1. bookVolume 29 (2021): Issue 3 (July 2021)
Journal Details
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Format
Journal
eISSN
2284-5623
First Published
08 Aug 2013
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4 times per year
Languages
English
access type Open Access

Insights into Innate Immune Response Against SARS-CoV-2 Infection

Published Online: 31 Jul 2021
Page range: 255 - 269
Received: 14 Jun 2021
Accepted: 10 Jul 2021
Journal Details
License
Format
Journal
eISSN
2284-5623
First Published
08 Aug 2013
Publication timeframe
4 times per year
Languages
English
Abstract

The innate immune system is mandatory for the activation of antiviral host defense and eradication of the infection. In this regard, dendritic cells, natural killer cells, macrophages, neutrophils representing the cellular component, and cytokines, interferons, complement or Toll-Like Receptors, representing the mediators of unspecific response act together for both activation of the adaptive immune response and viral clearance. Of great importance is the proper functioning of the innate immune response from the very beginning. For instance, in the early stages of viral infection, the defective interferon response leads to uncontrolled viral replication and pathogen evasion, while hypersecretion during the later stages of infection generates hyperinflammation. This cascade activation of systemic inflammation culminates with cytokine storm syndrome and hypercoagulability state, due to a close interconnection between them. Thus an unbalanced reaction, either under- or over- stimulation of the innate immune system will lead to an uncoordinated response and unfavorable disease outcomes. Since both cellular and humoral factors are involved in the time-course of the innate immune response, in this review we aimed to address their gradual involvement in the antiviral response with emphasis on key steps in SARS-CoV-2 infection.

Keywords

1. Zhou P, Yang X Lou, Wang XG, 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/s41586-020-2012-710.1038/s41586-020-2012-7709541832015507 Search in Google Scholar

2. World Health Organization (WHO). Statement on the second meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus (2019-nCoV). Geneva, Switzerland. 2020 (accessed 2021 Feb 14). Search in Google Scholar

3. Peeri NC, Shrestha N, Rahman MS, Zaki R, Tan Z, Bibi S, et al. The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned? Int J Epidemiol. 2020;49(3):717-726. DOI: 10.1093/ije/dyaa03310.1093/ije/dyaa033719773432086938 Search in Google Scholar

4. Worldometer. Coronavirus Update (Live): Cases and Deaths from COVID-19 Virus Pandemic. Worldometers. 2021(accessed 2021 June 10). Search in Google Scholar

5. Azkur AK, Akdis M, Azkur D, Sokolowska M, van de Veen W, Brüggen MC, et al. Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19. Allergy: European Journal of Allergy and Clinical Immunology. 2020;75:1564-1581. DOI: 10.1111/all.1436410.1111/all.14364727294832396996 Search in Google Scholar

6. Dong M, Zhang J, Ma X, Tan J, Chen L, Liu S, et al. ACE2, TMPRSS2 distribution and extrapulmonary organ injury in patients with COVID-19. Biomedicine and Pharmacotherapy. 2020;131:110678 DOI: 10.1016/j.biopha.2020.11067810.1016/j.biopha.2020.110678744494232861070 Search in Google Scholar

7. Blot M, Bour JB, Quenot JP, Bourredjem A, Nguyen M, Guy J, et al. The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome. J Transl Med. 2020;18(1):457. DOI: 10.1186/s12967-020-02646-910.1186/s12967-020-02646-9771126933272291 Search in Google Scholar

8. Campbell K, Steiner G, Wells D, Ribas A, Kalbasi A. Prioritization of SARS-CoV-2 epitopes using a pan-HLA and global population inference approach. bioRxiv.2020; 2020.03.30.016931. DOI: 10.1101/2020.03.30.01693110.1101/2020.03.30.016931723905532511325 Search in Google Scholar

9. Georgescu AM, Banescu C, Azamfirei R, Hutanu A, Moldovan V, Badea I, et al. Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression. BMC Infect Dis. 2020;20(1):1-11. DOI: 10.1186/s12879-020-4910-610.1186/s12879-020-4910-6707175432171247 Search in Google Scholar

10. Georgescu AM, Bănescu C, Badea I, Moldovan V, Huțanu A, Voidăzan S, et al. IL-6 gene polymorphisms and sepsis in ICU adult romanian patients: a prospective study. Rev Rom Med Lab. 2017;25(1):75-89. DOI: 10.1515/rrlm-2016-004410.1515/rrlm-2016-0044 Search in Google Scholar

11. Forbester JL, Humphreys IR. Genetic influences on viral-induced cytokine responses in the lung. Mucosal Immunology. 2021;14:14-25. DOI: 10.1038/s41385-020-00355-610.1038/s41385-020-00355-6765861933184476 Search in Google Scholar

12. Netea MG, Giamarellos-Bourboulis EJ, Domínguez-Andrés J, Curtis N, van Crevel R, van de Veerdonk FL, et al. Trained Immunity: a Tool for Reducing Susceptibility to and the Severity of SARS-CoV-2 Infection. Cell. 2020;181:969-77. DOI: 10.1016/j.cell.2020.04.04210.1016/j.cell.2020.04.042719690232437659 Search in Google Scholar

13. Aryal S. Anatomical Barriers of Immune System-Skin and Mucus. Microbe Notes Online Microbiology and Biology Study Notes. https://microbenotes.com/anatomical-barriers-of-immune-system-skin-and-mucus (accessed May 10, 2021) Search in Google Scholar

14. Yousef H, Sharma S. Anatomy, Skin, Epidermis. Stat-Pearls. StatPearls Publishing; 2018. http://www.ncbi.nlm.nih.gov/pubmed/29262154 Search in Google Scholar

15. Rahimi H, Tehranchinia Z. A Comprehensive Review of Cutaneous Manifestations Associated with COVID-19. BioMed Research International. 2020:1236520. DOI: 10.1155/2020/123652010.1155/2020/1236520736423232724793 Search in Google Scholar

16. Mawhirt SL, Frankel D, Diaz AM. Cutaneous Manifestations in Adult Patients with COVID-19 and Dermato-logic Conditions Related to the COVID-19 Pandemic in Health Care Workers. Current Allergy and Asthma Reports. 2020;20:75 DOI: 10.1007/s11882-020-00974-w10.1007/s11882-020-00974-w754973533047260 Search in Google Scholar

17. Rose-Sauld S, Dua A. COVID toes and other cutaneous manifestations of COVID-19. Journal of Wound Care. 2020;29:486-487. DOI: 10.12968/jowc.2020.29.9.48610.12968/jowc.2020.29.9.48632924822 Search in Google Scholar

18. Elgarhy LH, Salem ML. Could injured skin be a reservoir for SARS-CoV-2 virus spread? Clinics in Dermatology. 2020;38:762-763. DOI: 10.1016/j.clindermatol.2020.06.00410.1016/j.clindermatol.2020.06.004728273733341211 Search in Google Scholar

19. Medina-Enríquez MM, Lopez-León S, Carlos-Escalante JA, Aponte-Torres Z, Cuapio A, Wegman-Ostrosky T. ACE2: the molecular doorway to SARS-CoV-2. Cell and Bioscience. 2020;10:1-17. DOI: 10.1186/s13578-020-00519-810.1186/s13578-020-00519-8777280133380340 Search in Google Scholar

20. Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single-Cell RNA Expression Profiling of ACE2, the Receptor of SARS-CoV-2. Vol. 202, American Journal of Respiratory and Critical Care Medicine. 2020;202:756-759. DOI: 10.1164/rccm.202001-0179LE10.1164/rccm.202001-0179LE746241132663409 Search in Google Scholar

21. Yao XH, Li TY, He ZC, Ping YF, Liu HW, Yu SC, et al. A pathological report of three COVID-19 cases by minimally invasive autopsies. Chinese J Pathol. 2020;49(5):411-417. Search in Google Scholar

22. Zhang Y, Chen Y, Li Y, Huang F, Luo B, Yuan Y, et al. The ORF8 Protein of SARS-CoV-2 Mediates Immune Evasion through Down-regulating MHC-I. PNAS. 2021; 118(23): e2024202118 DOI: 10.1073/pnas.202420211810.1073/pnas.2024202118820191934021074 Search in Google Scholar

23. Nguyen A, David JK, Maden SK, Wood MA, Weeder BR, Nellore A, et al. Human Leukocyte Antigen Susceptibility Map for Severe Acute Respiratory Syndrome Coronavirus 2. J Virol. 2020;94(13): e00510-20 DOI: 10.1128/JVI.00510-2010.1128/JVI.00510-20730714932303592 Search in Google Scholar

24. Borges RC, Hohmann MS, Borghi SM. Dendritic cells in COVID-19 immunopathogenesis: insights for a possible role in determining disease outcome. International Reviews of Immunology. 2021;40(1-2):108-125 DOI: 10.1080/08830185.2020.184419510.1080/08830185.2020.184419533191813 Search in Google Scholar

25. Wang K, Chen W, Zhou Y-S, Lian J-Q, Zhang Z, Du P, et al. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein. Sig Transduct Target Ther. 2020;5:283. DOI: 10.1038/s41392-020-00426-x10.1038/s41392-020-00426-x771489633277466 Search in Google Scholar

26. Coutard B, Valle C, de Lamballerie X, Canard B, Seidah NG, Decroly E. The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Anti-viral Res. 2020;176:104742. DOI: 10.1016/j.antiviral.2020.10474210.1016/j.antiviral.2020.104742711409432057769 Search in Google Scholar

27. Yang D, Chu H, Hou Y, Chai Y, Shuai H, Lee AC-Y, et al. Attenuated Interferon and Proinflammatory Response in SARS-CoV-2-Infected Human Dendritic Cells Is Associated With Viral Antagonism of STAT1 Phosphorylation. J Infect Dis. 2020;222(5):734-45. DOI: 10.1093/infdis/jiaa35610.1093/infdis/jiaa356733779332563187 Search in Google Scholar

28. Zhou R, To KKW, Wong YC, Liu L, Zhou B, Li X, et al. Acute SARS-CoV-2 Infection Impairs Dendritic Cell and T Cell Responses. Immunity. 2020;53(4):864-877. e5. DOI: 10.1016/j.immuni.2020.07.02610.1016/j.immuni.2020.07.026740267032791036 Search in Google Scholar

29. 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):1036-1045.e9. DOI: 10.1016/j.cell.2020.04.02610.1016/j.cell.2020.04.026722758632416070 Search in Google Scholar

30. Zhou J, Chu H, Li C, Wong BHY, Cheng ZS, Poon VKM, et al. Active replication of middle east respiratory syndrome coronavirus and aberrant induction of inflammatory cytokines and chemokines in human macrophages: Implications for pathogenesis. J Infect Dis. 2014; 209(9):1331-1342. DOI: 10.1093/infdis/jit50410.1093/infdis/jit504710735624065148 Search in Google Scholar

31. Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124(2):188-195. DOI: 10.1182/blood-2014-05-55272910.1182/blood-2014-05-552729409368024876563 Search in Google Scholar

32. Magro G. SARS-CoV-2 and COVID-19: Is interleukin-6 (IL-6) the ‘culprit lesion’ of ARDS onset? What is there besides Tocilizumab? SGP130Fc. Cytokine: X. 2020;(2): 100029. DOI: 10.1016/j.cytox.2020.10002910.1016/j.cytox.2020.100029722464932421092 Search in Google Scholar

33. Garbers C, Monhasery N, Aparicio-Siegmund S, Lokau J, Baran P, Nowell MA, et al. The interleukin-6 receptor Asp358Ala single nucleotide polymorphism rs2228145 confers increased proteolytic conversion rates by ADAM proteases. Biochim Biophys Acta - Mol Basis Dis. 2014;1842(9):1485-1494. DOI: 10.1016/j.bbadis.2014.05.01810.1016/j.bbadis.2014.05.01824878322 Search in Google Scholar

34. Rose-John S. Il-6 trans-signaling via the soluble IL-6 receptor: Importance for the proinflammatory activities of IL-6. Int J Biol Sci. 2012;8(9):1237-1247. DOI: 10.7150/ijbs.498910.7150/ijbs.4989349144723136552 Search in Google Scholar

35. Martinez FO, Combes TW, Orsenigo F, Gordon S. Monocyte activation in systemic Covid-19 infection: Assay and rationale. EBioMedicine. 2020;59:102964 DOI: 10.1016/j.ebiom.2020.10296410.1016/j.ebiom.2020.102964745645532861199 Search in Google Scholar

36. Zhou Y, Fu B, Zheng X, Wang D, Zhao C, Qi Y, et al. Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients. National Science Review. 2020;7(6):998-1002. DOI: 10.1093/nsr/nwaa04110.1093/nsr/nwaa041710800534676125 Search in Google Scholar

37. Zhang N, Czepielewski RS, Jarjour NN, Erlich EC, Esaulova E, Saunders BT, et al. Expression of factor V by resident macrophages boosts host defense in the peritoneal cavity. J Exp Med. 2019;216(6):1291-1300. DOI: 10.1084/jem.2018202410.1084/jem.20182024654786631048328 Search in Google Scholar

38. Boumaza A, Gay L, Mezouar S, Diallo AB, Michel M, Desnues B, et al. Monocytes and macrophages, targets of SARS-CoV-2: The clue for Covid-19 immunoparalysis. J Infect Dis. 2021:jiab044. DOI: 10.1093/infdis/jiab04410.1093/infdis/jiab044792881733493287 Search in Google Scholar

39. Feng Z, Diao B, Wang R, Wang G, Wang C, Tan Y, et al. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly decimates human spleens and lymph nodes. medRx-iv.2020. DOI: 10.1101/2020.03.27.20045427 DOI: 10.1101/2020.03.27.2004542710.1101/2020.03.27.20045427 Search in Google Scholar

40. Park MD. Macrophages: a Trojan horse in COVID-19? Nat Rev Immunol. 2020;20(6):351. DOI: 10.1038/s41577-020-0317-210.1038/s41577-020-0317-2718693032303696 Search in Google Scholar

41. Marcenaro E, Carlomagno S, Pesce S, Moretta A, Sivori S. Bridging innate NK cell functions with adaptive immunity. Adv Exp Med Biol. Adv Exp Med Biol. 2011;780: 45-55. DOI: 10.1007/978-1-4419-5632-3_510.1007/978-1-4419-5632-3_521842364 Search in Google Scholar

42. Molgora M, Supino D, Mavilio D, Santoni A, Moretta L, Mantovani A, et al. The yin-yang of the interaction between myelomonocytic cells and NK cells. Scand J Immunol. 2018;88(3):e12705 DOI: 10.1111/sji.1270510.1111/sji.12705648539430048003 Search in Google Scholar

43. Zhao X-N, You Y, Wang G-L, Gao H-X, Duan L-J, Zhang S-B, et al. Longitudinal single-cell immune profiling revealed distinct innate immune response in asymptomatic COVID-19 patients. bioRxiv. 2020:2020.09.02.276865. DOI: 10.1101/2020.09.02.27686510.1101/2020.09.02.276865 Search in Google Scholar

44. Pinto D, Park Y-J, Beltramello M, Walls A, Tortorici MA, Bianchi S, et al. Structural and functional analysis of a potent sarbecovirus neutralizing antibody. bioRxiv. 2020; 10.1101/2020.04.07.023903 DOI: 10.2210/pdb-6ws6/pdb Search in Google Scholar

45. Li T, Qiu Z, Zhang L, Han Y, He W, Liu Z, et al. Significant Changes of Peripheral T Lymphocyte Subsets in Patients with Severe Acute Respiratory Syndrome. J Infect Dis. 2004;189(4):648-651. DOI: 10.1086/38153510.1086/381535710994614767818 Search in Google Scholar

46. Zheng M, Gao Y, Wang G, Song G, Liu S, Sun D, et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020;17:533-535. DOI: 10.1038/s41423-020-0402-210.1038/s41423-020-0402-2709185832203188 Search in Google Scholar

47. Bao C, Tao X, Cui W, Hao Y, Zheng S, Yi B, et al. Natural killer cells associated with SARS-CoV-2 viral RNA shedding, antibody response and mortality in COVID-19 patients. Exp Hematol Oncol. 2021;10(1):5 DOI: 10.1186/s40164-021-00199-110.1186/s40164-021-00199-1783928633504359 Search in Google Scholar

48. Galani IE, Andreakos E. Neutrophils in viral infections: Current concepts and caveats. J Leukoc Biol. 2015;98(4):557-564. DOI: 10.1189/jlb.4VMR1114-555R10.1189/jlb.4VMR1114-555R26160849 Search in Google Scholar

49. Borges L, Pithon-Curi TC, Curi R, Hatanaka E. COVID-19 and Neutrophils: The relationship between hyperinflammation and neutrophil extracellular traps. Mediators of Inflammation. 2020; 2020: 8829674. DOI: 10.1155/2020/882967410.1155/2020/8829674773240833343232 Search in Google Scholar

50. Barr FD, Ochsenbauer C, Wira CR, Rodriguez-Garcia M. Neutrophil extracellular traps prevent HIV infection in the female genital tract. Mucosal Immunol. 2018;11(5):1420-1428. DOI: 10.1038/s41385-018-0045-010.1038/s41385-018-0045-0616217329875403 Search in Google Scholar

51. Saitoh T, Komano J, Saitoh Y, Misawa T, Takahama M, Kozaki T, et al. Neutrophil extracellular traps mediate a host defense response to human immunodeficiency virus-1. Cell Host Microbe. 2012;12(1):109-116. DOI: 10.1016/j.chom.2012.05.01510.1016/j.chom.2012.05.01522817992 Search in Google Scholar

52. He Y, Yang FY, Sun EW. Neutrophil Extracellular Traps in Autoimmune Diseases. Chin Med J. 2018;131:1513-1519. DOI: 10.4103/0366-6999.23512210.4103/0366-6999.235122603268829941703 Search in Google Scholar

53. Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, Madison JA, et al. Neutrophil extracellular traps in COVID-19. JCI Insight. 2020;5(11);e138999 DOI: 10.1101/2020.04.30.2008673610.1101/2020.04.30.20086736727423432511553 Search in Google Scholar

54. Thierry AR, Roch B. SARS-CoV2 may evade innate immune response, causing uncontrolled neutrophil extracellular traps formation and multi-organ failure. Clin Sci (Lond). 2020;134:1295-1300. DOI: 10.1042/CS2020053110.1042/CS2020053132543703 Search in Google Scholar

55. Shi Y, Gauer JS, Baker SR, Philippou H, Connell SD, Ariëns RAS. Neutrophils can promote clotting via FXI and impact clot structure via neutrophil extracellular traps in a distinctive manner in vitro. Sci Rep. 2021;11(1):1718. DOI: 10.1038/s41598-021-81268-710.1038/s41598-021-81268-7781402833462294 Search in Google Scholar

56. Fuchs TA, Kremer Hovinga JA, Schatzberg D, Wagner DD, Lämmle B. Circulating DNA and myeloperoxidase indicate disease activity in patients with thrombotic microangiopathies. Blood. 2012;120(6):1157-1164. DOI: 10.1182/blood-2012-02-41219710.1182/blood-2012-02-412197341871222611154 Search in Google Scholar

57. Pfeiler S, Stark K, Massberg S, Engelmann B. Propagation of thrombosis by neutrophils and extracellular nucleosome networks. Haematologica. 2017;102(2):206-213. DOI: 10.3324/haematol.2016.14247110.3324/haematol.2016.142471528692927927771 Search in Google Scholar

58. Stiel L, Mayeur-Rousse C, Helms J, Meziani F, Mauvieux L. First visualization of circulating neutrophil extracellular traps using cell fluorescence during human septic shock-induced disseminated intravascular coagulation. Thromb Res. 2019;183:153-158. DOI: 10.1016/j.thromres.2019.09.03610.1016/j.thromres.2019.09.03631678710 Search in Google Scholar

59. Sabbione F, Keitelman IA, Iula L, Ferrero M, Giordano MN, Baldi P, et al. Neutrophil Extracellular Traps Stimulate Proinflammatory Responses in Human Airway Epithelial Cells. J Innate Immun. 2017;9(4):387-402. DOI: 10.1159/00046029310.1159/000460293673890128467984 Search in Google Scholar

60. Barbu EA, Mendelsohn L, Samsel L, Thein SL. Pro-inflammatory cytokines associate with NETosis during sickle cell vaso-occlusive crises. Cytokine. 2020;127:154933. DOI: 10.1016/j.cyto.2019.15493310.1016/j.cyto.2019.154933841974431778959 Search in Google Scholar

61. Cheng OZ, Palaniyar N. NET balancing: A problem in inflammatory lung diseases. Front Immunol. 2013;4:1. DOI: 10.3389/fimmu.2013.0000110.3389/fimmu.2013.00001355339923355837 Search in Google Scholar

62. Lee KH, Kronbichler A, Park DDY, Park YM, Moon H, Kim H, et al. Neutrophil extracellular traps (NETs) in autoimmune diseases: A comprehensive review. Autoimmun Rev. 2017;16(11):1160-1173. DOI: 10.1016/j.autrev.2017.09.01210.1016/j.autrev.2017.09.01228899799 Search in Google Scholar

63. Lin A, Loré K. Granulocytes: New members of the antigen-presenting cell family. Front Immunol. 2017;8:1781 DOI: 10.3389/fimmu.2017.0178110.3389/fimmu.2017.01781573222729321780 Search in Google Scholar

64. Leliefeld PHC, Koenderman L, Pillay J. How neutrophils shape adaptive immune responses. Front Immunol. 2015;6:471. DOI: 10.3389/fimmu.2015.0047110.3389/fimmu.2015.00471456841026441976 Search in Google Scholar

65. Mukherjee M, Lacy P, Ueki S. Eosinophil extracellular traps and inflammatory pathologies-untangling the web! Front Immunol. 2018;9:2763. DOI: 10.3389/fimmu.2018.0276310.3389/fimmu.2018.02763627523730534130 Search in Google Scholar

66. Nagase H, Okugawa S, Ota Y, Yamaguchi M, Tomizawa H, Matsushima K, et al. Expression and Function of Toll-Like Receptors in Eosinophils: Activation by Toll-Like Receptor 7 Ligand. J Immunol. 2003;171(8):3977-3982. DOI: 10.4049/jimmunol.171.8.397710.4049/jimmunol.171.8.397714530316 Search in Google Scholar

67. Lindsley AW, Schwartz JT, Rothenberg ME. Eosinophil responses during COVID-19 infections and coronavirus vaccination. J Allergy Clin Immunol. 2020;146(1):1-7. DOI: 10.1016/j.jaci.2020.04.02110.1016/j.jaci.2020.04.021719472732344056 Search in Google Scholar

68. Du Y, Tu L, Zhu P, Mu M, Wang R, Yang P, et al. Clinical features of 85 fatal cases of COVID-19 from Wuhan: A retrospective observational study. Am J Respir Crit Care Med. 2020;201(11):1372-1379. DOI: 10.1164/rccm.202003-0543OC10.1164/rccm.202003-0543OC725865232242738 Search in Google Scholar

69. 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;75(7):1730-1741. DOI: 10.1111/all.1423810.1111/all.1423832077115 Search in Google Scholar

70. Borgne P Le, Vuillaume LA, Alamé K, Lefebvre F, Chabrier S, Bérard L, et al. Do blood eosinophils predict in-hospital mortality or severity of disease in SARS-CoV-2 infection? A retrospective multicenter study. Microorganisms. 2021;9(2):334. DOI: 10.3390/microorganisms902033410.3390/microorganisms9020334791491633567583 Search in Google Scholar

71. Xia Z. Eosinopenia as an early diagnostic marker of COVID-19 at the time of the epidemic. E Clinical Medicine. 2020;23:100398 DOI: 10.1016/j.eclinm.2020.10039810.1016/j.eclinm.2020.100398729984832572392 Search in Google Scholar

72. Gralinski LE, Sheahan TP, Morrison TE, Menachery VD, Jensen K, Leist SR, et al. Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis. MBio. 2018;9(5):e01753-18 DOI: 10.1128/mBio.01753-1810.1128/mBio.01753-18617862130301856 Search in Google Scholar

73. Gao T, Hu M, Zhang X, Li H, Zhu L, Liu H, et al. Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation. medRxiv. 2020:2020.03.29.20041962. DOI: 10.1101/2020.03.29.2004196210.1101/2020.03.29.20041962 Search in Google Scholar

74. Yuen J, Pluthero FG, Douda DN, Riedl M, Cherry A, Ulanova M, et al. NETosing neutrophils activate complement both on their own NETs and bacteria via alternative and non-alternative pathways. Front Immunol. 2016;7:137. DOI: 10.3389/fimmu.2016.0013710.3389/fimmu.2016.00137483163627148258 Search in Google Scholar

75. Java A, Apicelli AJ, Kathryn Liszewski M, Coler-Reilly A, Atkinson JP, Kim AHJ, et al. The complement system in COVID-19: Friend and foe? JCI Insight. 2020;5(15):e140711. DOI: 10.1172/jci.insight.14071110.1172/jci.insight.140711745506032554923 Search in Google Scholar

76. Kurosawa S, Stearns-Kurosawa DJ. Complement, thrombotic microangiopathy and disseminated intravascular coagulation. J Intensive Care. 2014;2(1):65 DOI: 10.1186/s40560-014-0061-410.1186/s40560-014-0061-4433618025705421 Search in Google Scholar

77. Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z, et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost. 2020;18(6):1324-1329. DOI: 10.1111/jth.1485910.1111/jth.14859726473032306492 Search in Google Scholar

78. Khanmohammadi S, Rezaei N. Role of Toll-like receptors in the pathogenesis of COVID-19. J Med Virol. 2021;93(5):2735-2739. DOI: 10.1002/jmv.2682610.1002/jmv.26826801426033506952 Search in Google Scholar

79. Choudhury A, Mukherjee S. In silico studies on the comparative characterization of the interactions of SARS-CoV-2 spike glycoprotein with ACE-2 receptor homologs and human TLRs. J Med Virol. 2020;92(10):2105-2113. DOI: 10.1002/jmv.2598710.1002/jmv.25987726766332383269 Search in Google Scholar

80. Moreno-Eutimio MA, López-Macías C, Pastelin-Palacios R. Bioinformatic analysis and identification of single-stranded RNA sequences recognized by TLR7/8 in the SARS-CoV-2, SARS-CoV, and MERS-CoV genomes. Microbes Infect. 2020;22(4-5):226-229. DOI: 10.1016/j.micinf.2020.04.00910.1016/j.micinf.2020.04.009719207432361001 Search in Google Scholar

81. Cicco S, Cicco G, Racanelli V, Vacca A. Neutrophil Extracellular Traps (NETs) and Damage-Associated Molecular Patterns (DAMPs): Two Potential Targets for COVID-19 Treatment. Mediators of Inflammation 2020; 2020:7527953 DOI: 10.1155/2020/752795310.1155/2020/7527953736622132724296 Search in Google Scholar

82. Bezemer GFG, Garssen J. TLR9 and COVID-19: A Multidisciplinary Theory of a Multifaceted Therapeutic Target. Front Pharmacol. 2021;11:601685. DOI: 10.3389/fphar.2020.60168510.3389/fphar.2020.601685784458633519463 Search in Google Scholar

83. Fallerini C, Daga S, Mantovani S, Benetti E, Picchiotti N, Francisci D, et al. Association of toll-like receptor 7 variants with life-threatening COVID-19 disease in males: Findings from a nested case-control study. eLife. 2021;10:e67569 Search in Google Scholar

84. Li Y, Jerkic M, Slutsky AS, Zhang H. Molecular mechanisms of sex bias differences in COVID-19 mortality. Crit Care. 2020;24:405. DOI: 10.1186/s13054-020-03118-810.1186/s13054-020-03118-8734725632646459 Search in Google Scholar

85. Portela Sousa C, Brites C. Immune response in SARS-CoV-2 infection: the role of interferons type I and type III. Braz J Infect Dis. 2020;24(5):428-433. DOI: 10.1016/j.bjid.2020.07.01110.1016/j.bjid.2020.07.011744881732866437 Search in Google Scholar

86. Hadjadj J, Yatim N, Barnabei L, Corneau A, Boussier J, Smith N, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020;369(6504):718-724. DOI: 10.1126/science.abc602710.1126/science.abc6027740263232661059 Search in Google Scholar

87. Contoli M, Papi A, Tomassetti L, Rizzo P, Vieceli Dalla Sega F, Fortini F, et al. Blood Interferon-α Levels and Severity, Outcomes, and Inflammatory Profiles in Hospitalized COVID-19 Patients. Front Immunol. 2021;12:648004. DOI: 10.3389/fimmu.2021.64800410.3389/fimmu.2021.648004798545833767713 Search in Google Scholar

88. Nice TJ, Robinson BA, Van Winkle JA. The Role of Interferon in Persistent Viral Infection: Insights from Murine Norovirus. Trends in Microbiol. 2018;26(6):510-524. DOI: 10.1016/j.tim.2017.10.01010.1016/j.tim.2017.10.010595777829157967 Search in Google Scholar

89. 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.2016.01.00710.1016/j.chom.2016.01.007475272326867177 Search in Google Scholar

90. Taefehshokr N, Taefehshokr S, Hemmat N, Heit B. Covid-19: Perspectives on Innate Immune Evasion. Front Immunol. 2020;11:580641 DOI: 10.3389/fimmu.2020.58064110.3389/fimmu.2020.580641755424133101306 Search in Google Scholar

91. Major J, Crotta S, Llorian M, McCabe TM, Gad HH, Priestnall SL, et al. Type I and III interferons disrupt lung epithelial repair during recovery from viral infection. Science. 2020;369(6504):712-717. DOI: 10.1126/science.abc206110.1126/science.abc2061729250032527928 Search in Google Scholar

92. Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH, Zhang Y, et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020;370(6515):eabd4585. Search in Google Scholar

93. Liu QQ, Cheng A, Wang Y, Li H, Hu L, Zhao X, et al. Cytokines and their relationship with the severity and prognosis of coronavirus disease 2019 (COVID-19): A retrospective cohort study. BMJ Open. 2020;10:e041471. DOI: 10.1136/bmjopen-2020-04147110.1136/bmjopen-2020-041471770542633257492 Search in Google Scholar

94. Cauchois R, Koubi M, Delarbre D, Manet C, Carvelli J, Blasco VB, et al. Early IL-1 receptor blockade in severe inflammatory respiratory failure complicating COVID-19. PNAS. 2020;117(32):18951-18953. DOI: 10.1073/pnas.200901711710.1073/pnas.2009017117743099832699149 Search in Google Scholar

95. 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;27(6):879-882.e2. DOI: 10.1016/j.chom.2020.03.02110.1016/j.chom.2020.03.021719208932359396 Search in Google Scholar

96. Li Z, Xiao J, Xu X, Li W, Zhong R, Qi L, et al. M-CSF, IL-6, and TGF-β promote generation of a new subset of tissue repair macrophage for traumatic brain injury recovery. Sci Adv. 2021;7(11):6260-6272. DOI: 10.1126/sciadv.abb626010.1126/sciadv.abb6260795445533712456 Search in Google Scholar

97. Asensi V, Valle E, Meana A, Fierer J, Celada A, Alvarez V, et al. In vivo interleukin-6 protects neutrophils from apoptosis in osteomyelitis. Infect Immun. 2004;72(7):3823-3828. DOI: 10.1128/IAI.72.7.3823-3828.200410.1128/IAI.72.7.3823-3828.200442742815213123 Search in Google Scholar

98. Lauder SN, Jones E, Smart K, Bloom A, Williams AS, Hindley JP, et al. Interleukin-6 limits influenza-induced inflammation and protects against fatal lung pathology. Eur J Immunol. 2013;43(10):2613-2625. DOI: 10.1002/eji.20124301810.1002/eji.201243018388638623857287 Search in Google Scholar

99. Yang ML, Wang CT, Yang SJ, Leu CH, Chen SH, Wu CL, et al. IL-6 ameliorates acute lung injury in influenza virus infection. Sci Rep. 2017;7:43829 DOI: 10.1038/srep4382910.1038/srep43829 Search in Google Scholar

100. Diehl S, Anguita J, Hoffmeyer A, Zapton T, Ihle JN, Fikrig E, et al. Inhibition of Th1 differentiation by IL-6 is mediated by SOCS1. Immunity. 2000;13(6):805-815. DOI: 10.1016/S1074-7613(00)00078-910.1016/S1074-7613(00)00078-9 Search in Google Scholar

101. Gubernatorova EO, Gorshkova EA, Polinova AI, Drutskaya MS. IL-6: Relevance for immunopathology of SARS-CoV-2. Cytokine and Growth Factor Rev. 2020;53:13-24. DOI: 10.1016/j.cytogfr.2020.05.00910.1016/j.cytogfr.2020.05.009723791632475759 Search in Google Scholar

102. Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta. 2011;1813(5):878-888. DOI: 10.1016/j.bbamcr.2011.01.03410.1016/j.bbamcr.2011.01.03421296109 Search in Google Scholar

103. Zhang J, Hao Y, Ou W, Ming F, Liang G, Qian Y, et al. Serum interleukin-6 is an indicator for severity in 901 patients with SARS-CoV-2 infection: a cohort study. J Transl Med. 2020;18:406. DOI: 10.1186/s12967-020-02571-x10.1186/s12967-020-02571-x759495133121497 Search in Google Scholar

104. Sabaka P, Koščálová A, Straka I, Hodosy J, Lipták R, Kmotorková B, et al. Role of interleukin 6 as a predictive factor for a severe course of Covid-19: retrospective data analysis of patients from a long-term care facility during Covid-19 outbreak. BMC Infect Dis. 2021;21:308. DOI: 10.1186/s12879-021-05945-810.1186/s12879-021-05945-8800611233781216 Search in Google Scholar

105. Herold T, Jurinovic V, Arnreich C, Lipworth BJ, Hellmuth JC, von Bergwelt-Baildon M, et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol. 2020;146(1):128-136.e4. DOI: 10.1016/j.jaci.2020.05.00810.1016/j.jaci.2020.05.008723323932425269 Search in Google Scholar

106. 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). Front Immunol. 2020;11:827 DOI: 10.3389/fimmu.2020.0082710.3389/fimmu.2020.00827720590332425950 Search in Google Scholar

107. Del Valle DM, Kim-Schulze S, Huang HH, Beckmann ND, Nirenberg S, Wang B, et al. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636-1643. DOI: 10.1038/s41591-020-1051-910.1038/s41591-020-1051-9786902832839624 Search in Google Scholar

108. Li L, Chen C. Contribution of acute phase reaction proteins to the diagnosis and treatment of 2019 novel coronavirus disease (COVID-19). Epidemiol Infect. 2020;148:e164 DOI: 10.1017/S095026882000165X10.1017/S095026882000165X739914932713370 Search in Google Scholar

109. Castell J V., Gómez-Lechón MJ, David M, Andus T, Geiger T, Trullenque R, et al. Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes. FEBS Lett. 1989;242(2):237-239. DOI: 10.1016/0014-5793(89)80476-410.1016/0014-5793(89)80476-4 Search in Google Scholar

110. Yormaz B, Ergun D, Tulek B, Ergun R, Korez KM, Suerdem M, et al. The evaluation of prognostic value of acute phase reactants in the COVID-19. Bratislava Med J. 2020;121(9):628-633. DOI: 10.4149/BLL_2020_10310.4149/BLL_2020_10332990010 Search in Google Scholar

111. Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020;63(3):364-374. DOI: 10.1007/s11427-020-1643-810.1007/s11427-020-1643-8708856632048163 Search in Google Scholar

112. Ahmed S, Ansar Ahmed Z, Siddiqui I, Haroon Rashid N, Mansoor M, Jafri L. Evaluation of serum ferritin for prediction of severity and mortality in COVID-19- A cross sectional study. Ann Med Surg. 2021;63:102163. DOI: 10.1016/j.amsu.2021.02.00910.1016/j.amsu.2021.02.009787906533614024 Search in Google Scholar

113. Lino K, Guimarães GMC, Alves LS, Oliveira AC, Faustino R, Fernandes CS, et al. Serum ferritin at admission in hospitalized COVID-19 patients as a predictor of mortality. Brazilian J Infect Dis. 2021;25(2):101569. DOI: 10.1016/j.bjid.2021.10156910.1016/j.bjid.2021.101569795926633736948 Search in Google Scholar

114. Zinellu A, Paliogiannis P, Carru C, Mangoni AA. Serum amyloid A concentrations, COVID-19 severity and mortality: An updated systematic review and meta-analysis. Int J Infect Dis. 2021;105:668-674. DOI: 10.1016/j.ijid.2021.03.02510.1016/j.ijid.2021.03.025795967833737133 Search in Google Scholar

115. Ghahramani S, Tabrizi R, Lankarani KB, Kashani SMA, Rezaei S, Zeidi N, et al. Laboratory features of severe vs. non-severe COVID-19 patients in Asian populations: A systematic review and meta-analysis. Eur J Med Res. 2020;25:30. DOI: 10.1186/s40001-020-00432-310.1186/s40001-020-00432-3739694232746929 Search in Google Scholar

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