ABSTRACT
Middle East respiratory syndrome coronavirus (MERS-CoV) shedding and antibody responses are not fully understood, particularly in relation to underlying medical conditions, clinical manifestations, and mortality. We enrolled MERS-CoV-positive patients at a hospital in Saudi Arabia and periodically collected specimens from multiple sites for real-time reverse transcription PCR and serologic testing. We conducted interviews and chart abstractions to collect clinical, epidemiologic, and laboratory information. We found that diabetes mellitus among survivors was associated with prolonged MERS-CoV RNA detection in the respiratory tract. Among case-patients who died, development of robust neutralizing serum antibody responses during the second and third week of illness was not sufficient for patient recovery or virus clearance. Fever and cough among mildly ill patients typically aligned with RNA detection in the upper respiratory tract; RNA levels peaked during the first week of illness. These findings should be considered in the development of infection control policies, vaccines, and antibody therapeutics.
Subject(s)
Antibodies, Viral/immunology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Host-Pathogen Interactions/immunology , Middle East Respiratory Syndrome Coronavirus/physiology , Adult , Aged , Antibodies, Neutralizing , Antibodies, Viral/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Female , Genes, Viral , Humans , Male , Middle Aged , Middle East Respiratory Syndrome Coronavirus/classification , Public Health Surveillance , RNA, Viral , Saudi Arabia/epidemiology , Symptom Assessment , Viral LoadABSTRACT
With more than 1,700 laboratory-confirmed infections, Middle East respiratory syndrome coronavirus (MERS-CoV) remains a significant threat for public health. However, the lack of detailed data on modes of transmission from the animal reservoir and between humans means that the drivers of MERS-CoV epidemics remain poorly characterized. Here, we develop a statistical framework to provide a comprehensive analysis of the transmission patterns underlying the 681 MERS-CoV cases detected in the Kingdom of Saudi Arabia (KSA) between January 2013 and July 2014. We assess how infections from the animal reservoir, the different levels of mixing, and heterogeneities in transmission have contributed to the buildup of MERS-CoV epidemics in KSA. We estimate that 12% [95% credible interval (CI): 9%, 15%] of cases were infected from the reservoir, the rest via human-to-human transmission in clusters (60%; CI: 57%, 63%), within (23%; CI: 20%, 27%), or between (5%; CI: 2%, 8%) regions. The reproduction number at the start of a cluster was 0.45 (CI: 0.33, 0.58) on average, but with large SD (0.53; CI: 0.35, 0.78). It was >1 in 12% (CI: 6%, 18%) of clusters but fell by approximately one-half (47% CI: 34%, 63%) its original value after 10 cases on average. The ongoing exposure of humans to MERS-CoV from the reservoir is of major concern, given the continued risk of substantial outbreaks in health care systems. The approach we present allows the study of infectious disease transmission when data linking cases to each other remain limited and uncertain.
Subject(s)
Coronavirus Infections/transmission , Animals , Disease Reservoirs , Humans , Zoonoses/transmissionABSTRACT
Saudi Arabia has reported >80% of the Middle East respiratory syndrome coronavirus (MERS-CoV) cases worldwide. During April 2015-February 2016, Saudi Arabia identified and tested 57,363 persons (18.4/10,000 residents) with suspected MERS-CoV infection; 384 (0.7%) tested positive. Robust, extensive, and timely surveillance is critical for limiting virus transmission.
Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Population Surveillance , Saudi Arabia/epidemiology , Young AdultABSTRACT
BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans. Fundamental questions about circulating viruses and transmission routes remain. METHODS: We assessed routinely collected epidemiologic data for MERS-CoV cases reported in Saudi Arabia during 1 January-30 June 2015 and conducted a more detailed investigation of cases reported during February 2015. Available respiratory specimens were obtained for sequencing. RESULTS: During the study period, 216 MERS-CoV cases were reported. Full genome (n = 17) or spike gene sequences (n = 82) were obtained from 99 individuals. Most sequences (72 of 99 [73%]) formed a discrete, novel recombinant subclade (NRC-2015), which was detected in 6 regions and became predominant by June 2015. No clinical differences were noted between clades. Among 87 cases reported during February 2015, 13 had no recognized risks for secondary acquisition; 12 of these 13 also denied camel contact. Most viruses (8 of 9) from these 13 individuals belonged to NRC-2015. DISCUSSIONS: Our findings document the spread and eventual predominance of NRC-2015 in humans in Saudi Arabia during the first half of 2015. Our identification of cases without recognized risk factors but with similar virus sequences indicates the need for better understanding of risk factors for MERS-CoV transmission.
Subject(s)
Coronavirus Infections/epidemiology , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Adult , Aged , Aged, 80 and over , Cluster Analysis , Female , Humans , Male , Middle Aged , Middle East Respiratory Syndrome Coronavirus/classification , Middle East Respiratory Syndrome Coronavirus/genetics , Molecular Epidemiology , Phylogeny , Saudi Arabia/epidemiology , Sequence Analysis, DNA , Sequence Homology , Spike Glycoprotein, Coronavirus/genetics , Young AdultSubject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Environmental Exposure , Middle East Respiratory Syndrome Coronavirus , Seasons , Animals , Camelus/virology , Coronavirus Infections/history , Coronavirus Infections/virology , Genome, Viral , History, 21st Century , Humans , Middle East Respiratory Syndrome Coronavirus/classification , Middle East Respiratory Syndrome Coronavirus/genetics , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Phylogeny , Population Surveillance , Saudi Arabia/epidemiology , Whole Genome SequencingABSTRACT
Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with a wide range of clinical presentations, from asymptomatic or mildly ill to severe respiratory illness including death. We describe isolation of infectious MERS-CoV from the upper respiratory tract of a mildly ill 27-year-old female in Saudi Arabia 15 days after illness onset.
ABSTRACT
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.