Distinguishing features of Long COVID identified through immune profiling

Abstract

SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID. Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions; however, the basic biological mechanisms responsible for these debilitating symptoms are unclear. Here, 215 individuals were included in an exploratory, cross-sectional study to perform multi-dimensional immune phenotyping in conjunction with machine learning methods to identify key immunological features distinguishing Long COVID. Marked differences were noted in specific circulating myeloid and lymphocyte populations relative to matched control groups, as well as evidence of elevated humoral responses directed against SARS-CoV-2 among participants with Long COVID. Further, unexpected increases were observed in antibody responses directed against non-SARS-CoV-2 viral pathogens, particularly Epstein-Barr virus. Analysis of circulating immune mediators and various hormones also revealed pronounced differences, with levels of cortisol being uniformly lower among participants with Long COVID relative to matched control groups. Integration of immune phenotyping data into unbiased machine learning models identified significant distinguishing features critical in accurate classification of Long COVID, with decreased levels of cortisol being the most significant individual predictor. These findings will help guide additional studies into the pathobiology of Long COVID and may aid in the future development of objective biomarkers for Long COVID.

Proteomics of fibrin amyloid microclots in long COVID/post-acute sequelae of COVID-19 (PASC) shows many entrapped pro-inflammatory molecules that may also contribute to a failed fibrinolytic system

“…Conversely, a study performed by Klein et al suggest that autoantibodies have a limited role to play in the pathogenesis of long COVID [105]. Their findings point to the involvement of persistent viral antigen, reactivation of latent herpesviruses, and chronic inflammation in long COVID pathophysiology.…”

Understanding the Post COVID-19 Condition (Long COVID) in Adults and the Expected Burden for Ontario

“…Although some studies suggest certain biomarkers measured in blood samples may identify or predict those who will develop the condition, 39 the evidence in this field remains uncertain. However, the results of our meta-analysis (Figure 4) in combination with a recent study reporting on risk factors provide some insight.…”

Plasma proteomic signature predicts who will get persistent symptoms following SARS-CoV-2 infection

“…More than 30% of individuals have persistent symptoms following acute SARS-CoV-2 infection. 57 A clear cause has not yet been found but current theories 58,59 revolve around immune dysregulation, 60 clotting dysfunction or virus persistence. 61 We show that signature biomarkers at the time of seroconversion for SARS-CoV-2 associates with the persistence of symptoms at 12 months (Figure 5).…”