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Frontiers in immunology
2021;12 659018.

Immunological Biomarkers of Fatal COVID-19: A Study of 868 Patients.

Esperanza Mart��n-S��nchez, Juan Jos�� Garc��s, Catarina Maia, Susana Inog��s, Ascensi��n L��pez-D��az de Cerio, Francisco Carmona-Torre, Marta Marin-Oto, F��lix Alegre, Elvira Molano, Mirian Fernandez-Alonso, Cristina Perez, Cirino Botta, Aintzane Zabaleta, Ana Belen Alcaide, Manuel F Landecho, Marta Rua, Teresa P��rez-Warnisher, Laura Blanco, Sarai Sarvide, Amaia Vilas-Zornoza, Diego Alignani, Cristina Moreno, I��igo Pineda, Miguel Sogbe, Josepmaria Argemi, Bruno Paiva, Jos�� Ram��n Yuste
Author Information
  1. Esperanza Mart��n-S��nchez: Hematology Department, Cl��nica Universidad de Navarra, Pamplona, Spain.
  2. Juan Jos�� Garc��s: Hematology Department, Cl��nica Universidad de Navarra, Pamplona, Spain.
  3. Catarina Maia: Hematology Department, Cl��nica Universidad de Navarra, Pamplona, Spain.
  4. Susana Inog��s: Centro de Investigaci��n Biom��dica en Red, Pamplona, Spain.
  5. Ascensi��n L��pez-D��az de Cerio: Centro de Investigaci��n Biom��dica en Red, Pamplona, Spain.
  6. Francisco Carmona-Torre: Internal Medicine Department, Cl��nica Universidad de Navarra, Pamplona, Spain.
  7. Marta Marin-Oto: Neumology Department, Cl��nica Universidad de Navarra, Pamplona, Spain.
  8. F��lix Alegre: Internal Medicine Department, Cl��nica Universidad de Navarra, Pamplona, Spain.
  9. Elvira Molano: Internal Medicine Department, Cl��nica Universidad de Navarra, Madrid, Spain.
  10. Mirian Fernandez-Alonso: Immune and Infectious Inflammatory Diseases Research, Instituto de Investigaci��n Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
  11. Cristina Perez: Hemato-Oncology Department, Centro de Investigaci��n M��dica Aplicada (CIMA), Pamplona, Spain.
  12. Cirino Botta: Hematology Department, Hospital "Annunziata", Cosenza, Italy.
  13. Aintzane Zabaleta: Hematology Department, Cl��nica Universidad de Navarra, Pamplona, Spain.
  14. Ana Belen Alcaide: Neumology Department, Cl��nica Universidad de Navarra, Pamplona, Spain.
  15. Manuel F Landecho: Internal Medicine Department, Cl��nica Universidad de Navarra, Pamplona, Spain.
  16. Marta Rua: Microbiology Department, Cl��nica Universidad de Navarra, Pamplona, Spain.
  17. Teresa P��rez-Warnisher: Neumology Department, Cl��nica Universidad de Navarra, Madrid, Spain.
  18. Laura Blanco: Hemato-Oncology Department, Instituto de Investigaci��n Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
  19. Sarai Sarvide: Hemato-Oncology Department, Centro de Investigaci��n M��dica Aplicada (CIMA), Pamplona, Spain.
  20. Amaia Vilas-Zornoza: Hemato-Oncology Department, Centro de Investigaci��n M��dica Aplicada (CIMA), Pamplona, Spain.
  21. Diego Alignani: Hematology Department, Cl��nica Universidad de Navarra, Pamplona, Spain.
  22. Cristina Moreno: Hematology Department, Cl��nica Universidad de Navarra, Pamplona, Spain.
  23. I��igo Pineda: Internal Medicine Department, Cl��nica Universidad de Navarra, Pamplona, Spain.
  24. Miguel Sogbe: Internal Medicine Department, Cl��nica Universidad de Navarra, Pamplona, Spain.
  25. Josepmaria Argemi: Internal Medicine Department, Cl��nica Universidad de Navarra, Pamplona, Spain.
  26. Bruno Paiva: Hematology Department, Cl��nica Universidad de Navarra, Pamplona, Spain.
  27. Jos�� Ram��n Yuste: Internal Medicine Department, Cl��nica Universidad de Navarra, Pamplona, Spain.
PMID: 34012444 DOI: 10.3389/fimmu.2021.659018

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

COVID-19 SARS-CoV-2 biomarkers flow cytometry lymphopenia outcome survival

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MeSH Term

Adaptive Immunity
Adult
Aged
Aged, 80 and over
B-Lymphocytes
Biomarkers
COVID-19
Female
Humans
Immunity, Innate
Lymphopenia
Male
Middle Aged
Monocytes
Prognosis
SARS-CoV-2
Survival Analysis
Young Adult

Chemicals

Biomarkers
Journal Article Research Support, Non-U.S. Gov't

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