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.

MERS-CoV Confirmation among 6,873 suspected persons and relevant Epidemiologic and Clinical Features, Saudi Arabia - 2014 to 2019.

BACKGROUND: Of the three lethal coronaviruses, in addition to the ongoing pandemic-causing SARS-CoV 2, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) remains in circulation. Information on MERS-CoV has relied on small sample of patients. We updated the epidemiology, laboratory and clinical characteristics, and survival patterns of MERS-CoV retrospectively with the largest sample of followed patients. METHODS: We conducted a retrospective review of line-listed records of non-random, continuously admitted patients who were suspected (6,873) or confirmed with MERS-CoV (501) admitted to one of the four MERS-CoV referral hospitals in Saudi Arabia, 2014-2019. FINDINGS: Of the 6,873 MERS-CoV suspected persons, the majority were male (56%) and Saudi nationals (83%) and 95% had no known history that increased their risk of exposure to MERS-CoV patients or vectors (95%). More confirmed cases reported history that increased their risk of MERS-CoV infection (41%). Among the suspected, MERS-CoV confirmation (7.4% overall) was independently associated with being male, known transmission link to MERS-CoV patients or vectors, fever, symptoms for 7 days, admission through intensive care unit, and diabetes. Among persons with confirmed MERS-CoV, single symptoms were reported by 20%, 3-symptom combinations (fever, cough and dyspnea) reported by 21% and 2-symptom combinations (fever, cough) reported by 16%. Of the two-thirds (62%) of MERS-CoV confirmed patients who presented with co-morbidity, 32% had 2-"comorbidities (diabetes, hypertension). More than half of the MERS-CoV patents showed abnormal chest X-ray, elevated aspartate aminotransferase, and creatinine kinase. About a quarter of MERS-CoV patients had positive cultures on blood, urine, or respiratory secretions. During an average hospital stay of 18 days (range 11 to 30), 64% developed complications involving liver, lungs, or kidneys. Ventilation requirement (29% of MERS-CoV cases) was independently associated with abnormal chest X-ray, viremia (Ct value <30), elevated creatinine, and prothrombin time. Death (21% overall) was independently associated with older age, dyspnea and abnormal chest X-ray on admission, and low hemoglobulin levels. INTERPRETATIONS: With two-thirds of the symptomatic persons developing multiorgan complications MERS-CoV remains the coronavirus with the highest severity (29%) and case fatality rate (21%) among the three lethal coronaviruses. Metabolic abnormalities appear to be an independent risk factor for sustained MERS-CoV transmission. The poorly understood transmission dynamics and non-specific clinical and laboratory features call for high index of suspicion among respiratory disease experts to help early detection of outbreaks. We reiterate the need for case control studies on transmission. FUNDING: No special funding to declare.