Role of Tocilizumab in Down Regulating sCD163 Plasmatic Levels in a Cohort of COVID-19 Patients.


Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2022
Historique:
received: 08 02 2022
accepted: 09 03 2022
entrez: 21 4 2022
pubmed: 22 4 2022
medline: 23 4 2022
Statut: epublish

Résumé

CD163, a haptoglobin-hemoglobin scavenger receptor mostly expressed by monocytes and macrophages, is involved in the regulation of inflammatory processes. Following proteolytic cleavage after pro-inflammatory stimulation, CD163 is shed from the cell surface and its soluble form in plasma, sCD163, is a biomarker of monocyte/macrophage lineage activation.The assessment of sCD163 plasmatic levels in an early stage of the disease could have clinical utility in predicting the severity of COVID-19 pneumonia. The use of tocilizumab (monoclonal antibody anti-IL-6 receptor) in COVID-19 patients reduces lethality rate at 30 days. The aim of the study was to investigate the effect of tocilizumab on sCD163 plasmatic levels in a cohort of COVID-19 patients. In COVID-19 patients, on hospital admission (T0), after 7 days from hospitalization (T7) and after 45 days from discharge (T45) sCD163 plasmatic levels were evaluated, along with other laboratory parameters. COVID-19 patients were stratified into tocilizumab (TCZ) and non-tocilizumab (non-TCZ) groups. TCZ group was further divided into responder (R) and non-responder (NR) groups. Patients who died or required mechanical ventilation were defined as NR. As control group, healthy donors (HD) were enrolled. Seventy COVID-19 patients and 47 HD were enrolled. At T0, sCD163 plasmatic levels were higher in COVID-19 patients compared to HD (p<0.0001) and the longitudinal evaluation showed a reduction in sCD163 plasmatic levels at T7 compared to T0 (p=0.0211). At T0, both TCZ and non-TCZ groups showed higher sCD163 plasmatic levels compared to HD (p<0.0001 and p=0.0147, respectively). At T7, the longitudinal evaluation showed a significant reduction in sCD163 plasmatic levels (p=0.0030) only in the TCZ group, reaching levels comparable to those of HD. Conversely, not statistically significance in non-TCZ group was observed and, at T7, a statistically significance was found comparing non-TCZ group to HD (p=0.0019). At T0, R and NR groups showed not statistically significance in sCD163 plasmatic levels and both groups showed higher levels compared to HD (p=0.0001 and p=0.0340, respectively). The longitudinal evaluation showed significant reductions in both groups (R: p=0.0356; NR: p=0.0273) independently of the outcome. After 45 days of follow-up sCD163 plasmatic levels remain stable. sCD163 plasmatic levels are increased in COVID-19 pneumonia and is efficiently down-regulated by tocilizumab treatment regardless of the clinical outcome.

Sections du résumé

Background
CD163, a haptoglobin-hemoglobin scavenger receptor mostly expressed by monocytes and macrophages, is involved in the regulation of inflammatory processes. Following proteolytic cleavage after pro-inflammatory stimulation, CD163 is shed from the cell surface and its soluble form in plasma, sCD163, is a biomarker of monocyte/macrophage lineage activation.The assessment of sCD163 plasmatic levels in an early stage of the disease could have clinical utility in predicting the severity of COVID-19 pneumonia. The use of tocilizumab (monoclonal antibody anti-IL-6 receptor) in COVID-19 patients reduces lethality rate at 30 days. The aim of the study was to investigate the effect of tocilizumab on sCD163 plasmatic levels in a cohort of COVID-19 patients.
Methods
In COVID-19 patients, on hospital admission (T0), after 7 days from hospitalization (T7) and after 45 days from discharge (T45) sCD163 plasmatic levels were evaluated, along with other laboratory parameters. COVID-19 patients were stratified into tocilizumab (TCZ) and non-tocilizumab (non-TCZ) groups. TCZ group was further divided into responder (R) and non-responder (NR) groups. Patients who died or required mechanical ventilation were defined as NR. As control group, healthy donors (HD) were enrolled.
Results
Seventy COVID-19 patients and 47 HD were enrolled. At T0, sCD163 plasmatic levels were higher in COVID-19 patients compared to HD (p<0.0001) and the longitudinal evaluation showed a reduction in sCD163 plasmatic levels at T7 compared to T0 (p=0.0211). At T0, both TCZ and non-TCZ groups showed higher sCD163 plasmatic levels compared to HD (p<0.0001 and p=0.0147, respectively). At T7, the longitudinal evaluation showed a significant reduction in sCD163 plasmatic levels (p=0.0030) only in the TCZ group, reaching levels comparable to those of HD. Conversely, not statistically significance in non-TCZ group was observed and, at T7, a statistically significance was found comparing non-TCZ group to HD (p=0.0019). At T0, R and NR groups showed not statistically significance in sCD163 plasmatic levels and both groups showed higher levels compared to HD (p=0.0001 and p=0.0340, respectively). The longitudinal evaluation showed significant reductions in both groups (R: p=0.0356; NR: p=0.0273) independently of the outcome. After 45 days of follow-up sCD163 plasmatic levels remain stable.
Conclusion
sCD163 plasmatic levels are increased in COVID-19 pneumonia and is efficiently down-regulated by tocilizumab treatment regardless of the clinical outcome.

Identifiants

pubmed: 35444637
doi: 10.3389/fimmu.2022.871592
pmc: PMC9013773
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
tocilizumab I031V2H011

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

871592

Informations de copyright

Copyright © 2022 Marocco, Carraro, Zingaropoli, Nijhawan, Tortellini, Guardiani, Mengoni, Zuccalà, Belvisi, Kertusha, Parente, Del Borgo, Vullo, Ciardi, Mastroianni and Lichtner.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Raffaella Marocco (R)

Infectious Diseases Unit, Santa Maria (SM) Goretti Hospital, Sapienza University of Rome, Latina, Italy.

Anna Carraro (A)

Infectious Diseases Unit, Santa Maria (SM) Goretti Hospital, Sapienza University of Rome, Latina, Italy.
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Maria Antonella Zingaropoli (MA)

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Parni Nijhawan (P)

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Eeva Tortellini (E)

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Mariasilvia Guardiani (M)

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Fabio Mengoni (F)

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Paola Zuccalà (P)

Infectious Diseases Unit, Santa Maria (SM) Goretti Hospital, Sapienza University of Rome, Latina, Italy.

Valeria Belvisi (V)

Infectious Diseases Unit, Santa Maria (SM) Goretti Hospital, Sapienza University of Rome, Latina, Italy.

Blerta Kertusha (B)

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Alberico Parente (A)

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Cosmo Del Borgo (C)

Infectious Diseases Unit, Santa Maria (SM) Goretti Hospital, Sapienza University of Rome, Latina, Italy.

Vincenzo Vullo (V)

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Maria Rosa Ciardi (MR)

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Claudio Maria Mastroianni (CM)

Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Miriam Lichtner (M)

Infectious Diseases Unit, Santa Maria (SM) Goretti Hospital, Sapienza University of Rome, Latina, Italy.
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

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