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https://www.arca.fiocruz.br/handle/icict/70039
A SPATIALLY RESOLVED SINGLE- CELL LUNG ATLAS INTEGRATED WITH CLINICAL AND BLOOD SIGNATURES DISTINGUISHES COVID- 19 DISEASE TRAJECTORIES
Author
Silva Filho, João da
Herder, Vanessa
Gibbins, Matthew P.
Reis, Monique Freire dos
Melo, Gisely Cardoso
Haley, Michael J.
Judice, Carla Cristina
Val, Fernando Fonseca Almeida
Borba, Mayla
Tavella, Tatyana Almeida
Sampaio, Vanderson de Sousa
Attipa, Charalampos
McMonagle, Fiona
Wright, Derek
Lacerda, Marcus Vinicius Guimaraes de
Costa, Fabio Trindade Maranhão
Couper, Kevin N.
Monteiro, Wuelton Marcelo
Ferreira, Luiz Carlos de Lima
Moxon, Christopher Alan
Palmarini, Massimo
Marti, Matthias
Herder, Vanessa
Gibbins, Matthew P.
Reis, Monique Freire dos
Melo, Gisely Cardoso
Haley, Michael J.
Judice, Carla Cristina
Val, Fernando Fonseca Almeida
Borba, Mayla
Tavella, Tatyana Almeida
Sampaio, Vanderson de Sousa
Attipa, Charalampos
McMonagle, Fiona
Wright, Derek
Lacerda, Marcus Vinicius Guimaraes de
Costa, Fabio Trindade Maranhão
Couper, Kevin N.
Monteiro, Wuelton Marcelo
Ferreira, Luiz Carlos de Lima
Moxon, Christopher Alan
Palmarini, Massimo
Marti, Matthias
Affilliation
Centre for Integrative Parasitology, School of Infection and Immunity, University of Glasgow, Glasgow, UK
Institute of Parasitology Zurich (IPZ), VetSuisse Faculty, University of Zurich, Zurich, Switzerland
Centre for Integrative Parasitology, School of Infection and Immunity, University of Glasgow, Glasgow, UK
Universidade Federal do Amazonas, Manaus, AM, Brasil
Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, AM, Brasil
Department of Immunology, Immunity to Infection and Respiratory Medicine, University of Manchester, Manchester, UK
Department of Genetics, Evolution, Microbiology and Immunology, University of Campinas, Campinas, Brasil
Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, AM, Brasil
Delphina Rinaldi Abdel Aziz Emergency Hospital (HPSDRA ), Manaus, Brasil
Universidade Federal do Amazonas, Manaus, AM, Brasil
Centre for Integrative Parasitology, School of Infection and Immunity, University of Glasgow, Glasgow, UK
Centre for Integrative Parasitology, School of Infection and Immunity, University of Glasgow, Glasgow, UK
MRC -University of Glasgow Centre for Virus Research, Glasgow, UK
Fundação Oswaldo Cruz, Instituto Leônidas & Maria Deane, Manaus, AM, Brasil
Department of Genetics, Evolution, Microbiology and Immunology, University of Campinas, Campinas, Brasil
Department of Immunology, Immunity to Infection and Respiratory Medicine, University of Manchester, Manchester, UK
Centre for Integrative Parasitology, School of Infection and Immunity, University of Glasgow, Glasgow, UK
Centre for Integrative Parasitology, School of Infection and Immunity, University of Glasgow, Glasgow, UK
MRC -University of Glasgow Centre for Virus Research, Glasgow, UK
Centre for Integrative Parasitology, School of Infection and Immunity, University of Glasgow, Glasgow, UK
Institute of Parasitology Zurich (IPZ), VetSuisse Faculty, University of Zurich, Zurich, Switzerland
Centre for Integrative Parasitology, School of Infection and Immunity, University of Glasgow, Glasgow, UK
Universidade Federal do Amazonas, Manaus, AM, Brasil
Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, AM, Brasil
Department of Immunology, Immunity to Infection and Respiratory Medicine, University of Manchester, Manchester, UK
Department of Genetics, Evolution, Microbiology and Immunology, University of Campinas, Campinas, Brasil
Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, AM, Brasil
Delphina Rinaldi Abdel Aziz Emergency Hospital (HPSDRA ), Manaus, Brasil
Universidade Federal do Amazonas, Manaus, AM, Brasil
Centre for Integrative Parasitology, School of Infection and Immunity, University of Glasgow, Glasgow, UK
Centre for Integrative Parasitology, School of Infection and Immunity, University of Glasgow, Glasgow, UK
MRC -University of Glasgow Centre for Virus Research, Glasgow, UK
Fundação Oswaldo Cruz, Instituto Leônidas & Maria Deane, Manaus, AM, Brasil
Department of Genetics, Evolution, Microbiology and Immunology, University of Campinas, Campinas, Brasil
Department of Immunology, Immunity to Infection and Respiratory Medicine, University of Manchester, Manchester, UK
Centre for Integrative Parasitology, School of Infection and Immunity, University of Glasgow, Glasgow, UK
Centre for Integrative Parasitology, School of Infection and Immunity, University of Glasgow, Glasgow, UK
MRC -University of Glasgow Centre for Virus Research, Glasgow, UK
Centre for Integrative Parasitology, School of Infection and Immunity, University of Glasgow, Glasgow, UK
Abstract
COVID-19 is characterized by a broad range of symptoms and disease trajectories. Understanding the correlation between clinical biomarkers and lung pathology during acute COVID-19 is necessary to understand its diverse pathogenesis and inform more effective treatments. Here, we present an integrated analysis of longitudinal clinical parameters, peripheral blood markers, and lung pathology in 142 Brazilian patients hospitalized with COVID-19.
We identified core clinical and peripheral blood signatures differentiating disease progression between patients who recovered from severe disease compared with those who succumbed to the disease. Signatures were heterogeneous among fatal cases yet clustered into two patient groups: “early death” (<15 days until death) and “late death” (>15 days). Progression to early death was characterized systemically and in lung histopathological samples by rapid endothelial and myeloid activation and the presence of thrombi associated with SARS-CoV-2+macrophages. In contrast, progression to late death was associated with fibrosis, apoptosis, and SARS-CoV-2+epithelial cells in postmortem lung tissue. In late death cases, cytotoxicity, interferon, and T helper 17 (TH17) signatures were only detectable in the peripheral blood after 2 weeks of hospitalization. Progression to recovery was associated with higher lymphocyte counts, TH2 responses, and anti-inflammatory–mediated responses. By integrating antemortem longitudinal blood signatures and spatial single-cell lung signatures from postmortem lung samples, we defined clinical parameters that could be used to help predict COVID-19 outcomes.
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