Abstract:
Long COVID is a public health emergency affecting millions of people worldwide, characterized by heterogenous symptoms across multiple organs systems. Here, we discuss the current evidence linking thrombo-inflammation to Post-acute sequelae of COVID-19 (PASC).
Studies have found persistence of vascular damage with increased circulating markers of endothelial dysfunction, coagulation abnormalities with increased thrombin generation capacity, and abnormalities in platelet counts in PASC. Neutrophil phenotype resembles acute COVID-19 with an increase in activation and NETosis. These insights are potentially linked by elevated platelet-neutrophil aggregate formation. This hypercoagulable state in turn can lead to microvascular thrombosis, evidenced by microclots and elevated D-Dimer in the circulation, as well as perfusion abnormalities in the lung and brain of Long COVID patients. Also, COVID-19 survivors suffer from an increased rate of arterial and venous thrombotic events.
We discuss three important, potentially intertwined hypotheses, that might contribute to thromboinflammation in Long COVID: Lasting structural changes, most prominently endothelial damage, caused during initial infection, a persistent viral reservoir, and immunopathology driven by a misguided immune system.
Lastly, we outline the necessity for large, well-characterized clinical cohorts and mechanistic studies to clarify the contribution of thromboinflammation to Long COVID.
Source: Nicolai L, Kaiser R, Stark K. Thrombo-inflammation in Long COVID – the elusive key to post-infection sequelae? J Thromb Haemost. 2023 May 11:S1538-7836(23)00400-2. doi: 10.1016/j.jtha.2023.04.039. Epub ahead of print. PMID: 37178769; PMCID: PMC10174338. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10174338/ (Full text)