Complement Overactivation and Consumption Predicts In-Hospital Mortality in SARS-CoV-2 Infection
ObjectivesUncontrolled thromboinflammation plays an important role in the pathogenesis of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus. Complement was implicated as key contributor to this process, therefore we hypothesized that markers of the complement profile, indicative for the acti...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.663187/full |
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| author | György Sinkovits Blanka Mező Blanka Mező Marienn Réti Veronika Müller Zsolt Iványi János Gál László Gopcsa Péter Reményi Beáta Szathmáry Botond Lakatos János Szlávik Ilona Bobek Zita Z. Prohászka Zsolt Förhécz Dorottya Csuka Lisa Hurler Erika Kajdácsi László Cervenak Petra Kiszel Tamás Masszi István Vályi-Nagy István Vályi-Nagy Zoltán Prohászka Zoltán Prohászka |
| author_facet | György Sinkovits Blanka Mező Blanka Mező Marienn Réti Veronika Müller Zsolt Iványi János Gál László Gopcsa Péter Reményi Beáta Szathmáry Botond Lakatos János Szlávik Ilona Bobek Zita Z. Prohászka Zsolt Förhécz Dorottya Csuka Lisa Hurler Erika Kajdácsi László Cervenak Petra Kiszel Tamás Masszi István Vályi-Nagy István Vályi-Nagy Zoltán Prohászka Zoltán Prohászka |
| author_sort | György Sinkovits |
| collection | DOAJ |
| description | ObjectivesUncontrolled thromboinflammation plays an important role in the pathogenesis of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus. Complement was implicated as key contributor to this process, therefore we hypothesized that markers of the complement profile, indicative for the activation state of the system, may be related to the severity and mortality of COVID-19.MethodsIn this prospective cohort study samples of 102 hospitalized and 26 outpatients with PCR-confirmed COVID-19 were analyzed. Primary outcome was in-hospital, COVID-19 related mortality, and secondary outcome was COVID-19 severity as assessed by the WHO ordinal scale. Complement activity of alternative and classical pathways, its factors, regulators, and activation products were measured by hemolytic titration, turbidimetry, or enzyme-immunoassays. Clinical covariates and markers of inflammation were extracted from hospital records.ResultsIncreased complement activation was characteristic for hospitalized COVID-19 patients. Complement activation was significantly associated with markers of inflammation, such as interleukin-6, C-reactive protein, and ferritin. Twenty-five patients died during hospital stay due to COVID-19 related illness. Patients with uncontrolled complement activation leading to consumption of C3 and decrease of complement activity were more likely to die, than those who had complement activation without consumption. Cox models identified anaphylatoxin C3a, and C3 overactivation and consumption (ratio of C3a/C3) as predictors of in-hospital mortality [HR of 3.63 (1.55–8.45, 95% CI) and 6.1 (2.1–17.8), respectively].ConclusionIncreased complement activation is associated with advanced disease severity of COVID-19. Patients with SARS-CoV-2 infection are more likely to die when the disease is accompanied by overactivation and consumption of C3. These results may provide observational evidence and further support to studies on complement inhibitory drugs for the treatment of COVID-19. |
| first_indexed | 2024-12-19T12:05:09Z |
| format | Article |
| id | doaj.art-67ea6f4569ef49ea92cd7c5838956c30 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T12:05:09Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-67ea6f4569ef49ea92cd7c5838956c302022-12-21T20:22:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-03-011210.3389/fimmu.2021.663187663187Complement Overactivation and Consumption Predicts In-Hospital Mortality in SARS-CoV-2 InfectionGyörgy Sinkovits0Blanka Mező1Blanka Mező2Marienn Réti3Veronika Müller4Zsolt Iványi5János Gál6László Gopcsa7Péter Reményi8Beáta Szathmáry9Botond Lakatos10János Szlávik11Ilona Bobek12Zita Z. Prohászka13Zsolt Förhécz14Dorottya Csuka15Lisa Hurler16Erika Kajdácsi17László Cervenak18Petra Kiszel19Tamás Masszi20István Vályi-Nagy21István Vályi-Nagy22Zoltán Prohászka23Zoltán Prohászka24Department of Internal Medicine and Haematology, Semmelweis University, Budapest, HungaryDepartment of Internal Medicine and Haematology, Semmelweis University, Budapest, HungaryResearch Group for Immunology and Haematology, Semmelweis University–Eötvös Loránd Research Network (Office for Supported Research Groups), Budapest, HungaryDepartment of Haematology and Stem Cell Transplantation, Central Hospital of Southern Pest National Institute of Haematology and Infectious Diseases, Budapest, HungaryDepartment of Pulmonology, Semmelweis University, Budapest, HungaryDepartment of Anaesthesiology and Intensive Therapy, Semmelweis University, Budapest, HungaryDepartment of Anaesthesiology and Intensive Therapy, Semmelweis University, Budapest, HungaryDepartment of Haematology and Stem Cell Transplantation, Central Hospital of Southern Pest National Institute of Haematology and Infectious Diseases, Budapest, HungaryDepartment of Haematology and Stem Cell Transplantation, Central Hospital of Southern Pest National Institute of Haematology and Infectious Diseases, Budapest, HungaryDepartment of Infectology, Central Hospital of Southern Pest National Institute of Haematology and Infectious Diseases, Budapest, HungaryDepartment of Infectology, Central Hospital of Southern Pest National Institute of Haematology and Infectious Diseases, Budapest, HungaryDepartment of Infectology, Central Hospital of Southern Pest National Institute of Haematology and Infectious Diseases, Budapest, HungaryDepartment of Anaesthesiology and Intensive Therapy, Central Hospital of Southern Pest National Institute of Haematology and Infectious Diseases, Budapest, HungaryDepartment of Internal Medicine and Haematology, Semmelweis University, Budapest, HungaryDepartment of Internal Medicine and Haematology, Semmelweis University, Budapest, HungaryDepartment of Internal Medicine and Haematology, Semmelweis University, Budapest, HungaryDepartment of Internal Medicine and Haematology, Semmelweis University, Budapest, HungaryDepartment of Internal Medicine and Haematology, Semmelweis University, Budapest, HungaryDepartment of Internal Medicine and Haematology, Semmelweis University, Budapest, HungaryResearch Group for Immunology and Haematology, Semmelweis University–Eötvös Loránd Research Network (Office for Supported Research Groups), Budapest, HungaryDepartment of Internal Medicine and Haematology, Semmelweis University, Budapest, HungaryDepartment of Infectology, Central Hospital of Southern Pest National Institute of Haematology and Infectious Diseases, Budapest, HungaryDepartment of Anaesthesiology and Intensive Therapy, Central Hospital of Southern Pest National Institute of Haematology and Infectious Diseases, Budapest, HungaryDepartment of Internal Medicine and Haematology, Semmelweis University, Budapest, HungaryResearch Group for Immunology and Haematology, Semmelweis University–Eötvös Loránd Research Network (Office for Supported Research Groups), Budapest, HungaryObjectivesUncontrolled thromboinflammation plays an important role in the pathogenesis of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus. Complement was implicated as key contributor to this process, therefore we hypothesized that markers of the complement profile, indicative for the activation state of the system, may be related to the severity and mortality of COVID-19.MethodsIn this prospective cohort study samples of 102 hospitalized and 26 outpatients with PCR-confirmed COVID-19 were analyzed. Primary outcome was in-hospital, COVID-19 related mortality, and secondary outcome was COVID-19 severity as assessed by the WHO ordinal scale. Complement activity of alternative and classical pathways, its factors, regulators, and activation products were measured by hemolytic titration, turbidimetry, or enzyme-immunoassays. Clinical covariates and markers of inflammation were extracted from hospital records.ResultsIncreased complement activation was characteristic for hospitalized COVID-19 patients. Complement activation was significantly associated with markers of inflammation, such as interleukin-6, C-reactive protein, and ferritin. Twenty-five patients died during hospital stay due to COVID-19 related illness. Patients with uncontrolled complement activation leading to consumption of C3 and decrease of complement activity were more likely to die, than those who had complement activation without consumption. Cox models identified anaphylatoxin C3a, and C3 overactivation and consumption (ratio of C3a/C3) as predictors of in-hospital mortality [HR of 3.63 (1.55–8.45, 95% CI) and 6.1 (2.1–17.8), respectively].ConclusionIncreased complement activation is associated with advanced disease severity of COVID-19. Patients with SARS-CoV-2 infection are more likely to die when the disease is accompanied by overactivation and consumption of C3. These results may provide observational evidence and further support to studies on complement inhibitory drugs for the treatment of COVID-19.https://www.frontiersin.org/articles/10.3389/fimmu.2021.663187/fullSARS-CoV-2 infectionmortalityseveritycomplement systemcoronavirus disease (COVID-19)complement activation and consumption |
| spellingShingle | György Sinkovits Blanka Mező Blanka Mező Marienn Réti Veronika Müller Zsolt Iványi János Gál László Gopcsa Péter Reményi Beáta Szathmáry Botond Lakatos János Szlávik Ilona Bobek Zita Z. Prohászka Zsolt Förhécz Dorottya Csuka Lisa Hurler Erika Kajdácsi László Cervenak Petra Kiszel Tamás Masszi István Vályi-Nagy István Vályi-Nagy Zoltán Prohászka Zoltán Prohászka Complement Overactivation and Consumption Predicts In-Hospital Mortality in SARS-CoV-2 Infection Frontiers in Immunology SARS-CoV-2 infection mortality severity complement system coronavirus disease (COVID-19) complement activation and consumption |
| title | Complement Overactivation and Consumption Predicts In-Hospital Mortality in SARS-CoV-2 Infection |
| title_full | Complement Overactivation and Consumption Predicts In-Hospital Mortality in SARS-CoV-2 Infection |
| title_fullStr | Complement Overactivation and Consumption Predicts In-Hospital Mortality in SARS-CoV-2 Infection |
| title_full_unstemmed | Complement Overactivation and Consumption Predicts In-Hospital Mortality in SARS-CoV-2 Infection |
| title_short | Complement Overactivation and Consumption Predicts In-Hospital Mortality in SARS-CoV-2 Infection |
| title_sort | complement overactivation and consumption predicts in hospital mortality in sars cov 2 infection |
| topic | SARS-CoV-2 infection mortality severity complement system coronavirus disease (COVID-19) complement activation and consumption |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.663187/full |
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