Project description:Patients suffering from Coronavirus disease 2019 (COVID-19) can develop neurological sequelae, such as headache, neuroinflammatory or cerebrovascular disease. These conditions - here termed Neuro-COVID - are more frequent in patients with severe COVID-19. To understand the etiology of these neurological sequelae, we utilized single-cell sequencing and examined the immune cell profiles from the cerebrospinal fluid (CSF) of Neuro-COVID patients compared to patients with non-inflammatory and autoimmune neurological diseases or with viral encephalitis. The CSF of Neuro-COVID patients exhibited an expansion of dedifferentiated monocytes and of exhausted CD4+ T cells. Neuro-COVID CSF leukocytes featured an enriched interferon signature; however, this was less pronounced than in viral encephalitis. Repertoire analysis revealed broad clonal T cell expansion and curtailed interferon response in severe compared to mild Neuro-COVID patients. Collectively, our findings document the CSF immune compartment in Neuro-COVID patients and suggest compromised antiviral responses in this setting.
Project description:Immune characteristics associated with Coronavirus Disease-2019 (COVID-19) severity are currently unclear. We characterized bronchoalveolar lavage fluid (BALF) immune cells from patients with varying severity of COVID-19 disease and from healthy subjects using single-cell RNA-sequencing. Proinflammatory monocyte-derived macrophages were abundant in the BALF from severe COVID-9 patients. Moderate cases were characterized by the presence of highly clonally expanded tissue-resident CD8+ T cells. This atlas of the bronchoalveolar immune-microenvironment suggests potential mechanisms underlying pathogenesis and recovery in COVID-19.
Project description:To go further insight into the involvement of neutrophils in COVID-19 clinical expression, we performed a proteomic analysis of this blood cell type in COVID-19 patients and two non-infected SARS-CoV-2 control groups composed of healthy subjects and ARDS patients hospitalized in intensive care unit (ICU) respectively. All patients were from Guadeloupe and represent a homogeneous population. We have performed a quantitative proteomic study of neutrophiles from French hot spot COVID region, Guadeloupe, confirming the activation of type I IFN pathway and in some target of IFN as TAP proteins, specifically in COVID patients, but not in hospitalized ARDS non-COVID patients and described modification of the NET proteome potentially associated with ARDS.
Project description:Red blood cells (RBC) depleted whole blood from COVID-19 patients and controls was harvested and processed in order to performed 10X single cell RNA-seq. For COVID-19 patients 2 samples 10 days a part were analyzed.
Project description:Analysis of COVID-19 hospitalized patients, with different kind of symptoms, by human rectal swabs collection and 16S sequencing approach.
Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes a clinical disease called coronavirus disease 2019 (COVID-19). Approximately 20% of infected patients experience a severe manifestation of the disease, causing bilateral pneumonia and acute respiratory distress syndrome. Severe COVID-19 patients also have a pronounced coagulopathy with approximately 30% of patients experiencing thromboembolic complications. However, the cellular etiology driving the coagulopathy remains unknown. Here, we explore whether the prominent neutrophilia seen in severe COVID-19 patients contributes to inflammation-associated coagulation. We found in severe patients the emergence of a CD16Int low-density inflammatory band (LDIB) neutrophil population that trends over time with changes in disease status. These cells demonstrated spontaneous neutrophil extracellular trap (NET) formation, higher phagocytic capacity, enhanced cytokine production, and associated clinically with D-dimer, ferritin, and systemic IL-6 and TNF-α levels. Strikingly, LDIB neutrophils are the major immune cells within the bronchoalveolar lavage (BAL) fluid with increased CXCR3 and loss of CD44 and CD38 expression. We conclude that the LDIB subset contributes to COVID- 19-associated coagulopathy (CAC) and systemic inflammation and could be used as an adjunct clinical marker to monitor disease status and progression. Identifying patients who are trending towards LDIB crisis and implementing early, appropriate treatment could improve all-cause mortality rates for severe COVID-19 patients.
Project description:Dexamethasone improves the survival of COVID-19 patients in need of supplemental oxygen therapy. Hospitalized COVID-19 patients eligible for dexamethasone therapy were recruited from the general care ward in several centers in Greece and the Netherlands and whole blood transcriptomic analysis was performed before and after starting dexamethasone treatment. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy individuals and COVID-19 patients and stimulated with inactivated SARS-CoV-2 ex vivo in the presence or absence of dexamethasone and their transcriptome was assessed.
Project description:The ongoing SARS-CoV-2 pandemic has resulted in over 6.3 million deaths and 560 million COVID-19 cases worldwide. Clinical management of hospitalised patients is complex due to the heterogeneous course of COVID-19. Low-dose radiotherapy (LD-RT) is known to dampen localised chronic inflammation, and has been suggested to be used to reduce lung inflammation in COVID-19 patients. However, it is unknown whether SARS-CoV-2 alters the radiation response and associated radiation exposure related risk. We generated gene expression profiles from circulating leukocytes of hospitalised COVID-19 patients and healthy donors. The p53 signalling pathway was found to be dysregulated, with mRNA levels of p53, ATM and CHK2 being lower in COVID-19 patients. Several key p53 target genes involved in cell cycle arrest, apoptosis and p53 feedback inhibition were up-regulated in COVID-19 patients, while other p53 target genes were downregulated. This dysregulation has functional consequences as the transcription of p53-dependant genes (CCNG1, GADD45A, DDB2, SESN1, FDXR, APOBEC) was reduced 24 h after X-ray exposure ex-vivo to both low (100 mGy) or high (2 Gy) doses. In conclusion, SARS-CoV-2 infection affects a DNA damage response that may modify radiation-induced health risks in exposed COVID-19 patients.
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:The objective of this experiment was to compare the transcriptomic profile (NanoString platform) of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients with mild disease, and patients with severe COVID-19 with and without dexamethasone treatment, and healthy controls. We analyzed PBMCs from 4 mild COVID patients, 3 severe COVID patients,4 severe COVID patients treated with dexamethasone, and 5 healthy controls