COVID-19: Molecular and Cellular Response

In late December 2019, a vtiral pneumonia with an unknown agent was reported in Wuhan, China. A novel coronavirus was identified as the causative agent. Because of the human-to-human transmission and rapid spread; coronavirus disease 2019 (COVID-19) has rapidly increased to an epidemic scale and poses a severe threat to human health; it has been declared a public health emergency of international concern (PHEIC) by the World Health Organization (WHO). This review aims to summarize the recent research progress of COVID-19 molecular features and immunopathogenesis to provide a reference for further research in prevention and treatment of SARS coronavirus2 (SARS-CoV-2) infection based on the knowledge from researches on SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS-CoV).

[1]  T. White The Trinity , 2022 .

[2]  A. Raj,et al.  Sex differences in COVID-19 case fatality: do we know enough? , 2020, The Lancet Global Health.

[3]  K. Peter,et al.  Higher mortality of COVID-19 in males: sex differences in immune response and cardiovascular comorbidities , 2020, Cardiovascular research.

[4]  V. Galasso,et al.  Gender differences in COVID-19 attitudes and behavior: Panel evidence from eight countries , 2020, Proceedings of the National Academy of Sciences.

[5]  Arthur S Slutsky,et al.  Human recombinant soluble ACE2 in severe COVID-19 , 2020, The Lancet Respiratory Medicine.

[6]  A. Pradhan,et al.  Sex differences in severity and mortality from COVID-19: are males more vulnerable? , 2020, Biology of sex differences.

[7]  Vineet D. Menachery,et al.  Type I Interferon Susceptibility Distinguishes SARS-CoV-2 from SARS-CoV , 2020, Journal of Virology.

[8]  S. Farhadian,et al.  Sex differences in immune responses that underlie COVID-19 disease outcomes , 2020, Nature.

[9]  I. Adcock,et al.  The Immune Response and Immunopathology of COVID-19 , 2020, Frontiers in Immunology.

[10]  R. Cox,et al.  Not just antibodies: B cells and T cells mediate immunity to COVID-19 , 2020, Nature Reviews Immunology.

[11]  M. Endres,et al.  A SARS-CoV-2 neutralizing antibody protects from lung pathology in a COVID-19 hamster model , 2020, bioRxiv.

[12]  L. Carter,et al.  Functional SARS-CoV-2-specific immune memory persists after mild COVID-19 , 2020, medRxiv.

[13]  N. Rezaei,et al.  Primary Immunodeficiency Diseases in COVID-19 Pandemic: A Predisposing or Protective Factor? , 2020, The American Journal of the Medical Sciences.

[14]  Martin Linster,et al.  SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls , 2020, Nature.

[15]  Maciej Banach,et al.  Cytokine Storm in COVID-19—Immunopathological Mechanisms, Clinical Considerations, and Therapeutic Approaches: The REPROGRAM Consortium Position Paper , 2020, Frontiers in Immunology.

[16]  A. Sette,et al.  Pre-existing immunity to SARS-CoV-2: the knowns and unknowns , 2020, Nature Reviews Immunology.

[17]  Ying Li,et al.  Antibody responses against SARS‐CoV‐2 in COVID‐19 patients , 2020, Journal of medical virology.

[18]  A. Velde,et al.  Severe COVID-19: NLRP3 Inflammasome Dysregulated , 2020 .

[19]  T. Swartz,et al.  Targeting the NLRP3 Inflammasome in Severe COVID-19 , 2020, Frontiers in Immunology.

[20]  Quanlong Jiang,et al.  Individual variation of the SARS‐CoV‐2 receptor ACE2 gene expression and regulation , 2020, Aging cell.

[21]  S. Atal,et al.  IL-6 Inhibitors in the Treatment of Serious COVID-19: A Promising Therapy? , 2020, Pharmaceutical Medicine.

[22]  G. Keser,et al.  Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment , 2020, Clinical Rheumatology.

[23]  L. Dodd,et al.  Remdesivir for the Treatment of Covid-19 — Final Report , 2020, The New England journal of medicine.

[24]  A. Shah Novel Coronavirus-Induced NLRP3 Inflammasome Activation: A Potential Drug Target in the Treatment of COVID-19 , 2020, Frontiers in Immunology.

[25]  L. Rodríguez-Mañas,et al.  Use of renin–angiotensin–aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study , 2020, The Lancet.

[26]  H. Tang,et al.  Severe COVID-19: A Review of Recent Progress With a Look Toward the Future , 2020, Frontiers in Public Health.

[27]  G. Antonucci,et al.  Safety and efficacy of early high-dose IV anakinra in severe COVID-19 lung disease , 2020, Journal of Allergy and Clinical Immunology.

[28]  Malik Peiris,et al.  Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures , 2020, The Lancet Respiratory Medicine.

[29]  A. Zangrillo,et al.  Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study , 2020, The Lancet Rheumatology.

[30]  Fang Li,et al.  Cell entry mechanisms of SARS-CoV-2 , 2020, Proceedings of the National Academy of Sciences.

[31]  M. Merad,et al.  Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages , 2020, Nature Reviews Immunology.

[32]  D. Roden,et al.  Genetic susceptibility for COVID-19–associated sudden cardiac death in African Americans , 2020, Heart Rhythm.

[33]  Thomas Henry,et al.  Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions , 2020, Autoimmunity Reviews.

[34]  S. Surani,et al.  A Review of Neurological Complications of COVID-19 , 2020, Cureus.

[35]  B. Williams,et al.  Hypertension, renin–angiotensin–aldosterone system inhibition, and COVID-19 , 2020, The Lancet.

[36]  F. Rodríguez de Fonseca,et al.  Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: A delayed pandemic?? , 2020, Neurología (English Edition).

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

[38]  M. Tay,et al.  The trinity of COVID-19: immunity, inflammation and intervention , 2020, Nature Reviews Immunology.

[39]  E. Swenson,et al.  COVID-19 Lung Injury and High Altitude Pulmonary Edema: A False Equation with Dangerous Implications. , 2020, Annals of the American Thoracic Society.

[40]  Fabian J Theis,et al.  SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes , 2020, Nature Medicine.

[41]  M. Diamond,et al.  TMPRSS2 and TMPRSS4 mediate SARS-CoV-2 infection of human small intestinal enterocytes , 2020, bioRxiv.

[42]  T. Liang,et al.  Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study , 2020, BMJ.

[43]  Matthew D. Park,et al.  Macrophages: a Trojan horse in COVID-19? , 2020, Nature Reviews Immunology.

[44]  Nan Tang,et al.  SARS-CoV-2 and viral sepsis: observations and hypotheses , 2020, The Lancet.

[45]  F. R. de Fonseca,et al.  Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: a delayed pandemic? , 2020, Neurologia.

[46]  A. Topeli,et al.  Critically ill COVID-19 patient , 2020, Turkish journal of medical sciences.

[47]  C. Yancy,et al.  COVID-19 and African Americans. , 2020, JAMA.

[48]  Zhengrong Yang,et al.  Recurrence of positive SARS-CoV-2 viral RNA in recovered COVID-19 patients during medical isolation observation , 2020, Scientific Reports.

[49]  T. Lv,et al.  Encephalitis as a clinical manifestation of COVID-19 , 2020, Brain, Behavior, and Immunity.

[50]  L. Mao,et al.  Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. , 2020, JAMA neurology.

[51]  Jun Liu,et al.  Factors associated with prolonged viral RNA shedding in patients with COVID-19 , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[52]  Harapan Harapan,et al.  Coronavirus disease 2019 (COVID-19): A literature review , 2020, Journal of Infection and Public Health.

[53]  Robert J. Mason,et al.  Pathogenesis of COVID-19 from a cell biologic perspective , 2020, European Respiratory Journal.

[54]  K. Hashimoto,et al.  Nervous system involvement after infection with COVID-19 and other coronaviruses , 2020, Brain, Behavior, and Immunity.

[55]  Zhiyong Ma,et al.  Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia , 2020, The Journal of infectious diseases.

[56]  Hongyang Wang,et al.  Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing , 2020, Cell Discovery.

[57]  Manish Bansal,et al.  Cardiovascular disease and COVID-19 , 2020, Diabetes & Metabolic Syndrome: Clinical Research & Reviews.

[58]  K. Shi,et al.  Structural basis of receptor recognition by SARS-CoV-2 , 2020, Nature.

[59]  Shibo Jiang,et al.  Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine , 2020, Cellular & Molecular Immunology.

[60]  E. Holmes,et al.  The proximal origin of SARS-CoV-2 , 2020, Nature Medicine.

[61]  Usman Ali,et al.  Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms , 2020, ACS chemical neuroscience.

[62]  Fabian J Theis,et al.  SARS-CoV-2 Entry Genes Are Most Highly Expressed in Nasal Goblet and Ciliated Cells within Human Airways , 2020, Nature Medicine.

[63]  Srinivas Murthy,et al.  Care for Critically Ill Patients With COVID-19. , 2020, JAMA.

[64]  S. Xiao,et al.  Clinical outcomes of 402 patients with COVID‐2019 from a single center in Wuhan, China , 2020, medRxiv.

[65]  Vineet D. Menachery,et al.  Type I interferon susceptibility distinguishes SARS-CoV-2 from SARS-CoV. , 2020, bioRxiv.

[66]  A. Walls,et al.  Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein , 2020, Cell.

[67]  Chang Hu,et al.  Clinical features and outcomes of 221 patients with COVID-19 in Wuhan, China , 2020, medRxiv.

[68]  Xiaowei Li,et al.  Molecular immune pathogenesis and diagnosis of COVID-19 , 2020, Journal of Pharmaceutical Analysis.

[69]  Xiang Xie,et al.  COVID-19 and the cardiovascular system , 2020, Nature Reviews Cardiology.

[70]  Liang Peng,et al.  Recurrence of positive SARS-CoV-2 RNA in COVID-19: A case report , 2020, International Journal of Infectious Diseases.

[71]  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.

[72]  D. Gurwitz Angiotensin receptor blockers as tentative SARS‐CoV‐2 therapeutics , 2020, Drug development research.

[73]  Mario Plebani,et al.  Laboratory abnormalities in patients with COVID-2019 infection , 2020, Clinical chemistry and laboratory medicine.

[74]  H. G. Liu,et al.  [Cause analysis and treatment strategies of "recurrence" with novel coronavirus pneumonia (covid-19) patients after discharge from hospital]. , 2020, Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases.

[75]  J. Xiang,et al.  Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study , 2020, The Lancet.

[76]  T. Palaga,et al.  Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. , 2020, Asian Pacific journal of allergy and immunology.

[77]  De-Min Han,et al.  Gender Differences in Patients With COVID-19: Focus on Severity and Mortality , 2020, Frontiers in Public Health.

[78]  Taiwen Li,et al.  High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa , 2020, International Journal of Oral Science.

[79]  M. Letko,et al.  Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses , 2020, Nature Microbiology.

[80]  Shengqing Wan,et al.  Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations , 2020, Cell Discovery.

[81]  L. Mao,et al.  Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study , 2020, medRxiv.

[82]  H. Shan,et al.  Evidence for Gastrointestinal Infection of SARS-CoV-2 , 2020, Gastroenterology.

[83]  Bo Diao,et al.  Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19) , 2020, Frontiers in Immunology.

[84]  Min Kang,et al.  SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients , 2020, The New England journal of medicine.

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

[86]  Novel Coronavirus Pneumonia Emergency Response Epidemiol Team [The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China]. , 2020, Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi.

[87]  B. Canard,et al.  The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade , 2020, Antiviral Research.

[88]  E. Stoneman,et al.  The Novel Coronavirus: A Bird's Eye View , 2020, The international journal of occupational and environmental medicine.

[89]  Gengfu Xiao,et al.  Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro , 2020, Cell Research.

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

[91]  Kai Zhao,et al.  A pneumonia outbreak associated with a new coronavirus of probable bat origin , 2020, Nature.

[92]  Immune Cell , 2020, Definitions.

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

[94]  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.

[95]  Ralph S. Baric,et al.  Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus , 2020, Journal of Virology.

[96]  Hongzhou Lu,et al.  Drug treatment options for the 2019-new coronavirus (2019-nCoV). , 2020, Bioscience trends.

[97]  W. Zuo,et al.  Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov , 2020, bioRxiv.

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

[99]  Alain Le Coupanec,et al.  Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? , 2019, Viruses.

[100]  N. Jouvenet,et al.  Stimulation of Innate Immunity by Host and Viral RNAs. , 2019, Trends in immunology.

[101]  R. Plemper,et al.  Characterization of orally efficacious influenza drug with high resistance barrier in ferrets and human airway epithelia , 2019, Science Translational Medicine.

[102]  F. Delalande,et al.  Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cells , 2019, Nature Communications.

[103]  David K. Meyerholz,et al.  IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes. , 2019, The Journal of clinical investigation.

[104]  D. Sauter,et al.  Furin‐mediated protein processing in infectious diseases and cancer , 2019, Clinical & translational immunology.

[105]  N. Badae,et al.  Is the cardioprotective effect of the ACE2 activator diminazene aceturate more potent than the ACE inhibitor enalapril on acute myocardial infarction in rats? , 2019, Canadian journal of physiology and pharmacology.

[106]  Takeshi Ichinohe,et al.  Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome , 2019, Front. Microbiol..

[107]  Simon A. Jones,et al.  Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer , 2018, Nature Reviews Immunology.

[108]  Reza Taherkhani,et al.  Modulation of the immune response by Middle East respiratory syndrome coronavirus , 2018, Journal of cellular physiology.

[109]  K. Pyrć,et al.  Early events during human coronavirus OC43 entry to the cell , 2018, Scientific Reports.

[110]  P. Thomas,et al.  New fronts emerge in the influenza cytokine storm , 2017, Seminars in Immunopathology.

[111]  S. Perlman,et al.  Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology , 2017, Seminars in Immunopathology.

[112]  Yi Shi,et al.  Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains , 2017, Nature Communications.

[113]  G. Gao,et al.  T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV , 2016, Antiviral Research.

[114]  F. Weber,et al.  Interaction of SARS and MERS Coronaviruses with the Antiviral Interferon Response , 2016, Advances in Virus Research.

[115]  D. Libraty,et al.  A Model to Explain How the Bacille Calmette Guérin (BCG) Vaccine Drives Interleukin-12 Production in Neonates , 2016, PloS one.

[116]  A. Hajeer,et al.  Association of human leukocyte antigen class II alleles with severe Middle East respiratory syndrome-coronavirus infection , 2016, Annals of thoracic medicine.

[117]  G. Gao,et al.  Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses , 2016, Trends in Microbiology.

[118]  B. Rosenzweig,et al.  The Effect of Oseltamivir on the Disease Progression of Lethal Influenza A Virus Infection: Plasma Cytokine and miRNA Responses in a Mouse Model , 2016, Disease markers.

[119]  P. Daszak,et al.  Isolation and Characterization of a Novel Bat Coronavirus Closely Related to the Direct Progenitor of Severe Acute Respiratory Syndrome Coronavirus , 2015, Journal of Virology.

[120]  Ben Hu,et al.  Bat origin of human coronaviruses , 2015, Virology Journal.

[121]  T. Morio,et al.  Tocilizumab in systemic juvenile idiopathic arthritis in a real-world clinical setting: results from 1 year of postmarketing surveillance follow-up of 417 patients in Japan , 2015, Annals of the rheumatic diseases.

[122]  Wenjie Tan,et al.  Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I interferon production through both cytoplasmic and nuclear targets , 2015, Scientific Reports.

[123]  Lisa E. Gralinski,et al.  A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence , 2015, Nature Medicine.

[124]  G. Burmester,et al.  Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial , 2015, Annals of the rheumatic diseases.

[125]  I. Mori Transolfactory neuroinvasion by viruses threatens the human brain. , 2015, Acta virologica.

[126]  W. Liu,et al.  Functional polymorphisms of the CCL2 and MBL genes cumulatively increase susceptibility to severe acute respiratory syndrome coronavirus infection , 2015, Journal of Infection.

[127]  S. Perlman,et al.  Coronaviruses: An Overview of Their Replication and Pathogenesis , 2015, Methods in molecular biology.

[128]  G. Whittaker,et al.  Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein , 2014, Proceedings of the National Academy of Sciences.

[129]  P. Ades A controversial step forward: A commentary on the 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults. , 2014, Coronary artery disease.

[130]  F. Luft ACE in the hole , 2014, Journal of Molecular Medicine.

[131]  G. Lynch,et al.  Influence of HLA gene polymorphisms on susceptibility and outcome post infection with the SARS-CoV virus , 2014, Virologica Sinica.

[132]  Yang Yang,et al.  The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists , 2013, Protein & Cell.

[133]  J. Epstein,et al.  Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor , 2013, Nature.

[134]  C. Lang,et al.  Renin–Angiotensin–Aldosterone System Inhibitors in Heart Failure , 2013, Clinical pharmacology and therapeutics.

[135]  F. Weber,et al.  Middle East Respiratory Syndrome Coronavirus Accessory Protein 4a Is a Type I Interferon Antagonist , 2013, Journal of Virology.

[136]  Linqi Zhang,et al.  Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4 , 2013, Cell Research.

[137]  Yoko Ito,et al.  Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus. , 2013, American journal of respiratory cell and molecular biology.

[138]  G. Whittaker,et al.  Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein , 2012, Viruses.

[139]  Yen-Ju Chen,et al.  Human-leukocyte antigen class I Cw 1502 and class II DR 0301 genotypes are associated with resistance to severe acute respiratory syndrome (SARS) infection. , 2011, Viral immunology.

[140]  Yoko Ito,et al.  Innate immune response to influenza A virus in differentiated human alveolar type II cells. , 2011, American journal of respiratory cell and molecular biology.

[141]  E John Wherry,et al.  T cell exhaustion , 2011 .

[142]  Josef M. Penninger,et al.  Trilogy of ACE2: A peptidase in the renin–angiotensin system, a SARS receptor, and a partner for amino acid transporters , 2010, Pharmacology & Therapeutics.

[143]  G. Whittaker,et al.  Modifications to the Hemagglutinin Cleavage Site Control the Virulence of a Neurotropic H1N1 Influenza Virus , 2010, Journal of Virology.

[144]  F. Plummer,et al.  Neutralizing epitopes of the SARS-CoV S-protein cluster independent of repertoire, antigen structure or mAb technology , 2010, mAbs.

[145]  K. Mayer,et al.  Targeting Trojan Horse leukocytes for HIV prevention , 2010, AIDS.

[146]  S. Perlman,et al.  Coronaviruses post-SARS: update on replication and pathogenesis , 2009, Nature Reviews Microbiology.

[147]  B. Berkhout,et al.  Interaction of severe acute respiratory syndrome-coronavirus and NL63 coronavirus spike proteins with angiotensin converting enzyme-2 , 2008, The Journal of general virology.

[148]  A. McMichael,et al.  T Cell Responses to Whole SARS Coronavirus in Humans1 , 2008, The Journal of Immunology.

[149]  G. Bakris,et al.  The pathogenesis of diabetic nephropathy , 2008, Nature Clinical Practice Endocrinology &Metabolism.

[150]  David K. Meyerholz,et al.  Severe Acute Respiratory Syndrome Coronavirus Infection Causes Neuronal Death in the Absence of Encephalitis in Mice Transgenic for Human ACE2 , 2008, Journal of Virology.

[151]  S. Crotty,et al.  Resolution of a chronic viral infection after interleukin-10 receptor blockade , 2006, The Journal of Experimental Medicine.

[152]  L. Teyton,et al.  Interleukin-10 determines viral clearance or persistence in vivo , 2006, Nature Medicine.

[153]  S. Perlman,et al.  Immunopathogenesis of coronavirus infections: implications for SARS , 2005, Nature Reviews Immunology.

[154]  S. Diamond,et al.  Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[155]  Bo Zhang,et al.  Multiple organ infection and the pathogenesis of SARS , 2005, The Journal of experimental medicine.

[156]  Ben Berkhout,et al.  Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[157]  K. Kain,et al.  Fatal Severe Acute Respiratory Syndrome Is Associated with Multiorgan Involvement by Coronavirus , 2005, The Journal of infectious diseases.

[158]  R. D. de Groot,et al.  Natural History of a Recurrent Feline Coronavirus Infection and the Role of Cellular Immunity in Survival and Disease , 2005, Journal of Virology.

[159]  D. Furst Anakinra: review of recombinant human interleukin-I receptor antagonist in the treatment of rheumatoid arthritis. , 2004, Clinical therapeutics.

[160]  Larissa B. Thackray,et al.  CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[161]  C. Perry Clinical Features , 2004, Bristol medico-chirurgical journal.

[162]  B. Bosch,et al.  The Coronavirus Spike Protein Is a Class I Virus Fusion Protein: Structural and Functional Characterization of the Fusion Core Complex , 2003, Journal of Virology.

[163]  A. Xu,et al.  Profile of specific antibodies to the SARS-associated coronavirus. , 2003, The New England journal of medicine.

[164]  Obi L. Griffith,et al.  The Genome Sequence of the SARS-Associated Coronavirus , 2003, Science.

[165]  L. Poon,et al.  Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia : a prospective study , 2003 .

[166]  S. Aggarwal,et al.  Increased TNF-alpha-induced apoptosis in lymphocytes from aged humans: changes in TNF-alpha receptor expression and activation of caspases. , 1999, Journal of immunology.

[167]  S. Aggarwal,et al.  Increased TNF-α-Induced Apoptosis in Lymphocytes from Aged Humans: Changes in TNF-α Receptor Expression and Activation of Caspases , 1999, The Journal of Immunology.

[168]  R. Webster,et al.  Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus , 1998, The Lancet.

[169]  S. Perlman,et al.  Effect of olfactory bulb ablation on spread of a neurotropic coronavirus into the mouse brain , 1990, The Journal of experimental medicine.

[170]  M. Pensaert,et al.  Immunofluorescence studies on the pathogenesis of hemagglutinating encephalomyelitis virus infection in pigs after oronasal inoculation. , 1980, American journal of veterinary research.

[171]  M. Moosavi,et al.  Cytokine-targeted therapy in severely ill COVID-19 patients: Options and cautions , 2020 .

[172]  M. Rithanya,et al.  Molecular Immune Pathogenesis and Diagnosis of COVID-19 - A Review , 2020 .

[173]  China Cdc Weekly The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) — China, 2020 , 2020, China CDC weekly.

[174]  S. Sekaran,et al.  Disruption of the blood brain barrier is vital property of neurotropic viral infection of the central nervous system. , 2018, Acta virologica.

[175]  P. Song,et al.  CLINICAL OUTCOMES? , 2014 .

[176]  Hiroshi Kido,et al.  Role of host cellular proteases in the pathogenesis of influenza and influenza-induced multiple organ failure. , 2012, Biochimica et biophysica acta.

[177]  A. Davies,et al.  Immune Responses , 1971, Nature.