Alhetheel Abdulkarim, Albarrag Ahmed, Shakoor Zahid, Somily Ali, Barry Mazin, Altalhi Haifa, Bakhrebah Muhammed, Nassar Majed, Alfageeh Mohamed, Assiri Ayed, Alfaraj Sarah, Memish Ziad
King Saud University Medical City, Riyadh 11362, Saudi Arabia.
Department of Pathology, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia.
Vaccines (Basel). 2023 May 31;11(6):1048. doi: 10.3390/vaccines11061048.
Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with significant morbidity and mortality due to intense pulmonary inflammation. Enhanced chemokine-mediated leukocyte infiltration in lungs has been linked with unfavorable outcomes with respect to the disease. This cross-sectional study assessed the levels of chemokines among 46 MERS-CoV-infected patients (19 asymptomatic and 27 symptomatic) and 52 healthy controls using a customized Luminex human chemokine magnetic multiplex panel. The plasma levels of interferon-inducible protein (IP)-10 (568.5 ± 114.7 vs. 55.19 ± 5.85 pg/mL; < 0.0001), macrophage inflammatory protein (MIP)-1 alpha (MIP-1A) (30.78 ± 2.81 vs. 18.16 ± 0.91 pg/mL; < 0.0001), MIP-1B (36.63 ± 4.25 vs. 25.26 ± 1.51 pg/mL; < 0.003), monocyte chemoattractant protein (MCP)-1 (1267 ± 309.5 vs. 390.0 ± 35.51 pg/mL; < 0.0002), and monokine-induced gamma interferon (MIG) (28.96 ± 3.93 vs. 16.29 ± 1.69 pg/mL; < 0.001), interleukin (IL)-8 (147.9 ± 21.57 vs. 84.63 ± 10.62 pg/mL; < 0.004) were significantly higher in symptomatic patients than healthy controls. Likewise, the levels of IP-10 (247.6 ± 80.09 vs. 55.19 ± 5.85 pg/mL; < 0.0002) and MCP-1 (650.7 ± 149 pg/mL vs. 390 ± 35.51 pg/mL; < 0.02) were also significantly higher in asymptomatic patients compared to healthy controls. However, no differences were observed in the plasma levels of MIP-1A, MIP-1B, MIG, and IL-8 between asymptomatic patients and uninfected controls. Conversely, the mean plasma levels of regulated on activation normal T cell expressed and secreted (RANTES) (3039 ± 301.0 vs. 4390 ± 223 pg/mL; < 0.001) and eotaxin (176.9 ± 30.20 vs. 296.2 ± 28.11 pg/mL; < 0.01) were significantly lower in symptomatic MERS-CoV-infected patients compared to healthy controls. Likewise, the levels of eotaxin (162.7 ± 21.60 vs. 296.2 ± 28.11 pg/mL; < 0.01) were also significantly lower in asymptomatic patients. Interestingly, the level of MCP-1 (2139 ± 548.2 vs. 776.5 ± 165.3 pg/mL; < 0.004) was significantly higher in deceased symptomatic patients compared to recovered symptomatic patients. MCP-1 was the only chemokine associated with a higher risk of mortality. Symptomatic MERS-CoV-infected patients had a significant elevation of plasma chemokines and elevated MCP-1 levels were found to be associated with fatal outcomes.
中东呼吸综合征冠状病毒（MERS-CoV）因严重的肺部炎症而导致显著的发病率和死亡率。肺部趋化因子介导的白细胞浸润增强与该疾病的不良预后相关。这项横断面研究使用定制的Luminex人趋化因子磁性多重检测板，评估了46例MERS-CoV感染患者（19例无症状感染者和27例有症状感染者）及52名健康对照者体内的趋化因子水平。有症状患者血浆中干扰素诱导蛋白（IP）-10（568.5±114.7 vs. 55.19±5.85 pg/mL；<0.0001）、巨噬细胞炎性蛋白（MIP）-1α（MIP-1A）（30.78±2.81 vs. 18.16±0.91 pg/mL；<0.0001）、MIP-1β（MIP-1B）（36.63±4.25 vs. 25.26±1.51 pg/mL；<0.003）、单核细胞趋化蛋白（MCP）-1（1267±309.5 vs. 390.0±35.51 pg/mL；<0.0002）、单核因子诱导的γ干扰素（MIG）（28.96±3.93 vs. 16.29±1.69 pg/mL；<0.001）和白细胞介素（IL）-8（147.9±21.57 vs. 84.63±10.62 pg/mL；<0.004）水平显著高于健康对照者。同样，无症状患者体内IP-10（247.6±80.09 vs. 55.19±5.85 pg/mL；<0.0002）和MCP-1（650.7±149 pg/mL vs. 390±35.51 pg/mL；<0.02）水平也显著高于健康对照者。然而，无症状患者与未感染对照者的MIP-1A、MIP-1B、MIG和IL-8血浆水平未观察到差异。相反，有症状的MERS-CoV感染患者血浆中调节激活正常T细胞表达和分泌因子（RANTES）（3039±301.0 vs. 4390±223 pg/mL；<0.001）和嗜酸性粒细胞趋化因子（176.9±30.20 vs. 296.2±28.11 pg/mL；<0.01）的平均水平显著低于健康对照者。同样，无症状患者体内嗜酸性粒细胞趋化因子水平（162.7±21.60 vs. 296.2±28.11 pg/mL；<0.01）也显著降低。有趣的是，与康复的有症状患者相比，死亡的有症状患者体内MCP-1水平（2139±548.2 vs. 776.5±165.3 pg/mL；<0.004）显著升高。MCP-1是唯一与较高死亡风险相关的趋化因子。有症状的MERS-CoV感染患者血浆趋化因子显著升高，且MCP-1水平升高与致命结局相关。
