Project description:Although the majority of COVID-19 patients are asymptomatic or mildly symptomatic at diagnosis, some will subsequently progress to pneumonia, oxygen desaturation and other symptoms requiring active clinical management. However, molecular markers that identify high-risk patients early in the disease course (Days 1-8 from symptom onset) are scarce, due to the paucity of relevant longitudinal studies. We performed longitudinal single cell RNA-seq on 286 peripheral blood samples from 108 COVID-19 patients, 73 of which had at least one early sample. By examining discrete cell subtypes as well as continuous single cell states, we identified upregulation of type I IFN response genes as the predominant cellular prognostic signature of future disease severity. Type I IFN response was dynamic and complex, spiking early in progressors and then regressing to the cohort mean at the very next sampling, with the cohort mean itself receding to asymptomatic levels by Day 14 regardless of severity. Moreover, in severe and critical cases, IFN response was impaired during Days 5-8, partially due to upregulation of SOCS3 and other negative regulators. We have identified an early prognostic signature for predicting COVID-19 severity as well as potential mechanisms underlying the dysfunctional host immune response in severe disease.
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: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: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.