Abstract
Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8 + T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.
Keywords: COVID-19; PASC; RNAemia; antibodies; auto-antibodies; computational biology; immune system; immunology; long COVID; metabolomics; multi-omics; proteomics; single cell; single-cell CITE-seq; single-cell RNA-seq; single-cell TCR-seq; single-cell secretome; symptoms; transcriptome; viremia.
【저자키워드】 COVID-19, Transcriptome, immunology, antibodies, metabolomics, proteomics, Computational biology, immune system, Symptoms, viremia., Long COVID, single-cell RNA-seq, Single Cell, PASC, RNAemia, Auto-antibodies, Multi-omics, single-cell CITE-seq, single-cell TCR-seq, single-cell secretome, 【초록키워드】 Transcriptome, immunology, SARS-CoV-2, metabolomics, proteomics, Immunity, T cells, severity, Computational biology, Diagnosis, diabetes, immune system, risk factor, virus, CD8, immune, type 2 diabetes, T cell, Viremia, single-cell RNA-seq, Patient, COVID-19 diagnosis, Epstein-Barr virus, convalescence, Single Cell, detectability, PASC, Auto-antibodies, convalescent, chronic condition, disease, single-cell, association, COVID-19 patient, chronic conditions, early disease, Factor, Treatment strategies, Clinical data, multi, immunological, initial, exhibited, unique, resolved, exhibiting, immune states, 【제목키워드】 Factor, Multiple,