Abstract 263: Prothrombotic State Exists In Long-COVID Even After Mild Acute Infection

Long-term consequences of COVID-19 (long-COVID) are becoming a significant burden to health care. Many people remain symptomatic for months or years after recovery from COVID-19, including some who had only mild symptoms during acute infection. Sustained increases in pro-thrombotic markers have been reported in patients who were initially hospitalized with acute COVID-19. However, whether patients with less severe acute infection develop a prothrombotic-state during long-COVID is unclear. Our objective was to measure prothrombotic factors in long-COVID patients with mild disease (non-hospitalization) during acute infection. We recruited 47 consecutive adult patients with long-COVID symptoms seen in the Post-COVID clinic. All patients had a confirmed COVID-19 diagnosis by RT-PCR or antibody test during acute infection and had at least one of the symptoms of long-COVID per WHO criteria. Twenty asymptomatic healthy subjects not previously diagnosed with COVID-19 were recruited as controls. Markers of platelet activation and platelet-neutrophil aggregates (PNA) were quantified using whole blood flow cytometry. Serum levels of cell-free DNA (cfDNA) and citrullinated histones (H3Cit) and thrombin generation potential in plasma was measured. At the time of recruitment (6 weeks to 2 years after acute infection), the most common post-COVID symptoms included fatigue, chest pain, shortness of breath, headache, and dizziness. In whole blood, activation with TRAP caused increased surface expression of P-selectin without inducing activation of integrin αII b β 3 on platelets (P<0.001 and P=0.5 respectively vs control). Concurrently, there was increased PNA in the long-COVID cohort (P<0.01 vs. control). H3Cit and cfDNA were elevated in long-COVID (P<0.01 and P<0.05 respectively vs. control) and thrombin generation potential was increased, reflected by shorter lag-time, higher peak thrombin and increased velocity index (P<0.01, P<0.05 and P<0.0001 respectively vs control). Within the long-COVID cohort, these markers were not different for age, sex, BMI or time since infection. We conclude that a prothrombotic state persists for months to years in long-COVID patients who exhibited mild disease at the time of initial infection.