Clinical Progression and Cytokine Profiles of Middle East Respiratory Syndrome Coronavirus Infection

Kim, Eu Suk; Choe, Pyoeng Gyun; Park, Wan Beom; Oh, Hong Sang; Kim, Eun Jung; Nam, Eun Young; Na, Sun Hee; Kim, Moonsuk; Song, Kyoung-Ho; Bang, Ji Hwan; Park, Sang Won; Kim, Hong Bin; Kim, Nam Joong; Oh, Myoung-don

Acute renal impairment was initially reported as a characteristic feature of MERS (1). Subsequent studies from Saudi Arabia reported almost half of the patients with MERS required renal replacement therapy (17) (18) (19) . In this study, excluding Patient E who had metastatic bladder cancer with urinary obstruction, only one patient showed acute kidney injury. This striking difference in the incidence of renal impairment is likely due to the low prevalence of underlying conditions such as chronic renal diseases, diabetes and hypertension in our population. Evasion from immune system in humans is critical for MERS-CoV to survive and replicate in the host. MERS-CoV is known to inhibit recognition, delay IFN induction, and sequester IFN stimulated gene production until after peak viral titers had been achieved (20) . In a fatal MERS case, the patient could not induce the expression of key receptors, retinoic acid-inducible gene 1 (RIG-1) and melanoma differentiation-associated protein 5 (MDA-5) in response to MERS-CoV infection (21) . This resulted in a decreased expression of IFN regulatory factor 3 (IRF-3) and IRF-7 leading to a decreased expression of IFN-α. In our study, the serum levels of IFN-α in the severe MERS group was more frequently high than the mild group, even if we could not demonstrate any statistical significance. To the contrary, there was no apparent IFN-α response in the mild group ( Fig. 2A) . The level of IFN-α was also correlated with the log value of maximal RNA copies (Fig. 3A) . Taken together, IFN-α seems to surge during the clinical course of MERS in patients having severe disease with high viral loads but not in patients having mild disease. The absence of INF-α surge in severe cases of disease was related to worse outcome in previous study (21) , but we could not conclude the association of outcome with the serum level of IFN-α due to a limited number of fatal cases. Moreover, it is possible that the levels of serum INF-α merely reflected the level of exogenously injected pegylated IFN-α2a in this study. Therefore, the results of levels of serum INF-α should be read cautiously.