psychiatryПСИХИАТРИЯPsychiatry (Moscow) (Psikhiatriya)1683-83192618-6667FSBSI “The Mental Health Research Centre”; LLC «Publisher «MIA»10.30629/2618-6667-2021-19-4-76-89psychiatry-726Research ArticleНАУЧНЫЕ ОБЗОРЫSCIENTIFIC REVIEWSРоль системы комплемента в патогенезе вирусной инфекции SARS-CoV-2 при психических заболеванияхThe Role of the Complement System in the Pathogenesis of SARS-CoV-2 Viral Infection in Mental Illnesshttps://orcid.org/0000-0001-5166-4462ЧеремныхЕ. Г.CheremnykhE. G.

Елена Григорьевна Черемных, кандидат технических наук, лаборатория биохимии

Москва

Elena G. Cheremnykh, Cand. of Sci. (Techn.), Laboratory of Biochemistry

Moscow

elcher10@yandex.ruhttps://orcid.org/0000-0002-7105-7579ИвановП. А.IvanovP. A.

Павел Александрович Иванов, кандидат биологических наук, лаборатория нейроиммунологии

Москва

Pavel I. Ivanov, Cand. of Sci. (Biol.), Laboratory of Neuroimmunology

Moscow

ivanovpa@mail.ruhttps://orcid.org/0000-0003-4366-5558ФакторМ. И.FactorM. I.

Магнолия Иосифовна Фактор, кандидат биологических наук, лаборатория биохимии

Москва

Magnolia I. Faсtor, Cand. Sci. (Biol.), Laboratory of Biochemistry

Moscow

magnolia-faktor@mail.ruhttps://orcid.org/0000-0002-9137-0167ПоздняковаА. Н.PozdnyacovaA. N.

Анастасия Николаевна Позднякова, младший научный сотрудник, лаборатория нейрофизиологии

Москва

Anastasiya N. Pozdnyacova, Junior Researcher, Neurophysiology Laboratoriy

Moscow

fanianastya@gmail.comhttps://orcid.org/0000-0001-9301-2294ШиловЮ. Е.ShilovY. E.

Юрий Евгеньевич Шилов, кандидат биологических наук, лаборатория биохимии

Москва

Yuri E. Shilov, Cand. Sci. (Biol.), Laboratory of Biochemistry

Moscow

shilov.biochem@gmail.comhttps://orcid.org/0000-0003-1269-679XБрусовО. С.BrusovO. S.

Олег Сергеевич Брусов, кандидат биологических наук, заведующий лабораторией, лаборатория биохимии

Москва

Oleg S. Brusov, Cand. Sci. (Biol.), Head of the Laboratory of Biochemistry

Moscow

oleg.brusow@yandex.ruНаучный центр психического здоровьяРоссияMental Health Research CentreRussian Federation2021171220211947689Copyright © Черемных Е.Г., Иванов П.А., Фактор М.И., Позднякова А.Н., Шилов Ю.Е., Брусов О.С., 20212021Черемных Е.Г., Иванов П.А., Фактор М.И., Позднякова А.Н., Шилов Ю.Е., Брусов О.С.Cheremnykh E.G., Ivanov P.A., Factor M.I., Pozdnyacova A.N., Shilov Y.E., Brusov O.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.journalpsychiatry.com/jour/article/view/726

Введение: система комплемента может быть критическим фактором, определяющим исход коронавирусной инфекции COVID-19. Для многих психических заболеваний характерно системное стерильное воспаление, обязательным участником которого является система комплемента. Цель: представить анализ научных данных о роли системы комплемента в патогенезе вирусных заболеваний и особенностей течения COVID-19 у психически больных. Материал и методы: с помощью ключевых слов «система комплемента и коронавирусная инфекция 2019», «ингибирование системы комплемента», «коронавирусная инфекция 2019 и психические заболевания» проводился поиск научных статей в базах данных MEDLINE, PubMed и других источниках. Заключение: пациенты с психическими заболеваниями относятся к группе риска в силу физиологических и ментальных особенностей, а инфицирование вирусом SARS-CoV-2 может провоцировать рецидив основного заболевания. Терапевтическое ингибирование системы комплемента поможет снизить этот риск и уменьшить вероятность тяжелых осложнений при системном воспалении, вызванном этой инфекцией.

Introduction: the complement system can be a critical factor in the outcome of SARS-CoV-2 viral infection. Many mental illnesses are characterized by systemic sterile inflammation, in which the complement system is an obligatory participant. Purpose: to present an analysis of scientific data on the role of the complement system in the pathogenesis of viral diseases and the characteristics of the course of COVID-19 in mental patients. Material and methods: the keywords “complement system” “SARS-CoV-2”, “inhibition of the complement system”, “COVID-19” “mental illness” were used to search scientific articles in the databases MEDLINE, PubMed and other bibliographic sources. Conclusion: patients with mental illness are at risk due to physiological and mental characteristics, and infection with SARS-CoV-2 can provoke a relapse of the underlying disease. Therapeutic inhibition of complement system will help reduce this risk and reduce the likelihood of severe complications from systemic inflammation caused by this infection.

система комплементаSARS-CoV-2ингибирование системы комплементаCOVID-19психические заболеванияcomplement system and SARS-CoV-2complement system inhibitionCOVID-19 and mental illnessReferencesBohmwald K, Gálvez NMS, Ríos M, Kalergis AM. Neurologic Alterations Due to Respiratory Virus Infections Front. Cell. Neurosci. 2018;12:386. doi: 10.3389/fncel.2018.00386Bohmwald K, Gálvez NMS, Ríos M, Kalergis AM. Neurologic Alterations Due to Respiratory Virus Infections Front. Cell. Neurosci. 2018;12:386. doi: 10.3389/fncel.2018.00386Kwan WH, van der Touw W, Heeger PS. Complement regulation of T cell immunity. Immunol Res. 2012;54:247–253. doi: 10.1007/s12026-012-8327-1Kwan WH, van der Touw W, Heeger PS. Complement regulation of T cell immunity. Immunol Res. 2012;54:247–253. doi: 10.1007/s12026-012-8327-1Stephan AH, Barres BA, Stevens B. The Complement System: An Unexpected Role in Synaptic Pruning Development and disease. Annual Review of Neuroscience. 2012;35:369–389. http://doi.org/10.1146/annurev-neuro-061010-113810Stephan AH, Barres BA, Stevens B. The Complement System: An Unexpected Role in Synaptic Pruning Development and disease. Annual Review of Neuroscience. 2012;35:369–389. http://doi.org/10.1146/annurev-neuro-061010-113810Camous L, Roumenina L, Bigot S, Soumenya Brachemi, Fremeaux-Bacchi V, Lesavre P, Halbwachs-Mecarelli L. Complement alternative pathway acts as a positive feedback amplification of neutrophil activation. Blood. 2011;117:1340–1349. http://doi.org/10.1182/blood-2010-05-283564Camous L, Roumenina L, Bigot S, Soumenya Brachemi, Fremeaux-Bacchi V, Lesavre P, Halbwachs-Mecarelli L. Complement alternative pathway acts as a positive feedback amplification of neutrophil activation. Blood. 2011;117:1340–1349. http://doi.org/10.1182/blood-2010-05-283564Hourcade DE. The role of properdin in the assembly of the alternative pathway C3 convertases of complement. J Biol Chem. 2006 Jan 27;281(4):2128–2132. doi: 10.1074/jbc.M508928200 Epub 2005 Nov 21. PMID: 16301317Hourcade DE. The role of properdin in the assembly of the alternative pathway C3 convertases of complement. J Biol Chem. 2006 Jan 27;281(4):2128–2132. doi: 10.1074/jbc.M508928200 Epub 2005 Nov 21. PMID: 16301317Tenner AJ, Volkin DB. Complement subcomponent C1q secreted by cultured human monocytes has subunit structure identical with that of serum C1q. Biochem J. 1986; 233:451–458. doi: 10.1042/bj2330451Tenner AJ, Volkin DB. Complement subcomponent C1q secreted by cultured human monocytes has subunit structure identical with that of serum C1q. Biochem J. 1986; 233:451–458. doi: 10.1042/bj2330451Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010;11:785–797. doi: 10.1038/ni.1923Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010;11:785–797. doi: 10.1038/ni.1923Druart M, Le Magueresse C. Emerging Roles of Complement in Psychiatric Disorders. Front Psychiatry. 2019;10:573. doi: 10.3389/fpsyt.2019.00573 PMID: 31496960; PMCID: PMC6712161Druart M, Le Magueresse C. Emerging Roles of Complement in Psychiatric Disorders. Front Psychiatry. 2019;10:573. doi: 10.3389/fpsyt.2019.00573 PMID: 31496960; PMCID: PMC6712161Lambris JD, Ricklin D, Geisbrecht BV. Complement evasion by human pathogens. Nat Rev Microbiol. 2008;6(2):132. doi: 10.1038/nrmicro182Lambris JD, Ricklin D, Geisbrecht BV. Complement evasion by human pathogens. Nat Rev Microbiol. 2008;6(2):132. doi: 10.1038/nrmicro182Biro A, Rovo Z, Papp D, Cervenak L, Varga L, Fust G, Thielens NM, Arlaud GJ, Prohaszka Z. Studies on the interactions between C-reactive protein and complement proteins. Immunology. 2007;121(1):40–50. doi: 10.1111/j.1365-2567.2007.02535.xBiro A, Rovo Z, Papp D, Cervenak L, Varga L, Fust G, Thielens NM, Arlaud GJ, Prohaszka Z. Studies on the interactions between C-reactive protein and complement proteins. Immunology. 2007;121(1):40–50. doi: 10.1111/j.1365-2567.2007.02535.xRicklin D, Reis ES, Mastellos DC, Gros P, Jambris JD. Complement component C3 — The “Swiss Army Knife” of innate immunity and host defense. Immunol Rev. 2016;274(1):33–58. doi: 10.1111/imr.12500Ricklin D, Reis ES, Mastellos DC, Gros P, Jambris JD. Complement component C3 — The “Swiss Army Knife” of innate immunity and host defense. Immunol Rev. 2016;274(1):33–58. doi: 10.1111/imr.12500Sturfelt G, Truedsson L. Complement in the immunopathogenesis of rheumatic disease. Nature Reviews Rheumatology. 2012;8:458–468. doi: 10.1038/nrrheum.2012.75Sturfelt G, Truedsson L. Complement in the immunopathogenesis of rheumatic disease. Nature Reviews Rheumatology. 2012;8:458–468. doi: 10.1038/nrrheum.2012.75Amara U, Flierl MA, Rittirsch D, Klos A, Chen H, Acker B, Brückner UB, Nilsson B, Gebhard F, Lambris JD, Huber-Lang M. Molecular Intercommunication between the Complement and Coagulation Systems. J Immunol. 2010;185:5628–5636. doi: 10.4049/jimmunol.0903678Amara U, Flierl MA, Rittirsch D, Klos A, Chen H, Acker B, Brückner UB, Nilsson B, Gebhard F, Lambris JD, Huber-Lang M. Molecular Intercommunication between the Complement and Coagulation Systems. J Immunol. 2010;185:5628–5636. doi: 10.4049/jimmunol.0903678Oikonomopoulou K, Ricklin D, Ward PA, Lambris JD. Interactions between coagulation and complement — their role in inflammation. Semin Immunopathol. 2012;34(1):151–165. doi: 10.1007/s00281-011-0280-x.Oikonomopoulou K, Ricklin D, Ward PA, Lambris JD. Interactions between coagulation and complement — their role in inflammation. Semin Immunopathol. 2012;34(1):151–165. doi: 10.1007/s00281-011-0280-x.Landsem A, Fure H, Christiansen D, Nielsen EW, Osterud B, Mollnes TE, Brekke OL. The key roles of complement and tissue factor in Escherichia coli-induced coagulation in human whole blood. Clin. Exp. Immunol. 2015;182:81–89. doi: 10.1111/cei.12663Landsem A, Fure H, Christiansen D, Nielsen EW, Osterud B, Mollnes TE, Brekke OL. The key roles of complement and tissue factor in Escherichia coli-induced coagulation in human whole blood. Clin. Exp. Immunol. 2015;182:81–89. doi: 10.1111/cei.12663Krarup A, Wallis R, Presanis JS, Gál P, Sim RB. Simultaneous activation of complement and coagulation by MBL-associated serine protease 2. PLoS One 2(7):e623. doi: 10.1371/journal.pone.0000623Krarup A, Wallis R, Presanis JS, Gál P, Sim RB. Simultaneous activation of complement and coagulation by MBL-associated serine protease 2. PLoS One 2(7):e623. doi: 10.1371/journal.pone.0000623Hess K, Ajjan R, Phoenix F, Dobo J, Gál P., Schroeder V. Effects of MASP-1 of the complement system on activation of coagulation factors and plasma clot formation. PLoS One. 2012;7(4):e35690. doi: 10.1371/journal.pone.0035690Hess K, Ajjan R, Phoenix F, Dobo J, Gál P., Schroeder V. Effects of MASP-1 of the complement system on activation of coagulation factors and plasma clot formation. PLoS One. 2012;7(4):e35690. doi: 10.1371/journal.pone.0035690Fletcher-Sandersjooa A, Bellander BM. Is COVID-19 associated thrombosis caused by overactivation of the complement cascade? Thrombosis Research. 2020;194:36–41. http://doi.org/10.1016/j.thromres.2020:06.027Fletcher-Sandersjooa A, Bellander BM. Is COVID-19 associated thrombosis caused by overactivation of the complement cascade? Thrombosis Research. 2020;194:36–41. http://doi.org/10.1016/j.thromres.2020:06.027Wallace EM, Perkins SM, Sim PB, Willis AC, Feighery C, Jackson J. Degradation of C1-inhibitor by plasmin: implications for the control of inammatory processes. Mol Med. 1997;3(6):385–396.Wallace EM, Perkins SM, Sim PB, Willis AC, Feighery C, Jackson J. Degradation of C1-inhibitor by plasmin: implications for the control of inammatory processes. Mol Med. 1997;3(6):385–396.Foley JH, Walton BL, Aleman MM, O’Byrne AM, Lei V, Harrasser M, Foley KA, Wolberg AS, Conway EM. Complement activation in arterial and venous thrombosis is mediated by plasmin. EBioMedicine. 2016;5:175–182. doi: 10.1016/j.ebiom.2016.02.011Foley JH, Walton BL, Aleman MM, O’Byrne AM, Lei V, Harrasser M, Foley KA, Wolberg AS, Conway EM. Complement activation in arterial and venous thrombosis is mediated by plasmin. EBioMedicine. 2016;5:175–182. doi: 10.1016/j.ebiom.2016.02.011Foley JH, Conway EM. Cross talk pathways between coagulation and inflammation. Circ. Res. 2016;118:1392–1408. doi: 10.1161/CIRCRESAHA.116.306853Foley JH, Conway EM. Cross talk pathways between coagulation and inflammation. Circ. Res. 2016;118:1392–1408. doi: 10.1161/CIRCRESAHA.116.306853Dobó J, Schroeder V, Jenny L, Cervenak L, Závodszky P, Gál P. Multiple roles of complement MASP-1 at the interface of innate immune response and coagulation. Mol Immunol. 2014;61:69–78. doi: 10.1016/j.molimm.2014.05.013Dobó J, Schroeder V, Jenny L, Cervenak L, Závodszky P, Gál P. Multiple roles of complement MASP-1 at the interface of innate immune response and coagulation. Mol Immunol. 2014;61:69–78. doi: 10.1016/j.molimm.2014.05.013Wiedmer T, Esmon CT, Sims PJ. Complement proteins C5b-9 stimulate procoagulant activity through platelet prothrombinase. Blood. 1986;68:875–880.Wiedmer T, Esmon CT, Sims PJ. Complement proteins C5b-9 stimulate procoagulant activity through platelet prothrombinase. Blood. 1986;68:875–880.Hamad OA, Bäck J, Nilsson PH, NilssonB, Ekdahl KN. Platelets, complement, and contact activation: partners in inflammation and thrombosis. Advances in Experimental Medicine and Biology. 2012;946:185–205. doi: 10.1007/978-1-4614-0106-3_11Hamad OA, Bäck J, Nilsson PH, NilssonB, Ekdahl KN. Platelets, complement, and contact activation: partners in inflammation and thrombosis. Advances in Experimental Medicine and Biology. 2012;946:185–205. doi: 10.1007/978-1-4614-0106-3_11Subramaniam S, Jurk K, Hobohm L, Jackel S, Saffarzadeh M, Schwierczek K, Wenzel P, Langer F, Reinhardt C, Ruf W. Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development. Blood. 2017;129:2291–2302. doi: 10.1182/blood-2016-11-749879Subramaniam S, Jurk K, Hobohm L, Jackel S, Saffarzadeh M, Schwierczek K, Wenzel P, Langer F, Reinhardt C, Ruf W. Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development. Blood. 2017;129:2291–2302. doi: 10.1182/blood-2016-11-749879Nilsson PH. Interaction between platelets and complement with implication for the regulation at surfaces. Doctoral dissertation, School of Natural Sciences, Linnaeus University 2012; ISBN: 978-91- 86983-46-8Nilsson PH. Interaction between platelets and complement with implication for the regulation at surfaces. Doctoral dissertation, School of Natural Sciences, Linnaeus University 2012; ISBN: 978-91- 86983-46-8Java A, Kim AHJ, Kulkarni HS. The complement system in COVID-19: friend and foe? JCI Insight. 2020; https://doi.org/10.1172/jci.insight.140711Java A, Kim AHJ, Kulkarni HS. The complement system in COVID-19: friend and foe? JCI Insight. 2020; https://doi.org/10.1172/jci.insight.140711Yang T, Xu C. Physiology and Pathophysiology of the Intrarenal Renin-Angiotensin System: An Update. J Am Soc Nephrol. 2017;28:1040–1049. doi: 10.1681/ASN.2016070734Yang T, Xu C. Physiology and Pathophysiology of the Intrarenal Renin-Angiotensin System: An Update. J Am Soc Nephrol. 2017;28:1040–1049. doi: 10.1681/ASN.2016070734Wiesea OJ, Allwoodb BW, Zemlin AE. COVID-19 and the renin-angiotensin system (RAS): A spark that sets the forest alight? Medical Hypotheses. 2020;144:110231. http://doi.org/10.1016/j.mehy.2020.110231Wiesea OJ, Allwoodb BW, Zemlin AE. COVID-19 and the renin-angiotensin system (RAS): A spark that sets the forest alight? Medical Hypotheses. 2020;144:110231. http://doi.org/10.1016/j.mehy.2020.110231Shagdarsuren E, Wellner M, Braesen JH, Park JK, Fiebeler A, Henke N, Dechend R, Gratze P, Luft FC, Muller DN. Complement Activation in Angiotensin II-Induced Organ Damage. Circ Res. 2005;97:716–724. doi: 10.1161/01.RES.0000182677.89816.38Shagdarsuren E, Wellner M, Braesen JH, Park JK, Fiebeler A, Henke N, Dechend R, Gratze P, Luft FC, Muller DN. Complement Activation in Angiotensin II-Induced Organ Damage. Circ Res. 2005;97:716–724. doi: 10.1161/01.RES.0000182677.89816.38Stoermer KA, Morrison TE. Complement and viral pathogenesis. Virology. 2011;411:362–373. doi: 10.1016/j.virol.2010.12.045Stoermer KA, Morrison TE. Complement and viral pathogenesis. Virology. 2011;411:362–373. doi: 10.1016/j.virol.2010.12.045Matricardi PM, Dal Negro RW, Nisini R. The first, holistic immunological model of COVID-19: Implications for prevention, diagnosis, and public health measures. Pediatr Allergy Immunol. 2020;31(5):454–470. doi: 10.1111/pai.13271 Epub 2020 Jun 5. PMID: 32359201; PMCID: PMC7267459Matricardi PM, Dal Negro RW, Nisini R. The first, holistic immunological model of COVID-19: Implications for prevention, diagnosis, and public health measures. Pediatr Allergy Immunol. 2020;31(5):454–470. doi: 10.1111/pai.13271 Epub 2020 Jun 5. PMID: 32359201; PMCID: PMC7267459To KF, Lo AWI. Exploring the pathogenesis of severe acute respiratory syndrome (SARS): the tissue distribution of the coronavirus (SARS-CoV) and its putative receptor, angiotensin-converting enzyme 2 (ACE2). J Pathol. 2004;203:740–743. doi: 10.1002/path.1597To KF, Lo AWI. Exploring the pathogenesis of severe acute respiratory syndrome (SARS): the tissue distribution of the coronavirus (SARS-CoV) and its putative receptor, angiotensin-converting enzyme 2 (ACE2). J Pathol. 2004;203:740–743. doi: 10.1002/path.1597Anand P, Puranik A, Aravamudan M, Venkatakrishnan AJ, Soundararajan V. SARS-CoV-2 strategically mimics proteolytic activation of human EnaC. Cite as: eLife. 2020;9:e58603. doi: 10.7554/eLife.58603Anand P, Puranik A, Aravamudan M, Venkatakrishnan AJ, Soundararajan V. SARS-CoV-2 strategically mimics proteolytic activation of human EnaC. Cite as: eLife. 2020;9:e58603. doi: 10.7554/eLife.58603Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450–454. doi: 10.1038/nature02145Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450–454. doi: 10.1038/nature02145McBride R, Van Zyl M, Fielding BC. The Coronavirus Nucleocapsid Is a Multifunctional Protein. Viruses. 2014;6(8);2991–3018. https://doi.org/10.3390/v6082991McBride R, Van Zyl M, Fielding BC. The Coronavirus Nucleocapsid Is a Multifunctional Protein. Viruses. 2014;6(8);2991–3018. https://doi.org/10.3390/v6082991Risitano M, Mastellos DC, Huber-Lang M, Yancopoulou D, Garlanda C, Ciceri F, Lambris JD Complement as a target in COVID-19? Nat Rev Immunol. 2020;20(6):343–344. http://doi.org/10.1038/s41577-020-0320-7Risitano M, Mastellos DC, Huber-Lang M, Yancopoulou D, Garlanda C, Ciceri F, Lambris JD Complement as a target in COVID-19? Nat Rev Immunol. 2020;20(6):343–344. http://doi.org/10.1038/s41577-020-0320-7Veerhuis R, Nielsen HM, Tenner AJ. Complement in the brain. Mol Immunol. 2011;48(14):1592–1603. doi: 10.1016/j.molimm.2011.04.003. Epub 2011 May 4. PMID: 21546088; PMCID: PMC3142281Veerhuis R, Nielsen HM, Tenner AJ. Complement in the brain. Mol Immunol. 2011;48(14):1592–1603. doi: 10.1016/j.molimm.2011.04.003. Epub 2011 May 4. PMID: 21546088; PMCID: PMC3142281Aiyaz M, Lupton MK, Proitsi P, Powell JF, Lovestone S. Complement activation as a biomarker for Alzheimer’s disease. Immunobiology. 2012;217(2):204–215. doi: 10.1016/j.imbio.2011.07.023Aiyaz M, Lupton MK, Proitsi P, Powell JF, Lovestone S. Complement activation as a biomarker for Alzheimer’s disease. Immunobiology. 2012;217(2):204–215. doi: 10.1016/j.imbio.2011.07.023Mayilyan KR, Weinberger DR, Sim RB. The Complement System in Schizophrenia Drug. News Perspect. 2008;21(4):200–210. doi: 10.1358/dnp.2008.21.4.1213349Mayilyan KR, Weinberger DR, Sim RB. The Complement System in Schizophrenia Drug. News Perspect. 2008;21(4):200–210. doi: 10.1358/dnp.2008.21.4.1213349Oliveira J, Oliveira-Maia AJ, Tamouza R, Brown AS, Leboyer M. Infectious and immunogenetic factors in bipolar disorder. Acta Psychiatr Scand. 2017;136(4):409–423. doi: 10.1111/acps.12791Oliveira J, Oliveira-Maia AJ, Tamouza R, Brown AS, Leboyer M. Infectious and immunogenetic factors in bipolar disorder. Acta Psychiatr Scand. 2017;136(4):409–423. doi: 10.1111/acps.12791Corbett BA, Kantor AB, Schulman H, Walker WL, Lit L, Ashwood P, Rocke DM, Sharp FR. A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins. Mol Psychiatry. 2007;12(3):292–306. doi: 10.1038/sj.mp.4001943 Epub 2006 Dec 26. PMID: 17189958Corbett BA, Kantor AB, Schulman H, Walker WL, Lit L, Ashwood P, Rocke DM, Sharp FR. A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins. Mol Psychiatry. 2007;12(3):292–306. doi: 10.1038/sj.mp.4001943 Epub 2006 Dec 26. PMID: 17189958Mongan D, Cannon M, Cotter DR. COVID-19, hypercoagulation and what it could mean for patients with psychotic disorders. Brain Behav Immun. 2020 Aug;88(2):9–10. doi: 10.1016/j.bbi.2020.05.067Mongan D, Cannon M, Cotter DR. COVID-19, hypercoagulation and what it could mean for patients with psychotic disorders. Brain Behav Immun. 2020 Aug;88(2):9–10. doi: 10.1016/j.bbi.2020.05.067Håvik B, Le Hellard S, Rietschel M, Lybæk H, Djurovic S, Mattheisen M, Mühleisen TW, Degenhardt F, Priebe L, Maier W, Breuer R, Schulze TG, Agartz I, Melle I, Hansen T, Bramham CR, Nöthen MM, Stevens B, Werge T, Andreassen OA, Cichon S, Steen Vidar M. The Complement Control-Related Genes CSMD1 and CSMD2 Associate to Schizophrenia. Biol Psychiatry. 2011;70:35–42. doi: 10.1016/j.biopsychHåvik B, Le Hellard S, Rietschel M, Lybæk H, Djurovic S, Mattheisen M, Mühleisen TW, Degenhardt F, Priebe L, Maier W, Breuer R, Schulze TG, Agartz I, Melle I, Hansen T, Bramham CR, Nöthen MM, Stevens B, Werge T, Andreassen OA, Cichon S, Steen Vidar M. The Complement Control-Related Genes CSMD1 and CSMD2 Associate to Schizophrenia. Biol Psychiatry. 2011;70:35–42. doi: 10.1016/j.biopsychGood P. Evidence the U.S. autism epidemic initiated by acetaminophen (Tylenol) is aggravated by oral antibiotic amoxicillin/clavulanate (Augmentin) and now exponentially by herbicide glyphosate (Roundup). Clinical Nutrition. 2017;171–183. http://doi.org/10.1016/j.clnespGood P. Evidence the U.S. autism epidemic initiated by acetaminophen (Tylenol) is aggravated by oral antibiotic amoxicillin/clavulanate (Augmentin) and now exponentially by herbicide glyphosate (Roundup). Clinical Nutrition. 2017;171–183. http://doi.org/10.1016/j.clnespMayilyan KR, Dodds AW, Boyajyan AS, Soghoyan AF, Sim RB. Complement C4B protein in schizophrenia. World J Biol Psychiatry. 2008;9(3):225–230. doi: 10.1080/15622970701227803 PMID: 17853297Mayilyan KR, Dodds AW, Boyajyan AS, Soghoyan AF, Sim RB. Complement C4B protein in schizophrenia. World J Biol Psychiatry. 2008;9(3):225–230. doi: 10.1080/15622970701227803 PMID: 17853297Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR, Kamitaki N, Tooley K, Presumey J, Baum M, Van Doren V, Genovese G, Rose SA, Handsaker RE; Schizophrenia Working Group of the Psychiatric Genomics Consortium, Daly MJ, Carroll MC, Stevens B, McCarroll SA. Schizophrenia risk from complex variation of complement component 4. Nature. 2016;530(7589):177–183. doi: 10.1038/nature16549 Epub 2016 Jan 27. PMID: 26814963; PMCID: PMC4752392Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR, Kamitaki N, Tooley K, Presumey J, Baum M, Van Doren V, Genovese G, Rose SA, Handsaker RE; Schizophrenia Working Group of the Psychiatric Genomics Consortium, Daly MJ, Carroll MC, Stevens B, McCarroll SA. Schizophrenia risk from complex variation of complement component 4. Nature. 2016;530(7589):177–183. doi: 10.1038/nature16549 Epub 2016 Jan 27. PMID: 26814963; PMCID: PMC4752392Najjar S, Pearlman DM, Alper K, Najjar A, Devinsky O. Neuro inflammation and psychiatric illness. J Neuroinflammation. 2013;10:43. doi: 10.1186/1742-2094- 10-43 PMID: 23547920; PMCID: PMC3626880.Najjar S, Pearlman DM, Alper K, Najjar A, Devinsky O. Neuro inflammation and psychiatric illness. J Neuroinflammation. 2013;10:43. doi: 10.1186/1742-2094- 10-43 PMID: 23547920; PMCID: PMC3626880.Hoirisch-Clapauch S, Amaral OB, Mezzasalma MAU, Panizzutti R, Nardi AE. Dysfunction in the coagulation system and schizophrenia. Transl Psychiatry. 2016;6:e704. doi: 10.1038/tp.2015.204Hoirisch-Clapauch S, Amaral OB, Mezzasalma MAU, Panizzutti R, Nardi AE. Dysfunction in the coagulation system and schizophrenia. Transl Psychiatry. 2016;6:e704. doi: 10.1038/tp.2015.204English JA, Lopez LM, O’Gorman A, Föcking M, Hryniewiecka M, Scaife S, Sabherwal S, Wynne K, Dicker P, Rutten BPF, Lewis J, Cannon M, Cagney G, Cotter DR. Blood-Based Protein Changes in Childhood Are Associated With Increased Risk for Later Psychotic Disorder: Evidence From a Nested Case–Control Study of the ALSPAC Longitudinal Birth Cohort. Schizophr Bull. 2018;44(2):297–306. doi: 10.1093/schbul/sbx075English JA, Lopez LM, O’Gorman A, Föcking M, Hryniewiecka M, Scaife S, Sabherwal S, Wynne K, Dicker P, Rutten BPF, Lewis J, Cannon M, Cagney G, Cotter DR. Blood-Based Protein Changes in Childhood Are Associated With Increased Risk for Later Psychotic Disorder: Evidence From a Nested Case–Control Study of the ALSPAC Longitudinal Birth Cohort. Schizophr Bull. 2018;44(2):297–306. doi: 10.1093/schbul/sbx075Taquet M, Luciano S, Geddes JR, Harrison PJ. Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA. The Lancet Psychiatry. 2020. https://doi.org/10.1016/S2215-0366(20)30462-4Taquet M, Luciano S, Geddes JR, Harrison PJ. Bidirectional associations between COVID-19 and psychiatric disorder: retrospective cohort studies of 62 354 COVID-19 cases in the USA. The Lancet Psychiatry. 2020. https://doi.org/10.1016/S2215-0366(20)30462-4Noris M, Benigni A, Remuzzi G. The case of Complement activation in COVID-19 multiorgan impact. Kidney International. http://doi.org/10.1016/j.kint.2020.05.013Noris M, Benigni A, Remuzzi G. The case of Complement activation in COVID-19 multiorgan impact. Kidney International. http://doi.org/10.1016/j.kint.2020.05.013Thurman JM. Many drugs for many targets: novel treatments for complement-mediated glomerular disease. Nephrol Dial Transplant. 2017;32(1):i57–i64. doi: 10.1093/ndt/gfw228Thurman JM. Many drugs for many targets: novel treatments for complement-mediated glomerular disease. Nephrol Dial Transplant. 2017;32(1):i57–i64. doi: 10.1093/ndt/gfw228Horiuchi T, Tsukamoto H. Complement-targeted therapy: development of C5- and C5a-targeted inhibition. Inflamm Regen. 2016;36:11. doi: 10.1186/s41232-016-0013-6 PMID: 29259684; PMCID: PMC5725830Horiuchi T, Tsukamoto H. Complement-targeted therapy: development of C5- and C5a-targeted inhibition. Inflamm Regen. 2016;36:11. doi: 10.1186/s41232-016-0013-6 PMID: 29259684; PMCID: PMC5725830Ricklin D, Lambris JD. Progress and trends in complement therapeutics. Adv Exp Med Biol. 2013;735:1–22. PMID: 23402016Ricklin D, Lambris JD. Progress and trends in complement therapeutics. Adv Exp Med Biol. 2013;735:1–22. PMID: 23402016Diurno F, Numis FG, Porta G, Cirillo F, Maddaluno S, Ragozzino A, De Negri P, Di Gennaro C, Pagano A, Allegorico E, Bressy L, Bosso G, Ferrara A, Serra C, Montisci A, D’Amico M, Schiano Lo Morello S, Di Costanzo G, Tucci AG, Marchetti P, Di Vincenzo U, Sorrentino I, Casciotta A, Fusco M, Buonerba C, Berretta M, Ceccarelli M, Nunnari G, Diessa Y, Cicala S, Facchini G. Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience. Eur Rev Med Pharmacol Sci. 2020;24(7):4040–4047. doi: 10.26355/eurrev_202004_20875 PMID: 32329881Diurno F, Numis FG, Porta G, Cirillo F, Maddaluno S, Ragozzino A, De Negri P, Di Gennaro C, Pagano A, Allegorico E, Bressy L, Bosso G, Ferrara A, Serra C, Montisci A, D’Amico M, Schiano Lo Morello S, Di Costanzo G, Tucci AG, Marchetti P, Di Vincenzo U, Sorrentino I, Casciotta A, Fusco M, Buonerba C, Berretta M, Ceccarelli M, Nunnari G, Diessa Y, Cicala S, Facchini G. Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience. Eur Rev Med Pharmacol Sci. 2020;24(7):4040–4047. doi: 10.26355/eurrev_202004_20875 PMID: 32329881

The authors declare that there are no conflicts of interest present.