Chemokine Levels among Patients with Middle East Respiratory Syndrome Coronavirus Infection

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 & PLUSMN; 114.7 vs. 55.19 & PLUSMN; 5.85 pg/mL; p < 0.0001), macrophage inflammatory protein (MIP)-1 alpha (MIP-1A) (30.78 & PLUSMN; 2.81 vs. 18.16 & PLUSMN; 0.91 pg/mL; p < 0.0001), MIP-1B (36.63 & PLUSMN; 4.25 vs. 25.26 & PLUSMN; 1.51 pg/mL; p < 0.003), monocyte chemoattractant protein (MCP)-1 (1267 & PLUSMN; 309.5 vs. 390.0 & PLUSMN; 35.51 pg/mL; p < 0.0002), and monokine-induced gamma interferon (MIG) (28.96 & PLUSMN; 3.93 vs. 16.29 & PLUSMN; 1.69 pg/mL; p < 0.001), interleukin (IL)-8 (147.9 & PLUSMN; 21.57 vs. 84.63 & PLUSMN; 10.62 pg/mL; p < 0.004) were significantly higher in symptomatic patients than healthy controls. Likewise, the levels of IP-10 (247.6 & PLUSMN; 80.09 vs. 55.19 & PLUSMN; 5.85 pg/mL; p < 0.0002) and MCP-1 (650.7 & PLUSMN; 149 pg/mL vs. 390 & PLUSMN; 35.51 pg/mL; p < 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 & PLUSMN; 301.0 vs. 4390 & PLUSMN; 223 pg/mL; p < 0.001) and eotaxin (176.9 & PLUSMN; 30.20 vs. 296.2 & PLUSMN; 28.11 pg/mL; p < 0.01) were significantly lower in symptomatic MERS-CoV-infected patients compared to healthy controls. Likewise, the levels of eotaxin (162.7 & PLUSMN; 21.60 vs. 296.2 & PLUSMN; 28.11 pg/mL; p < 0.01) were also significantly lower in asymptomatic patients. Interestingly, the level of MCP-1 (2139 & PLUSMN; 548.2 vs. 776.5 & PLUSMN; 165.3 pg/mL; p < 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.

Automated summary

Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with intense pulmonary inflammation and chemokines play a role in leukocyte infiltration. This study found significantly higher levels of IP-10, MIP-1A, MIP-1B, MCP-1, and MIG in symptomatic MERS-CoV-infected patients compared to healthy controls. Asymptomatic patients also had elevated levels of IP-10 and MCP-1. Increased MCP-1 levels were associated with fatal outcomes.