Coagulation Abnormalities in Post-Acute COVID-19 Syndrome: A Cross-Sectional Study

Background: COVID-19, a respiratory infectious disease caused by SARS-CoV-2, is increasingly recognized for its potential to induce a range of persistent symptoms known as “Long COVID.” The pathophysiology of this post-acute sequelae is intricate, involving a convergence of viral and host factors. Specifically, thrombotic microangiopathy, endothelial inflammation, hyperactivated platelets, and fibrin-like microthrombi are among the coagulation and vascular abnormalities that can affect every organ system. Despite the significance of these coagulation disturbances, there remains a critical need for a clearer understanding of the duration and pivotal transitions of post-infection coagulation abnormalities. To address this gap, this study aims to evaluate the long-term coagulation changes in patients following COVID-19 infection to understand the key turning points in the progression of coagulation abnormalities post-infection and the enduring impact on patient health. Methods: This study included a cohort of 1,473 hospitalized COVID-19 patients aged 18 years and older, excluding individuals with active malignancies undergoing chemotherapy or severe hematological disorders. For comparative analysis, a control group consisting of 2,310 non-COVID-19 hospitalized patients was established. Comprehensive clinical information and laboratory data were collected at multiple time points: baseline (acute phase), 1, 2, 3, 4-6, and 7-12 months post-infection. The data encompassed inflammatory markers, including erythrocyte sedimentation rate (ESR), lymphocyte count, lactate dehydrogenase (LDH), interleukin-6 (IL-6), and interleukin-8 (IL-8), as well as coagulation parameters such as prothrombin time (PT), prothrombin activity (PTA), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, fibrin degradation products (FDPs), D-dimer, antithrombin III (AT-III) and platelet count. Statistical analyses to compare differences in laboratory indicators between groups were conducted using independent samples t-tests or Mann-Whitney U tests, depending on data distribution. Longitudinal data were analyzed using generalized estimating equations (GEE) to assess changes in inflammatory markers and coagulation parameters over time. Results: In the acute phase of COVID-19, patients exhibited significant hematological and inflammatory disturbances, including reduced lymphocyte counts (p<0.001), elevated ESR (p<0.001), and increased IL-6 levels (p=0.001). Coagulation abnormalities were pronounced, with decreased platelet counts , prolonged PT, reduced PTA, elevated fibrinogen , increased D-dimer and FDPs , alongside decreased AT-III activity (all p<0.001), suggesting a consumptive coagulopathy linked to the inflammatory response. Longitudinal analysis revealed that while lymphocyte counts returned to normal by one month (p<0.001), LDH levels remained elevated for up to two months (p<0.001). The recovery of coagulation function was significantly delayed. Prolongations in PT (p=0.013), INR (p=0.008), and PTR (p=0.012), along with reduced PTA (p=0.001), persisted for two months, indicating a gradual but incomplete normalization and a reduced bleeding risk. FDP levels (p=0.017) normalized by three months, while abnormalities in TT (p=0.008) extended beyond six months. Despite a significant decrease in D-dimer levels by three months (p=0.001), 66.96% of patients still had abnormal D-dimer levels at 12 months, reflecting ongoing microthrombotic activity and hyperfibrinolysis. Additionally, platelet count decrease persisted beyond 12 months, indicating sustained consumption. Correspondingly, ESR levels decreased significantly by two months (p<0.001) yet remained abnormal in 57.31% of patients at 12 months. Conclusion: This study highlights persistent coagulation abnormalities and a slow recovery of coagulation function in COVID-19 patients, extending up to a year post-infection. These findings underscore the importance of continued monitoring and potential therapeutic interventions to manage the long-term risks associated with coagulation dysfunction in patients with Long COVID. This work provides crucial insights into the prolonged nature of these abnormalities and their implications for clinical practice, particularly in managing thrombotic risks.