun,et al.  Attaching clinical significance to COVID-19-associated diarrhea , 2020, Life Sciences.

[5]  B. Reinius,et al.  Natural killer cell immunotypes related to COVID-19 disease severity , 2020, Science Immunology.

[6]  N. Sultana,et al.  Multisystem inflammatory syndrome associated with COVID-19 in children in Pakistan , 2020, The Lancet Child & Adolescent Health.

[7]  K. Seino,et al.  Macrophage activation syndrome and COVID-19 , 2020, Inflammation and regeneration.

[8]  G. Batiha,et al.  Investigating Virological, Immunological, and Pathological Avenues to Identify Potential Targets for Developing COVID-19 Treatment and Prevention Strategies , 2020, Vaccines.

[9]  I. Artika,et al.  Molecular biology of coronaviruses: current knowledge , 2020, Heliyon.

[10]  P. Brindley,et al.  Therapeutic plasma exchange in adult critically ill patients with life-threatening SARS-CoV-2 disease: A pilot study , 2020, Journal of Critical Care.

[11]  Chunrui Li,et al.  Risk factors for developing into critical COVID-19 patients in Wuhan, China: A multicenter, retrospective, cohort study , 2020, EClinicalMedicine.

[12]  Z. Memish,et al.  Lung Injury in COVID-19—An Emerging Hypothesis , 2020, ACS chemical neuroscience.

[13]  A. Thierry Host/genetic factors associated with COVID-19 call for precision medicine , 2020, Precision clinical medicine.

[14]  M. Chung,et al.  New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis , 2020, BMC Medicine.

[15]  P. Davies,et al.  Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicentre observational study , 2020, The Lancet Child & Adolescent Health.

[16]  D. Gladstone,et al.  Regulatory T Cells for Treating Patients With COVID-19 and Acute Respiratory Distress Syndrome: Two Case Reports , 2020, Annals of Internal Medicine.

[17]  B. Pitard,et al.  Potential of regulatory T-cell-based therapies in the management of severe COVID-19 , 2020, European Respiratory Journal.

[18]  K. Muhammad,et al.  Nanomedicine as a promising approach for diagnosis, treatment and prophylaxis against COVID-19 , 2020, Nanomedicine.

[19]  M. Usman,et al.  COVID-19 and Liver Injury: A Systematic Review and Meta-Analysis , 2020, Cureus.

[20]  T. Mogensen,et al.  Deciphering the Role of Host Genetics in Susceptibility to Severe COVID-19 , 2020, Frontiers in Immunology.

[21]  Simon Li,et al.  Multisystem Inflammatory Syndrome in U.S. Children and Adolescents , 2020, The New England journal of medicine.

[22]  C. von Kalle,et al.  COVID-19 severity correlates with airway epithelium–immune cell interactions identified by single-cell analysis , 2020, Nature Biotechnology.

[23]  R. Auer,et al.  Flattening the COVID-19 Curve With Natural Killer Cell Based Immunotherapies , 2020, Frontiers in Immunology.

[24]  N. E. Ferreira,et al.  First case of SARS-COV-2 sequencing in cerebrospinal fluid of a patient with suspected demyelinating disease , 2020, Journal of Neurology.

[25]  R. Ranjbar,et al.  An updated review of the association of host genetic factors with susceptibility and resistance to COVID‐19 , 2020, Journal of cellular physiology.

[26]  Yuan Wang,et al.  Identifying airborne transmission as the dominant route for the spread of COVID-19 , 2020, Proceedings of the National Academy of Sciences.

[27]  S. Vanni,et al.  Interleukin-6 as prognosticator in patients with COVID-19 , 2020, Journal of Infection.

[28]  Jérémie F. Cohen,et al.  Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study , 2020, BMJ.

[29]  R. Sagkan,et al.  Structural variations and expression profiles of the SARS‐CoV‐2 host invasion genes in lung cancer , 2020, Journal of medical virology.

[30]  Shelly L. Miller,et al.  How can airborne transmission of COVID-19 indoors be minimised? , 2020, Environment International.

[31]  M. Ono,et al.  T-Cell Hyperactivation and Paralysis in Severe COVID-19 Infection Revealed by Single-Cell Analysis , 2020, bioRxiv.

[32]  L. León,et al.  Hospital admissions in inflammatory rheumatic diseases during the peak of COVID-19 pandemic: incidence and role of disease-modifying agents , 2020, medRxiv.

[33]  M. Bosmann Complement Activation during Critical Illness: Current Findings and an Outlook in the Era of COVID-19 , 2020, American journal of respiratory and critical care medicine.

[34]  W. Wang,et al.  Viral and host factors related to the clinical outcome of COVID-19 , 2020, Nature.

[35]  Cong Ye,et al.  The immunology of COVID-19: is immune modulation an option for treatment? , 2020, The Lancet Rheumatology.

[36]  N. Henninger,et al.  SARS2-CoV-2 and Stroke in a New York Healthcare System , 2020, Stroke.

[37]  B. Lipworth,et al.  Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19 , 2020, Journal of Allergy and Clinical Immunology.

[38]  L. Bonnemains,et al.  Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic , 2020, Circulation.

[39]  D. Bennett,et al.  COVID-19 pneumonia in a large cohort of patients treated with biological and targeted synthetic antirheumatic drugs , 2020, Annals of the Rheumatic Diseases.

[40]  Giuseppe Magro,et al.  SARS-CoV-2 and COVID-19: Is interleukin-6 (IL-6) the ‘culprit lesion’ of ARDS onset? What is there besides Tocilizumab? SGP130Fc , 2020, Cytokine: X.

[41]  Angelo Mazza,et al.  An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study , 2020, The Lancet.

[42]  I. Amit,et al.  Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19 , 2020, Nature Medicine.

[43]  C. D. Dela Cruz,et al.  COVID-19 vulnerability: the potential impact of genetic susceptibility and airborne transmission , 2020, Human Genomics.

[44]  Jian Chen,et al.  Association between ABO blood groups and risk of SARS‐CoV‐2 pneumonia , 2020, British journal of haematology.

[45]  A. Julià,et al.  Incidence of COVID-19 in a cohort of adult and paediatric patients with rheumatic diseases treated with targeted biologic and synthetic disease-modifying anti-rheumatic drugs , 2020, Seminars in Arthritis and Rheumatism.

[46]  Marco Maria Fontanella,et al.  SARS-CoV-2 can induce brain and spine demyelinating lesions , 2020, Acta Neurochirurgica.

[47]  G. Cooke,et al.  Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[48]  Kwok-Hung Chan,et al.  Triple combination of interferon beta-1b, lopinavir–ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial , 2020, The Lancet.

[49]  J. Rose,et al.  SARS-CoV-2 in wastewater: State of the knowledge and research needs , 2020, Science of The Total Environment.

[50]  J. Knight,et al.  Interferon-Induced Transmembrane Protein 3 Genetic Variant rs12252-C Associated With Disease Severity in Coronavirus Disease 2019 , 2020, The Journal of infectious diseases.

[51]  Xiaohu Zheng,et al.  Effective treatment of severe COVID-19 patients with tocilizumab , 2020, Proceedings of the National Academy of Sciences.

[52]  X. Tang,et al.  Antibody responses to SARS-CoV-2 in patients with COVID-19 , 2020, Nature Medicine.

[53]  J. Sejvar,et al.  Neurological associations of COVID-19 , 2020, The Lancet Neurology.

[54]  H. Hou,et al.  The laboratory tests and host immunity of COVID-19 patients with different severity of illness. , 2020, JCI insight.

[55]  Ahmed Yaqinuddin,et al.  Innate immunity in COVID-19 patients mediated by NKG2A receptors, and potential treatment using Monalizumab, Cholroquine, and antiviral agents , 2020, Medical Hypotheses.

[56]  T. Zhang,et al.  COVID-19-Associated Acute Disseminated Encephalomyelitis: A Case Report , 2020, medRxiv.

[57]  J. Sheng,et al.  Current epidemiological and clinical features of COVID-19; a global perspective from China , 2020, Journal of Infection.

[58]  Dong Men,et al.  Detectable Serum Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load (RNAemia) Is Closely Correlated With Drastically Elevated Interleukin 6 Level in Critically Ill Patients With Coronavirus Disease 2019 , 2020, Clinical Infectious Diseases.

[59]  Abhinav Nellore,et al.  Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2 , 2020, Journal of Virology.

[60]  Nathaniel Hupert,et al.  Clinical Characteristics of Covid-19 in New York City , 2020, The New England journal of medicine.

[61]  M. Woodward,et al.  The impact of 2019 novel coronavirus on heart injury: A Systematic review and Meta-analysis , 2020, Progress in Cardiovascular Diseases.

[62]  S. Kremer,et al.  Neurologic Features in Severe SARS-CoV-2 Infection , 2020, The New England journal of medicine.

[63]  A. Carr A new clinical trial to test high-dose vitamin C in patients with COVID-19 , 2020, Critical Care.

[64]  S. Merler,et al.  Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. , 2020, JAMA.

[65]  Roland Eils,et al.  SARS‐CoV‐2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells , 2020, The EMBO journal.

[66]  D. McGonagle,et al.  The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease , 2020, Autoimmunity Reviews.

[67]  Huji Xu,et al.  Digestive system is a potential route of COVID-19: an analysis of single-cell coexpression pattern of key proteins in viral entry process , 2020, Gut.

[68]  Dingding Shen,et al.  Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? , 2020, The Lancet Neurology.

[69]  Roberto Maroldi,et al.  Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19). , 2020, JAMA cardiology.

[70]  Ke Ma,et al.  Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study , 2020, BMJ.

[71]  Han Zhang,et al.  Coronavirus Disease 2019 (COVID-19) CT Findings: A Systematic Review and Meta-analysis , 2020, Journal of the American College of Radiology.

[72]  M. D. De Buyzere,et al.  The host’s angiotensin-converting enzyme polymorphism may explain epidemiological findings in COVID-19 infections , 2020, Clinica Chimica Acta.

[73]  F. Diekmann,et al.  Case report of COVID-19 in a kidney transplant recipient: Does immunosuppression alter the clinical presentation? , 2020, American Journal of Transplantation.

[74]  Z. Tian,et al.  Functional exhaustion of antiviral lymphocytes in COVID-19 patients , 2020, Cellular & Molecular Immunology.

[75]  Fenglian Ma,et al.  Coronavirus fulminant myocarditis treated with glucocorticoid and human immunoglobulin , 2020, European heart journal.

[76]  Hyeshik Chang,et al.  The Architecture of SARS-CoV-2 Transcriptome , 2020, Cell.

[77]  Jie Hao,et al.  Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection , 2020, Frontiers of Medicine.

[78]  G. Herrler,et al.  SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor , 2020, Cell.

[79]  M. Torcia,et al.  Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2 , 2020, bioRxiv.

[80]  P. Mehta,et al.  COVID-19: consider cytokine storm syndromes and immunosuppression , 2020, The Lancet.

[81]  K. Yuen,et al.  Clinical Characteristics of Coronavirus Disease 2019 in China , 2020, The New England journal of medicine.

[82]  Ting Yu,et al.  Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study , 2020, The Lancet Respiratory Medicine.

[83]  Lei Zhao,et al.  Multiple Enzyme Release, Inflammation Storm and Hypercoagulability Are Prominent Indicators For Disease Progression In COVID-19: A Multi-Centered, Correlation Study with CT Imaging Score , 2020 .

[84]  C. Akdis,et al.  Clinical characteristics of 140 patients infected with SARS‐CoV‐2 in Wuhan, China , 2020, Allergy.

[85]  Jiyuan Zhang,et al.  Pathological findings of COVID-19 associated with acute respiratory distress syndrome , 2020, The Lancet Respiratory Medicine.

[86]  Lijuan Xiong,et al.  Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients , 2020, EBioMedicine.

[87]  Suxin Wan,et al.  Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP) , 2020, medRxiv.

[88]  Jue Fan,et al.  Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection , 2020, bioRxiv.

[89]  E. Holmes,et al.  A new coronavirus associated with human respiratory disease in China , 2020, Nature.

[90]  S. Lindstrom,et al.  First Case of 2019 Novel Coronavirus in the United States , 2020, The New England journal of medicine.

[91]  I. Kickbusch,et al.  Response to the emerging novel coronavirus outbreak , 2020, BMJ.

[92]  E. Holmes,et al.  Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding , 2020, The Lancet.

[93]  Ting Yu,et al.  Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study , 2020, The Lancet.

[94]  Y. Hu,et al.  Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China , 2020, The Lancet.

[95]  Qianyun Liu,et al.  Emerging coronaviruses: Genome structure, replication, and pathogenesis , 2020, Journal of medical virology.

[96]  Ping Chen,et al.  Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission , 2020, Science China Life Sciences.

[97]  R. Tattersall,et al.  Haemophagocytic lymphohisticytosis—an underrecognized hyperinflammatory syndrome , 2019, Rheumatology.

[98]  N. Gupta,et al.  The stimulation of thrombosis by hypoxia. , 2019, Thrombosis research.

[99]  H. Ljunggren,et al.  NK cells are activated and primed for skin-homing during acute dengue virus infection in humans , 2019, Nature Communications.

[100]  Yi Fan,et al.  Bat Coronaviruses in China , 2019, Viruses.

[101]  S. Sakaguchi,et al.  Human FOXP3+ Regulatory T Cell Heterogeneity and Function in Autoimmunity and Cancer. , 2019, Immunity.

[102]  K. Nichols,et al.  The Immunology of Macrophage Activation Syndrome , 2019, Front. Immunol..

[103]  G. Lombardi,et al.  Past, Present, and Future of Regulatory T Cell Therapy in Transplantation and Autoimmunity , 2019, Front. Immunol..

[104]  R. Fouchier,et al.  Transmission routes of respiratory viruses among humans , 2018, Current Opinion in Virology.

[105]  H. Ljunggren,et al.  NK Cell Responses to Human Tick-Borne Encephalitis Virus Infection , 2016, The Journal of Immunology.

[106]  D. Falzarano,et al.  SARS and MERS: recent insights into emerging coronaviruses , 2016, Nature Reviews Microbiology.

[107]  David K. Meyerholz,et al.  Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice , 2016, Cell Host & Microbe.

[108]  B. Miller,et al.  Hypoxia mediated pulmonary edema: potential influence of oxidative stress, sympathetic activation and cerebral blood flow , 2015, BMC Physiology.

[109]  A. Rudensky,et al.  A Distinct Function of Regulatory T Cells in Tissue Protection , 2015, Cell.

[110]  Q. Ying,et al.  Formation of urban fine particulate matter. , 2015, Chemical reviews.

[111]  S. Weiss,et al.  Coronavirus Pathogenesis , 2011, Advances in Virus Research.

[112]  H. Ljunggren,et al.  Rapid expansion and long-term persistence of elevated NK cell numbers in humans infected with hantavirus , 2011, The Journal of experimental medicine.

[113]  P. Sham,et al.  Significance of the Myxovirus Resistance A (MxA) Gene — 123C>A Single-Nucleotide Polymorphism in Suppressed Interferon β Induction of Severe Acute Respiratory Syndrome Coronavirus Infection , 2010, The Journal of infectious diseases.

[114]  Eric Vivier,et al.  Functions of natural killer cells , 2008, Nature Immunology.

[115]  Fang Li,et al.  Structural Analysis of Major Species Barriers between Humans and Palm Civets for Severe Acute Respiratory Syndrome Coronavirus Infections , 2008, Journal of Virology.

[116]  J. Habbema,et al.  Association of SARS susceptibility with single nucleic acid polymorphisms of OAS1 and MxA genes: a case-control study , 2006, BMC infectious diseases.

[117]  John L. Sullivan,et al.  Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus , 2003, Nature.

[118]  J. Luban SARS-CoV-2 , 2020 .

[119]  V. Georgiev,et al.  National Institute of Allergy and Infectious Diseases, NI , 2008 .