Researchers aimed to track the clinical course and characterize the global and COVID-specific immunity in the blood of individuals with long COVID.
Two recent studies have analyzed the blood of patients with long COVID, aiming to unravel the mysteries surrounding its development. The research explores immune dysregulation, thromboinflammation, and potential biomarkers, offering a promising direction for future diagnostic and therapeutic research.
Approximately 10% of patients diagnosed with severe SARS-CoV-2 infections develop long COVID. 1 Long COVID can affect people of all ages and follows severe as well as mild disease. The researchers in both studies aimed to track the clinical course and characterize the global and COVID-specific immunity in the blood of individuals with long COVID. Symptoms of long COVID can include fatigue, post-exertional malaise, cognitive impairment, and involve multiple organs.
In the first study, “improper crosstalk between cellular and humoral adaptive immunity of patients with COVID led to immune dysregulation, inflammation, and clinical symptoms associated with long COVID,” the researchers reported in Nature Immunity. 1
Researchers analyzed blood samples to obtain a phenotypic characterization of T cells from patients with long COVID and those without long COVID, 8 months after infection (these were taken before COVID-19 vaccination or reinfection). Patients in the long COVID cohort had higher body mass index and incidence of hypertension than controls.
Our analysis suggested an improper crosstalk between the cellular and humoral adaptive immunity in long COVID, which can lead to immune dysregulation, inflammation, and clinical symptoms associated with this debilitating condition.
“We found that long COVID individuals exhibited systemic inflammation and immune dysregulation. This was evidenced by global differences in T cell subset distribution implying ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets,” reported Timothy J. Henrich, MD, of the Division of Experimental Medicine, University of California, San Francisco, CA, and colleagues.
“Our analysis suggested an improper crosstalk between the cellular and humoral adaptive immunity in long COVID, which can lead to immune dysregulation, inflammation, and clinical symptoms associated with this debilitating condition,” wrote the authors.
In the second article, Swiss researchers Cervia-Hasler et al identified serum protein changes as the likely cause of long COVID-19. 2 The researchers examined blood serum from 113 patients who either fully recovered from COVID-19 or developed long COVID, or 39 health controls who were never infected. The researchers measured serum levels of 6596 human proteins across study participants. Their findings were reported in Science.
Patients with acute COVID-19 were followed for up to one year, with their blood tested at baseline, 6 months, and when possible 12 months. Patients with long COVID exhibited changes to blood serum proteins, usually elevation, indicating “dysregulated activation of the complement system, altered coagulation, and tissue injury, suggesting ongoing thromboinflammatory responses,” the authors wrote. The elevated serum biomarkers overlapped between patients who developed long COVID and those who experienced severe acute COVID-19, noted the researchers.
The authors showed that, at the cellular level, “the thromboinflammatory signature associated with long COVID was linked with increased monocyte-platelet aggregates.” In particular, the blood antimicrobial defense system of complement and pentraxin 3 was particularly associated with long COVID development. “Dysregulation of complement proteins could contribute to the thromboinflammation associated with long COVID.”
Study findings identified potential biomarkers for long COVID and new treatment strategies that warrant further diagnostic and therapeutic investigation, noted a press release from the American Association for the Advancement of Science.
“Although therapeutic interventions with coagulation and complement inhibitors in acute COVID-19 produced mixed results, the pathological features specific for long COVID suggest potential interventions for clinical testing,” commented Wolfram Ruf in a related Perspective in Science. 3