Skip to main content
ISTH 2024 Main banner
Back
CME Evaluation

Oral Communication Session

Vascular Biology, Blood Cells, and Immunothrombosis

Session: Lung pathology

OC 19.4 - Low grade inflammation results in a distinctive platelet activation phenotype supporting pulmonary impairment in Long-COVID patients

Sunday, June 23, 2024
10:15 – 10:30 ICT
Room: 208 A-D
Background: Long-COVID syndrome is characterized by symptoms persisting after acute infection remission. We previously documented that, in acute COVID-19 patients, platelets show a prothrombotic phenotype. Our hypothesis is that this phenotype can sustain the residual pulmonary impairment observed in Long-COVID patients.

Aims: To characterize platelet activation persistence, the underlying mechanisms and the possible relationship with pulmonary function 6-month after acute COVID-19 remission.

Methods: Among 204 enrolled subjects with a 6-month follow-up post-SARS-CoV-2 infection, 34 patients reporting symptoms suggestive of Long-COVID were compared with 34 COVID-Recovered asymptomatic patients and 34 healthy subjects (HS). Platelet activation (P-selectin, Tissue Factor [TF], platelet-monocyte and platelet-granulocyte aggregates [PMA and PGA]) profile was analyzed by flow-cytometry; ex vivo thrombus formation by collagen-coated microfluidic chambers. Plasma levels of C-reactive protein (CRP), Interleukin-6 (IL-6), D-Dimer and fibrinogen, and lung diffusion (DLNO) and pulmonary CT scan were evaluated.

Results: A 7-fold higher levels of CRP, but not IL-6, were measured in Long-COVID compared to COVID-Recovered patients. The percentage of PGA and PMA was also persistently greater than in COVID-Recovered (1.5-fold, p=0.0065; 1.3-fold, p=0.0273, respectively) and HS (1.5-fold, p=0.0015; 2-fold, p< 0.0001, respectively). PGA and PMA were associated with residual lung damage at CT (p=0.0043 and p=0.0056, respectively) and DLNO (p=0.0360 and p=0.0487, respectively). Ex vivo, blood from Long-COVID patients formed, on collagen-coated-surfaces, a number of microthrombi significantly greater than blood from HS. Plasma from Long-COVID patients mixed with HS blood induced P-selectin expression and platelet-leukocyte aggregate formation through a CRP- and IL-6-dependent mechanism, features prevented by Fcγ-receptor inhibitor, tocilizumab, aspirin, and P2Y12 antagonist.

Conclusion(s): Long-COVID patients present increased CRP levels together with a high percentage of platelet-leukocyte aggregates that significantly correlate with residual parenchymal damage. In ex vivo experiments, low-grade inflammation in Long-COVID plasma mediates platelet activation blunted by antiplatelet and antiinflammatory drugs, thus suggesting a potential therapeutic option in this clinical setting.