ABSTRACT
MERS-CoV, a highly pathogenic virus in humans, is associated with high morbidity and case fatality. Inflammatory responses have a significant impact on MERS-CoV pathogenesis and disease outcome. However, CD4+ T-cell induced immune responses during acute MERS-CoV infection are barely detectable, with potent inhibition of effector T cells and downregulation of antigen presentation. The local pulmonary immune response, particularly the Th1 and Th2-related immune response during acute severe MERS-CoV infection is not fully understood. In this study, we offer the first insights into the pulmonary gene expression profile of Th1 and Th2-related cytokines/chemokines (Th1 & Th2 responses) during acute MERS-CoV infection using RT2 Profiler PCR Arrays. We also quantified the expression level of primary inflammatory cytokines/chemokines. Our results showed a downregulation of Th2, inadequate (partial) Th1 immune response and high expression levels of inflammatory cytokines IL-1α and IL-1ß and the neutrophil chemoattractant chemokine IL-8 (CXCL8) in the lower respiratory tract of MERS-CoV infected patients. Moreover, we identified a high viral load in all included patients. We also observed a correlation between inflammatory cytokines, Th1, and Th2 downregulation and the case fatality rate. Th1 and Th2 response downregulation, high expression of inflammatory cytokines, and high viral load may contribute to lung inflammation, severe infection, the evolution of pneumonia and ARDS, and a higher case fatality rate. Further study of the molecular mechanisms underlying the Th1 and Th2 regulatory pathways will be vital for active vaccine development and the identification of novel therapeutic strategies.
Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/pathology , Cytokines/blood , Middle East Respiratory Syndrome Coronavirus/immunology , Th1 Cells/immunology , Th2 Cells/immunology , Adult , Aged , Aged, 80 and over , Bronchi/immunology , Bronchi/pathology , Bronchi/virology , Coronavirus Infections/mortality , Cytokines/genetics , Cytokines/immunology , Down-Regulation/genetics , Down-Regulation/immunology , Female , Humans , Immunity, Innate/genetics , Immunity, Innate/immunology , Inflammation/genetics , Inflammation/immunology , Male , Middle Aged , Viral Load , Virus Replication/immunologyABSTRACT
We characterized exposures and demographics of Middle East respiratory syndrome coronavirus cases reported to the Saudi Arabia Ministry of Health during July 1-October 31, 2017, and June 1-September 16, 2018. Molecular characterization of available specimens showed that circulating viruses during these periods continued to cluster within lineage 5.
Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Middle East Respiratory Syndrome Coronavirus , Adolescent , Adult , Aged , Aged, 80 and over , Child , Coronavirus Infections/history , Disease Outbreaks , Female , Genome, Viral , Genomics/methods , History, 21st Century , Humans , Male , Middle Aged , Middle East Respiratory Syndrome Coronavirus/classification , Middle East Respiratory Syndrome Coronavirus/genetics , Phylogeny , Population Surveillance , Saudi Arabia/epidemiology , Young AdultABSTRACT
OBJECTIVE: To investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications. DESIGN: Outbreak investigation. SETTING: Cases presented in 4 healthcare facilities in Riyadh, Saudi Arabia: a tertiary-care hospital, a specialty pulmonary hospital, an outpatient clinic, and an outpatient dialysis unit. METHODS: Contact tracing and testing were performed following reports of cases at 2 hospitals. Laboratory results were confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) and/or genome sequencing. We assessed exposures and determined seropositivity among available healthcare personnel (HCP) cases and HCP contacts of cases. RESULTS: In total, 48 cases were identified, involving patients, HCP, and family members across 2 hospitals, an outpatient clinic, and a dialysis clinic. At each hospital, transmission was linked to a unique index case. Moreover, 4 cases were associated with superspreading events (any interaction where a case patient transmitted to ≥5 subsequent case patients). All 4 of these patients were severely ill, were initially not recognized as MERS-CoV cases, and subsequently died. Genomic sequences clustered separately, suggesting 2 distinct outbreaks. Overall, 4 (24%) of 17 HCP cases and 3 (3%) of 114 HCP contacts of cases were seropositive. CONCLUSIONS: We describe 2 distinct healthcare-associated outbreaks, each initiated by a unique index case and characterized by multiple superspreading events. Delays in recognition and in subsequent implementation of control measures contributed to secondary transmission. Prompt contact tracing, repeated testing, HCP furloughing, and implementation of recommended transmission-based precautions for suspected cases ultimately halted transmission.
Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Cross Infection/transmission , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Adult , Aged , Aged, 80 and over , Base Sequence , Contact Tracing , Cross Infection/epidemiology , Cross Infection/virology , Disease Outbreaks , Female , Health Personnel , Humans , Infection Control/methods , Male , Middle Aged , Middle East Respiratory Syndrome Coronavirus/genetics , RNA, Viral/genetics , Saudi Arabia/epidemiologyABSTRACT
During July-August 2015, the number of cases of Middle East respiratory syndrome (MERS) reported from Saudi Arabia increased dramatically. We reviewed the 143 confirmed cases from this period and classified each based upon likely transmission source. We found that the surge in cases resulted predominantly (90%) from secondary transmission largely attributable to an outbreak at a single healthcare facility in Riyadh. Genome sequencing of MERS coronavirus from 6 cases demonstrated continued circulation of the recently described recombinant virus. A single unique frameshift deletion in open reading frame 5 was detected in the viral sequence from 1 case.