Mij
Senior Member (Voting Rights)
Abstract
Background: Long COVID is a persistent and episodic multi-system condition that impacts quality of life and functional status. Underlying pathologies include viral persistence, endothelial dysfunction, platelet hyperactivation/dysregulation, and the presence of anomalous deposits, also referred to as fibrinaloid complexes or microclots. Exercise is sometimes suggested to be beneficial for people with Long COVID despite minimal exertion being shown to exacerbate symptoms in many cases. To date, changes in microclot dynamics, inflammation, and biomarker profile in response to exercise remain unstudied in people living with Long COVID.
Methods: 46 people living with Long COVID with a low risk of experiencing post-exertional malaise (PEM) completed two submaximal cardiopulmonary exercise tests, separated by 24 hours. Thirteen individuals were ineligible for participation for the following reasons: high-risk of PEM (n=9), a severe orthopaedic condition (n=1), a severe cardiac issue (n=1) or were unable to commit to the study requirements (n=2). Venous blood was collected pre- and post-exercise for cytokine profiling and for imaging flow cytometry analysis of microclots. Changes in large and small microclot populations and their association with inflammatory and vascular injury markers were assessed using fixed-effects and instrumental variable statistical models.
Results: No adverse events were reported in this study on either CPET day. At the first ventilatory threshold (VT1),
O2 was 9.7 ± 1.9 ml•kg•min-1 and decreased on day 2 (8.9 ± 1.9 ml•kg•min-1; p=0.003). O2 pulse at VT1 was lower on day 2 (day 1 vs. day 2; 8.3 ± 2.4 vs. 7.5 ± 1.9 mL/b; p<0.001). CPET induced the fragmentation of large microclots (100–3000 µm²) and caused an increase in small microclots (<30 µm²) after repeated exertion. Fragmentation correlated with increases in cytokines associated with pro- and anti-inflammation, as well as vascular injury.
Conclusion: This study provides the first evidence of a biological basis that might explain exercise-induced symptom exacerbation in people with Long COVID through microclot fragmentation, which may contribute to systemic inflammation. This has important implications for Long COVID rehabilitation practices that seek to improve health outcomes through exercise therapies that may have the capacity to be harmful for people living with Long COVID and underscores the need for targeted therapeutic strategies that consider microclot clearance and endothelial repair.
LINK
Background: Long COVID is a persistent and episodic multi-system condition that impacts quality of life and functional status. Underlying pathologies include viral persistence, endothelial dysfunction, platelet hyperactivation/dysregulation, and the presence of anomalous deposits, also referred to as fibrinaloid complexes or microclots. Exercise is sometimes suggested to be beneficial for people with Long COVID despite minimal exertion being shown to exacerbate symptoms in many cases. To date, changes in microclot dynamics, inflammation, and biomarker profile in response to exercise remain unstudied in people living with Long COVID.
Methods: 46 people living with Long COVID with a low risk of experiencing post-exertional malaise (PEM) completed two submaximal cardiopulmonary exercise tests, separated by 24 hours. Thirteen individuals were ineligible for participation for the following reasons: high-risk of PEM (n=9), a severe orthopaedic condition (n=1), a severe cardiac issue (n=1) or were unable to commit to the study requirements (n=2). Venous blood was collected pre- and post-exercise for cytokine profiling and for imaging flow cytometry analysis of microclots. Changes in large and small microclot populations and their association with inflammatory and vascular injury markers were assessed using fixed-effects and instrumental variable statistical models.
Results: No adverse events were reported in this study on either CPET day. At the first ventilatory threshold (VT1),
O2 was 9.7 ± 1.9 ml•kg•min-1 and decreased on day 2 (8.9 ± 1.9 ml•kg•min-1; p=0.003). O2 pulse at VT1 was lower on day 2 (day 1 vs. day 2; 8.3 ± 2.4 vs. 7.5 ± 1.9 mL/b; p<0.001). CPET induced the fragmentation of large microclots (100–3000 µm²) and caused an increase in small microclots (<30 µm²) after repeated exertion. Fragmentation correlated with increases in cytokines associated with pro- and anti-inflammation, as well as vascular injury.Conclusion: This study provides the first evidence of a biological basis that might explain exercise-induced symptom exacerbation in people with Long COVID through microclot fragmentation, which may contribute to systemic inflammation. This has important implications for Long COVID rehabilitation practices that seek to improve health outcomes through exercise therapies that may have the capacity to be harmful for people living with Long COVID and underscores the need for targeted therapeutic strategies that consider microclot clearance and endothelial repair.
LINK
