Assessment of Proinflammatory Cytokines Among Patients with Middle East Respiratory Syndrome Coronavirus Infection.

Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with significant morbidity and mortality. This study was performed to assess the proinflammatory cytokines profile among MERS-CoV patients. A total of 46 MERS-CoV-infected patients (27 symptomatic and 19 asymptomatic) were assessed and compared with 52 normal healthy controls for plasma levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-17, IL-7, IL-6, interferon (IFN)-α, and IL-15 using a customized luminex kit. Whereas asymptomatic MERS-CoV patients and controls were no different; the mean plasma levels among MERS-CoV symptomatic patients were significantly higher than the normal controls: IL-1ß (16.89 ± 1.23 vs. 12.80 ± 0.59 pg/mL; p < 0.001), TNF-α (14.04 ± 0.93 vs. 10.35 ± 0.29 pg/mL; p < 0.0001), IL-17 (14.3 ± 0.89 vs. 11.47 ± 0.61 pg/mL; p < 0.001), IL-7 (21.56 ± 1.00 vs. 16.31 ± 0.30 pg/mL; p < 0.0001), IL-6 (156.5 ± 37.90 vs. 18.60 ± 1.59 pg/mL; p < 0.0001), and IFN-α (68.73 ± 13.06 vs. 23.57 ± 1.05 pg/mL; p < 0.0001). The mean plasma levels of IL-7 (24.81 ± 1.63 vs. 19.79 ± 0.94 pg/mL; p < 0.01), IL-6 (312.7 ± 94.67 vs. 101.2 ± 25.67 pg/mL; p < 0.01), and IFN-α (89.00 ± 18.97 vs. 51.05 ± 8.68 pg/mL; p < 0.05) were significantly elevated among MERS-CoV symptomatic patients with fatal outcome compared with MERS-CoV symptomatic patients who survived. Only IL-7 was found to have a higher risk ratio of mortality (4.76, 95% confidence interval: 1.5-14.94; p < 0.01). No differences were observed in IL-15 levels among the groups. Significantly elevated proinflammatory cytokines among symptomatic MERS-CoV-infected patients may contribute to manifestations of cytokine storm frequently observed among critically ill MERS-CoV patients and IL-7 may serve as a marker for disease activity.

Differential expression of carcinoembryonic antigen-related cell adhesion molecule-5 (CEACAM5) and dipeptidyl peptidase-4 (DPP4) with detection of Middle East respiratory syndrome-coronavirus in peripheral blood.

BACKGROUND: Middle East respiratory syndrome-coronavirus (MERS-CoV) utilizes CD26 (dipeptidyl peptidase-4) and CD66e or CEACAM5 (carcinoembryonic antigen-related cell adhesion molecule 5) receptors for cell infection. Peripheral blood mononuclear cells (PBMCs) play a critical role in mounting adaptive immune response against the virus. This study was performed to assess the expression of CD26 and CD66e on PBMCs and their susceptibility to MERS-CoV infection. METHODS: Surface expression of CD26 and CD66e receptors on PBMCs from MERS-CoV patients (n = 20) and healthy controls (n = 20) was assessed by flow cytometry and the soluble forms were determined by enzyme-linked immunosorbent assay (ELISA). MERS-CoV UpE and Orf1a genes in PBMCs were detected by using Altona diagnostics reverse transcription polymerase chain reaction (RT-PCR) kit. RESULTS: Mean fluorescent intensity (MFI) of CD66e was significantly higher on CD4 + lymphocytes (462.4 ± 64.35 vs 325.1 ± 19.69; p < 0.05) and CD8 + lymphocytes (533.8 ± 55.32 vs 392.4 ± 37.73; p < 0.04) from patients with MERS-CoV infection compared to the normal controls. No difference in MFI for CD66e was observed on monocytes (381.8 ± 40.34 vs 266.8 ± 20.6; p = 0.3) between the patients and controls. Soluble form of CD66e among MERS-CoV patients was also higher than the normal controls (mean= 338.7 ± 58.75 vs 160.7 ± 29.49 ng/mL; p < 0.01). Surface expression of CD26 on PBMCs and its soluble form were no different between the groups. MERS-CoV was detected by RT-PCR in 16/20 (80%) patients from whole blood, among them 8 patients were tested in PBMCs, 4/8 (50%) patients were positive. CONCLUSION: Increased expression levels of CD66e (CEACAM5) may contribute to increased susceptibility of PBMCs to MERS-CoV infection and disease progression.