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

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.

Diagnostic delays in 537 symptomatic cases of Middle East respiratory syndrome coronavirus infection in Saudi Arabia

“…The finding of the current study that the severity of illness is associated with a prolonged time interval between onset and diagnosis is consistent with the study by Kim et al, (2016b). The estimated time interval between onset and diagnosis in patients with severe illness was 6.19 days, while it was 5.06 days in patients with a stable condition.…”

“…The average time interval to a confirmed diagnosis after symptom onset was 5.6 days (median 4 days). Kim et al reported a similar median estimate (5 days) in a sample of MERS patients in the Republic of Korea (Kim et al, 2016b).…”

“…The study reported that the serological assays were highly sensitive at 21 days following the onset of illness (Park et al, 2015). Kim et al investigated the clinical progression and cytokine profiles after the first appearance of illness in a Korean population with MERS-CoV (Kim et al, 2016b). Their study reported that the time interval was associated with a poor outcome in patients with severe illness.…”

“…Their study reported that the time interval was associated with a poor outcome in patients with severe illness. The median time interval from symptom onset to transfer to the isolation unit was reported to be 5 days, with a range of 2-11 days (Kim et al, 2016b). More studies are warranted to investigate the time interval from symptom onset to diagnosis and the factors associated with this interval in other MERS populations, specifically in Saudi Arabia, where MERS-CoV was first reported and where the world's largest outbreaks occur.…”

MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract

“…Taken together, the high expression of inflammatory cytokines/ chemokines IL-1 α and IL-1β, IL-8 (CXCL8), IL-18, CXCR3, SOCS5, and CCR2 in the lower respiratory tracts of MERS-CoV infected patients confirmed the lung immunopathology [46,[77][78][79][80]. Therefore, the high expression of inflammatory cytokines and downregulation of the Th1 and Th2 immune responses in the lower respiratory tracts of MERS-CoV infected patients may contribute to a more severe infection, higher case fatality, lung inflammation, and immunopathology.…”