Proteomic analysis of bronchoalveolar lavage fluid in COVID-19 patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Hao-Long Zeng
PROVIDER: PXD022085 | iProX | Tue Oct 20 00:00:00 BST 2020
REPOSITORIES: iProX
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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.
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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.
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Project description:As many as 10–30% of the nearly 750 million survivors of COVID-19 develop persistent symptoms that define the post-acute sequelae of COVID-19 (PASC) syndrome. To understand the molecular basis of this syndrome, we combined a machine learning based analysis of lung computed tomography (CT) with flow cytometry and single cell RNA-sequencing analysis of bronchoalveolar lavage fluid and nasal curettage samples in a cohort of thirty-five patients with respiratory symptoms and radiographic abnormalities more than 90 days after infection with COVID-19. CT images from patients with PASC revealed primarily fibrotic abnormalities involving 73 +/- 28% of the lung, most of which improved on subsequent imaging. The presence of profibrotic monocyte-derived alveolar macrophages in BAL fluid was significantly associated with increased levels of alveolar cytokines and fibrotic abnormalities on CT. Persistent infection with SARS-CoV-2 was identified in 6 patients and secondary bacterial or viral infections in two others. These findings suggest persistent alveolar inflammation characterized by the ongoing recruitment of monocyte derived alveolar macrophages is associated with fibrotic CT changes in some COVID-19 survivors with implications for diagnosis and therapy.
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Project description:As many as 10–30% of the nearly 750 million survivors of COVID-19 develop persistent symptoms that define the post-acute sequelae of COVID-19 (PASC) syndrome. To understand the molecular basis of this syndrome, we combined a machine learning based analysis of lung computed tomography (CT) with flow cytometry and single cell RNA-sequencing analysis of bronchoalveolar lavage fluid and nasal curettage samples in a cohort of thirty-five patients with respiratory symptoms and radiographic abnormalities more than 90 days after infection with COVID-19. CT images from patients with PASC revealed primarily fibrotic abnormalities involving 73 +/- 28% of the lung, most of which improved on subsequent imaging. The presence of profibrotic monocyte-derived alveolar macrophages in BAL fluid was significantly associated with increased levels of alveolar cytokines and fibrotic abnormalities on CT. Persistent infection with SARS-CoV-2 was identified in 6 patients and secondary bacterial or viral infections in two others. These findings suggest persistent alveolar inflammation characterized by the ongoing recruitment of monocyte derived alveolar macrophages is associated with fibrotic CT changes in some COVID-19 survivors with implications for diagnosis and therapy.
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Project description:As many as 10–30% of the nearly 750 million survivors of COVID-19 develop persistent symptoms that define the post-acute sequelae of COVID-19 (PASC) syndrome. To understand the molecular basis of this syndrome, we combined a machine learning based analysis of lung computed tomography (CT) with flow cytometry and single cell RNA-sequencing analysis of bronchoalveolar lavage fluid and nasal curettage samples in a cohort of thirty-five patients with respiratory symptoms and radiographic abnormalities more than 90 days after infection with COVID-19. CT images from patients with PASC revealed primarily fibrotic abnormalities involving 73 +/- 28% of the lung, most of which improved on subsequent imaging. The presence of profibrotic monocyte-derived alveolar macrophages in BAL fluid was significantly associated with increased levels of alveolar cytokines and fibrotic abnormalities on CT. Persistent infection with SARS-CoV-2 was identified in 6 patients and secondary bacterial or viral infections in two others. These findings suggest persistent alveolar inflammation characterized by the ongoing recruitment of monocyte derived alveolar macrophages is associated with fibrotic CT changes in some COVID-19 survivors with implications for diagnosis and therapy.
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