Subclinical Hypercoagulable Viscoelastic Characteristics Associated with Post-Acute Sequelae of SARS-CoV2 Physical Symptoms in COVID-19 ALI/ARDS Survivors

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Abstract
Background: Evidence suggests that thrombo-inflammation underlies post-acute sequelae of SARS CoV-2 (PASC). Rotational Thromboelastometry (ROTEM) identifies hypercoagulability related to thrombo-inflammation in hospitalized patients. We sought to determine whether COVID-19 acute lung injury/acute respiratory distress syndrome (ALI/ARDS) survivors with PASC have evidence of hypercoagulability identifiable on ROTEM at 15 months after discharge. Methods: We conducted a single-center prospective cohort study of 93 adults hospitalized for COVID-19 ALI/ARDS in 2020. At 15-month follow-up, participants not receiving dual antiplatelet therapy or anticoagulation and without genetic coagulation disorders underwent ROTEM testing and completed symptom questionnaires. Cross-sectional associations between ROTEM parameters and PASC using the 12 symptoms and scoring from the RECOVER definition were tested using generalized additive models with propensity score adjustment for demographics, comorbidities, and aspirin use. Sensitivity analyses evaluated associations with specific PASC symptom phenotypes: patient-reported moderate or greater post-exertional malaise (PEM), fatigue, or brain fog. Results: Participants had a mean age of 55 years (SD, 11); 40% were women; 54% required mechanical ventilation, 18% received non-rebreather mask or non-invasive ventilation only, and 28% received nasal cannula oxygen only. At 15-month follow-up, 24% had PASC, 43% had PEM, 27% had fatigue, and 20% had brain fog. In adjusted analyses, increased fibrinogen contribution to clot strength (FIBTEM maximum clot firmness [MCF]), showed direct, linear associations with PASC risk. FIBTEM MCF values above reference ranges were more common in those with PASC (13 [59%] vs 20 [28%], p < 0.01). Similar associations were observed for PEM and fatigue, but not brain fog. Conclusions: Among survivors of COVID-19 ALI/ARDS, at 15 months after hospitalization, PASC, PEM, and fatigue, but not brain fog, are associated with subclinical hypercoagulable clotting characteristics identified on ROTEM that are driven by fibrinogen dysregulation. Further work is needed to evaluate the role of long-term coagulation abnormalities in persistent post-COVID physical symptoms and to explore potential therapeutic approaches.
Funding Information
  • U.S. Department of War (W81XWH2110217 and W81XWH2110216)
  • National Center for Advancing Translational Sciences (UL1TR001873)

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