The study also warned of broader implications of its findings, including the continued need to prevent the spread of COVID-19. It emphasized that “the best way to prevent Long COVID and its myriad complications, including the risk of serious cardiovascular sequelae, is to prevent SARS-CoV-2 infection in the first place.”
The authors also sounded an alarm about the need for governments and health systems globally to be prepared to deal with the likely significant contribution of the COVID-19 pandemic to a dramatic rise in the burden of cardiovascular diseases.
“Because of the chronic nature of these conditions, they will likely have long-lasting consequences for patients and health systems and also have broad implications on economic productivity and life expectancy,” according to the study. “Addressing the challenges posed by Long COVID will require a much-needed, but so far lacking, urgent and coordinated long-term global response strategy.”
Researchers pointed out that it remains unclear exactly how COVID-19 leads to the development of cardiovascular diseases in the post-acute phase of the disease. They posited that the complications might be caused by lingering damage from direct viral invasion of cardiomyocytes and subsequent cell death, endothelial cell infection and endotheliitis, transcriptional alteration of multiple cell types in heart tissue, complement activation and complement-mediated coagulopathy and microangiopathy, downregulation of ACE2 and dysregulation of the renin-angiotensin-aldosterone system, autonomic dysfunction, elevated levels of pro-inflammatory cytokines and activation of TGF-β signaling through the Smad pathway to induce subsequent fibrosis and scarring of cardiac tissue.
“An aberrant persistent hyperactivated immune response, autoimmunity or persistence of the virus in immune-privileged sites has also been cited as putative explanations of extrapulmonary (including cardiovascular) post-acute sequelae of COVID-19,” they added. “Integration of the SARS-CoV-2 genome into DNA of infected human cells, which might then be expressed as chimeric transcripts fusing viral with cellular sequences, has also been hypothesized as a putative mechanism for continued activation of the immune-inflammatory-procoagulant cascade.”
The study team calls for more research, explaining that better understanding of the biologic mechanisms will be necessary to develop better prevention and treatment strategies.
One limitation of the study is that participants were largely older white men who were veterans. Another is that is looked at the situation at a point in time but, with mutations, COVID-19 is constantly changing.
“In summary, using a national cohort of people with COVID-19, we show that risk and 12-month burden of incident cardiovascular disease are substantial and span several cardiovascular disease categories (ischemic and non-ischemic heart disease, dysrhythmias and others),” researchers concluded. “The risks and burdens of cardiovascular disease were evident even among those whose acute COVID-19 did not necessitate hospitalization. Care pathways of people who survived the acute episode of COVID-19 should include attention to cardiovascular health and disease.”
- Xie Y, Xu E, Bowe B, Al-Aly Z. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022 Feb 7. doi: 10.1038/s41591-022-01689-3. Epub ahead of print. PMID: 35132265.
