Uncontrolled Innate and Impaired Adaptive Immune Responses in Patients with COVID-19 Acute Respiratory Distress Syndrome

• Published in: American journal of respiratory and critical care medicine Vol. 202; no. 11; pp. 1509 - 1519
• Main Authors: Hue, Sophie, Beldi-Ferchiou, Asma, Bendib, Inés, Surenaud, Mathieu, Fourati, Slim, Frapard, Thomas, Rivoal, Simon, Razazi, Keyvan, Carteaux, Guillaume, Delfau-Larue, Marie-Héléne, Mekontso-Dessap, Armand, Audureau, Etienne, de Prost, Nicolas
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01.12.2020
• Subjects: Adult; Aged; Antibodies, Viral - blood; Chemokines - blood; COVID-19; COVID-19 - blood; COVID-19 - epidemiology; COVID-19 - immunology; COVID-19 - physiopathology; Female; Flow cytometry; France - epidemiology; Humans; Immune response; Immunity, Innate; Intensive care; Life Sciences; Male; Middle Aged; Mortality; Original; Pandemics; Prospective Studies; Respiratory Distress Syndrome - blood; Respiratory Distress Syndrome - epidemiology; Respiratory Distress Syndrome - immunology; Respiratory Distress Syndrome - physiopathology; Severe acute respiratory syndrome coronavirus 2; Viral Load; France; COVID-19; SARS-CoV-2; cytokines; chemokines; ARDS
• ISSN: 1073-449X; 1535-4970; 1535-4970
• DOI: 10.1164/rccm.202005-1885OC

Uncontrolled inflammatory innate response and impaired adaptive immune response are associated with clinical severity in patients with coronavirus disease (COVID-19). To compare the immunopathology of COVID-19 acute respiratory distress syndrome (ARDS) with that of non-COVID-19 ARDS, and to identify biomarkers associated with mortality in patients with COVID-19 ARDS. 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. The primary clinical endpoint of the study was mortality at Day 28. Flow cytometry analyses and serum cytokine measurements were performed at Days 1-2 and 4-6 of ICU admission. As compared with patients with non-COVID-19 ARDS (  = 36), those with COVID-19 (  = 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%,  = 0.030). Patients with COVID-19 showed profound and sustained T CD4 (  = 0.002), CD8 (  < 0.0001), and B (  < 0.0001) lymphopenia, higher HLA-DR expression on monocytes (  < 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 (  = 0.047) and GM-CSF (  = 0.050) were higher and nasopharyngeal RT-PCR cycle threshold values lower (  = 0.010) in patients with COVID-19 who were dead at Day 28. 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 nasopharyngeal SARS-CoV-2 viral load, were associated with Day-28 mortality.