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.
Front Immunol. 2022 Apr 4;13:871592. doi: 10.3389/fimmu.2022.871592. eCollection 2022.
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.
CD163 是一种主要由单核细胞和巨噬细胞表达的触珠蛋白-血红蛋白清道夫受体,参与炎症过程的调节。在促炎刺激后经蛋白水解切割后,CD163 从细胞表面脱落,其可溶性形式 sCD163 存在于血浆中,是单核/巨噬细胞系激活的生物标志物。在疾病的早期阶段评估 sCD163 血浆水平可能对预测 COVID-19 肺炎的严重程度具有临床意义。在 COVID-19 患者中使用托珠单抗(抗 IL-6 受体的单克隆抗体)可降低 30 天的死亡率。本研究的目的是研究托珠单抗对 COVID-19 患者 sCD163 血浆水平的影响。
在 COVID-19 患者入院时(T0)、住院后 7 天(T7)和出院后 45 天(T45)评估 sCD163 血浆水平,并评估其他实验室参数。COVID-19 患者分为托珠单抗(TCZ)和非托珠单抗(非 TCZ)组。TCZ 组进一步分为应答者(R)和非应答者(NR)组。死亡或需要机械通气的患者定义为 NR。健康供体(HD)被招募为对照组。
共纳入 70 例 COVID-19 患者和 47 例 HD。在 T0 时,COVID-19 患者的 sCD163 血浆水平明显高于 HD(p<0.0001),纵向评估显示 T7 时 sCD163 血浆水平较 T0 时降低(p=0.0211)。在 T0 时,TCZ 组和非 TCZ 组的 sCD163 血浆水平均明显高于 HD(p<0.0001 和 p=0.0147)。在 T7 时,仅 TCZ 组的 sCD163 血浆水平显著降低(p=0.0030),达到与 HD 相当的水平。相反,非 TCZ 组无统计学意义,且 T7 时非 TCZ 组与 HD 比较有统计学意义(p=0.0019)。在 T0 时,R 组和 NR 组的 sCD163 血浆水平无统计学意义,且两组均明显高于 HD(p=0.0001 和 p=0.0340)。两组的纵向评估均显示出明显的降低(R:p=0.0356;NR:p=0.0273),与结局无关。随访 45 天后 sCD163 血浆水平保持稳定。
COVID-19 肺炎患者 sCD163 血浆水平升高,托珠单抗治疗可有效下调,无论临床结局如何。