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Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19.

ABSTRACT: Blood myeloid cells are known to be dysregulated in coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2. It is unknown whether the innate myeloid response differs with disease severity and whether markers of innate immunity discriminate high-risk patients. Thus, we performed high-dimensional flow cytometry and single-cell RNA sequencing of COVID-19 patient peripheral blood cells and detected disappearance of non-classical CD14^LowCD16^High monocytes, accumulation of HLA-DR^Low classical monocytes (Human Leukocyte Antigen - DR isotype), and release of massive amounts of calprotectin (S100A8/S100A9) in severe cases. Immature CD10^LowCD101^-CXCR4^+/- neutrophils with an immunosuppressive profile accumulated in the blood and lungs, suggesting emergency myelopoiesis. Finally, we show that calprotectin plasma level and a routine flow cytometry assay detecting decreased frequencies of non-classical monocytes could discriminate patients who develop a severe form of COVID-19, suggesting a predictive value that deserves prospective evaluation.

SUBMITTER: Silvin A

PROVIDER: S-EPMC7405878 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19.

Silvin Aymeric A Chapuis Nicolas N Dunsmore Garett G Goubet Anne-Gaëlle AG Dubuisson Agathe A Derosa Lisa L Almire Carole C Hénon Clémence C Kosmider Olivier O Droin Nathalie N Rameau Philippe P Catelain Cyril C Alfaro Alexia A Dussiau Charles C Friedrich Chloé C Sourdeau Elise E Marin Nathalie N Szwebel Tali-Anne TA Cantin Delphine D Mouthon Luc L Borderie Didier D Deloger Marc M Bredel Delphine D Mouraud Severine S Drubay Damien D Andrieu Muriel M Lhonneur Anne-Sophie AS Saada Véronique V Stoclin Annabelle A Willekens Christophe C Pommeret Fanny F Griscelli Frank F Ng Lai Guan LG Zhang Zheng Z Bost Pierre P Amit Ido I Barlesi Fabrice F Marabelle Aurélien A Pène Frédéric F Gachot Bertrand B André Fabrice F Zitvogel Laurence L Ginhoux Florent F Fontenay Michaela M Solary Eric E

Cell 20200805 6

Blood myeloid cells are known to be dysregulated in coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2. It is unknown whether the innate myeloid response differs with disease severity and whether markers of innate immunity discriminate high-risk patients. Thus, we performed high-dimensional flow cytometry and single-cell RNA sequencing of COVID-19 patient peripheral blood cells and detected disappearance of non-classical CD14<sup>Low</sup>CD16<sup>High</sup> monocytes, accumulation of HLA ...[more]

PMID: 32810439

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Project description:BackgroundCalprotectin is an inflammatory marker mainly released by activated neutrophils that is increased in acute severe COVID-19. After initial recovery, some patients have persistent respiratory impairment with reduced diffusion capacity of the lungs for carbon monoxide (DLCO) months after infection. Underlying causes of this persistent impairment are unclear. We aimed to investigate the correlation between circulating calprotectin, persistent lung functional impairment and intensive care unit (ICU) stay after COVID-19 in two university hospital centres in Switzerland.MethodsCalprotectin levels were measured in serum from 124 patients (50% male) from the Bern cohort (post-ICU and non-ICU patients) and 68 (76% male) from the Lausanne cohort (only post-ICU patients) four months after COVID-19. Calprotectin was correlated with clinical parameters. Multivariate linear regression (MLR) was performed to evaluate the independent association of calprotectin in different models.ResultsOverall, we found that post-ICU patients, compared to non-ICU, were significantly older (age 59.4 ± 13.6 (Bern), 60.5 ± 12.0 (Lausanne) vs. 48.8 ± 13.4 years) and more obese (BMI 28.6 ± 4.5 and 29.1 ± 5.3 vs. 25.2 ± 6.0 kg/m2, respectively). 48% of patients from Lausanne and 44% of the post-ICU Bern cohort had arterial hypertension as a pre-existing comorbidity vs. only 10% in non-ICU patients. Four months after COVID-19 infection, DLCO was lower in post-ICU patients (75.96 ± 19.05% predicted Bern, 71.11 ± 18.50% Lausanne) compared to non-ICU (97.79 ± 21.70% predicted, p < 0.01). The post-ICU cohort in Lausanne had similar calprotectin levels when compared to the cohort in Bern (Bern 2.74 ± 1.15 µg/ml, Lausanne 2.49 ± 1.13 µg/ml vs. non-ICU 1.86 ± 1.02 µg/ml; p-value < 0.01). Calprotectin correlated negatively with DLCO (r= -0.290, p < 0.001) and the forced vital capacity (FVC) (r= -0.311, p < 0.001).ConclusionsSerum calprotectin is elevated in post-ICU patients in two independent cohorts and higher compared to non-ICU patients four months after COVID-19. In addition, there is a negative correlation between calprotectin levels and DLCO or FVC. The relationship between inflammation and lung functional impairment needs further investigations.Trial registrationNCT04581135.

Dataset Information

Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19.

Publications

Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19.

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