Research: Recovered COVID-19 patients could be at risk of developing blood clots

Individuals who have recovered from COVID-19, particularly those with pre-existing cardiovascular conditions, could be at risk of developing blood clots due to a prolonged and overactive immune response, according to a research team, led by LKCMedicine Nanyang Assistant Professor Christine Cheung.

The team investigated the possible link between the coronavirus and an increased risk of blood clot formation, shedding new light on “long-haul COVID” – the name given to the medium-and long-term health consequences of COVID-19. 

The team which includes researchers from NTU Singapore, Agency for Science, Technology and Research (A*STAR), Singapore Immunology Network (SIgN), and the National Centre for Infectious Diseases, Singapore (NCID), collected and analysed blood samples from 30 COVID-19 patients a month after they recovered from the infection and were discharged from hospital.

They found that all recovered COVID-19 patients had signs of blood vessel damage, possibly from a lingering immune response, which may trigger the formation of blood clots.

Christine Cheung

The findings could help to explain why some people who have recovered from COVID-19 exhibit symptoms of blood clotting complications after their initial recovery. In some cases, they are at increased risk of heart attack, stroke, or organ failure when blood clots block major arteries to vital organs.

Their findings were published on peer-reviewed scientific journal eLife on 23 March.

“With more people recovering from COVID-19, we started hearing from clinicians about patients returning with blood clotting issues after they had been discharged and cleared of the virus. This makes a strong case for the close monitoring of recovered COVID-19 patients, especially those with pre-existing cardiovascular conditions such as hypertension and diabetes who have weakened blood vessels,” said Asst Prof Cheung.

She shared that about half of the COVID-19 patients tested in the study had had pre-existing cardiovascular conditions which put them at a higher risk of having blood clots. These patients had more pronounced blood vessel dysfunction compared with the group who had no cardiovascular risks.

How blood vessels get damaged from post-recovery overactive immune system

The study revealed that recovered COVID-19 patients had twice the normal number of circulating endothelial cells (CECs) that had been shed from damaged blood vessel walls. The elevated levels of CECs indicate that blood vessel injury is still apparent after recovering from viral infection.

The research team found that recovered COVID-19 patients continued to produce high levels of cytokines – proteins produced by immune cells that activate the immune response against pathogens – even in the absence of the virus.

They also found that there is an unusually high number of immune cells, known as T cells, that attack and destroy viruses present in the blood of recovered COVID-19 patients.

The presence of both cytokines and higher levels of immune cells suggests that the immune systems of recovered COVID-19 patients remain activated even once the virus was gone. The researchers hypothesise that these persistently activated immune responses may attack the blood vessels of recovered COVID-19 patients, causing even more damage and increasing the risk of blood clot formation further.

The study’s first author Florence Chioh, a Research Assistant at LKCMedicine said, “While COVID-19 is mainly a respiratory infection, the virus may also attack the linings of blood vessels, causing inflammation and damage. Leakage from these damaged vessels triggers the formation of blood clots that may result in the sort of complications seen in the patients during hospitalisation.”

What the study means for post-hospitalisation care for at-risk COVID-19 patients

The research team said, the key findings can help inform guidelines for post-hospitalisation care of COVID-19 patients, who might be susceptible to ‘long-haul COVID’ symptoms.

In January this year, the World Health Organization (WHO) released a recommendation in their revised clinical management guidelines, targeted at the risk of blood clot formation. For hospitalised patients, WHO recommended the use of low dose anticoagulants for preventing the blood clots forming in blood vessels.

Asst Prof Cheung said those with cardiovascular conditions need to be more cautious since their underlying conditions already weaken their vascular systems. “It’s a double blow with COVID-19. As we gain greater understanding of complications COVID ‘long-haulers’ face, there is hope to encourage vaccine take-up rate to protect oneself from both the virus and its long-term complications,” she added.

Moving forward, the team is investigating the longer-term effects of COVID-19 in patients who have recovered from the infection for at least six months or longer.