Project description:Aging and COVID-19 are known to influence DNA methylation, potentially affecting the rate of aging and the risk of disease. The physiological functions of 54 volunteers—including maximal oxygen uptake (VO₂ max), grip strength, and vertical jump—were assessed just before the COVID-19 pandemic and again three years later. Of these volunteers, 27 had contracted COVID-19. Eight epigenetic clocks were used to assess the rate of aging during the three-year period: DNAmAge showed accelerated aging and five clocks showed slowed aging (DNAmAgeSkinBlood, DNAmAgeHannum, DNAmFitAge, PhenoAge, and DNAmTL). When we considered only females, we observed a stronger effect in the increase of DNAmAge acceleration, while we observed slowed aging in the case of SkinBloodClock, and DNAmTL. The methylation of the promoter region of the H1FNT genes, which encodes testis-specific histone H1 family member N (H1fnt) and plays a crucial role in spermatogenesis decreased the most significantly. In contrast, the promoter of CSTL1, which encodes Cystatin-like 1, showed the most significant increase. We found that having COVID-19 during the 3-year study period significantly increased the progress of aging assessed by DNAmGrimAge, DNAmGrimAge2, and DNAmFitAge (p=0.024, 0.047, 0.032, respectively after we adjusted the analysis for baseline variables). The data suggest that COVID-19 may have a mild long-term effect on epigenetic aging.
Project description: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 autoantibodies. 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.
Project description:Genome-wide DNA methylation analysis of COVID-19 severity using the Illumina HumanMethylationEPIC microarray platform to analyze over 850,000 methylation sites, comparing COVID-19 patients during and one year after infection, using whole blood tissue.
Project description:6 patients with severe COVID-19 were followed longitudinally during hospitalization and up to 1 year after infection, when they also received a vaccine. For each time point and patient, PBMCs were collected and split into 3 pools: 1/3 was sequenced straight; from 1/3 of the samples B cells were enriched (B cell enrichment kit from StemCell) and from 1/3 of the samples, antigen-specific cells were sorted using barcoded N, S and RBD probes. All samples were further stained using a cocktail of 181 barcoded Abs. For all samples we have sequences gene-expression, B cell receptor and Cell surface proteins.
Project description:The host response to COVID-19 pathophysiology over the first days of infection remains largely unclear especially the mechanisms in the blood compartment. We report here on a longitudinal proteomic analysis of acute phase COVID-19 patients, for which we used blood plasma and MRM proteomics with internal standards as well as DIA. We measured samples on admission for 49 patients, of which 21 with additional samples on days 2, 4, 7, and 14 after admission. We also measured 30 externally obtained samples from healthy individuals for comparison at baseline.
Project description:To trace immune responses in COVID-19 patients with severity, we performed in-depth, longitudinal single-cell multiomics involving T-cell receptor (TCR)/B-cell receptor (BCR) sequencing, feature barcoded antibody (Ab) panel detection (i.e., cellular indexing of transcriptomes and epitopes by sequencing, CITE-seq) followed by RNA sequencing in a single-cell resolution.
Project description:Longitudinal cohort: 773 host response genes were profiled in previously vaccinated (n=16) and unvaccinated (n=14) COVID-19+ participants along with 5 healthy uninfected controls across a 2-week observational window Single timepoint cohort: 773 host response genes were profiled in 6 healthy uninfected participants
Project description:In managing patients with coronavirus disease 2019 (COVID-19), early identification of those at high risk and real-time monitoring of disease progression to severe COVID-19 is a major challenge. We aimed to identify early prognostic protein markers and to discover surrogate protein markers that effectively reflect the clinical progression of the disease. We performed in-depth proteome profiling on 137 sera, longitudinally collected from 25 patients with COVID-19 (non-severe patients, n = 13; patients who progressed to severe COVID-19, n = 12). We identified 11 potential biomarkers, including the novel markers IGLV3-19 and BNC2, as early prognostic indicators of severe COVID-19. These potential biomarkers are mainly involved in biological processes associated with humoral immune response, interferon signalling, acute phase response, lipid metabolism, and platelet degranulation. We further revealed that the longitudinal changes of 40 proteins persistently increased or decreased as the disease progressed to severe COVID-19. These 40 potential biomarkers could effectively reflect the clinical progression of the disease. This study supports the development of protein biomarkers, which might enable better predicting and monitoring progression to severe COVID-19.
Project description:Type I interferon (IFN-I) neutralizing autoantibodies have been found in some critical COVID-19 patients; however, their prevalence and longitudinal dynamics across the disease severity scale, and functional effects on circulating leukocytes remain unknown. Here, in 284 COVID-19 patients, we found IFN-I autoantibodies in 19% of critical, 6% of severe and none of the moderate cases. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single- cell epitope and transcriptome sequencing from 54 COVID-19 patients, 15 non-COVID-19 patients and 11 non-hospitalized healthy controls, revealed a lack of IFN-I stimulated gene (ISG-I) response in myeloid cells from critical cases, including those producing anti-IFN-I autoantibodies. Moreover, surface protein analysis showed an inverse correlation of the inhibitory receptor LAIR-1 with ISG-I expression response early in the disease course. This aberrant ISG-I response in critical patients with and without IFN-I autoantibodies, supports a unifying model for disease pathogenesis involving ISG-I suppression via convergent mechanisms.
Project description:We performed longitudinal plasma proteomics analysis and determined absolute protein levels in a Canadian cohort (n=74) at admission day to hospital for acute COVID-19 and at 3 and 6 months after diagnosis of acute COVID-19. We measured plasma protein on a triple quadrupole mass spectrometer operated in multiple reaction monitoring mode and used internal standards to deduce protein absolute concentrations. We used a validated panel of 269 surrogate heavy labeled peptides. We also measured % predicted forced vital capacity (FVC, %) and diffusing capacity of the lungs for carbon monoxide (DLCO, %) by routine pulmonary function testing. We did functional enrichment and pathway analyses and determined proteins that were increased or decreased from hospital admission to 3-months and 6-months, compared females to males and determined associations of proteins with FVC% and DLCO%.