Increased sCD163 and sCD14 plasmatic levels and depletion of peripheral blood pro-inflammatory monocytes, myeloid and plasmacytoid dendritic cells in patients with severe COVID-19 pneumonia

<strong>Background: </strong>Emerging evidence argues that monocytes, circulating innate immune cells, are principal players in COVID-19 pneumonia. The study aimed to investigate the role of soluble (s)CD163 and sCD14 plasmatic levels in predicting disease severity and characterize peripheral blood monocytes and dendritic cells (DCs), in patients with COVID-19 pneumonia (COVID-19 subjects). <strong>Methods:</strong> On admission, in COVID-19 subjects sCD163 and sCD14 plasmatic levels, and peripheral blood monocyte and DC subsets were compared to healthy donors (HDs). According to clinical outcome, COVID-19 subjects were divided into ARDS and non-ARDS groups. <strong>Results:</strong> Compared to HDs, COVID-19 subjects showed higher sCD163 (p&lt;0.0001) and sCD14 (p&lt;0.0001) plasmatic levels. We observed higher sCD163 plasmatic levels in the ARDS group compared to the non-ARDS one (p=0.002). The cut-off for sCD163 plasmatic level greater than 2032 ng/ml was predictive of disease severity (AUC: 0.6786, p=0.0022; sensitivity 56.7% [CI: 44.1-68.4] specificity 73.8% [CI: 58.9-84.7]). Positive correlation between plasmatic levels of sCD163, LDH and IL-6 and between plasmatic levels of sCD14, D-dimer and ferritin were found. Compared to HDs, COVID-19 subjects showed lower percentages of non-classical (p=0.0012) and intermediate monocytes (p=0.0447), slanDCs (p&lt;0.0001), myeloid DCs (mDCs, p&lt;0.0001) and plasmacytoid DCs (pDCs, p=0.0014). Compared to the non-ARDS group, the ARDS group showed lower percentages of non-classical monocytes (p=0.0006), mDCs (p=0.0346) and pDCs (p=0.0492). <strong>Conclusions:</strong> The increase in sCD163 and sCD14 plasmatic levels, observed on hospital admission in COVID-19 subjects, especially in those who developed ARDS, and the correlations of these monocyte/macrophage activation markers with typical inflammatory markers of COVID-19 pneumonia, underline their potential use to assess the risk of progression of the disease. In an early stage of the disease, the assessment of sCD163 plasmatic levels could have clinical utility in predicting the severity of COVID-19 pneumonia.**背景：** 越来越多的研究证据表明，单核细胞（monocytes）作为循环固有免疫细胞，是新型冠状病毒肺炎（COVID-19肺炎）发病的核心参与角色。本研究旨在探讨可溶性（soluble）CD163与可溶性CD14血浆水平在预测疾病严重程度中的作用，并对新型冠状病毒肺炎受试者的外周血单核细胞及树突状细胞（dendritic cells, DCs）亚群进行特征分析。 **方法：** 入院时，对比新型冠状病毒肺炎受试者与健康供体（healthy donors, HDs）的可溶性CD163、可溶性CD14血浆水平，以及外周血单核细胞和树突状细胞亚群；根据临床结局将新型冠状病毒肺炎受试者分为急性呼吸窘迫综合征（acute respiratory distress syndrome, ARDS）组与非ARDS组。 **结果：** 与健康供体相比，新型冠状病毒肺炎受试者的可溶性CD163（p<0.0001）与可溶性CD14（p<0.0001）血浆水平显著升高。急性呼吸窘迫综合征组的可溶性CD163血浆水平高于非ARDS组（p=0.002）。可溶性CD163血浆水平>2032 ng/ml的截断值可预测疾病严重程度（曲线下面积（AUC）：0.6786，p=0.0022；灵敏度56.7%[置信区间（CI）：44.1~68.4]，特异度73.8%[CI：58.9~84.7]）。研究发现，可溶性CD163血浆水平与乳酸脱氢酶（LDH）、白细胞介素6（IL-6）呈正相关，可溶性CD14血浆水平与D-二聚体、铁蛋白呈正相关。与健康供体相比，新型冠状病毒肺炎受试者的非经典单核细胞（p=0.0012）、中间型单核细胞（p=0.0447）、slan树突状细胞（slanDCs）、髓系树突状细胞（myeloid DCs, mDCs，p<0.0001）及浆细胞样树突状细胞（plasmacytoid DCs, pDCs，p=0.0014）占比均更低。与非ARDS组相比，急性呼吸窘迫综合征组的非经典单核细胞（p=0.0006）、髓系树突状细胞（p=0.0346）及浆细胞样树突状细胞（p=0.0492）占比更低。 **结论：** 新型冠状病毒肺炎受试者入院时检测到的可溶性CD163与可溶性CD14血浆水平升高（尤其在进展为急性呼吸窘迫综合征的受试者中），且这些单核细胞/巨噬细胞激活标志物与新型冠状病毒肺炎典型炎症标志物存在相关性，这提示二者可用于评估疾病进展风险。在疾病早期阶段，检测可溶性CD163血浆水平可用于预测新型冠状病毒肺炎的严重程度，具备临床应用价值。