J Korean Med Sci.  2016 Nov;31(11):1717-1725. 10.3346/jkms.2016.31.11.1717.

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

Affiliations
  • 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. mdohmd@snu.ac.kr

Abstract

Clinical progression over time and cytokine profiles have not been well defined in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. We included 17 patients with laboratory-confirmed MERS-CoV during the 2015 outbreak in Korea. Clinical and laboratory parameters were collected prospectively. Serum cytokine and chemokine levels in serial serum samples were measured using enzyme-linked immunosorbent assay. All patients presented with fever. The median time to defervescence was 18 days. Nine patients required oxygen supplementation and classified into severe group. In the severe group, chest infiltrates suddenly began to worsen around day 7 of illness, and dyspnea developed at the end of the first week and became apparent in the second week. Median time from symptom onset to oxygen supplementation was 8 days. The severe group had higher neutrophil counts during week 1 than the mild group (4,500 vs. 2,200/µL, P = 0.026). In the second week of illness, the severe group had higher serum levels of IL-6 (54 vs. 4 pg/mL, P = 0.006) and CXCL-10 (2,642 vs. 382 pg/mL, P < 0.001). IFN-α response was not observed in mild cases. Our data shows that clinical condition may suddenly deteriorate around 7 days of illness and the serum levels of IL-6 and CXCL-10 was significantly elevated in MERS-CoV patients who developed severe diseases.

Keyword

MERS; Coronavirus; Clinical Progression; Cytokine; Chemokine; IFN-α; IL-6; CXCL-10; Severity

MeSH Terms

Adult
Aged
Body Temperature
Chemokine CXCL10/blood
Chemokines/blood
Coronavirus Infections/blood/complications/*pathology
Creatinine/blood
Cytokines/*blood
Disease Progression
Dyspnea/etiology
Enzyme-Linked Immunosorbent Assay
Female
Humans
Hyperbaric Oxygenation
Interferon-gamma/blood
Interleukin-6/blood
Leukocyte Count
Male
Middle Aged
Neutrophils/cytology
Prothrombin Time
Severity of Illness Index
Chemokine CXCL10
Chemokines
Cytokines
Interleukin-6
Interferon-gamma
Creatinine

Figure

  • Fig. 1 Changes of body temperature and laboratory parameters over time after symptom onset in the patients with MERS-CoV infection. Shown are body temperature (A), neutrophil count (B), lymphocyte count (C), platelet count (D), serum albumin (E), prothrombin time (F), and serum creatinine (G). The severe cases were the patients who required oxygen supplementation or mechanical ventilation, whereas the mild cases were those who did not required oxygen supplementation.

  • Fig. 2 Changes of the serum levels of cytokine and chemokine over time after symptom onset in the patient with MERS-CoV infection. IFN-α (A), IL-6 (B), and CXCL-10 (C) increased during the course of disease, especially in the severe group. The following patients received pegylated IFN-α2a injection: Patient A (Day 5, 10, 17), Patient B (Day 11, 18), Patient C (Day 6, 13), Patient D (Day 10, 17), Patient E (Day 12), Patient G (Day 8, 15), Patient K (Day 9), Patient P (Day 4), Patient Q (Day 2, 8).

  • Fig. 3 Correlation between serum cytokines and chemokine concentration at the first week of illness and the peak MERS-CoV viral load in respiratory specimens. Hollow circles mean the values measured after the administration of pegylated IFN-α2a. Spearman’s rank correlation coefficient was used to assess correlations. (A) IFN-α, ρ = 0.938, P = 0.001; (B) IL-6, ρ = −0.320, P = 0.440; (C) CXCL-10, ρ = 0.419, P = 0.301.


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