Role of inflammation in the pathogenesis of novel coronavirus infection

Abstract

The activation of various types of epithelial, endothelial, and immunocompetent cells, along with hyperproduction of cytokines and other proinflammatory mediators and activation of the complement system, plays a crucial in the pathogenesis of coronavirus disease 2019 (COVID-19). These conditions leads to severe inflammation and acute respiratory distress syndrome. Hyperinflammatory reactions in the lungs and other tissues result in significant tissue damage and organ dysfunction. A specific feature of severe acute respiratory syndrome coronavirus 2 infection is the combination of cell death and inflammation. In COVID-19, not only pneumocytes but also many other cells are killed. These cells undergo programed cell death through three main pathways: apoptosis, pyroptosis, and necroptosis. These processes help protect organisms from intracellular pathogens by releasing them from infected cells, which then bind to specific receptors and antibodies, undergo opsonization, and are phagocytosed. Localized inflammation aims to eliminate these pathogens, but severe inflammation is an important component of the immunopathogenesis of COVID-19. The immunopathogenesis of COVID-19, particularly the role of inflammation in the development of severe clinical signs, is now largely understood. This disease has a complex immunopathology, including excessive activation of adaptive and innate branches of the immune system and interactions between immune cells and affected tissues.

Keywords

COVID-19 / inflammation / cytokines / complement

References

[1] Biancolella M, Colona VL, Luzzatto L, et al. COVID-19 annual update: a narrative review. Hum Genomics. 2023;17(1):68. doi: 10.1186/s40246-023-00515-2

[2] Biancolella M., Colona V.L., Luzzatto L., et al. COVID-19 annual update: a narrative review // Hum Genomics. 2023. Vol. 17, N 1. P. 68. doi: 10.1186/s40246-023-00515-2

[3] Gusev E, Sarapultsev A, Solomatina L, Chereshnev V. SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19. Int J Mol Sci. 2022;23(3):1716. doi: 10.3390/ijms23031716

[4] Gusev E., Sarapultsev A., Solomatina L., Chereshnev V. SARS-CoV-2-Specific Immune Response and the Pathogenesis of COVID-19 // Int J Mol Sci. 2022. Vol. 23, N 3. P. 1716. doi: 10.3390/ijms23031716

[5] Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;20(6):363–374. doi: 10.1038/s41577-020-0311-8

[6] Tay M.Z., Poh C.M., Rénia L., MacAry P.A., Ng L.F.P. The trinity of COVID-19: immunity, inflammation and intervention // Nat Rev Immunol. 2020. Vol. 20, N 6. P. 363–374. doi: 10.1038/s41577-020-0311-8

[7] Mohandas S, Jagannathan P, Henrich TJ, et al. RECOVER Mechanistic Pathways Task Force. Immune mechanisms underlying COVID-19 pathology and post-acute sequelae of SARS-CoV-2 infection (PASC). Elife. 2023;12:e86014. doi: 10.7554/eLife.86014

[8] Mohandas S., Jagannathan P., Henrich T.J., et al. RECOVER Mechanistic Pathways Task Force. Immune mechanisms underlying COVID-19 pathology and post-acute sequelae of SARS-CoV-2 infection (PASC) // Elife. 2023. Vol. 12. P. e86014. doi: 10.7554/eLife.86014

[9] Stein SR, Ramelli SC, Grazioli A, et al. SARS-CoV-2 infection and persistence in the human body and brain at autopsy. Nature. 2022;612(7941):758–763. doi: 10.1038/s41586-022-05542-y

[10] Stein S.R., Ramelli S.C., Grazioli A., et al. SARS-CoV-2 infection and persistence in the human body and brain at autopsy // Nature. 2022. Vol. 612, N 7941. P. 758–763. doi: 10.1038/s41586-022-05542-y

[11] Batiha GE, Al-Kuraishy HM, Al-Gareeb AI, Welson NN. Pathophysiology of Post-COVID syndromes: a new perspective. Virol J. 2022;19(1):158. doi: 10.1186/s12985-022-01891-2

[12] Batiha G.E., Al-Kuraishy H.M., Al-Gareeb A.I., Welson N.N. Pathophysiology of Post-COVID syndromes: a new perspective // Virol J. 2022. Vol. 19, N 1. P. 158. doi: 10.1186/s12985-022-01891-2

[13] Burnham EL, Janssen WJ, Riches DW, Moss M, Downey GP. The fibroproliferative response in acute respiratory distress syndrome: mechanisms and clinical significance. Eur Respir J. 2014;43(1):276–285. doi: 10.1183/09031936.00196412

[14] Burnham E.L., Janssen W.J., Riches D.W., Moss M, Downey GP. The fibroproliferative response in acute respiratory distress syndrome: mechanisms and clinical significance // Eur Respir J. 2014. Vol. 43, N 1. P. 276–285. doi: 10.1183/09031936.00196412

[15] Bordallo B, Bellas M, Cortez AF, Vieira M, Pinheiro M. Severe COVID-19: what have we learned with the immunopathogenesis? Adv Rheumatol. 2020;60(1):50. doi: 10.1186/s42358-020-00151-7

[16] Bordallo B., Bellas M., Cortez A.F., Vieira M., Pinheiro M. Severe COVID-19: what have we learned with the immunopathogenesis? // Adv Rheumatol. 2020. Vol. 60, N 1. P. 50. doi: 10.1186/s42358-020-00151-7

[17] Zhang H, Zhou P, Wei Y, et al. Histopathologic Changes and SARS-CoV-2 Immunostaining in the Lung of a Patient With COVID-19. Annals of Internal Medicine. 2020;172(9):629–632. doi: 10.7326/m20-0533

[18] Zhang H., Zhou P., Wei Y., et al. Histopathologic Changes and SARS-CoV-2 Immunostaining in the Lung of a Patient With COVID-19 // Annals of Internal Medicine. 2020. Vol. 172, N 9. P. 629–632. doi: 10.7326/m20-0533

[19] Bader SM, Cooney JP, Pellegrini M, Doerflinger M. Programmed cell death: the pathways to severe COVID-19? Biochem J. 2022;479(5):609–628. doi: 10.1042/BCJ20210602

[20] Bader S.M., Cooney J.P., Pellegrini M., Doerflinger M. Programmed cell death: the pathways to severe COVID-19? // Biochem J. 2022. Vol. 479, N 5. P. 609–628. doi: 10.1042/BCJ20210602

[21] Karki R, Sharma BR, Tuladhar S, et al. Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes. Cell. 2021;184(1):149–168. doi: 10.1016/j.cell.2020.11.025

[22] Karki R., Sharma B.R., Tuladhar S., et al. Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes // Cell. 2021. Vol. 184, N 1. P. 149–168. doi: 10.1016/j.cell.2020.11.025

[23] Veras FP, Pontelli MC, Silva CM, et al. SARS-CoV-2-triggered neutrophil extracellular traps mediate COVID-19 pathology. J Exp Med. 2020;217(12):e20201129. doi: 10.1084/jem.20201129

[24] Veras F.P., Pontelli M.C., Silva C.M., et al. SARS-CoV-2-triggered neutrophil extracellular traps mediate COVID-19 pathology // J Exp Med. 2020. Vol. 217, N 12. P. e20201129. doi: 10.1084/jem.20201129

[25] Thiam HR, Wong SL, Wagner DD, Waterman CM. Cellular mechanisms of NETosis. Annu Rev Cell Dev Biol. 2020;36:191–218. doi: 10.1146/annurev-cellbio-020520-111016

[26] Thiam H.R., Wong S.L., Wagner D.D., Waterman C.M. Cellular mechanisms of NETosis // Annu Rev Cell Dev Biol. 2020. Vol. 36. P. 191–218. doi: 10.1146/annurev-cellbio-020520-111016

[27] Twaddell SH, Baines KJ, Grainge C, Gibson PG. The emerging role of neutrophil extracellular traps in respiratory disease. Chest. 2019;156(4):774–782. doi: 10.1016/j.chest.2019.06.012

[28] Twaddell S.H., Baines K.J., Grainge C., Gibson P.G. The emerging role of neutrophil extracellular traps in respiratory disease // Chest. 2019. Vol. 156, N 4. P. 774–782. doi: 10.1016/j.chest.2019.06.012

[29] Skendros P, Mitsios A, Chrysanthopoulou A, et al. Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis. J Clin Invest. 2020;130(11):6151–6157. doi: 10.1172/JCI141374

[30] Skendros P., Mitsios A., Chrysanthopoulou A., et al. Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis // J Clin Invest. 2020. Vol. 130, N 11. P. 6151–6157. doi: 10.1172/JCI141374

[31] Cesta MC, Zippoli M, Marsiglia C, et al. Neutrophil activation and neutrophil extracellular traps (NETs) in COVID-19 ARDS and immunothrombosis. Eur J Immunol. 2023;53(1):e2250010. doi: 10.1002/eji.202250010

[32] Cesta M.C., Zippoli M., Marsiglia C., et al. Neutrophil activation and neutrophil extracellular traps (NETs) in COVID-19 ARDS and immunothrombosis // Eur J Immunol. 2023. Vol. 53, N 1. P. e2250010. doi: 10.1002/eji.202250010

[33] Arcanjo A, Logullo J, Menezes CCB, et al. The emerging role of neutrophil extracellular traps in severe acute respiratory syndrome coronavirus 2 (COVID-19). Sci Rep. 2020;10(1):19630. doi: 10.1038/s41598-020-76781-0

[34] Arcanjo A., Logullo J., Menezes C.C.B., et al. The emerging role of neutrophil extracellular traps in severe acute respiratory syndrome coronavirus 2 (COVID-19) // Sci Rep. 2020. Vol. 10, N 1. P. 19630. doi: 10.1038/s41598-020-76781-0

[35] Vanderbeke L, Van Mol P, Van Herck Y, et al. Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity. Nature Communications. 2021;12(1):4117. doi: 10.1038/s41467-021-24360-w

[36] Vanderbeke L., Van Mol P., Van Herck Y., et al. Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity // Nature Communications. 2021. Vol. 12, N 1. P. 4117. doi: 10.1038/s41467-021-24360-w

[37] Junqueira C, Crespo Â, Ranjbar S, et al. FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation. Nature. 2022;606(7914):576–584. doi: 10.1038/s41586-022-04702-4

[38] Junqueira C., Crespo Â., Ranjbar S., et al. FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation // Nature. 2022. Vol. 606, N 7914. P. 576–584. doi: 10.1038/s41586-022-04702-4

[39] Sefik E, Qu R, Junqueira C, et al. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature. 2022;606(7914):585–593. doi: 10.1038/s41586-022-04802-1

[40] Sefik E., Qu R., Junqueira C., et al. Inflammasome activation in infected macrophages drives COVID-19 pathology // Nature. 2022. Vol. 606, N 7914. P. 585–593. doi: 10.1038/s41586-022-04802-1

[41] Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol. 2020;20(6):355–362. doi: 10.1038/s41577-020-0331-4

[42] Merad M., Martin J.C. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages // Nat Rev Immunol. 2020. Vol. 20, N 6. P. 355–362. doi: 10.1038/s41577-020-0331-4

[43] Merad M, Blish CA, Sallusto F, Iwasaki A. The Immunology and Immunopathology of COVID-19. Science. 2022;375(6585):1122–1127. doi: 10.1126/science.abm8108

[44] Merad M., Blish C.A., Sallusto F., Iwasaki A. The Immunology and Immunopathology of COVID-19 // Science. 2022. Vol. 375, N 6585. P. 1122–1127. doi: 10.1126/science.abm8108

[45] Song JW, Zhang C, Fan X, et al. Immunological and inflammatory profiles in mild and severe cases of COVID-19. Nat Commun. 2020;11(1):3410. doi: 10.1038/s41467-020-17240-2

[46] Song J.-W., Zhang C., Fan X., et al. Immunological and inflammatory profiles in mild and severe cases of COVID-19 // Nat Commun. 2020. Vol. 11, N 1. P. 3410. doi: 10.1038/s41467-020-17240-2

[47] O’Sullivan JM, Gonagle DM, Ward SE, Preston RJS, O’Donnell JS. Endothelial cells orchestrate COVID-19 coagulopathy. Lancet Haematol. 2020;7(8):e553–e555. doi: 10.1016/S2352-3026(20)30215-5

[48] O’Sullivan J.M., Gonagle D.M., Ward S.E., Preston R.J.S., O’Donnell J.S. Endothelial cells orchestrate COVID-19 coagulopathy // Lancet Haematol. 2020. Vol. 7, N 8. P. e553–e555. doi: 10.1016/S2352-3026(20)30215-5

[49] Koupenova M, Corkrey HA, Vitseva O, et al. SARS-CoV-2 initiates programmed cell death in platelets. Circ Res. 2021;129(6):631–646. doi: 10.1161/CIRCRESAHA.121.319117

[50] Koupenova M., Corkrey H.A., Vitseva O., et al. SARS-CoV-2 initiates programmed cell death in platelets // Circ Res. 2021. Vol. 129, N 6. P. 631–646. doi: 10.1161/CIRCRESAHA.121.319117

[51] Barbosa LC, Gonçalves TL, de Araujo LP, Rosario LVO, Ferrer VP. Endothelial cells and SARS-CoV-2: An intimate relationship. Vascul Pharmacol. 2021;137:106829. doi: 10.1016/j.vph.2021.106829

[52] Barbosa L.C., Gonçalves T.L., de Araujo L.P., Rosario L.V.O., Ferrer V.P. Endothelial cells and SARS-CoV-2: An intimate relationship // Vascul Pharmacol. 2021. Vol. 137. P. 106829. doi: 10.1016/j.vph.2021.106829

[53] Chan NC, Weitz JI. COVID-19 coagulopathy, thrombosis, and bleeding. Blood. 2020;136(4):381–383. doi: 10.1182/blood.2020007335

[54] Chan N.C., Weitz J.I. COVID-19 coagulopathy, thrombosis, and bleeding // Blood. 2020. Vol. 136, N 4. P. 381–383. doi: 10.1182/blood.2020007335

[55] Hariri LP, North CM, Shih AR, et al. Lung Histopathology in Coronavirus Disease 2019 as Compared With Severe Acute Respiratory Sydrome and H1N1 Influenza: A Systematic Review. Chest. 2021;159(1):73–84. doi: 10.1016/j.chest.2020.09.259

[56] Hariri L.P., North C.M., Shih A.R., et al. Lung Histopathology in Coronavirus Disease 2019 as Compared With Severe Acute Respiratory Sydrome and H1N1 Influenza: A Systematic Review // Chest. 2021. Vol. 159, N 1. P. 73–84. doi: 10.1016/j.chest.2020.09.259

[57] Bailey AL, Dmytrenko O, Greenberg L. SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis. JACC Basic Transl Sci. 2021;6(4):331–345. doi: 10.1016/j.jacbts.2021.01.002

[58] Bailey A.L., Dmytrenko O., Greenberg L. SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis // JACC Basic Transl Sci. 2021. Vol. 6, N 4. P. 331–345. doi: 10.1016/j.jacbts.2021.01.002

[59] Huang I, Pranata R. Lymphopenia in severe coronavirus disease-2019 (COVID-19): systematic review and meta-analysis. J Intensive Care. 2020;8:36. doi: 10.1186/s40560-020-00453-4

[60] Huang I., Pranata R. Lymphopenia in severe coronavirus disease-2019 (COVID-19): systematic review and meta-analysis // J Intensive Care. 2020. Vol. 8. P. 36. doi: 10.1186/s40560-020-00453-4

[61] Li S, Jiang L, Li X, et al. Clinical and pathological investigation of patients with severe COVID-19. JCI Insight. 2020;5(12):e138070. doi: 10.1172/jci.insight.138070

[62] Li S., Jiang L., Li X., et al. Clinical and pathological investigation of patients with severe COVID-19 // JCI Insight. 2020. Vol. 5, N 12. P. e138070. doi: 10.1172/jci.insight.138070

[63] Yang L, Liu S, Liu J, et al. COVID-19: Immunopathogenesis and Immunotherapeutics. Signal Transduct Target Ther. 2020;5(1):128. doi: 10.1038/s41392-020-00243-2

[64] Yang L., Liu S., Liu J., et al. COVID-19: Immunopathogenesis and Immunotherapeutics // Signal Transduct Target Ther. 2020. Vol. 5, N 1. P. 128. doi: 10.1038/s41392-020-00243-2

[65] Zheng M, Gao Y, Wang G, et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020;17(5):533–535. doi: 10.1038/s41423-020-0402-2

[66] Zheng M., Gao Y., Wang G., et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients // Cell Mol Immunol. 2020. Vol. 17, N 5. P. 533–535. doi: 10.1038/s41423-020-0402-2

[67] Zheng HY, Zhang M, Yang CX, 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. 2020;17(5):541–543. doi: 10.1038/s41423-020-0401-3

[68] Zheng H.Y., Zhang M., Yang C.X., 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. 2020. Vol. 17, N 5. P. 541–543. doi: 10.1038/s41423-020-0401-3

[69] Yang Y, Shen C, Li J, et al. Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19. J Allergy Clin Immunol. 2020;146(1):119–127.e4. doi: 10.1016/j.jaci.2020.04.027

[70] Yang Y., Shen C., Li J., et al. Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19 // J Allergy Clin Immunol. 2020. Vol. 146, N 1. P. 119–127.e4. doi: 10.1016/j.jaci.2020.04.027

[71] Sinha A, Singh AK, Kadni TS, Mullick J, Sahu A. Virus-Encoded Complement Regulators: Current Status. Viruses. 2021;13(2):208. doi: 10.3390/v13020208

[72] Sinha A., Singh A.K., Kadni T.S., Mullick J., Sahu A. Virus-Encoded Complement Regulators: Current Status // Viruses. 2021. Vol. 13, N 2. P. 208. doi: 10.3390/v13020208

[73] Savitt AG, Manimala S, White T, et al. SARS-CoV-2 Exacerbates COVID-19 Pathology Through Activation of the Complement and Kinin Systems. Front Immunol. 2021;12:767347. doi: 10.3389/fimmu.2021.767347

[74] Savitt A.G., Manimala S., White T., et al. SARS-CoV-2 Exacerbates COVID-19 Pathology Through Activation of the Complement and Kinin Systems // Front Immunol. 2021. Vol. 12. P. 767347. doi: 10.3389/fimmu.2021.767347

[75] Yu J, Yuan X, Chen H, et al. Direct Activation of the Alternative Complement Pathway by SARS-CoV-2 Spike Proteins is Blocked by Factor D Inhibition. Blood. 2020;136(18):2080–2089. doi: 10.1182/blood.2020008248

[76] Yu J., Yuan X., Chen H., et al. Direct Activation of the Alternative Complement Pathway by SARS-CoV-2 Spike Proteins is Blocked by Factor D Inhibition // Blood. 2020. Vol. 136, N 18. P. 2080–2089. doi: 10.1182/blood.2020008248

[77] Gao T, Zhu L, Liu H, et al. Highly Pathogenic Coronavirus N Protein Aggravates Lung Injury by MASP-2-Mediated Complement Over-Activation. Signal Transduct Target Ther. 2022;7(1):318. doi: 10.1038/s41392-022-01133-5

[78] Gao T., Zhu L., Liu H., et al. Highly Pathogenic Coronavirus N Protein Aggravates Lung Injury by MASP-2-Mediated Complement Over-Activation // Signal Transduct Target Ther. 2022. Vol. 7, N 1. P. 318. doi: 10.1038/s41392-022-01133-5

[79] Noris M, Benigni A, Remuzzi G. The case of complement activation in COVID-19 multiorgan impact. Kidney Int. 2020;98(2):314–322. doi: 10.1016/j.kint.2020.05.013

[80] Noris M., Benigni A., Remuzzi G. The case of complement activation in COVID-19 multiorgan impact // Kidney Int. 2020.Vol. 98, N 2. P. 314–322. doi: 10.1016/j.kint.2020.05.013

[81] Keragala CB, Draxler DF, McQuilten ZK, Medcalf RL. Haemostasis and innate immunity — a complementary relationship: a review of the intricate relationship between coagulation and complement pathways. Br J Haematol. 2018;180(6):782–798. doi: 10.1111/bjh.15062

[82] Keragala C.B., Draxler D.F., McQuilten Z.K., Medcalf R.L. Haemostasis and innate immunity — a complementary relationship: a review of the intricate relationship between coagulation and complement pathways // Br J Haematol. 2018. Vol. 180, N 6. P. 782–798. doi: 10.1111/bjh.15062

[83] Jodele S, Köhl J. Tackling COVID-19 Infection Through Complement-Targeted Immunotherapy. Br J Pharmacol. 2020;178(14):2832–2848. doi: 10.1111/bph.15187

[84] Jodele S., Köhl J. Tackling COVID-19 Infection Through Complement-Targeted Immunotherapy // Br J Pharmacol. 2020. Vol. 178, N 14. P. 2832–2848. doi: 10.1111/bph.15187

[85] Wang R, Xiao H, Guo R, Li Y., Shen B. The role of C5a in acute lung injury induced by highly pathogenic viral infections. Emerg Microbes Infect. 2015;4(5):e28. doi: 10.1038/emi.2015.28

[86] Wang R., Xiao H., Guo R., Li Y., Shen B. The role of C5a in acute lung injury induced by highly pathogenic viral infections // Emerg Microbes Infect. 2015. Vol. 4, N 5. P. e28. doi: 10.1038/emi.2015.28

[87] Diao B, Wang C, Wang R, et al. Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Nat Commun. 2021;12(1):2506. doi: 10.1038/s41467-021-22781-1

[88] Diao B., Wang C., Wang R., et al. Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection // Nat Commun. 2021. Vol. 12, N 1. P. 2506. doi: 10.1038/s41467-021-22781-1

[89] Lee MH, Perl DP, Steiner J, et al. Neurovascular injury with complement activation and inflammation in COVID-19. Brain. 2022;145(7):2555–2568. doi: 10.1093/brain/awac151

[90] Lee M.H., Perl D.P., Steiner J., et al. Neurovascular injury with complement activation and inflammation in COVID-19 // Brain. 2022. Vol. 145, N 7. P. 2555–2568. doi: 10.1093/brain/awac151

[91] Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579(7798):265–269. doi: 10.1038/s41586-020-2008-3

[92] Wu F., Zhao S., Yu B., et al. A new coronavirus associated with human respiratory disease in China // Nature. 2020. Vol. 579, N 7798. P. 265–269. doi: 10.1038/s41586-020-2008-3

[93] Batah S, Fabro A. Pulmonary pathology of ARDS in COVID-19: A pathological review for clinicians. Respir Med. 2021;176:106239. doi: 10.1016/j.rmed.2020.106239

[94] Batah S., Fabro A. Pulmonary pathology of ARDS in COVID-19: A pathological review for clinicians // Respir Med. 2021. Vol. 176. P. 106239. doi: 10.1016/j.rmed.2020.106239

[95] Liu J, Li S, Liu J, et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine. 2020;55:102763. doi: 10.1016/j.ebiom.2020.102763

[96] Liu J., Li S., Liu J., et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients // EBioMedicine. 2020. Vol. 55. P. 102763. doi: 10.1016/j.ebiom.2020.102763

[97] Maxwell AJ, Ding J, You Y, et al. Identifcation of key signaling pathways induced by SARS-CoV-2 that underlie thrombosis and vascular injury in COVID-19 patients. J Leukoc Biol. 2021;109(1):35–47. doi: 10.1002/JLB.4COVR0920-552RR

[98] Maxwell A.J., Ding J., You Y., et al. Identifcation of key signaling pathways induced by SARS-CoV-2 that underlie thrombosis and vascular injury in COVID-19 patients // J Leukoc Biol. 2021. Vol. 109, N 1. P. 35–47. doi: 10.1002/JLB.4COVR0920-552RR

[99] Ahsan S, Draghici S. Identifying significantly impacted pathways and putative mechanisms with iPathwayGuide. Curr Protoc Bioinforma. 2017;57:7.15.1–7.15.30. doi: 10.1002/cpbi.24

[100] Ahsan S., Draghici S. Identifying significantly impacted pathways and putative mechanisms with iPathwayGuide // Curr Protoc Bioinforma. 2017. Vol. 57. P. 7.15.1–7.15.30. doi: 10.1002/cpbi.24

[101] Bhattacharya P, Budnick I, Singh M, et al. Dual role of GM-CSF as a pro-inflammatory and a regulatory cytokine: implications for immune therapy. J Interferon Cytokine Res. 2015;35(8):585–599. doi: 10.1089/jir.2014.0149

[102] Bhattacharya P., Budnick I., Singh M., et al. Dual role of GM-CSF as a pro-inflammatory and a regulatory cytokine: implications for immune therapy // J Interferon Cytokine Res. 2015. Vol. 35, N 8. P. 585–599. doi: 10.1089/jir.2014.0149

[103] Lagunas-Rangel FA. Neutrophil-to-lymphocyte ratio and lymphocyte-to-C-reactive protein ratio in patients with severe coronavirus disease 2019 (COVID-19): a meta-analysis. J Med Virol. 2020;8(10):1733–1734. doi: 10.1002/jmv.25819

[104] Lagunas-Rangel F.A. Neutrophil-to-lymphocyte ratio and lymphocyte-to-C-reactive protein ratio in patients with severe coronavirus disease 2019 (COVID-19): a meta-analysis // J Med Virol. 2020. Vol. 8, N 10. P. 1733–1734. doi: 10.1002/jmv.25819

[105] Lu Q, Liu J, Zhao S, et al. SARS-CoV-2 exacerbates proinflammatory responses in myeloid cells through C-type lectin receptors and Tweety family member 2. Immunity. 2021;54(6):1304–1319.e9. doi: 10.1016/j.immuni.2021.05.006

[106] Lu Q., Liu J., Zhao S., et al. SARS-CoV-2 exacerbates proinflammatory responses in myeloid cells through C-type lectin receptors and Tweety family member 2 // Immunity. 2021. Vol. 54, N 6. P. 1304–1319.e9. doi: 10.1016/j.immuni.2021.05.006

[107] Radermecker C, Detrembleur N, Guiot J, et al. Neutrophil extracellular traps infiltrate the lung airway, interstitial, and vascular compartments in severe COVID-19. J Exp Med. 2020;217(12). doi: 10.1084/jem.20201012

[108] Radermecker C., Detrembleur N., Guiot J., et al. Neutrophil extracellular traps infiltrate the lung airway, interstitial, and vascular compartments in severe COVID-19 // J Exp Med. 2020. Vol. 217, N 12. doi: 10.1084/jem.20201012

[109] Van den Berg RH, Faber-Krol MC, Sim RB, et al. The first subcomponent of complement, C1q, triggers the production of IL-8, IL-6, and monocyte chemoattractant peptide-1 by human umbilical vein endothelial cells. J Immunol. 1998;161(12):6924–6930.

[110] Van den Berg R.H., Faber-Krol M.C., Sim R.B., et al. The first subcomponent of complement, C1q, triggers the production of IL-8, IL-6, and monocyte chemoattractant peptide-1 by human umbilical vein endothelial cells // J Immunol. 1998. Vol. 161, N 12. P. 6924–6930.

[111] Afrin LB, Weinstock LB, Molderings GJ. COVID-19 hyperinflammation and post-COVID-19 illness may be rooted in mast cell activation syndrome. Int J Infec Dis. 2020;100:327–332. doi: 10.1016/j.ijid.2020.09.016

[112] Afrin L.B., Weinstock L.B., Molderings G.J. COVID-19 hyperinflammation and post-COVID-19 illness may be rooted in mast cell activation syndrome // Int J Infec Dis. 2020. Vol. 100. P. 327–332. doi: 10.1016/j.ijid.2020.09.016

[113] Theoharides TC. COVID-19, pulmonary mast cells, cytokine storms, and beneficial actions of luteolin. Biofactors. 2020;46(3):306–308. doi: 10.1002/biof.1633

[114] Theoharides T.C. COVID-19, pulmonary mast cells, cytokine storms, and beneficial actions of luteolin // Biofactors. 2020. Vol. 46, N 3. P. 306–308. doi: 10.1002/biof.1633

[115] Caillet-Saguy C, Durbesson F, Rezelj VV, et al. Host PDZ-containing proteins targeted by SARS-CoV-2. FEBS J. 2021;288(17):5148–5162. doi: 10.1111/febs.15881

[116] Caillet-Saguy C., Durbesson F., Rezelj V.V., et al. Host PDZ-containing proteins targeted by SARS-CoV-2 // FEBS J. 2021. Vol. 288, N 17. P. 5148–5162. doi: 10.1111/febs.15881

[117] Tsilioni I, Theoharides TC. Recombinant SARS-CoV-2 Spike Protein Stimulates Secretion of Chymase, Tryptase, and IL-1β from Human Mast Cells, Augmented by IL-33. Int J Mol Sci. 2023;24(11):9487. doi: 10.3390/ijms24119487

[118] Tsilioni I., Theoharides T.C. Recombinant SARS-CoV-2 Spike Protein Stimulates Secretion of Chymase, Tryptase, and IL-1β from Human Mast Cells, Augmented by IL-33 // Int J Mol Sci. 2023. Vol. 24, N 11. P. 9487. doi: 10.3390/ijms24119487

RIGHTS & PERMISSIONS

Eco-Vector