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Severe COVID-19 increases risk of future cardiovascular events

Study: COVID-19 severity and risk of subsequent cardiovascular events. Image Credit: Yurchanka Siarhei / Shutterstock.com

To date, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the virus responsible for the coronavirus disease 2019 (COVID-19), has infected over 603 million individuals and claimed more than 6.4 million lives worldwide.

About 30% of COVID-19 survivors continue to experience a wide range of persistent symptoms for several weeks since their initial diagnosis. This condition is commonly referred to as post-acute sequelae of SARS-CoV-2 infection (PASC) or “long COVID.”

Study: COVID-19 severity and risk of subsequent cardiovascular events. Image Credit: Yurchanka Siarhei / Shutterstock.com

Study: COVID-19 severity and risk of subsequent cardiovascular events. Image Credit: Yurchanka Siarhei / Shutterstock.com

Background

Even though multisystem inflammatory syndrome is the most common PASC syndrome in adults and children, a wide range of other symptoms, including sleep difficulties, persistent fatigue, type 1 diabetes, and neurological disorders, have been reported. The incidence of these symptoms varies from one person to another based on their demographic and clinical characteristics.

Several studies have indicated the manifestation of multiple cardiovascular complications, such as arrhythmia, hypertension, acute myocardial infarction, thromboembolism, and cerebrovascular accidents, in individuals who have recovered from COVID-19. However, a limited number of studies have confirmed that severe COVID-19 leads to a high risk of cardiovascular diseases.

A recent Clinical Infectious Diseases journal study determines the relationship between COVID-19 severity and risk of subsequent cardiovascular events (CVEs) in a large cohort.

Study findings

A retrospective cohort study was performed using nationwide health insurance claims data of adults from the United States Health Verity Real-Time Insights and Evidence database. Increased COVID-19 severity was found to enhance the risk of developing subsequent CVEs among individuals without a cardiac history in previous years. 

As compared to COVID-19 patients who required outpatient care, those who required hospital admission were more likely to experience CVEs. Among COVID-19 hospitalized patients, those admitted to the intensive care unit (ICU) were almost 80% more likely to develop CVEs than non-ICU hospitalized patients.

In fact, non-ICU hospitalized patients exhibited only a 28% possibility of experiencing CVEs thirty days after initial COVID-19 symptoms. Additionally, as compared to COVID-19 outpatients, hospitalized patients were more likely to be admitted for a CVE after recovering from COVID-19.

In younger adults, the incidence of cardiovascular sequelae was lower as compared to older adults. Aside from CVEs, other severe outcomes, such as thrombotic events and cerebrovascular accidents, were observed in patients who recovered from severe COVID-19. However, such observations were less likely in COVID-19 patients who required only outpatient care.

The study findings emphasize the importance of vaccination, as demonstrated by its ability to reduce severe disease. Similarly, prompt antiviral treatment of acute COVID-19 has been recommended, which would help reduce the possibility of transition to severe illness.

Both COVID-19 vaccination and timely therapeutic interventions would alleviate the risk of severe COVID-19 and subsequently decrease the possibility of experiencing CVEs.

The findings of the present study are consistent with previous research that has reported a higher incidence of myocarditis and pericarditis in patients who recovered from severe SARS-CoV-2 infection. Nevertheless, it was observed that elevated cardiovascular risk after acute infection may not be exclusive to COVID-19.

In fact, some other diseases that have been associated with an increased risk of long-term CVEs are influenza and pneumonia bacteremia. Additionally, 22-65% of sepsis survivors are at an increased risk of CVEs.

The underlying mechanism responsible for the increased risk of CVEs following SARS-CoV-2 infection has not been determined. SARS-CoV-2 infects cardiac myocytes through their interaction with the angiotensin-converting enzyme 2 (ACE-2) receptor, which might remain persistent; therefore, this interaction induces chronic inflammatory responses and subsequent tissue damage or fibrosis.

Another mechanism related to the development of CVEs following recovery from COVID-19 is an autoimmune response to cardiac antigens that causes delayed damage to cardiac tissues. Anti-heart antibodies also correlated with cardiovascular manifestation and COVID-19.

Viral toxicity is another possible mechanism that might cause long-term cardiac damage or thrombosis in vasculitis. However, in the future, more research is needed to confirm the mechanisms related to cardiac damage after SARS-CoV-2 infection.

Conclusions

Due to the lack of a COVID-19-negative control group, the authors failed to quantify the elevated risk of CVEs in COVID-19 patients. The unwanted inclusion of patients with a history of CVEs could have overestimated the result as well. The impact of vaccination status on the incidence of CVE was not studied.

Despite these limitations, the present study strongly emphasized that patients who recovered from severe COVID-19 were at a greater risk of developing CVEs. As compared to COVID-19 patients who required outpatient care, those who were admitted to the ICU were at a higher risk of experiencing CVEs.

The importance of COVID-19 vaccination in preventing severe infection was strongly emphasized in this study.

Journal reference:

  • Wiemken, L. T., McGrath, L. J., Andersen, K. M., et al. (2022). COVID-19 severity and risk of subsequent cardiovascular events. Clinical Infectious Diseases. doi:10.1093/cid/ciac661.
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Study provides new understanding of the earliest molecular events in Type 1 Diabetes pathogenesis

Study provides new understanding of the earliest molecular events in Type 1 Diabetes pathogenesis

For the first time, researchers have revealed that during the development of Type 1 Diabetes (T1D), when insulin-producing cells in the pancreas are under attack from T lymphocytes, the cells lining the pancreatic duct reprogram themselves in an attempt to suppress autoimmune T cell responses. This study is published today in Nature Metabolism.

The first events that occur in a patient heading towards Type 1 Diabetes, the events that trigger autoimmunity, have been difficult for researchers to pin down because of our inability to biopsy the pancreas, and the fact that clinical diagnosis is only made once massive beta cell destruction has occurred. That is why it is so important to develop a better understanding of the earliest molecular events in T1D pathogenesis, so we can uncover more about biomarker identification and disease prevention.”


Golnaz Vahedi, PhD, senior author, associate professor of Genetics and member of the Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine at the University of Pennsylvania

Autoimmune diseases, which affect as many as 23.5 million Americans, occur when the body’s immune system attacks and destroys healthy organs, tissues and cells. There are more than 80 types of autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease, and T1D. In T1D, immune cells called T lymphocytes attack and destroy insulin-secreting pancreatic beta cells and the pancreas stops producing insulin, the hormone that controls blood sugar levels.

“Although it might be an ultimately unsuccessful attempt of the pancreas to limit the adaptive T cell response responsible for destroying beta cells, this finding that the ductal cells are capable of playing this suppressive role towards autoimmune T cell responses is unprecedented,” said co-senior author Klaus Kaestner, PhD, the Thomas and Evelyn Suor Butterworth Professor in Genetics. “Our study shows that these cells, which had never previously been linked to immunity, may change themselves to protect the pancreas.”

Established in 2016, the Human Pancreas Analysis Program (HPAP) is supported by a $28 million grant from the National Institutes of Health with major contributions from Penn, the University of Florida and Vanderbilt University. The HPAP, which is co-directed by Kaestner and Ali Naji MD, PhD, the J. William White Professor of Surgical Research, started collecting pancreatic tissues from hundreds of deceased organ donors diagnosed with T1D. Because many T1D patients harbor beta cell autoantibodies called Glutamic Acid Decarboxylase (GAD) in their bloodstream years before clinical diagnosis, HPAP also collects samples from autoantibody-positive donors, who are at risk for developing T1D but have not received that diagnosis.

“Our study took those quality tissue samples and created high-resolution measurements of millions of cells from patients at various stages of T1D progression, resulting in a single-cell atlas of pancreatic islets,” said co-senior author R. Babak Faryabi, PhD, an assistant professor of Pathology and Laboratory Medicine and a core member of Epigenetics Institute at Penn.

Blood tests to check for levels of GAD are common for patients with, or at risk for, T1D, and doctors use it as a diagnostic tool. Another finding of this study is the new understanding of what is happening on a molecular level in the pancreas and how it correlates to the findings of the GAD test.

“Our study is the first to show that even when a person is not clinically considered to have T1D, high levels detected in their GAD test indicate large-scale transcriptional remodeling of their beta cells,” said Naji, a study co-senior author. “It solidifies to clinicians to closely monitor patients with increasing levels of GAD, as we now know what cellular and molecular changes are in motion in relation to those levels.”

Although researchers do not yet know whether these transcriptional changes are contributing to or are consequences of disease pathogenesis, the discovery of molecular phenotypic changes in pancreatic cells of autoantibody-positive individuals advances the understanding of early pancreatic changes occurring in T1D, and sets the course for continued research in this area.

Source:

Journal reference:

Fasolino, M., et al. (2022) Single-cell multi-omics analysis of human pancreatic islets reveals novel cellular states in type 1 diabetes. Nature Metabolism. doi.org/10.1038/s42255-022-00531-x.