High CD169 Monocyte/Lymphocyte Ratio Reflects Immunophenotype Disruption and Oxygen Need in COVID-19 Patients.

Antonella Minutolo,Sandro Grelli,Ines Ait Belkacem,Guido Rasi,Loredana Sarmati,Fabrice Malergue,Marta Zordan,Massimo Andreoni,Martina Giudice,Marco Iannetta,Emanuela Balestrieri,Claudia Matteucci,Paola Sinibaldi-Vallebona,Marialaura Fanelli,Vita Petrone,Pietro Vitale

doi:10.3390/pathogens10121639

Antonella Minutolo, Sandro Grelli + Show 14 more

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https://doi.org/10.3390/pathogens10121639

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Abstract

Background: Sialoadhesin (CD169) has been found to be overexpressed in the blood of COVID-19 patients and identified as a biomarker in early disease. We analyzed CD169 in the blood cells of COVID-19 patients to assess its role as a predictive marker of disease progression and clinical outcomes. Methods: The ratio of the median fluorescence intensity of CD169 between monocytes and lymphocytes (CD169 RMFI) was analyzed by flow cytometry in blood samples of COVID-19 patients (COV) and healthy donors (HDs) and correlated with immunophenotyping, inflammatory markers, cytokine mRNA expression, pulmonary involvement, and disease progression. Results: CD169 RMFI was high in COV but not in HDs, and it correlated with CD8 T-cell senescence and exhaustion markers, as well as with B-cell maturation and differentiation in COV. CD169 RMFI correlated with blood cytokine mRNA levels, inflammatory markers, and pneumonia severity in patients who were untreated at sampling, and was associated with the respiratory outcome throughout hospitalization. Finally, we also report the first evidence of the specific ability of the spike protein of SARS-CoV-2 to trigger CD169 RMFI in a dose-dependent manner in parallel with IL-6 and IL-10 gene transcription in HD PBMCs stimulated in vitro. Conclusion: CD169 is induced by the spike protein and should be considered as an early biomarker for evaluating immune dysfunction and respiratory outcomes in COVID-19 patients.

Highlights

Coronavirus disease-19 (COVID-19), caused by severe acute respiratory coronavirus-2(SARS-CoV-2), has led to a global pandemic characterized by high morbidity and mortality.As a consequence of derailed cellular and humoral immune-response activation, numerous individuals develop persistent inflammation associated with a cytokine storm and diffuse organ involvement, mainly associated with severe disease, including acute respiratory distress syndrome (ARDS) [1]
Sixty-eight (68) hospitalized patients who tested positive for SARS-CoV-2 RNA (COV) were screened for CD169 expression using flow cytometry and compared to 57 healthy donors (HDs)
The MFI of CD169 was not significantly changed in lymphocytes, whereas it increased in monocytes from COVID patients compared with healthy donors (p = 0.010) (Supplementary Figure S1A and Table 1)

Summary

Introduction

Coronavirus disease-19 (COVID-19), caused by severe acute respiratory coronavirus-2(SARS-CoV-2), has led to a global pandemic characterized by high morbidity and mortality.As a consequence of derailed cellular and humoral immune-response activation, numerous individuals develop persistent inflammation associated with a cytokine storm and diffuse organ involvement, mainly associated with severe disease, including acute respiratory distress syndrome (ARDS) [1]. In response to SARS-CoV-2 infection, host cells immediately produce cytokines, including type I interferon (IFN-I), which, in addition to showing antiviral activity, induces the expression of genes involved in limiting the viral spread. We analyzed CD169 in the blood cells of COVID-19 patients to assess its role as a predictive marker of disease progression and clinical outcomes. Methods: The ratio of the median fluorescence intensity of CD169 between monocytes and lymphocytes (CD169 RMFI) was analyzed by flow cytometry in blood samples of COVID-19 patients (COV) and healthy donors (HDs) and correlated with immunophenotyping, inflammatory markers, cytokine mRNA expression, pulmonary involvement, and disease progression. CD169 RMFI correlated with blood cytokine mRNA levels, inflammatory markers, and pneumonia severity in patients who were untreated at sampling, and was associated with the respiratory outcome throughout hospitalization. Conclusion: CD169 is induced by the spike protein and should be considered as an early biomarker for evaluating immune dysfunction and respiratory outcomes in COVID-19 patients

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Conclusion