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

Overview

Journal Pathogens

Date 2021 Dec 28

PMID 34959594

Citations 8

Authors

Antonella Minutolo

Vita Petrone

Marialaura Fanelli

Marco Iannetta

Martina Giudice

Ines Ait Belkacem

Marta Zordan

Pietro Vitale

Guido Rasi

Paola Sinibaldi-Vallebona

Loredana Sarmati

Massimo Andreoni

Fabrice Malergue

Emanuela Balestrieri

Sandro Grelli

Claudia Matteucci

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Ortillon M, Coudereau R, Cour M, Rimmele T, Godignon M, Gossez M . Monocyte CD169 expression in COVID-19 patients upon intensive care unit admission. Cytometry A. 2021; 99(5):466-471. PMC: 8014094. DOI: 10.1002/cyto.a.24315. View

Chamoto K, Al-Habsi M, Honjo T . Role of PD-1 in Immunity and Diseases. Curr Top Microbiol Immunol. 2017; 410:75-97. DOI: 10.1007/82_2017_67. View

Balestrieri E, Minutolo A, Petrone V, Fanelli M, Iannetta M, Malagnino V . Evidence of the pathogenic HERV-W envelope expression in T lymphocytes in association with the respiratory outcome of COVID-19 patients. EBioMedicine. 2021; 66:103341. PMC: 8082064. DOI: 10.1016/j.ebiom.2021.103341. View

Bourgoin P, Soliveres T, Barbaresi A, Loundou A, Ait Belkacem I, Arnoux I . CD169 and CD64 could help differentiate bacterial from CoVID-19 or other viral infections in the Emergency Department. Cytometry A. 2021; 99(5):435-445. PMC: 8014466. DOI: 10.1002/cyto.a.24314. View

Perez-Zsolt D, Munoz-Basagoiti J, Rodon J, Elosua-Bayes M, Raich-Regue D, Risco C . SARS-CoV-2 interaction with Siglec-1 mediates trans-infection by dendritic cells. Cell Mol Immunol. 2021; 18(12):2676-2678. PMC: 8591443. DOI: 10.1038/s41423-021-00794-6. View

Merad M, Martin J . Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol. 2020; 20(6):355-362. PMC: 7201395. DOI: 10.1038/s41577-020-0331-4. View

Ji P, Zhu J, Zhong Z, Li H, Pang J, Li B . Association of elevated inflammatory markers and severe COVID-19: A meta-analysis. Medicine (Baltimore). 2020; 99(47):e23315. PMC: 7676531. DOI: 10.1097/MD.0000000000023315. View

Klaas M, Crocker P . Sialoadhesin in recognition of self and non-self. Semin Immunopathol. 2012; 34(3):353-64. DOI: 10.1007/s00281-012-0310-3. View

Pino M, Erkizia I, Benet S, Erikson E, Fernandez-Figueras M, Guerrero D . HIV-1 immune activation induces Siglec-1 expression and enhances viral trans-infection in blood and tissue myeloid cells. Retrovirology. 2015; 12:37. PMC: 4423124. DOI: 10.1186/s12977-015-0160-x. View

10.

Comins-Boo A, Gutierrez-Larranaga M, Roa-Bautista A, Guiral Foz S, Garcia M, Gonzalez Lopez E . Validation of a Quick Flow Cytometry-Based Assay for Acute Infection Based on CD64 and CD169 Expression. New Tools for Early Diagnosis in COVID-19 Pandemic. Front Med (Lausanne). 2021; 8:655785. PMC: 8044950. DOI: 10.3389/fmed.2021.655785. View

11.

Wang W, Ye L, Ye L, Li B, Gao B, Zeng Y . Up-regulation of IL-6 and TNF-alpha induced by SARS-coronavirus spike protein in murine macrophages via NF-kappaB pathway. Virus Res. 2007; 128(1-2):1-8. PMC: 7114322. DOI: 10.1016/j.virusres.2007.02.007. View

12.

To K, Sridhar S, Chiu K, Hung D, Li X, Hung I . Lessons learned 1 year after SARS-CoV-2 emergence leading to COVID-19 pandemic. Emerg Microbes Infect. 2021; 10(1):507-535. PMC: 8006950. DOI: 10.1080/22221751.2021.1898291. View

13.

Bogie J, Boelen E, Louagie E, Delputte P, Elewaut D, van Horssen J . CD169 is a marker for highly pathogenic phagocytes in multiple sclerosis. Mult Scler. 2017; 24(3):290-300. DOI: 10.1177/1352458517698759. View

14.

Sosa-Hernandez V, Torres-Ruiz J, Cervantes-Diaz R, Romero-Ramirez S, Paez-Franco J, Meza-Sanchez D . B Cell Subsets as Severity-Associated Signatures in COVID-19 Patients. Front Immunol. 2020; 11:611004. PMC: 7744304. DOI: 10.3389/fimmu.2020.611004. View

15.

Perez-Zsolt D, Erkizia I, Pino M, Garcia-Gallo M, Martin M, Benet S . Anti-Siglec-1 antibodies block Ebola viral uptake and decrease cytoplasmic viral entry. Nat Microbiol. 2019; 4(9):1558-1570. DOI: 10.1038/s41564-019-0453-2. View

16.

Doehn J, Tabeling C, Biesen R, Saccomanno J, Madlung E, Pappe E . CD169/SIGLEC1 is expressed on circulating monocytes in COVID-19 and expression levels are associated with disease severity. Infection. 2021; 49(4):757-762. PMC: 8023546. DOI: 10.1007/s15010-021-01606-9. View

17.

Wadaa-Allah A, Emhamed M, Sadeq M, Ben Hadj Dahman N, Ullah I, Farrag N . Efficacy of the current investigational drugs for the treatment of COVID-19: a scoping review. Ann Med. 2021; 53(1):318-334. PMC: 7971293. DOI: 10.1080/07853890.2021.1875500. View

18.

Bedin A, Makinson A, Picot M, Mennechet F, Malergue F, Pisoni A . Monocyte CD169 Expression as a Biomarker in the Early Diagnosis of Coronavirus Disease 2019. J Infect Dis. 2020; 223(4):562-567. PMC: 7717347. DOI: 10.1093/infdis/jiaa724. View

19.

Ohnishi K, Yamaguchi M, Erdenebaatar C, Saito F, Tashiro H, Katabuchi H . Prognostic significance of CD169-positive lymph node sinus macrophages in patients with endometrial carcinoma. Cancer Sci. 2016; 107(6):846-52. PMC: 4968600. DOI: 10.1111/cas.12929. View

20.

Di Micco P, Russo V, Carannante N, Imparato M, Cardillo G, Lodigiani C . Prognostic Value of Fibrinogen among COVID-19 Patients Admitted to an Emergency Department: An Italian Cohort Study. J Clin Med. 2020; 9(12). PMC: 7767519. DOI: 10.3390/jcm9124134. View