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Nature Nov 2023Post-acute infection syndromes may develop after acute viral disease. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as...
Post-acute infection syndromes may develop after acute viral disease. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.
Topics: Humans; Antibodies, Viral; Biomarkers; Cross-Sectional Studies; Herpesvirus 4, Human; Hydrocortisone; Immunophenotyping; Lymphocytes; Machine Learning; Myeloid Cells; Post-Acute COVID-19 Syndrome; SARS-CoV-2
PubMed: 37748514
DOI: 10.1038/s41586-023-06651-y -
Nature Communications Jan 2024A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. A distinctive symptom of patients with long COVID is...
A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. A distinctive symptom of patients with long COVID is post-exertional malaise, which is associated with a worsening of fatigue- and pain-related symptoms after acute mental or physical exercise, but its underlying pathophysiology is unclear. With this longitudinal case-control study (NCT05225688), we provide new insights into the pathophysiology of post-exertional malaise in patients with long COVID. We show that skeletal muscle structure is associated with a lower exercise capacity in patients, and local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise. This study highlights novel pathways that help to understand the pathophysiology of post-exertional malaise in patients suffering from long COVID and other post-infectious diseases.
Topics: Humans; Post-Acute COVID-19 Syndrome; SARS-CoV-2; Case-Control Studies; COVID-19; Fatigue; Musculoskeletal Abnormalities; Muscle, Skeletal; Pain; Plaque, Amyloid
PubMed: 38177128
DOI: 10.1038/s41467-023-44432-3