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

Abstract

BackgroundCD163, 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.MethodsIn 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.ResultsSeventy 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.ConclusionsCD163 plasmatic levels are increased in COVID-19 pneumonia and is efficiently down-regulated by tocilizumab treatment regardless of the clinical outcome.

Tissue Inhibitor of Matrix Metalloproteinases-1 (TIMP-1) and Pulmonary Involvement in COVID-19 Pneumonia

“…Finally, as already reported [58][59][60], we confirmed the increase in plasma levels of sCD163 and sCD14 on the hospital admission of COVID-19 patients, especially in those who developed ARDS, highlighting their potential use when assessing the risk of progression in the disease.…”

“…In this single-centre observational study, during the first wave of the COVID-19 pandemic, 129 COVID-19 patients (72 males, 57 females) with a median age (IQR) of 64 (55-77) years were enrolled. As the control group, 53 HD (30 males, 23 females) with a median age (IQR) of 60 (57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68) years were included in the study.…”

Biomarkers of Neurological Damage: From Acute Stage to Post-Acute Sequelae of COVID-19

“…As a marker of inflammation, sCD163 is elevated in a range of diseases [ 34 , 43 , 53 , 54 ] and it was largely investigated in COVID-19 pneumonia [ 42 , 43 , 44 , 55 ]. As previously reported, a potential use to assess the risk of disease progression has been proposed, because an increase in plasma levels of sCD163 was observed on hospital admission in COVID-19 patients, especially in those who developed ARDS, as well as its correlation with typical inflammatory markers of COVID-19 pneumonia [ 43 , 44 ]. To the best of our knowledge, there is no information on the assessment of sCD163 in the CSF of COVID-19 patients nor on its correlation with NS at both the acute stage and post-COVID.…”

“…In the CNS, sCD163 is probably shed by macrophages and microglia, triggered by complex immune-modulating mechanisms in the microenvironment [ 34 ]. Although plasma levels of sCD163 were deeply investigated in the acute stage of COVID-19 and correlate to COVID-19 severity [ 42 , 43 , 44 ], data on CSF levels of sCD163 are lacking.…”