About: Alveolitis in severe SARS-CoV-2 pneumonia is driven by self-sustaining circuits between infected alveolar macrophages and T cells

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About: Alveolitis in severe SARS-CoV-2 pneumonia is driven by self-sustaining circuits between infected alveolar macrophages and T cells Goto Sponge NotDistinct Permalink

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Alveolitis in severe SARS-CoV-2 pneumonia is driven by self-sustaining circuits between infected alveolar macrophages and T cells
Creator	Gottardi, Cara Wunderink, Richard Walter, James Singer, Benjamin Abdala-Valencia, Hiam Argento, A Bharat, Ankit Misharin, Alexander Morales-Nebreda, Luisa Qi, Chao Abbott, Darryl Borkowski, Nicole Donayre, Alvaro Donnelly, Helen Goldberg, Isaac Grant, Rogan Guzman, Estefany Kang, Mengjia Kihshen, Hermon Klug, Zasu Kruser, Jacqueline Lu, Ziyan Malsin, Elizabeth Markov, Nikolay Nannapaneni, Prasanth Pawlowski, Anna Pickens, Chiagozie Politanska, Yuliya Schneider, Daniel Scott Budinger, G Shilatifard, Ali Sichizya, Lango Smith, Sean Swaminathan, Suchitra
source	BioRxiv
abstract	Some patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) develop severe pneumonia and the acute respiratory distress syndrome (ARDS) [1]. Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from other types of pneumonia [2]. We collected bronchoalveolar lavage fluid samples from 86 patients with SARS-CoV-2-induced respiratory failure and 252 patients with known or suspected pneumonia from other pathogens and subjected them to flow cytometry and bulk transcriptomic profiling. We performed single cell RNA-Seq in 5 bronchoalveolar lavage fluid samples collected from patients with severe COVID-19 within 48 hours of intubation. In the majority of patients with SARS-CoV-2 infection at the onset of mechanical ventilation, the alveolar space is persistently enriched in alveolar macrophages and T cells without neutrophilia. Bulk and single cell transcriptomic profiling suggest SARS-CoV-2 infects alveolar macrophages that respond by recruiting T cells. These T cells release interferon-gamma to induce inflammatory cytokine release from alveolar macrophages and further promote T cell recruitment. Our results suggest SARS-CoV-2 causes a slowly unfolding, spatially-limited alveolitis in which alveolar macrophages harboring SARS-CoV-2 transcripts and T cells form a positive feedback loop that drives progressive alveolar inflammation. This manuscript is accompanied by an online resource: https://www.nupulmonary.org/covid-19/ One sentence summary SARS-CoV-2-infected alveolar macrophages form positive feedback loops with T cells in patients with severe COVID-19.
has issue date	2020-08-05(xsd:dateTime)
bibo:doi	10.1101/2020.08.05.238188
has license	biorxiv
sha1sum (hex)	b9cfbfc32e43577970ad88c937e14458870c9492
schema:url	https://doi.org/10.1101/2020.08.05.238188
resource representing a document's title	Alveolitis in severe SARS-CoV-2 pneumonia is driven by self-sustaining circuits between infected alveolar macrophages and T cells
schema:publication	bioRxiv
resource representing a document's body	covid:b9cfbfc32e43577970ad88c937e14458870c9492#body_text
is schema:about of	named entity 'SUGGEST' named entity 'INFECTED' named entity 'CAUSES' named entity 'KNOWN' named entity 'SAMPLES' named entity 'DISTINCT' named entity 'CLINICAL FEATURES' named entity 'COLLECTED' named entity 'ALVEOLITIS' named entity 'PNEUMONIA' named entity 'FLOW CYTOMETRY' named entity 'HAVE' named entity 'ORG' named entity 'RESPONSE TO VIRUS' covid:arg/b9cfbfc32e43577970ad88c937e14458870c9492 named entity 'bronchoalveolar lavage fluid' named entity 'pathogens' named entity 'infection' named entity 'alveolar' named entity 'inflammatory cytokine' named entity 'severe pneumonia' named entity 'SARS-CoV-2' named entity 'pneumonia' named entity 'flow cytometry' named entity 'SARS-CoV-2' named entity 'alveolar macrophages' named entity 'alveolar macrophages' named entity 'alveolar macrophages' named entity 'type 2' named entity 'mechanical ventilation' named entity 'coronaviruses' named entity 'distal' named entity 'SARS-CoV-2' named entity 'mechanical ventilation' named entity 'intubation' named entity 'pneumonia' named entity 'bronchoscope' named entity 'Statistical analysis' named entity 'granulocytes' named entity 'normal range' named entity 'physiology' named entity 'CXCR3' named entity 'bacterial pathogen' named entity 'normal saline' named entity 'single cell' named entity 't-tests' named entity 'infection' named entity 'human subjects research' named entity 'body mass index' named entity 'neutrophilia' named entity 'neuromuscular blockade'

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