Impaired Antibody Response Is Associated with Histone-Release, Organ Dysfunction and Mortality in Critically Ill COVID-19 Patients
Purpose: the pathophysiologic mechanisms explaining differences in clinical outcomes following COVID-19 are not completely described. This study aims to investigate antibody responses in critically ill patients with COVID-19 in relation to inflammation, organ failure and 30-day survival. Methods: Al...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-06-01
|
| Series: | Journal of Clinical Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2077-0383/11/12/3419 |
| _version_ | 1797486006345138176 |
|---|---|
| author | Rickard Lagedal Oskar Eriksson Anna Sörman Joram B. Huckriede Bjarne Kristensen Stephanie Franzén Anders Larsson Anders Bergqvist Kjell Alving Anders Forslund Barbro Persson Kristina N. Ekdahl Pablo Garcia de Frutos Bo Nilsson Gerry A. F. Nicolaes Miklos Lipcsey Michael Hultström Robert Frithiof |
| author_facet | Rickard Lagedal Oskar Eriksson Anna Sörman Joram B. Huckriede Bjarne Kristensen Stephanie Franzén Anders Larsson Anders Bergqvist Kjell Alving Anders Forslund Barbro Persson Kristina N. Ekdahl Pablo Garcia de Frutos Bo Nilsson Gerry A. F. Nicolaes Miklos Lipcsey Michael Hultström Robert Frithiof |
| author_sort | Rickard Lagedal |
| collection | DOAJ |
| description | Purpose: the pathophysiologic mechanisms explaining differences in clinical outcomes following COVID-19 are not completely described. This study aims to investigate antibody responses in critically ill patients with COVID-19 in relation to inflammation, organ failure and 30-day survival. Methods: All patients with PCR-verified COVID-19 and gave consent, and who were admitted to a tertiary Intensive care unit (ICU) in Sweden during March–September 2020 were included. Demography, repeated blood samples and measures of organ function were collected. Analyses of anti-SARS-CoV-2 antibodies (IgM, IgA and IgG) in plasma were performed and correlated to patient outcome and biomarkers of inflammation and organ failure. Results: A total of 115 patients (median age 62 years, 77% male) were included prospectively. All patients developed severe respiratory dysfunction, and 59% were treated with invasive ventilation. Thirty-day mortality was 22.6% for all included patients. Patients negative for any anti-SARS-CoV-2 antibody in plasma during ICU admission had higher 30-day mortality compared to patients positive for antibodies. Patients positive for IgM had more ICU-, ventilator-, renal replacement therapy- and vasoactive medication-free days. IgA antibody concentrations correlated negatively with both SAPS3 and maximal SOFA-score and IgM-levels correlated negatively with SAPS3. Patients with antibody levels below the detection limit had higher plasma levels of extracellular histones on day 1 and elevated levels of kidney and cardiac biomarkers, but showed no signs of increased inflammation, complement activation or cytokine release. After adjusting for age, positive IgM and IgG antibodies were still associated with increased 30-day survival, with odds ratio (OR) 7.1 (1.5–34.4) and 4.2 (1.1–15.7), respectively. Conclusion: In patients with severe COVID-19 requiring intensive care, a poor antibody response is associated with organ failure, systemic histone release and increased 30-day mortality. |
| first_indexed | 2024-03-09T23:26:59Z |
| format | Article |
| id | doaj.art-148bcf7a57894262bac7961e4c62147c |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T23:26:59Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-148bcf7a57894262bac7961e4c62147c2023-11-23T17:15:44ZengMDPI AGJournal of Clinical Medicine2077-03832022-06-011112341910.3390/jcm11123419Impaired Antibody Response Is Associated with Histone-Release, Organ Dysfunction and Mortality in Critically Ill COVID-19 PatientsRickard Lagedal0Oskar Eriksson1Anna Sörman2Joram B. Huckriede3Bjarne Kristensen4Stephanie Franzén5Anders Larsson6Anders Bergqvist7Kjell Alving8Anders Forslund9Barbro Persson10Kristina N. Ekdahl11Pablo Garcia de Frutos12Bo Nilsson13Gerry A. F. Nicolaes14Miklos Lipcsey15Michael Hultström16Robert Frithiof17Department of Surgical Sciences, Anaesthesia and Intensive Care, Uppsala University, 752 36 Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, 752 36 Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, 752 36 Uppsala, SwedenDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6211 LK Maastricht, The NetherlandsThermo Fisher Scientific, 3450 Allerod, DenmarkDepartment of Surgical Sciences, Anaesthesia and Intensive Care, Uppsala University, 752 36 Uppsala, SwedenDepartment of Medical Sciences, Uppsala University, 752 36 Uppsala, SwedenDepartment of Medical Sciences, Section of Clinical Microbiology, Uppsala University, 752 36 Uppsala, SwedenDepartment of Women’s and Children’s Health, Uppsala University, 752 36 Uppsala, SwedenDepartment of Women’s and Children’s Health, Uppsala University, 752 36 Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, 752 36 Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, 752 36 Uppsala, SwedenDepartment of Cell Death and Proliferation, IIBB-CSIC, IDIBAPS and CIBERCV, 08036 Barcelona, SpainDepartment of Immunology, Genetics and Pathology, Uppsala University, 752 36 Uppsala, SwedenDepartment of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6211 LK Maastricht, The NetherlandsDepartment of Surgical Sciences, Anaesthesia and Intensive Care, Uppsala University, 752 36 Uppsala, SwedenDepartment of Surgical Sciences, Anaesthesia and Intensive Care, Uppsala University, 752 36 Uppsala, SwedenDepartment of Surgical Sciences, Anaesthesia and Intensive Care, Uppsala University, 752 36 Uppsala, SwedenPurpose: the pathophysiologic mechanisms explaining differences in clinical outcomes following COVID-19 are not completely described. This study aims to investigate antibody responses in critically ill patients with COVID-19 in relation to inflammation, organ failure and 30-day survival. Methods: All patients with PCR-verified COVID-19 and gave consent, and who were admitted to a tertiary Intensive care unit (ICU) in Sweden during March–September 2020 were included. Demography, repeated blood samples and measures of organ function were collected. Analyses of anti-SARS-CoV-2 antibodies (IgM, IgA and IgG) in plasma were performed and correlated to patient outcome and biomarkers of inflammation and organ failure. Results: A total of 115 patients (median age 62 years, 77% male) were included prospectively. All patients developed severe respiratory dysfunction, and 59% were treated with invasive ventilation. Thirty-day mortality was 22.6% for all included patients. Patients negative for any anti-SARS-CoV-2 antibody in plasma during ICU admission had higher 30-day mortality compared to patients positive for antibodies. Patients positive for IgM had more ICU-, ventilator-, renal replacement therapy- and vasoactive medication-free days. IgA antibody concentrations correlated negatively with both SAPS3 and maximal SOFA-score and IgM-levels correlated negatively with SAPS3. Patients with antibody levels below the detection limit had higher plasma levels of extracellular histones on day 1 and elevated levels of kidney and cardiac biomarkers, but showed no signs of increased inflammation, complement activation or cytokine release. After adjusting for age, positive IgM and IgG antibodies were still associated with increased 30-day survival, with odds ratio (OR) 7.1 (1.5–34.4) and 4.2 (1.1–15.7), respectively. Conclusion: In patients with severe COVID-19 requiring intensive care, a poor antibody response is associated with organ failure, systemic histone release and increased 30-day mortality.https://www.mdpi.com/2077-0383/11/12/3419COVID-19SARS-CoV-2critical careantibody responseNEThistones |
| spellingShingle | Rickard Lagedal Oskar Eriksson Anna Sörman Joram B. Huckriede Bjarne Kristensen Stephanie Franzén Anders Larsson Anders Bergqvist Kjell Alving Anders Forslund Barbro Persson Kristina N. Ekdahl Pablo Garcia de Frutos Bo Nilsson Gerry A. F. Nicolaes Miklos Lipcsey Michael Hultström Robert Frithiof Impaired Antibody Response Is Associated with Histone-Release, Organ Dysfunction and Mortality in Critically Ill COVID-19 Patients Journal of Clinical Medicine COVID-19 SARS-CoV-2 critical care antibody response NET histones |
| title | Impaired Antibody Response Is Associated with Histone-Release, Organ Dysfunction and Mortality in Critically Ill COVID-19 Patients |
| title_full | Impaired Antibody Response Is Associated with Histone-Release, Organ Dysfunction and Mortality in Critically Ill COVID-19 Patients |
| title_fullStr | Impaired Antibody Response Is Associated with Histone-Release, Organ Dysfunction and Mortality in Critically Ill COVID-19 Patients |
| title_full_unstemmed | Impaired Antibody Response Is Associated with Histone-Release, Organ Dysfunction and Mortality in Critically Ill COVID-19 Patients |
| title_short | Impaired Antibody Response Is Associated with Histone-Release, Organ Dysfunction and Mortality in Critically Ill COVID-19 Patients |
| title_sort | impaired antibody response is associated with histone release organ dysfunction and mortality in critically ill covid 19 patients |
| topic | COVID-19 SARS-CoV-2 critical care antibody response NET histones |
| url | https://www.mdpi.com/2077-0383/11/12/3419 |
| work_keys_str_mv | AT rickardlagedal impairedantibodyresponseisassociatedwithhistonereleaseorgandysfunctionandmortalityincriticallyillcovid19patients AT oskareriksson impairedantibodyresponseisassociatedwithhistonereleaseorgandysfunctionandmortalityincriticallyillcovid19patients AT annasorman impairedantibodyresponseisassociatedwithhistonereleaseorgandysfunctionandmortalityincriticallyillcovid19patients AT jorambhuckriede impairedantibodyresponseisassociatedwithhistonereleaseorgandysfunctionandmortalityincriticallyillcovid19patients AT bjarnekristensen impairedantibodyresponseisassociatedwithhistonereleaseorgandysfunctionandmortalityincriticallyillcovid19patients AT stephaniefranzen impairedantibodyresponseisassociatedwithhistonereleaseorgandysfunctionandmortalityincriticallyillcovid19patients AT anderslarsson impairedantibodyresponseisassociatedwithhistonereleaseorgandysfunctionandmortalityincriticallyillcovid19patients AT andersbergqvist impairedantibodyresponseisassociatedwithhistonereleaseorgandysfunctionandmortalityincriticallyillcovid19patients AT kjellalving impairedantibodyresponseisassociatedwithhistonereleaseorgandysfunctionandmortalityincriticallyillcovid19patients AT andersforslund impairedantibodyresponseisassociatedwithhistonereleaseorgandysfunctionandmortalityincriticallyillcovid19patients AT barbropersson impairedantibodyresponseisassociatedwithhistonereleaseorgandysfunctionandmortalityincriticallyillcovid19patients AT kristinanekdahl impairedantibodyresponseisassociatedwithhistonereleaseorgandysfunctionandmortalityincriticallyillcovid19patients AT pablogarciadefrutos impairedantibodyresponseisassociatedwithhistonereleaseorgandysfunctionandmortalityincriticallyillcovid19patients AT bonilsson impairedantibodyresponseisassociatedwithhistonereleaseorgandysfunctionandmortalityincriticallyillcovid19patients AT gerryafnicolaes impairedantibodyresponseisassociatedwithhistonereleaseorgandysfunctionandmortalityincriticallyillcovid19patients AT mikloslipcsey impairedantibodyresponseisassociatedwithhistonereleaseorgandysfunctionandmortalityincriticallyillcovid19patients AT michaelhultstrom impairedantibodyresponseisassociatedwithhistonereleaseorgandysfunctionandmortalityincriticallyillcovid19patients AT robertfrithiof impairedantibodyresponseisassociatedwithhistonereleaseorgandysfunctionandmortalityincriticallyillcovid19patients |