Dayal, Pradeep study Long COVID’s impact across multiple organ systems

According to a new publication developed by several department members, people diagnosed with Long COVID may be vulnerable to a range of health complications long after the initial infection resolves.  

This study found that adults with clinically recognized Long COVID faced higher risks of cardiovascular, renal, and pulmonary conditions than individuals who recovered from COVID-19 without developing Long COVID. The findings, published in the Journal of the American Heart Association, were based on health records from more than 2.6 million adults in the global TriNetX database.  

For senior author  Sanjana Dayal, PhD, professor of Hematology-Oncology and recently appointed chair of an NIH study section, the results reinforce the need to view Long COVID as a condition that can affect multiple organ systems.   

“We believe it was important to take a broader, multi-organ view of Long COVID because the condition does not appear to be confined to a single organ system,” Dayal says. “Patients with Long COVID can experience symptoms and complications affecting cardiovascular, pulmonary, renal, neurologic, and other organ systems, suggesting a complex and systemic disease process.” 

The research team compared adults diagnosed with Long COVID to individuals who had COVID-19 but did not later receive a Long COVID diagnosis. After matching for age, sex, and other factors, the investigators examined 15 cardiovascular, renal, and pulmonary outcomes. The analysis revealed trends that may help researchers better understand how Long COVID affects different people.  

For example, the study identified differences between men and women. Younger women demonstrated greater relative risks for several cardiovascular and kidney-related outcomes, while younger men showed greater relative risks for some pulmonary outcomes. According to Dayal, those patterns raise important questions about the biological mechanisms causing adverse outcomes related to Long COVID.  

“It remains unclear whether these differences are driven by sex-related variations in immune responses, vascular function, underlying comorbidities, or a combination of these factors,” she says. “Understanding the mechanisms underlying these sex-specific effects could provide important insights into the pathophysiology of clinical conditions in Long COVID and help identify individuals at greatest risk for specific complications.”  

This study also identified a trend that challenges the popular assumption that younger patients are largely protected from long-term consequences of COVID-19. While older adults had the highest absolute rates of complications, the study found that the increase in risk was often greatest among younger adults.   

First author Akash Pradeep said the elevated risks observed among younger adults were one of the study’s most surprising findings. Pradeep worked on the study with Dayal as an undergraduate researcher and spent nearly two years helping bring the project to publication.  

“In general, when most of the population hears of COVID, they tend to think it mainly affects older people,” Pradeep said. “Something the study brought up was that younger adults were more at risk for a lot of cardiovascular and renal outcomes, younger women in particular.”  

Pradeep helped design database queries, collect data, run analyses, and troubleshoot challenges throughout the study. His work with Internal Medicine research was especially important ahead of his first year of medical school at Carver College of Medicine. Pradeep plans to continue pursuing clinical research throughout his medical training and credits the project and Dayal’s mentorship with helping shape that goal.  

While researchers continue working to understand why some people develop these long-term organ complications, Dayal says more work is needed to connect large-scale clinical findings with the biological mechanisms behind Long COVID or Long COVID-associated conditions.   

Both Dayal and Pradeep acknowledge the support of the other co-authors— Izola Ramalho, PhD; Martha Carvour, MD, PhD; Srija Sivamurugan, MD; Upinder Singh, MD; and Alejandro Comellas, MD— during the analysis, data presentation, and interpretation of clinical input. Dayal says that their colleagues helped her and Pradeep shape the study meaningfully.