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

Sophie Hue, Asma Beldi-Ferchiou, Inès Bendib, Mathieu Surenaud, Slim Fourati, Thomas Frapard, Simon Rivoal, Keyvan Razazi, Guillaume Carteaux, Marie-Hélène Delfau-Larue, Armand Mekontso Dessap, Etienne Audureau, Nicolas de Prost
American Journal of Respiratory and Critical Care Medicine 2020 August 31

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 (

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