Manuscript Detail

Title: Uncontrolled Innate and Impaired Adaptive Immune Responses in Patients with COVID-19 ARDS

Authors: Hue, Sophie et al

Abstract: RATIONALE: Uncontrolled inflammatory innate response and impaired adaptive immune response are associated with clinical severity in patients with Coronavirus disease 2019 (COVID-19). OBJECTIVES: To compare the immunopathology of COVID-19 acute respiratory distress syndrome (ARDS) to that of non-COVID-19 ARDS, and to identify biomarkers associated with mortality in patients with COVID-19 ARDS. METHODS: Prospective observational monocenter study. Immunocompetent patients diagnosed with RT-PCR-confirmed SARS-CoV-2 infection and ARDS admitted between March 8 and March 30, 2020 were included and compared with patients with non-COVID-19 ARDS. The primary clinical endpoint of the study was mortality at day 28. Flow cytometry analyses and serum cytokines measurements were performed at days 1-2 and 4-6 of ICU admission. MEASUREMENTS AND MAIN RESULTS: As compared with patients with non-COVID-19 ARDS (n=36), those with COVID-19 (n=38) were not significantly different regarding age, gender, and SOFA and SAPS II scores but exhibited a higher day-28 mortality (34% vs 11%, p=0.030). COVID-19 patients showed profound and sustained T CD4+ (p=0.002), CD8+ (p<0.0001) and B (p<0.0001) lymphopenia, higher HLA-DR expression on monocytes (p<0.001) and higher serum concentrations of EGF, GM-CSF, IL-10, CCL2/MCP-1, CCL3/MIP-1a, CXCL10/IP-10, CCL5/RANTES, and CCL20/MIP-3a. After adjusting on age and SOFA, serum CXCL10/IP-10 (p=0.047) and GM-CSF (p=0.050) were higher and naso-pharyngeal RT-PCR cycle threshold values lower (p=0.010) in COVID-19 patients who were dead at day-28. CONCLUSIONS: Profound global lymphopenia and a "chemokine signature" were observed in COVID-19 ARDS. Increased serum concentrations of CXCL10/IP-10 and GM-CSF, together with higher naso-pharyngeal SARS-CoV-2 viral load, were associated with day-28 mortality. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Journal: Am. j. respir. crit. care med

Curator: Danielle Dillard

Author-provided data:

paper: Hue, S., Beldi-Ferchiou, A., Bendib, I., Surenaud, M., Fourati, S., Frapard, T., Rivoal, S., Razazi, K., Carteaux, G., Delfau-Larue, M., Mekontso D. A., Audureau, E. and de Prost. N. (2020). Uncontrolled Innate and Impaired Adaptive Immune Responses in Patients with COVID-19 ARDS. Am. j. respir. crit. care med https://doi.org/10.1164/rccm.202005-1885OC
contributor: Nicolas de Prost
contributor_organization: Université Paris Est-Créteil
contributor_email: nicolas.de-prost@aphp.fr

- description: Prospective observational monocenter study. Immunocompetent patients diagnosed with RT-PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and ARDS admitted between March 8 and March 30, 2020, were included and compared with patients with non-COVID-19 ARDS. As compared with patients with non-COVID-19 ARDS (n = 36), those with COVID-19 (n = 38) were not significantly different regarding age, sex, and Sequential Organ Failure Assessment and Simplified Acute Physiology Score II scores but exhibited a higher Day-28 mortality (34% vs. 11%, P = 0.030).
- exact_source: Figure 1
- tissue: Blood and serum
- immune_exposure: patients with severe COVID-19
- cohort: adults admitted in the intensive care unit
- comparison: severe COVID-19 patients vs non-COVID-19 patients with acute respiratory distress syndrome
- repository_id:
- platform:
- response_components:
- response_behavior: Down: Patients with COVID-19 showed profound and sustained T CD4+ (P = 0.002), CD8+ (P 0.0001), and B (P 0.0001) lymphopenia;
- description:
- exact_source: Figures 1 and 2, Table 3
- tissue: Blood and serum
- immune_exposure: patients with severe COVID-19
- cohort: adults admitted in the intensive care unit
- comparison: severe COVID-19 patients vs non-COVID-19 patients with acute respiratory distress syndrome
- repository_id:
- platform:
- response_components:
- response_behavior: Up: Patients with COVID-19 showed higher HLA-DR expression on monocytes (P 0.001) and higher serum concentrations of EGF (epithelial growth factor), GM-CSF, IL-10, CCL2/MCP-1, CCL3/MIP-1a, CXCL10/IP-10, CCL5/RANTES, and CCL20/MIP-3a. After adjusting on age and Sequential Organ Failure Assessment, serum CXCL10/IP-10 (P = 0.047) and GM-CSF (P = 0.050) were higher in patients with COVID-19 who were dead at Day 28.

Volunteer to review