COVID-19 Severity and Thrombo-Inflammatory Response Linked to Ethnicity
Beate Heissig,
Yousef Salama,
Roman Iakoubov,
Joerg Janne Vehreschild,
Ricardo Rios,
Tatiane Nogueira,
Maria J. G. T. Vehreschild,
Melanie Stecher,
Hirotake Mori,
Julia Lanznaster,
Eisuke Adachi,
Carolin Jakob,
Yoko Tabe,
Maria Ruethrich,
Stefan Borgmann,
Toshio Naito,
Kai Wille,
Simon Valenti,
Martin Hower,
Nobutaka Hattori,
Siegbert Rieg,
Tetsutaro Nagaoka,
Bjoern-Erik Jensen,
Hiroshi Yotsuyanagi,
Bernd Hertenstein,
Hideoki Ogawa,
Christoph Wyen,
Eiki Kominami,
Christoph Roemmele,
Satoshi Takahashi,
Jan Rupp,
Kazuhisa Takahashi,
Frank Hanses,
Koichi Hattori,
on behalf of the LEOSS Study Group
Affiliations
Beate Heissig
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Yousef Salama
An-Najah Center for Cancer and Stem Cell Research, Faculty of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, Nablus 99900800, Palestine
Roman Iakoubov
Department of Internal Medicine II, University Hospital Rechts der Isar, School of Medicine, Technical University, 81675 Munich, Germany
Joerg Janne Vehreschild
Medical Department II, University Hospital of Frankfurt, 60590 Frankfurt, Germany
Ricardo Rios
Institute of Computing, Federal University of Bahia, Salvador 40110060, Brazil
Tatiane Nogueira
Institute of Computing, Federal University of Bahia, Salvador 40110060, Brazil
Maria J. G. T. Vehreschild
Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, 60590 Frankfurt am Main, Germany
Melanie Stecher
Department I for Internal Medicine, University Hospital of Cologne, University of Cologne, 50937 Cologne, Germany
Hirotake Mori
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Julia Lanznaster
Klinikum Passau, 94032 Passau, Germany
Eisuke Adachi
IMSUT Hospital of The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Carolin Jakob
Department I for Internal Medicine, University Hospital of Cologne, University of Cologne, 50937 Cologne, Germany
Yoko Tabe
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Maria Ruethrich
Universitaetsklinikum, 07747 Jena, Germany
Stefan Borgmann
Ingolstadt Hospital, 85049 Ingolstadt, Germany
Toshio Naito
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Kai Wille
Johannes Wesling Klinikum Minden, Ruhr-Universitaet, 44801 Bochum, Germany
Simon Valenti
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Martin Hower
Klinikum Dortmund gGmbH, Hospital of University Witten/Herdecke, 44137 Dortmund, Germany
Nobutaka Hattori
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Siegbert Rieg
Universitaetsklinikum, 79106 Freiburg, Germany
Tetsutaro Nagaoka
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Bjoern-Erik Jensen
Universitaetsklinikum, 40225 Duesseldorf, Germany
Hiroshi Yotsuyanagi
IMSUT Hospital of The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Bernd Hertenstein
Klinikum Bremen-Mitte, 28205 Bremen, Germany
Hideoki Ogawa
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Christoph Wyen
Praxis am Ebertplatz Koeln, 50668 Köln, Germany
Eiki Kominami
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Christoph Roemmele
Internal Medicine III—Gastroenterology and Infectious Diseases, University Hospital of Augsburg, 86156 Augsburg, Germany
Satoshi Takahashi
IMSUT Hospital of The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Jan Rupp
Department of Infectious Diseases and Microbiology, University Hospital Schleswig-Holstein/Campus Luebeck, 23538 Luebeck, Germany
Kazuhisa Takahashi
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Frank Hanses
Emergency Department and Department for Infectious Diseases and Infection Control, University Hospital Regensburg, 93053 Regensburg, Germany
Koichi Hattori
School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan
Although there is strong evidence that SARS-CoV-2 infection is associated with adverse outcomes in certain ethnic groups, the association of disease severity and risk factors such as comorbidities and biomarkers with racial disparities remains undefined. This retrospective study between March 2020 and February 2021 explores COVID-19 risk factors as predictors for patients’ disease progression through country comparison. Disease severity predictors in Germany and Japan were cardiovascular-associated comorbidities, dementia, and age. We adjusted age, sex, body mass index, and history of cardiovascular disease comorbidity in the country cohorts using a propensity score matching (PSM) technique to reduce the influence of differences in sample size and the surprisingly young, lean Japanese cohort. Analysis of the 170 PSM pairs confirmed that 65.29% of German and 85.29% of Japanese patients were in the uncomplicated phase. More German than Japanese patients were admitted in the complicated and critical phase. Ethnic differences were identified in patients without cardiovascular comorbidities. Japanese patients in the uncomplicated phase presented a suppressed inflammatory response and coagulopathy with hypocoagulation. In contrast, German patients exhibited a hyperactive inflammatory response and coagulopathy with hypercoagulation. These differences were less pronounced in patients in the complicated phase or with cardiovascular diseases. Coagulation/fibrinolysis-associated biomarkers rather than inflammatory-related biomarkers predicted disease severity in patients with cardiovascular comorbidities: platelet counts were associated with severe illness in German patients. In contrast, high D-dimer and fibrinogen levels predicted disease severity in Japanese patients. Our comparative study indicates that ethnicity influences COVID-19-associated biomarker expression linked to the inflammatory and coagulation (thrombo-inflammatory) response. Future studies will be necessary to determine whether these differences contributed to the less severe disease progression observed in Japanese COVID-19 patients compared with those in Germany.
