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Hypercoagulability, endotheliopathy, and inflammation approximating 1 year after recovery: Assessing the long-term
Bingwen Eugene Fan1,2,3,4, Shiun Woei Wong3,4,5, Christina Lai Lin Sum6
1Department of Haematology, Tan Tock Seng Hospital, Singapore.
Insights
Long COVID can cause persistent hypercoagulability and endotheliopathy for up to 16 months post-recovery. Elevated D-dimer, Factor VIII, and inflammatory markers indicate ongoing risks in some recovered patients.
Area of Science:
- Cardiovascular Medicine
- Infectious Diseases
- Hematology
Background:
- COVID-19 is associated with significant short-term hemostatic and endothelial disturbances.
- Long-term sequelae of COVID-19, including persistent vascular dysfunction, require further investigation.
Purpose of the Study:
- To evaluate the persistence of hypercoagulability, endotheliopathy, and inflammation in COVID-19 convalescent patients up to 16 months post-recovery.
- To compare hemostatic, endothelial, and inflammatory profiles with healthy controls.
Main Methods:
- Prospective evaluation of 39 recovered COVID-19 patients (mean follow-up 12.7 months).
- Analysis of hemostatic markers (D-dimer, Factor VIII, thrombin generation via Thromboscreen), endothelial markers (vWF:Ag, ICAM-1), and inflammatory markers (IL-6).
- Comparison with a control group of 124 healthy volunteers.
Main Results:
- Elevated D-dimer (17.9%) and Factor VIII (48.7%) were observed in convalescent patients.
- Increased thrombin generation (ETP, peak height) and delayed lag time were noted.
- Higher median levels of vWF:Ag, ICAM-1, and IL-6 were found compared to controls.
- One patient experienced acute ischemic limb without prior cardiovascular risk factors.
Conclusions:
- Hypercoagulability, endothelial dysfunction, and inflammation persist in a subset of patients up to 16 months after COVID-19 recovery.
- These findings highlight the potential for long-term vascular complications following COVID-19.
- Further research is needed to understand the clinical implications and management of these persistent abnormalities.
Abstract:
Sustained hypercoagulability and endotheliopathy are present in convalescent COVID-19 patients for up to 4 months from recovery. The hemostatic, endothelial, and inflammatory profiles of 39 recovered COVID-19 patients were evaluated up to 16 months after recovery from COVID-19. These values were compared with a control group of healthy volunteers (n = 124). 39 patients (71.8% males, median age 43 years) were reviewed at a mean of 12.7 ± 3.6 months following recovery. One patient without cardiovascular risk factors had post COVID-19 acute ischaemic limb. Elevated D-dimer and Factor VIII levels above normal ranges were noted in 17.9% (7/39) and 48.7% (19/39) of patients respectively, with a higher median D-dimer 0.34 FEU μg/mL (IQR 0.28, 0.46) (p < .001) and Factor VIII 150% (IQR 171, 203) (p = .004), versus controls. Thrombin generation (Thromboscreen) showed a higher median endogenous thrombin potential (ETP) of 1352 nM*min (IQR 1152, 1490) (p = .002) and a higher median peak height of 221.4 nM (IQR 170.2, 280.4) (p = 0.01) and delayed lag time 2.4 min (1.42-2.97) (p = 0.0002) versus controls. Raised vWF:Ag and ICAM-1 levels were observed in 17.9% (7/39) and 7.7% (3/39) of patients respectively, with a higher median VWF:Ag 117% (IQR 86, 154) (p = 0.02) and ICAM-1 54.1 ng/mL (IQR 43.8, 64.1) (p = .004) than controls. IL-6 was noted to be raised in 35.9% (14/39) of patients, with a higher median IL-6 of 1.5 pg/mL (IQR 0.6, 3.0) (p = 0.004) versus controls. Subgroup analysis stratifying patients by COVID-19 severity and COVID-19 vaccination preceding SARS-CoV-2 infection did not show statistically significant differences. Hypercoagulability, endothelial dysfunction, and inflammation are still detectable in some patients approximately 1 year after recovery from COVID-19.
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