TMA mediated by the complement cascade has been identified as a potential cause for severe manifestations of COVID-19 in adults.
Investigators at the Children's Hospital of Philadelphia (CHOP) have found that a biomarker related to blood vessel damage was elevated in children with the coronavirus disease 2019 (COVID-19). This was true even if the children showed minimal or no symptoms of the virus.
A secondary finding identified that a high proportion of the children with the illness met diagnostic and clinical criteria for thrombotic microangiopathy (TMA), a syndrome that involves clotting in the small blood vessels.
The study, published in the journal Blood Advances, analyzed 50 pediatric patients at CHOP who were hospitalized with an acute COVID-19 infection. 18 of the patients were diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C), a post-viral inflammatory response to COVID-19. The investigators used a soluble C5b9 (sC5b9), an indicator of severity in TMA, as a biomarker for complement activation and TMA.
The findings saw elevations of C5b9 in the patients with a severe infection and MIS-C, while also showing elevated C5b9 in patients who had minimal symptoms or were asymptomatic. The prospective study collected data from patients when admitted to the hospital, and also obtained laboratory data retrospectively so that they were able to evaluate whether the patients met the clinical criteria for TMA.
19 (86%) of the patients who had a complete set of data met the criteria for TMA. However, the levels of sC5b9 were found to be elevated in both patients who did and did not meet criteria for TMA.
"Although most children with COVID-19 do not have severe disease, our study shows that there may be other effects of SARS-CoV-2 that are worthy of investigation," David T. Teachey, co-senior author on the study said. "Future studies are needed to determine if hospitalized children with SARS-CoV-2 should be screened for TMA, if TMA-directed management is helpful, and if there are any short- or long-term clinical consequences of complement activation and endothelial damage in children with COVID-19 or MIS-C. The most important takeaway from this study is we have more to learn about SARS-CoV-2. We should not make guesses about the short and long-term impact of infection."