TY - JOUR
T1 - Thrombocytopenia is associated with a dysregulated host response in severe COVID-19
AU - Appelman, Brent
AU - Michels, Erik H. A.
AU - de Brabander, Justin
AU - Peters-Sengers, Hessel
AU - van Amstel, Rombout B. E.
AU - Noordzij, Sophie M.
AU - Klarenbeek, Augustijn M.
AU - van Linge, Christine C. A.
AU - Chouchane, Osoul
AU - Schuurman, Alex R.
AU - Reijnders, Tom D. Y.
AU - Amsterdam UMC COVID-19 biobank study group
AU - Douma, Renée A.
AU - Bos, Lieuwe D. J.
AU - CovidPredict Study Group
AU - Wiersinga, W. Joost
AU - van der Poll, Tom
AU - Hollmann, M.W.
N1 - Funding Information: This work was supported by the Talud Foundation (Stichting Talud) for the Amsterdam UMC Corona Research Fund, and the Netherlands Organisation for Health Research and Development (ZonMw; TURN-COVID grant number 10430142110001 to WJW). E.H.A.M., J.d.B and C.C.A.v.L. received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 847786 (FAIR). H.P.S. was supported by the Dutch Kidney Foundation (Kolff Grant number 19OK009). O.C. was supported by O.C. the Landsteiner Foundation (LSBR # 1901). TDYR was supported by research program ‘NACTAR’, project ‘MDR-phage’ (grant number 16447) which is financed by the Dutch research council (NWO). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. Funding Information: This work was supported by the Talud Foundation (Stichting Talud) for the Amsterdam UMC Corona Research Fund, and the Netherlands Organisation for Health Research and Development (ZonMw; TURN-COVID grant number 10430142110001 to WJW). E.H.A.M., J.d.B and C.C.A.v.L. received funding from the European Union 's Horizon 2020 research and innovation program under grant agreement No 847786 (FAIR). H.P.S. was supported by the Dutch Kidney Foundation (Kolff Grant number 19OK009 ). O.C. was supported by O.C. the Landsteiner Foundation (LSBR # 1901 ). TDYR was supported by research program ‘NACTAR’, project ‘MDR-phage’ (grant number 16447 ) which is financed by the Dutch research council (NWO). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2023 The Authors
PY - 2023/9/1
Y1 - 2023/9/1
N2 - Background: Thrombocytopenia is associated with increased mortality in COVID-19 patients. Objective: To determine the association between thrombocytopenia and alterations in host response pathways implicated in disease pathogenesis in patients with severe COVID-19. Patients/methods: We studied COVID-19 patients admitted to a general hospital ward included in a national (CovidPredict) cohort derived from 13 hospitals in the Netherlands. In a subgroup, 43 host response biomarkers providing insight in aberrations in distinct pathophysiological domains (coagulation and endothelial cell function; inflammation and damage; cytokines and chemokines) were determined in plasma obtained at a single time point within 48 h after admission. Patients were stratified in those with normal platelet counts (150-400 × 109/L) and those with thrombocytopenia (<150 × 109/L). Results: 6.864 patients were enrolled in the national cohort, of whom 1.348 had thrombocytopenia and 5.516 had normal platelets counts; the biomarker cohort consisted of 429 patients, of whom 85 with thrombocytopenia and 344 with normal platelet counts. Plasma D-dimer levels were not different in thrombocytopenia, although patients with moderate-severe thrombocytopenia (<100 × 109/L) showed higher D-dimer levels, indicating enhanced coagulation activation. Patients with thrombocytopenia had lower plasma levels of many proinflammatory cytokines and chemokines, and antiviral mediators, suggesting involvement of platelets in inflammation and antiviral immunity. Thrombocytopenia was associated with alterations in endothelial cell biomarkers indicative of enhanced activation and a relatively preserved glycocalyx integrity. Conclusion: Thrombocytopenia in hospitalized patients with severe COVID-19 is associated with broad host response changes across several pathophysiological domains. These results suggest a role of platelets in the immune response during severe COVID-19.
AB - Background: Thrombocytopenia is associated with increased mortality in COVID-19 patients. Objective: To determine the association between thrombocytopenia and alterations in host response pathways implicated in disease pathogenesis in patients with severe COVID-19. Patients/methods: We studied COVID-19 patients admitted to a general hospital ward included in a national (CovidPredict) cohort derived from 13 hospitals in the Netherlands. In a subgroup, 43 host response biomarkers providing insight in aberrations in distinct pathophysiological domains (coagulation and endothelial cell function; inflammation and damage; cytokines and chemokines) were determined in plasma obtained at a single time point within 48 h after admission. Patients were stratified in those with normal platelet counts (150-400 × 109/L) and those with thrombocytopenia (<150 × 109/L). Results: 6.864 patients were enrolled in the national cohort, of whom 1.348 had thrombocytopenia and 5.516 had normal platelets counts; the biomarker cohort consisted of 429 patients, of whom 85 with thrombocytopenia and 344 with normal platelet counts. Plasma D-dimer levels were not different in thrombocytopenia, although patients with moderate-severe thrombocytopenia (<100 × 109/L) showed higher D-dimer levels, indicating enhanced coagulation activation. Patients with thrombocytopenia had lower plasma levels of many proinflammatory cytokines and chemokines, and antiviral mediators, suggesting involvement of platelets in inflammation and antiviral immunity. Thrombocytopenia was associated with alterations in endothelial cell biomarkers indicative of enhanced activation and a relatively preserved glycocalyx integrity. Conclusion: Thrombocytopenia in hospitalized patients with severe COVID-19 is associated with broad host response changes across several pathophysiological domains. These results suggest a role of platelets in the immune response during severe COVID-19.
KW - COVID-19
KW - Host immune response
KW - Mortality
KW - Platelets
KW - Thrombocytopenia
UR - http://www.scopus.com/inward/record.url?scp=85166562329&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.thromres.2023.07.008
DO - https://doi.org/10.1016/j.thromres.2023.07.008
M3 - Article
C2 - 37541167
SN - 0049-3848
VL - 229
SP - 187
EP - 197
JO - Thrombosis research
JF - Thrombosis research
ER -