Article Impact Level: HIGH Data Quality: STRONG Summary of Nature Microbiology, 1–13. https://doi.org/10.1038/s41564-024-01838-z Dr. Jane E. Sinclair et al.
Points
- This study examines the role of chronic inflammation in the post-acute sequelae of COVID-19 (PASC), specifically in cardiovascular symptoms (PASC-CVS), which affect millions worldwide.
- Blood samples showed that individuals with prolonged PASC-CVS had significantly elevated levels of pro-inflammatory cytokines, indicating a persistent inflammatory response even 68 weeks post-infection.
- Gene analysis in PASC-CVS patients revealed an upregulation in inflammatory pathways, including neutrophil degranulation, antimicrobial peptides, and interferon signaling.
- Elevated cytokine levels in PASC-CVS patients were linked to impaired heart cell function, with reduced cardiomyocyte amplitude and upstroke velocity observed after cytokine exposure.
- The study highlights the need for tailored therapeutic strategies to address chronic inflammation’s long-term impact on cardiovascular health in individuals with PASC.
Summary
This research paper investigates the role of chronic inflammation in post-acute sequelae of COVID-19 (PASC) with a particular focus on cardiovascular symptoms (PASC-CVS). An estimated 65 million people globally suffer from PASC, with 21% to 28% of individuals reporting chest pain and heart palpitations five months post-hospital discharge. The study analyzed blood samples from three groups: 25 individuals with prolonged PASC-CVS, 11 recovered individuals, and 14 SARS-CoV-2-negative individuals. Notably, it was found that participants with PASC-CVS exhibited significantly elevated levels of pro-inflammatory cytokines, including IL-12, IL-1β, and IL-6, indicating a persistent inflammatory response. The study highlights that, at 68 weeks post-infection, over 400 differentially expressed genes (DEGs) were identified in individuals with PASC compared to less than 200 in recovered individuals.
The findings suggest that individuals with PASC-CVS have distinct inflammatory pathways activated over a prolonged period. The gene set enrichment analysis revealed a significant upregulation of pathways related to neutrophil degranulation, antimicrobial peptides, and interferon signaling in PASC-CVS patients. Furthermore, the study reported a correlation between elevated cytokine levels and compromised cardiomyocyte function, demonstrating that exposure to a cytokine cocktail mimicking those found in PASC-CVS led to reduced cardiomyocyte amplitude and upstroke velocity (p < 0.05) at both 24 and 48 hours post-treatment. These results suggest that trace-level pro-inflammatory cytokines may adversely affect cardiac cell function.
Overall, the study emphasizes the complex nature of PASC-CVS and the potential for chronic inflammation to influence cardiovascular health long after the initial SARS-CoV-2 infection. Understanding these mechanisms is crucial, as the persistence of inflammation may underlie the diverse symptoms experienced by individuals suffering from PASC, ultimately necessitating tailored therapeutic approaches.
Link to the article: https://www.nature.com/articles/s41564-024-01838-z
References Sinclair, J. E., Vedelago, C., Ryan, F. J., Carney, M., Redd, M. A., Lynn, M. A., Grubor-Bauk, B., Cao, Y., Henders, A. K., Chew, K. Y., Gilroy, D., Greaves, K., Labzin, L., Ziser, L., Ronacher, K., Wallace, L. M., Zhang, Y., Macauslane, K., Ellis, D. J., … Short, K. R. (2024). Post-acute sequelae of SARS-CoV-2 cardiovascular symptoms are associated with trace-level cytokines that affect cardiomyocyte function. Nature Microbiology, 1–13. https://doi.org/10.1038/s41564-024-01838-z
