Frontiers in Immunology (May 2021)
Immunological Biomarkers of Fatal COVID-19: A Study of 868 Patients
- Esperanza Martín-Sánchez,
- Esperanza Martín-Sánchez,
- Esperanza Martín-Sánchez,
- Esperanza Martín-Sánchez,
- Juan José Garcés,
- Juan José Garcés,
- Juan José Garcés,
- Juan José Garcés,
- Catarina Maia,
- Catarina Maia,
- Catarina Maia,
- Catarina Maia,
- Susana Inogés,
- Susana Inogés,
- Susana Inogés,
- Ascensión López-Díaz de Cerio,
- Ascensión López-Díaz de Cerio,
- Ascensión López-Díaz de Cerio,
- Francisco Carmona-Torre,
- Francisco Carmona-Torre,
- Francisco Carmona-Torre,
- Marta Marin-Oto,
- Félix Alegre,
- Elvira Molano,
- Mirian Fernandez-Alonso,
- Mirian Fernandez-Alonso,
- Cristina Perez,
- Cristina Perez,
- Cristina Perez,
- Cirino Botta,
- Aintzane Zabaleta,
- Aintzane Zabaleta,
- Aintzane Zabaleta,
- Aintzane Zabaleta,
- Ana Belen Alcaide,
- Manuel F. Landecho,
- Marta Rua,
- Teresa Pérez-Warnisher,
- Laura Blanco,
- Laura Blanco,
- Sarai Sarvide,
- Sarai Sarvide,
- Sarai Sarvide,
- Amaia Vilas-Zornoza,
- Amaia Vilas-Zornoza,
- Amaia Vilas-Zornoza,
- Diego Alignani,
- Diego Alignani,
- Diego Alignani,
- Diego Alignani,
- Cristina Moreno,
- Cristina Moreno,
- Cristina Moreno,
- Iñigo Pineda,
- Miguel Sogbe,
- Josepmaria Argemi,
- Bruno Paiva,
- Bruno Paiva,
- Bruno Paiva,
- Bruno Paiva,
- José Ramón Yuste,
- José Ramón Yuste,
- José Ramón Yuste
Affiliations
- Esperanza Martín-Sánchez
- Hematology Department, Clínica Universidad de Navarra, Pamplona, Spain
- Esperanza Martín-Sánchez
- Hemato-Oncology Department, Centro de Investigación Médica Aplicada (CIMA), Pamplona, Spain
- Esperanza Martín-Sánchez
- Hemato-Oncology Department, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Esperanza Martín-Sánchez
- Centro de Investigación Biomédica en Red, Pamplona, Spain
- Juan José Garcés
- Hematology Department, Clínica Universidad de Navarra, Pamplona, Spain
- Juan José Garcés
- Hemato-Oncology Department, Centro de Investigación Médica Aplicada (CIMA), Pamplona, Spain
- Juan José Garcés
- Hemato-Oncology Department, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Juan José Garcés
- Centro de Investigación Biomédica en Red, Pamplona, Spain
- Catarina Maia
- Hematology Department, Clínica Universidad de Navarra, Pamplona, Spain
- Catarina Maia
- Hemato-Oncology Department, Centro de Investigación Médica Aplicada (CIMA), Pamplona, Spain
- Catarina Maia
- Hemato-Oncology Department, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Catarina Maia
- Centro de Investigación Biomédica en Red, Pamplona, Spain
- Susana Inogés
- Centro de Investigación Biomédica en Red, Pamplona, Spain
- Susana Inogés
- Immunology and Immunotherapy Department, Clínica Universidad de Navarra, Pamplona, Spain
- Susana Inogés
- Hematology Service and Cell Therapy Area, Clínica Universidad de Navarra, Pamplona, Spain
- Ascensión López-Díaz de Cerio
- Centro de Investigación Biomédica en Red, Pamplona, Spain
- Ascensión López-Díaz de Cerio
- Immunology and Immunotherapy Department, Clínica Universidad de Navarra, Pamplona, Spain
- Ascensión López-Díaz de Cerio
- Hematology Service and Cell Therapy Area, Clínica Universidad de Navarra, Pamplona, Spain
- Francisco Carmona-Torre
- Internal Medicine Department, Clínica Universidad de Navarra, Pamplona, Spain
- Francisco Carmona-Torre
- Division of Infectious Diseases, Clínica Universidad de Navarra, Pamplona, Spain
- Francisco Carmona-Torre
- Immune and Infectious Inflammatory Diseases Research, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Marta Marin-Oto
- 0Neumology Department, Clínica Universidad de Navarra, Pamplona, Spain
- Félix Alegre
- Internal Medicine Department, Clínica Universidad de Navarra, Pamplona, Spain
- Elvira Molano
- 1Internal Medicine Department, Clínica Universidad de Navarra, Madrid, Spain
- Mirian Fernandez-Alonso
- Immune and Infectious Inflammatory Diseases Research, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Mirian Fernandez-Alonso
- 2Microbiology Department, Clínica Universidad de Navarra, Pamplona, Spain
- Cristina Perez
- Hemato-Oncology Department, Centro de Investigación Médica Aplicada (CIMA), Pamplona, Spain
- Cristina Perez
- Hemato-Oncology Department, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Cristina Perez
- Centro de Investigación Biomédica en Red, Pamplona, Spain
- Cirino Botta
- 3Hematology Department, Hospital “Annunziata”, Cosenza, Italy
- Aintzane Zabaleta
- Hematology Department, Clínica Universidad de Navarra, Pamplona, Spain
- Aintzane Zabaleta
- Hemato-Oncology Department, Centro de Investigación Médica Aplicada (CIMA), Pamplona, Spain
- Aintzane Zabaleta
- Hemato-Oncology Department, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Aintzane Zabaleta
- Centro de Investigación Biomédica en Red, Pamplona, Spain
- Ana Belen Alcaide
- 0Neumology Department, Clínica Universidad de Navarra, Pamplona, Spain
- Manuel F. Landecho
- Internal Medicine Department, Clínica Universidad de Navarra, Pamplona, Spain
- Marta Rua
- 2Microbiology Department, Clínica Universidad de Navarra, Pamplona, Spain
- Teresa Pérez-Warnisher
- 4Neumology Department, Clínica Universidad de Navarra, Madrid, Spain
- Laura Blanco
- Hemato-Oncology Department, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Laura Blanco
- Centro de Investigación Biomédica en Red, Pamplona, Spain
- Sarai Sarvide
- Hemato-Oncology Department, Centro de Investigación Médica Aplicada (CIMA), Pamplona, Spain
- Sarai Sarvide
- Hemato-Oncology Department, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Sarai Sarvide
- Centro de Investigación Biomédica en Red, Pamplona, Spain
- Amaia Vilas-Zornoza
- Hemato-Oncology Department, Centro de Investigación Médica Aplicada (CIMA), Pamplona, Spain
- Amaia Vilas-Zornoza
- Hemato-Oncology Department, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Amaia Vilas-Zornoza
- Centro de Investigación Biomédica en Red, Pamplona, Spain
- Diego Alignani
- Hematology Department, Clínica Universidad de Navarra, Pamplona, Spain
- Diego Alignani
- Hemato-Oncology Department, Centro de Investigación Médica Aplicada (CIMA), Pamplona, Spain
- Diego Alignani
- Hemato-Oncology Department, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Diego Alignani
- Centro de Investigación Biomédica en Red, Pamplona, Spain
- Cristina Moreno
- Hematology Department, Clínica Universidad de Navarra, Pamplona, Spain
- Cristina Moreno
- Hemato-Oncology Department, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Cristina Moreno
- Centro de Investigación Biomédica en Red, Pamplona, Spain
- Iñigo Pineda
- Internal Medicine Department, Clínica Universidad de Navarra, Pamplona, Spain
- Miguel Sogbe
- Internal Medicine Department, Clínica Universidad de Navarra, Pamplona, Spain
- Josepmaria Argemi
- Internal Medicine Department, Clínica Universidad de Navarra, Pamplona, Spain
- Bruno Paiva
- Hematology Department, Clínica Universidad de Navarra, Pamplona, Spain
- Bruno Paiva
- Hemato-Oncology Department, Centro de Investigación Médica Aplicada (CIMA), Pamplona, Spain
- Bruno Paiva
- Hemato-Oncology Department, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Bruno Paiva
- Centro de Investigación Biomédica en Red, Pamplona, Spain
- José Ramón Yuste
- Internal Medicine Department, Clínica Universidad de Navarra, Pamplona, Spain
- José Ramón Yuste
- Division of Infectious Diseases, Clínica Universidad de Navarra, Pamplona, Spain
- José Ramón Yuste
- Immune and Infectious Inflammatory Diseases Research, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- DOI
- https://doi.org/10.3389/fimmu.2021.659018
- Journal volume & issue
-
Vol. 12
Abstract
Information on the immunopathobiology of coronavirus disease 2019 (COVID-19) is rapidly increasing; however, there remains a need to identify immune features predictive of fatal outcome. This large-scale study characterized immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection using multidimensional flow cytometry, with the aim of identifying high-risk immune biomarkers. Holistic and unbiased analyses of 17 immune cell-types were conducted on 1,075 peripheral blood samples obtained from 868 COVID-19 patients and on samples from 24 patients presenting with non-SARS-CoV-2 infections and 36 healthy donors. Immune profiles of COVID-19 patients were significantly different from those of age-matched healthy donors but generally similar to those of patients with non-SARS-CoV-2 infections. Unsupervised clustering analysis revealed three immunotypes during SARS-CoV-2 infection; immunotype 1 (14% of patients) was characterized by significantly lower percentages of all immune cell-types except neutrophils and circulating plasma cells, and was significantly associated with severe disease. Reduced B-cell percentage was most strongly associated with risk of death. On multivariate analysis incorporating age and comorbidities, B-cell and non-classical monocyte percentages were independent prognostic factors for survival in training (n=513) and validation (n=355) cohorts. Therefore, reduced percentages of B-cells and non-classical monocytes are high-risk immune biomarkers for risk-stratification of COVID-19 patients.
Keywords
