Project description:The on-going COVID-19 pandemic requires a deeper understanding of the long-term antibody responses that persist following SARS-CoV-2 infection. To that end, we determined epitope-specific IgG antibody responses in COVID-19 convalescent sera collected at 5 months post-diagnosis and compared that to sera from naïve individuals. Each serum sample was reacted with a high-density peptide microarray representing the complete proteome of SARS-CoV-2 as 15 mer peptides with 11 amino acid overlap and homologs of spike glycoprotein, nucleoprotein, membrane protein, and envelope small membrane protein from related human coronaviruses. Binding signatures were compared between COVID-19 convalescent patients and naïve individuals using the web service tool EPIphany.

2022-02-05 | E-MTAB-10740 | biostudies-arrayexpress

Gene expression profiles of 65 blood samples recovered from 46 COVID-19 convalescent patients and 10 healthy donors were analyzed by RNA-Sequencing.

Project description:Purpose: Following a severe COVID-19 infection, a proportion of individuals develop prolonged symptoms. We investigated the immunological dysfunction that underlies the persistence of symptoms months after the resolution of acute COVID-19. Methods: We analyzed cytokines, cell phenotypes, SARS-CoV-2 spike-specific and neutralizing antibodies, and whole blood gene expression profiles in convalescent severe COVID-19 patients 1, 3, and 6 months following hospital discharge. Results: We observed persistent abnormalities until month 6 marked by i) high serum levels of monocyte/macrophage and endothelial activation markers, chemotaxis, and hematopoietic cytokines, ii) a high frequency of central memory CD4+ and effector CD8+ T cells; iii) a decrease in anti-SARS-CoV-2 spike and neutralizing antibodies, iv) an upregulation of genes related to platelet, neutrophil activation, erythrocytes, myeloid cell differentiation and RUNX1 signaling. We identified a “core gene signature” associated with a history of thrombotic events, with upregulation of a set of genes involved in neutrophil activation, platelet, hematopoiesis, and blood coagulation. Conclusion: The lack of restoration of gene expression to a normal profile after up to six months of follow-up, even in asymptomatic patients who experienced severe COVID-19, signals the need to carefully extend their clinical follow-up and propose preventive measures.

2023-03-29 | GSE227116 | GEO

A single-cell atlas of lymphocyte adaptive immune repertoires and transcriptomes reveals age-related differences in convalescent COVID-19 patients

Project description:We utilize single-cell sequencing (scSeq) of lymphocyte immune repertoires and transcriptomes to quantitatively profile the adaptive immune response in COVID-19 patients of varying age. Our scSeq analysis defines the adaptive immune repertoire and transcriptome in convalescent COVID-19 patients and shows important age-related differences implicated in immunity against SARS-CoV-2.

2021-03-20 | E-MTAB-10169 | biostudies-arrayexpress

RNAseq analysis of human CD4+ regulatory Tregs and Tconvs in COVID-19 and healthy donors isolated from peripheral blood.

Project description:RNAseq analysis of human CD4+ regulatory Tregs and Tconvs in COVID-19 and healthy donors isolated from peripheral blood.

2021-07-07 | GSE179448 | GEO

Whole blood transciptome analysis in severe Covid-19 patients and healthy donors

Project description:The identification of COVID-19 patients with high-risk of severe disease is a challenge in routine care. We performed blood RNA-seq gene expression analyses in severe hospitalized patients compared to healthy donors. Supervised and unsupervised analyses revealed a high abundance of CD177, a specific neutrophil activation marker, contributing to the clustering of severe patients. Gene abundance correlated with high serum levels of CD177 in severe patients. These results highlight neutrophil activation as a hallmark of severe disease and CD177 assessment as a reliable prognostic marker for routine care.

2021-05-27 | GSE171110 | GEO

Convalescent COVID-19 patients without comorbidities display similar immunophenotypes over time despite divergent disease severities

Project description:COVID-19, the disease caused by SARS-CoV-2 infection, can assume a highly variable disease course, ranging from asymptomatic infection, which constitutes the majority of cases, to severe respiratory failure. This implies a diverse host immune response to SARS-CoV-2. However, the immunological underpinnings underlying these divergent disease courses remain elusive. We therefore set out to longitudinally characterize immune signatures of convalescent COVID-19 patients stratified according to their disease severity. Our unique convalescent COVID-19 cohort consists of 74 patients not confounded by comorbidities. This is the first study of which we are aware that excludes immune abrogations associated with non-SARS-CoV-2 related risk factors of disease severity. Patients were followed up and analyzed longitudinally (2, 4 and 6 weeks after infection) by high-dimensional flow cytometric profiling of peripheral blood mononuclear cells (PBMCs), in-depth serum analytics, and transcriptomics. Immune phenotypes were correlated to disease severity. Convalescence was overall associated with uniform immune signatures, but distinct immune signatures for mildly versus severely affected patients were detectable within a 2-week time window after infection.

2021-07-30 | GSE181032 | GEO

Functional reprogramming of monocytes in acute and convalescent severe COVID-19 patients [RNA-seq]

Project description:Severe COVID-19 disease is associated with dysregulation of the myeloid compartment during acute infection. Survivors frequently experience long-lasting sequelae but little is known about the eventual persistence of this immune alteration. Herein, we evaluated Toll-like receptor-induced cytokine responses in a cohort of mild to critical patients during acute or convalescent phases (n=97). In the acute phase, we observed impaired cytokine production by monocytes in the most severe patients. This capacity was globally restored in convalescent patients. Yet, we observed increased responsiveness to TLR1/2 ligation in patients that recovered from severe disease, indicating that these cells display distinct functional properties at the different stages of the disease. We identified a specific transcriptomic and epigenomic state in monocytes from acute severe patients that can account for their functional refractoriness. The molecular profile of monocytes from recovering patients was distinct and characterized by increased chromatin accessibility at AP-1 and MAF loci. These results demonstrate that severe COVID-19 infection has a profound impact on the differentiation status and function of circulating monocytes both during the acute and the convalescent phases in a completely distinct manner. This could have important implications for our understanding of short and long-term COVID19-related morbidity.

2022-04-01 | GSE198256 | GEO

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