TIME COURSE OF THE DEVELOPMENT OF IMMUNOTHROMBOSIS DURING COVID-19 HOSPITALIZATION
Introduction: Hypercoagulability in COVID-19 has been attributed to immunothrombosis, a process that involves the formation of neutrophils extracellular traps (NETs). The moment of the COVID-19 evolution in which immunothrombosis mechanisms are triggered is not established. Aim: To describe the kine...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-10-01
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| Series: | Hematology, Transfusion and Cell Therapy |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2531137921010397 |
| _version_ | 1819026949507383296 |
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| author | JD Oliveira BMM Fonseca CO Vaz KHO Soares JCS Mariolano GA Locachevic GV Damiani EV Paula FA Orsi |
| author_facet | JD Oliveira BMM Fonseca CO Vaz KHO Soares JCS Mariolano GA Locachevic GV Damiani EV Paula FA Orsi |
| author_sort | JD Oliveira |
| collection | DOAJ |
| description | Introduction: Hypercoagulability in COVID-19 has been attributed to immunothrombosis, a process that involves the formation of neutrophils extracellular traps (NETs). The moment of the COVID-19 evolution in which immunothrombosis mechanisms are triggered is not established. Aim: To describe the kinetics of NETs release during COVID-19 hospitalization associating with thrombosis and death. Methods: We quantified citrullinated H3 and inflammatory cytokines (TNF-α, IL-6), markers of NETs release, on 4 time points during COVID-19 hospitalization (admission, day 4, day 8 and last day) between May and July 2020. The association between changes in these markers levels and clinical outcomes was determined. Results: 101 patients were included, the median days in-hospital were 15, 62% were men, 27% were obese, 43% were diabetic, 54% were hypertensive, 59% were critically ill, 11% had a thrombotic event and 21% died. IL-6 levels were high on admission in survivors (median 25.32, IQR 24.19-28.15) and non-survivors (median 24.19, IQR 12.51-27.19), but gradually decreased on day 4 (median 12.07, IQR 6.32-17.81), day 8 (median 9.34, IQR 5.18-17.59) and last day (median 8.64, IQR 4.81-14.89) in survivors. TNF-α levels remained 2 times higher in non-survivors: admission (median 1.60, IQR 0.64-2.26), day 4 (median 1.78, IQR 1.02-2.60), day 8 (median 1.65, IQR 0.93-2.5), last day (median 2.41, IQR 1.31-4.06); than in survivors: admission (median 0.81, IQR 0.52-1.26), day 4 (median 0.84, IQR 0.44-1.16), day 8 (median 0.72, IQR 0.44-1.24), last day (median 0.69, IQR 0.4-1.14). CitH3 levels were similar between non-survivors at the beginning of hospitalization: admission (median 1.03, IQR 0.43-4.34), day 4 (median 1.1, IQR 0.65-3.45); as for survivors: admission (median 1.20, IQR 0.45-2.60), day 4 (median 1.27, IQR 0.64-3.29). On day 8, citH3 increased by 3-fold (median 3.80, IQR 1.98-10.15) in non-survivors and 2-fold (median 2.60, IQR 1.22-5.01) in survivors. While IL-6 and TNF-α levels were similar between patients with and without thrombosis, citH3 levels increased shortly on day 4, before the occurrence of a thrombotic event: admission (median 1.64, IQR 0.44-4.14), day 4 (median 3.21, IQR 2.57-9.31); but it didn't change on non-thrombotic event patients: admission (median 1.05, IQR 0.44-2.50), day 4 (median 1.06, IQR 0.58-2.95). Conclusion: Markers of inflammation and immunothrombosis were associated with poor outcomes in COVID-19; however, these disorders were detected in different moments during COVID-19 course. While an increased inflammatory response was observed since the beginning of hospitalization, markers of immunothrombosis arose latter during the course of the disease. Acknowledgment of the time-course of immunothrombosis development in COVID-19 is important for planning therapeutic strategies against this pathological process. |
| first_indexed | 2024-12-21T05:34:42Z |
| format | Article |
| id | doaj.art-3b47500271f74278a35b6c6b41c09b20 |
| institution | Directory Open Access Journal |
| issn | 2531-1379 |
| language | English |
| last_indexed | 2024-12-21T05:34:42Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Hematology, Transfusion and Cell Therapy |
| spelling | doaj.art-3b47500271f74278a35b6c6b41c09b202022-12-21T19:14:27ZengElsevierHematology, Transfusion and Cell Therapy2531-13792021-10-0143S516S517TIME COURSE OF THE DEVELOPMENT OF IMMUNOTHROMBOSIS DURING COVID-19 HOSPITALIZATIONJD Oliveira0BMM Fonseca1CO Vaz2KHO Soares3JCS Mariolano4GA Locachevic5GV Damiani6EV Paula7FA Orsi8Department of Clinical Medicine, Faculdade de Ciências Médicas (FCM), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, BrazilFaculdade de Ciências Médicas (FCM), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, BrazilDepartment of Clinical Medicine, Faculdade de Ciências Médicas (FCM), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, BrazilDepartment of Clinical Pathology, Hospital de Clínicas, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, BrazilDepartment of Clinical Pathology, Hospital de Clínicas, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, BrazilDepartment of Clinical Pathology, Hospital de Clínicas, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, BrazilFaculdade de Ciências Médicas (FCM), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil; Department of Biology, Instituto Federal de Educação Ciência e Tecnologia de São Paulo, São Paulo, SP, BrazilFaculdade de Ciências Médicas (FCM), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil; Centro de Hematologia e Hemoterapia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, BrazilCentro de Hematologia e Hemoterapia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil; Department of Clinical Pathology, Faculdade de Ciências Médicas (FCM), Universidade Estadual de Campinas (UNICAMP), Campinas, SP, BrazilIntroduction: Hypercoagulability in COVID-19 has been attributed to immunothrombosis, a process that involves the formation of neutrophils extracellular traps (NETs). The moment of the COVID-19 evolution in which immunothrombosis mechanisms are triggered is not established. Aim: To describe the kinetics of NETs release during COVID-19 hospitalization associating with thrombosis and death. Methods: We quantified citrullinated H3 and inflammatory cytokines (TNF-α, IL-6), markers of NETs release, on 4 time points during COVID-19 hospitalization (admission, day 4, day 8 and last day) between May and July 2020. The association between changes in these markers levels and clinical outcomes was determined. Results: 101 patients were included, the median days in-hospital were 15, 62% were men, 27% were obese, 43% were diabetic, 54% were hypertensive, 59% were critically ill, 11% had a thrombotic event and 21% died. IL-6 levels were high on admission in survivors (median 25.32, IQR 24.19-28.15) and non-survivors (median 24.19, IQR 12.51-27.19), but gradually decreased on day 4 (median 12.07, IQR 6.32-17.81), day 8 (median 9.34, IQR 5.18-17.59) and last day (median 8.64, IQR 4.81-14.89) in survivors. TNF-α levels remained 2 times higher in non-survivors: admission (median 1.60, IQR 0.64-2.26), day 4 (median 1.78, IQR 1.02-2.60), day 8 (median 1.65, IQR 0.93-2.5), last day (median 2.41, IQR 1.31-4.06); than in survivors: admission (median 0.81, IQR 0.52-1.26), day 4 (median 0.84, IQR 0.44-1.16), day 8 (median 0.72, IQR 0.44-1.24), last day (median 0.69, IQR 0.4-1.14). CitH3 levels were similar between non-survivors at the beginning of hospitalization: admission (median 1.03, IQR 0.43-4.34), day 4 (median 1.1, IQR 0.65-3.45); as for survivors: admission (median 1.20, IQR 0.45-2.60), day 4 (median 1.27, IQR 0.64-3.29). On day 8, citH3 increased by 3-fold (median 3.80, IQR 1.98-10.15) in non-survivors and 2-fold (median 2.60, IQR 1.22-5.01) in survivors. While IL-6 and TNF-α levels were similar between patients with and without thrombosis, citH3 levels increased shortly on day 4, before the occurrence of a thrombotic event: admission (median 1.64, IQR 0.44-4.14), day 4 (median 3.21, IQR 2.57-9.31); but it didn't change on non-thrombotic event patients: admission (median 1.05, IQR 0.44-2.50), day 4 (median 1.06, IQR 0.58-2.95). Conclusion: Markers of inflammation and immunothrombosis were associated with poor outcomes in COVID-19; however, these disorders were detected in different moments during COVID-19 course. While an increased inflammatory response was observed since the beginning of hospitalization, markers of immunothrombosis arose latter during the course of the disease. Acknowledgment of the time-course of immunothrombosis development in COVID-19 is important for planning therapeutic strategies against this pathological process.http://www.sciencedirect.com/science/article/pii/S2531137921010397 |
| spellingShingle | JD Oliveira BMM Fonseca CO Vaz KHO Soares JCS Mariolano GA Locachevic GV Damiani EV Paula FA Orsi TIME COURSE OF THE DEVELOPMENT OF IMMUNOTHROMBOSIS DURING COVID-19 HOSPITALIZATION Hematology, Transfusion and Cell Therapy |
| title | TIME COURSE OF THE DEVELOPMENT OF IMMUNOTHROMBOSIS DURING COVID-19 HOSPITALIZATION |
| title_full | TIME COURSE OF THE DEVELOPMENT OF IMMUNOTHROMBOSIS DURING COVID-19 HOSPITALIZATION |
| title_fullStr | TIME COURSE OF THE DEVELOPMENT OF IMMUNOTHROMBOSIS DURING COVID-19 HOSPITALIZATION |
| title_full_unstemmed | TIME COURSE OF THE DEVELOPMENT OF IMMUNOTHROMBOSIS DURING COVID-19 HOSPITALIZATION |
| title_short | TIME COURSE OF THE DEVELOPMENT OF IMMUNOTHROMBOSIS DURING COVID-19 HOSPITALIZATION |
| title_sort | time course of the development of immunothrombosis during covid 19 hospitalization |
| url | http://www.sciencedirect.com/science/article/pii/S2531137921010397 |
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