The ongoing reports from people who have recovered from COVID-19, of serious complications due to blood clots, have brought to the forefront the need to investigate and understand the role of SARS-CoV-2 infection on vascular health. A new study finds that vascular complications, some of which can lead to heart attacks and strokes, may be caused by a lingering immune response in the blood vessels after recovery.

This work is published in eLife in the paper, “Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation.”

During the initial stages of infection, SARS-CoV-2 may attack the lining of the blood vessels which can trigger inflammation and an immune response. “This can result in blood vessel damage in the short term,” explained first author Florence Chioh, research assistant at the Lee Kong Chian School of Medicine (LKCMedicine), Nanyang Technological University, Singapore. “For our study, we wanted to investigate what happens in the blood vessels of COVID-19 survivors over the longer term.”

Chioh and colleagues collected blood samples from COVID-19 survivors within a month of their recovery and discharge from the hospital. They found that, in comparison with healthy individuals, COVID-19 survivors have twice as many damaged blood vessel cells, called circulating endothelial cells (CECs), floating in their blood. Even more of these damaged blood vessel cells were found in survivors who had conditions such as hypertension or diabetes that can also damage the blood vessels.

In addition to signs of blood vessel damage, the team found that survivors had an abundance of the inflammatory proteins known as cytokines that are produced by immune cells. The authors wrote: “Several proinflammatory and activated T lymphocyte-associated cytokines sustained from acute infection to recovery phase, which correlated positively with CEC measures, implicating cytokine-driven endothelial dysfunction.”

Notably, they also found higher frequency of effector T cells in the COVID-19 convalescents compared to healthy controls. The activation markers detected on CECs, they noted, “mapped to counter receptors found primarily on cytotoxic CD8+ T cells, raising the possibility of cytotoxic effector cells targeting activated endothelial cells.”

“We show that an overactive immune system is the likely cause of blood vessel damage seen in some COVID-19 survivors,” Chioh said. “This may cause ‘leakiness’ in the blood vessels that increases the risk of blood clots.”

The findings may help explain why some COVID-19 survivors, so-called “long-haulers,” report lasting COVID-19 symptoms or why some experience strokes or heart attacks weeks or months after recovery. They may also suggest potential strategies to help prevent these complications.

“Our work suggests that COVID-19 patients, especially those with underlying chronic conditions, may benefit from close post-recovery monitoring,” added Christine Cheung, PhD, assistant professor at LKCMedicine. “This would help identify high-risk individuals who may need blood thinners or preventative therapy to protect them from debilitating blood-clotting complications.”