![]() ![]() Subsets of convalescent COVID-19 patients may also develop new or aggravated sequelae for months to years following resolution of acute COVID-19, comprising a nascent clinical syndrome known as post-acute sequelae of COVID-19 (PASC) or Long COVID. Outcomes following COVID-19 are varied, ranging from complete recovery to a significantly increased risk of an assortment of adverse clinical events - even among those with initially mild disease 2, 25. The acute phase of COVID-19 has been studied extensively and in severe cases presents with extensive immunological and multi-organ system dysfunction 20– 24. SARS-CoV-2 is a zoonotic betacoronavirus responsible for more than 6 million deaths since its initial detection in late 2019 19. Yet despite their ubiquity and historical record, the basic biology underlying the development of PAIS following viral infections remains unclear 18. Moreover, post-acute infection syndromes (PAIS) following acute viral diseases have been described for more than a century 14– 17. Clinical sequelae can manifest following a variety of acute infections across a diverse range of viral families 4– 13. Recovery from viral infections is heterogeneous and chronic symptoms may persist in a subset of convalescent individuals. ![]() 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. 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. 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. ![]() Further, unexpected increases were observed in antibody responses directed against non-SARS-CoV-2 viral pathogens, particularly Epstein-Barr virus. 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. 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. Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions 1– 3 however, the basic biological mechanisms responsible for these debilitating symptoms are unclear. 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 1– 3. ![]()
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