The COVID-19 pandemic has challenged not only health systems all over the world, but also some of our most fundamental medical knowledge. A common rule of thumb in virology is that viral infections are self-limiting—that is, they run their course and go away once the virus is cleared or upon the death of the host.
But mounting evidence from a subset of COVID-19 survivors has called this into question. Dubbed long-haulers, these patients continue to suffer from symptoms months after their supposed recovery.
“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,” said Christine Cheung, study lead and Principal Investigator at A*STAR’s Institute of Molecular and Cell Biology (IMCB) and Assistant Professor at the Lee Kong Chian School of Medicine, Nanyang Technological University.
Along with researchers and collaborators from the Nanyang Technological University, the National Center of Infectious Diseases, and A*STAR’s Infectious Disease Labs (ID Labs), Cheung sought to investigate the state of vascular health in COVID-19 survivors, as well as identify the mechanisms that could explain this clotting conundrum.
Running blood samples through flow cytometry, the team found that recovered COVID-19 patients had significantly higher levels of circulating endothelial cells (CECs)—a common biomarker for vascular damage—compared to healthy controls.
At the same time, survivors continued to produce cytokines, which are proteins that facilitate the inflammatory response to pathogens, even after the initial infection had resolved. Compared to controls, blood concentrations of proinflammatory cytokines such as interleukins 2, 1β, and 17A were elevated in samples from COVID-19 patients collected during the early convalescent phase, some seven days after hospital discharge.
The vascular damage and persistent immune activation in COVID-19 patients seemed to be more than a coincidence, according to the researchers. For instance, levels of CEC correlated significantly with the proinflammatory cytokines and survivors had more effector CD8+ and CD4+ T cells than controls. Taken together, these may imply that the inflammatory mechanism stays activated in COVID-19 long-haulers, damaging blood vessels and leading to blood clots.
According to Cheung, their results could help guide post-discharge care and monitoring of COVID-19 survivors, though more experiments are needed to confirm if the prolonged immune response triggers vascular damage in long-haulers. Moving forward, the team is continuing to collect data to assess the effects of COVID-19 even beyond the six-month mark.
“As we gain a greater understanding of the complications COVID ‘long-haulers’ face, [we] hope to encourage vaccine take-up rate to protect oneself from both the virus and its long-term complications,” Cheung added.
The A*STAR-affiliated researchers contributing to this research are from the Institute of Molecular and Cell Biology (IMCB) and the Singapore Immunology Network (SIgN).
