title: Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity.
abstract: Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS.
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Chan-Ki
authors.initials: CK
authors.lastname: Min
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Shinhye
authors.initials: S
authors.lastname: Cheon
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Na-Young
authors.initials: NY
authors.lastname: Ha
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Kyung Mok
authors.initials: KM
authors.lastname: Sohn
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Abdimadiyeva
authors.initials: A
authors.lastname: Aigerim
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyun Mu
authors.initials: HM
authors.lastname: Shin
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ji-Yeob
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Inn
authors.affiliation: Department of Radiology, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Jin-Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Moon
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Myung-Sik
authors.initials: MS
authors.lastname: Choi
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Republic of Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.|Institute of Endemic Disease, Seoul National University Medical Research Center and Bundang Hospital, Seoul, Republic of Korea.
authors.forename: Nam-Hyuk
authors.initials: NH
authors.lastname: Cho
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Yeon-Sook
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018352:Coronavirus Infections / Q000150:complications / Q000276:immunology* / Q000401:mortality / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D007964:Leukocytosis / Q000209:etiology* / Q000401:mortality; D008231:Lymphopenia / Q000209:etiology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D065207:Middle East Respiratory Syndrome Coronavirus / Q000502:physiology*; D011014:Pneumonia / Q000209:etiology / Q000401:mortality; D012720:Severity of Illness Index; D013921:Thrombocytopenia / Q000209:etiology* / Q000401:mortality; D019562:Viral Load; D017201:Virus Shedding
chemical_list: D016207:Cytokines; D004815:Epidermal Growth Factor