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

While IL-6 is one of the important proinflammatory cytokines having diverse biological activities in many clinical situations including respiratory viral infections, the change of serum IL-6 level during MERS-CoV infection has not been clearly documented yet. Increases in serum IL-6 during early phase of respiratory viral infections was revealed in human cases of severe seasonal influenza (22) , pandemic 2009 A/H1N1 influenza pneumonia (23) , and fatal A/H7N9 avian influenza (8, 24) . In case of SARS-CoV infections, elevated levels of IL-6 subsequent to the peak viral replication were observed in all of 8 pneumonia cases included (13) . IL-6 was induced in MERS-CoV-infected human monocyte-derived macrophages (25) and was significantly upregulated in the lung lesions of the MERS-CoV-infected animals (26) . In our study, overall IL-6 levels were not significantly higher in the severe MERS group than in the mild group. However, IL-6 levels in the severe MERS group were higher during the 2nd and the 3rd week after symptom onset with statistical significance when we analyzed a temporal trend (Supplementary Fig. 2) . CXCL-10, also known as IFN-γ-inducible protein 10 (IP-10), is a chemoattractant which is expressed in inflammed bronchial epithelial cells in response to IFN-γ. CXCL-10 seems to play an important role in severe respiratory viral illnesses. Uncontrolled durable secretion of CXCL-10, after the first week following the onset of symptoms was associated with poor outcome in a severe MERS case (21) . High serum level of CXCL-10 was also documented in other severe respiratory viral illnesses such as severe A/H7N9 avian influenza (24) , A/H5N1 avian influenza (7), severe seasonal influenza (22) , and SARS (9) . In this study the levels of serum CXCL-10 were significantly higher in the severe MERS group than in the mild group in the second and third week of illness ( Supplementary Fig. 2) . During the clinical course, the serum levels of CXCL-10 and IL-6 showed a peak around second week after symptom onset in the severe group (Fig. 2C ). This dynamic in proinflammatory cytokine response shows a good temporal correlation with chest infiltrates showing a peak at second weeks after symptom onset in severe MERS cases. Therefore, our study suggests that elevated levels of serum IL-6 and CXCL-10 may be associated with the severity of pneumonia in MERS.