New study pinpoints key markers for Long COVID diagnosis

By Hugo Francisco de SouzaFeb 18 2024Reviewed by Susha Cheriyedath, M.Sc. In a recent preprint* uploaded to the medRxiv server, an international team of researchers conducted a large-scale systems-level immunological screening of more than 1,000 confirmed COVID-19 patients to identify diagnostic markers of Long-term COVID-19.

COVID-19 and the need for Long COVID diagnosis The ongoing Severe Acute Respiratory Syndrome Coronavirus 2 caused Coronavirus disease 2019 viral pandemic is one of the worst in human memory, estimated to have infected more than 700 million individuals since its discovery in Wuhan, China, in late 2019.

About the study In the present study, researchers screened more than 1000 prospective patients enrolled at Long COVID clinics in Belgium and Sweden to elucidate the shared mechanisms of Long COVID pathology and subsequently develop a sensitive and reliable diagnostic test for the condition. Only subjects with a clinically confirmed mild or moderate COVID-19 infection were included. Severe cases were excluded due to overlapping symptoms with those of the post-intensive care syndrome.

Since these assays revealed that antigen responses were only depicted by about 10% of the study cohort, suggesting its unreliability and poor sensitivity as a diagnostic tool, researchers used a 51-parameter-panel mass cytometry assay to investigate possible immunological correlates. The Olinks assay was further conducted to measure levels of cytokines and other plasma proteins in patients’ plasma samples.

Study findings The present study reveals that, while IgG response to SARS-CoV-2 spike proteins as measured by the SIMAO assay can be used as a sensitive Long COVID marker, IgA and IgM cannot due to their detection in ~10% of afflicted patients. This suggests that memory CD8+ T cells were restrained, and their clonal expansion is restricted by SARS-CoV-2, inconsistent with the previously hypothesized exhausted phenotype pathology.

Results highlight that in Long COVID cases, the elevated serologic response was inversely correlated to expanding CD8+ T cell populations, elucidating the role of the restrained antiviral T cell response as a crucial component of Long COVID pathology. Current and future work aimed at understanding the genetic basis of this revelation may allow for the development of clinical therapeutics capable of treating this hitherto incurable condition.

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