COVID-19 Severity and Thrombo-Inflammatory Response Linked to Ethnicity

Abstract

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.

Urokinase-type plasminogen activator and plasminogen activator inhibitor-1 complex as a serum biomarker for COVID-19

“…The coagulation markers D-dimer and fibrinogen were elevated in patients in the complicated compared to the uncomplicated phase but just above the upper limit of average values, confirming recent reports (5). Coagulation-associated factors like platelet counts or prothrombin time (PT INR) in both patient groups were similar and in a normal range.…”

“…However, Sridharan et al reported that D-dimer levels are ineffective as a prognostic marker of COVID-19-associated thrombosis (8). We showed that Japanese COVID-19 patients presented with low D-dimer levels even in the complicated phase (5). A low thrombosis incidence and fewer severe cases were reported in Japan compared to other countries globally (9).…”

“…No thrombotic events occurred in any of the 69 patients during their hospital stays. Circulating COVID-19 severity markers associated with inflammation and coagulation were tested in a univariate model at admission (5). Patients in the complicated phase had higher C-reactive protein (CRP), procalcitonin, ferritin, and interleukin 6 (IL6) levels (Table 3).…”

“…Impaired blood clot dissolution (hypofibrinolysis) and hypercoagulation, inflammation, and endotheliopathy contribute to the pathogenesis of coronavirus disease-2019 (COVID-19) (1)(2)(3)(4)(5)(6).…”

Coagulopathy and adverse outcomes in hospitalized patients with COVID-19: results from the NOR-Solidarity trial

“…D-dimer was determined at the different centers using 3 different assays, and no strategy was used to harmonize levels, although the 2 major assays used seem to be quite comparable [ 41 ]. We did not have complete demographic data on all patients and no data on race/ethnicity, which could influence levels and effects of the measured parameters as it may impact inflammation and coagulation [ 42 , 43 ], and the lack of such data is a limitation to the study. While we use the phrase “associated with” frequently, this does not imply causality.…”