Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission - PubMed [Internet]. [cited 2022 May 9]. Available from: https://pubmed.ncbi.nlm.nih.gov/29680581/
Healthcare worker exposure to Middle East respiratory syndrome coronavirus (MERS-CoV): Revision of screening strategies urgently needed - PubMed [Internet]. [cited 2022 May 9]. Available from: https://pubmed.ncbi.nlm.nih.gov/29649550/
Sarah H Alfaraj, Jaffar A Al-Tawfiq, Talal A Altuwaijri, Marzouqa Alanazi, Nojoom Alzahrani, Ziad A Memish
Middle East respiratory syndrome coronavirus transmission among health care workers: Implication for infection control.
Am J Infect Control. 2018 Feb;46(2):165-168. doi: 10.1016/j.ajic.2017.08.010. Epub 2017 Sep 25.
Abstract/Text
BACKGROUND: Many outbreaks of Middle East respiratory syndrome coronavirus (MERS-CoV) have occurred in health care settings and involved health care workers (HCWs). We describe the occurrence of an outbreak among HCWs and attempt to characterize at-risk exposures to improve future infection control interventions.
METHODS: This study included an index case and all HCW contacts. All contacts were screened for MERS-CoV using polymerase chain reaction.
RESULTS: During the study period in 2015, the index case was a 30-year-old Filipino nurse who had a history of unprotected exposure to a MERS-CoV-positive case on May 15, 2015, and had multiple negative tests for MERS-CoV. Weeks later, she was diagnosed with pulmonary tuberculosis and MERS-CoV infection. A total of 73 staff were quarantined for 14 days, and nasopharyngeal swabs were taken on days 2, 5, and 12 postexposure. Of those contacts, 3 (4%) were confirmed positive for MERS-CoV. An additional 18 staff were quarantined and had MERS-CoV swabs. A fourth case was confirmed positive on day 12. Subsequent contact investigations revealed a fourth-generation transmission. Only 7 (4.5%) of the total 153 contacts were positive for MERS-CoV.
CONCLUSIONS: The role of HCWs in MERS-CoV transmission is complex. Although most MERS-CoV-infected HCWs are asymptomatic or have mild disease, fatal infections can occur and HCWs can play a major role in propagating health care facility outbreaks. This investigation highlights the need to continuously review infection control guidance relating to the role of HCWs in MERS-CoV transmission in health care outbreaks, especially as it relates to the complex questions on definition of risky exposures, who to test, and the frequency of MERS-CoV testing; criteria for who to quarantine and for how long; and clearance and return to active duty criteria.
Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
Esam I Azhar, Anwar M Hashem, Sherif A El-Kafrawy, Sayed Sartaj Sohrab, Asad S Aburizaiza, Suha A Farraj, Ahmed M Hassan, Muneera S Al-Saeed, Ghazi A Jamjoom, Tariq A Madani
Detection of the Middle East respiratory syndrome coronavirus genome in an air sample originating from a camel barn owned by an infected patient.
MBio. 2014 Jul 22;5(4):e01450-14. doi: 10.1128/mBio.01450-14. Epub 2014 Jul 22.
Abstract/Text
Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel betacoronavirus that has been circulating in the Arabian Peninsula since 2012 and causing severe respiratory infections in humans. While bats were suggested to be involved in human MERS-CoV infections, a direct link between bats and MERS-CoV is uncertain. On the other hand, serological and virological data suggest dromedary camels as the potential animal reservoirs of MERS-CoV. Recently, we isolated MERS-CoV from a camel and its infected owner and provided evidence for the direct transmission of MERS-CoV from the infected camel to the patient. Here, we extend this work and show that identical MERS-CoV RNA fragments were detected in an air sample collected from the same barn that sheltered the infected camel in our previous study. These data indicate that the virus was circulating in this farm concurrently with its detection in the camel and in the patient, which warrants further investigations for the possible airborne transmission of MERS-CoV. Importance: This work clearly highlights the importance of continuous surveillance and infection control measures to control the global public threat of MERS-CoV. While current MERS-CoV transmission appears to be limited, we advise minimal contact with camels, especially for immunocompromised individuals, and the use of appropriate health, safety, and infection prevention and control measures when dealing with infected patients. Also, detailed clinical histories of any MERS-CoV cases with epidemiological and laboratory investigations carried out for any animal exposure must be considered to identify any animal source.
Copyright © 2014 Azhar et al.
厚生労働省健康局結核感染症課：健感発0707第2号 平成29年7月7日. 中東呼吸器症候群（MERS）の国内発生時の対応について. Available from: http://idsc.tokyo-eiken.go.jp/assets/diseases/medical/notice/170707_1.pdf?20181122
Health Protection Agency (HPA) UK Novel Coronavirus Investigation team
Evidence of person-to-person transmission within a family cluster of novel coronavirus infections, United Kingdom, February 2013.
Euro Surveill. 2013 Mar 14;18(11):20427. Epub 2013 Mar 14.
Abstract/Text
In February 2013, novel coronavirus (nCoV) infection was diagnosed in an adult male in the United Kingdom with severe respiratory illness, who had travelled to Pakistan and Saudi Arabia 10 days before symptom onset. Contact tracing identified two secondary cases among family members without recent travel: one developed severe respiratory illness and died, the other an influenza-like illness. No other severe cases were identified or nCoV detected in respiratory samples among 135 contacts followed for 10 days.
Benoit Guery, Julien Poissy, Loubna el Mansouf, Caroline Séjourné, Nicolas Ettahar, Xavier Lemaire, Fanny Vuotto, Anne Goffard, Sylvie Behillil, Vincent Enouf, Valérie Caro, Alexandra Mailles, Didier Che, Jean-Claude Manuguerra, Daniel Mathieu, Arnaud Fontanet, Sylvie van der Werf, MERS-CoV study group
Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission.
Lancet. 2013 Jun 29;381(9885):2265-72. doi: 10.1016/S0140-6736(13)60982-4. Epub 2013 May 30.
Abstract/Text
BACKGROUND: Human infection with a novel coronavirus named Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia and the Middle East in September, 2012, with 44 laboratory-confirmed cases as of May 23, 2013. We report detailed clinical and virological data for two related cases of MERS-CoV disease, after nosocomial transmission of the virus from one patient to another in a French hospital.
METHODS: Patient 1 visited Dubai in April, 2013; patient 2 lives in France and did not travel abroad. Both patients had underlying immunosuppressive disorders. We tested specimens from the upper (nasopharyngeal swabs) or the lower (bronchoalveolar lavage, sputum) respiratory tract and whole blood, plasma, and serum specimens for MERS-CoV by real-time RT-PCR targeting the upE and Orf1A genes of MERS-CoV.
FINDINGS: Initial clinical presentation included fever, chills, and myalgia in both patients, and for patient 1, diarrhoea. Respiratory symptoms rapidly became predominant with acute respiratory failure leading to mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Both patients developed acute renal failure. MERS-CoV was detected in lower respiratory tract specimens with high viral load (eg, cycle threshold [Ct] values of 22·9 for upE and 24 for Orf1a for a bronchoalveolar lavage sample from patient 1; Ct values of 22·5 for upE and 23·9 for Orf1a for an induced sputum sample from patient 2), whereas nasopharyngeal specimens were weakly positive or inconclusive. The two patients shared the same room for 3 days. The incubation period was estimated at 9-12 days for the second case. No secondary transmission was documented in hospital staff despite the absence of specific protective measures before the diagnosis of MERS-CoV was suspected. Patient 1 died on May 28, due to refractory multiple organ failure.
INTERPRETATION: Patients with respiratory symptoms returning from the Middle East or exposed to a confirmed case should be isolated and investigated for MERS-CoV with lower respiratory tract sample analysis and an assumed incubation period of 12 days. Immunosuppression should also be taken into account as a risk factor.
FUNDING: French Institute for Public Health Surveillance, ANR grant Labex Integrative Biology of Emerging Infectious Diseases, and the European Community's Seventh Framework Programme projects EMPERIE and PREDEMICS.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Korea Centers for Disease Control and Prevention
Middle East Respiratory Syndrome Coronavirus Outbreak in the Republic of Korea, 2015.
Osong Public Health Res Perspect. 2015 Aug;6(4):269-78. doi: 10.1016/j.phrp.2015.08.006. Epub 2015 Sep 5.
Abstract/Text
OBJECTIVES: The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the Republic of Korea started from the index case who developed fever after returning from the Middle East. He infected 26 cases in Hospital C, and consecutive nosocomial transmission proceeded throughout the nation. We provide an epidemiologic description of the outbreak, as of July 2015.
METHODS: Epidemiological research was performed by direct interview of the confirmed patients and reviewing medical records. We also analyzed the incubation period, serial interval, the characteristics of superspreaders, and factors associated with mortality. Full genome sequence was obtained from sputum specimens of the index patient.
RESULTS: A total of 186 confirmed patients with MERS-CoV infection across 16 hospitals were identified in the Republic of Korea. Some 44.1% of the cases were patients exposed in hospitals, 32.8% were caregivers, and 13.4% were healthcare personnel. The most common presenting symptom was fever and chills. The estimated incubation period was 6.83 days and the serial interval was 12.5 days. A total of 83.2% of the transmission events were epidemiologically linked to five superspreaders, all of whom had pneumonia at presentation and contacted hundreds of people. Older age [odds ratio (OR) = 4.86, 95% confidence interval (CI) 1.90-12.45] and underlying respiratory disease (OR = 4.90, 95% CI 1.64-14.65) were significantly associated with mortality. Phylogenetic analysis showed that the MERS-CoV of the index case clustered closest with a recent virus from Riyadh, Saudi Arabia.
CONCLUSION: A single imported MERS-CoV infection case imposed a huge threat to public health and safety. This highlights the importance of robust preparedness and optimal infection prevention control. The lessons learned from the current outbreak will contribute to more up-to-date guidelines and global health security.
Sung-Han Kim, So Young Chang, Minki Sung, Ji Hoon Park, Hong Bin Kim, Heeyoung Lee, Jae-Phil Choi, Won Suk Choi, Ji-Young Min
Extensive Viable Middle East Respiratory Syndrome (MERS) Coronavirus Contamination in Air and Surrounding Environment in MERS Isolation Wards.
Clin Infect Dis. 2016 Aug 1;63(3):363-9. doi: 10.1093/cid/ciw239. Epub 2016 Apr 18.
Abstract/Text
BACKGROUND: The largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) outside the Middle East occurred in South Korea in 2015 and resulted in 186 laboratory-confirmed infections, including 36 (19%) deaths. Some hospitals were considered epicenters of infection and voluntarily shut down most of their operations after nearly half of all transmissions occurred in hospital settings. However, the ways that MERS-CoV is transmitted in healthcare settings are not well defined.
METHODS: We explored the possible contribution of contaminated hospital air and surfaces to MERS transmission by collecting air and swabbing environmental surfaces in 2 hospitals treating MERS-CoV patients. The samples were tested by viral culture with reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence assay (IFA) using MERS-CoV Spike antibody, and electron microscopy (EM).
RESULTS: The presence of MERS-CoV was confirmed by RT-PCR of viral cultures of 4 of 7 air samples from 2 patients' rooms, 1 patient's restroom, and 1 common corridor. In addition, MERS-CoV was detected in 15 of 68 surface swabs by viral cultures. IFA on the cultures of the air and swab samples revealed the presence of MERS-CoV. EM images also revealed intact particles of MERS-CoV in viral cultures of the air and swab samples.
CONCLUSIONS: These data provide experimental evidence for extensive viable MERS-CoV contamination of the air and surrounding materials in MERS outbreak units. Thus, our findings call for epidemiologic investigation of the possible scenarios for contact and airborne transmission, and raise concern regarding the adequacy of current infection control procedures.
© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
Sun Young Cho, Ji-Man Kang, Young Eun Ha, Ga Eun Park, Ji Yeon Lee, Jae-Hoon Ko, Ji Yong Lee, Jong Min Kim, Cheol-In Kang, Ik Joon Jo, Jae Geum Ryu, Jong Rim Choi, Seonwoo Kim, Hee Jae Huh, Chang-Seok Ki, Eun-Suk Kang, Kyong Ran Peck, Hun-Jong Dhong, Jae-Hoon Song, Doo Ryeon Chung, Yae-Jean Kim
MERS-CoV outbreak following a single patient exposure in an emergency room in South Korea: an epidemiological outbreak study.
Lancet. 2016 Sep 3;388(10048):994-1001. doi: 10.1016/S0140-6736(16)30623-7. Epub 2016 Jul 9.
Abstract/Text
BACKGROUND: In 2015, a large outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred following a single patient exposure in an emergency room at the Samsung Medical Center, a tertiary-care hospital in Seoul, South Korea. We aimed to investigate the epidemiology of MERS-CoV outbreak in our hospital.
METHODS: We identified all patients and health-care workers who had been in the emergency room with the index case between May 27 and May 29, 2015. Patients were categorised on the basis of their exposure in the emergency room: in the same zone as the index case (group A), in different zones except for overlap at the registration area or the radiology suite (group B), and in different zones (group C). We documented cases of MERS-CoV infection, confirmed by real-time PCR testing of sputum samples. We analysed attack rates, incubation periods of the virus, and risk factors for transmission.
FINDINGS: 675 patients and 218 health-care workers were identified as contacts. MERS-CoV infection was confirmed in 82 individuals (33 patients, eight health-care workers, and 41 visitors). The attack rate was highest in group A (20% [23/117] vs 5% [3/58] in group B vs 1% [4/500] in group C; p<0·0001), and was 2% (5/218) in health-care workers. After excluding nine cases (because of inability to determine the date of symptom onset in six cases and lack of data from three visitors), the median incubation period was 7 days (range 2-17, IQR 5-10). The median incubation period was significantly shorter in group A than in group C (5 days [IQR 4-8] vs 11 days [6-12]; p<0·0001). There were no confirmed cases in patients and visitors who visited the emergency room on May 29 and who were exposed only to potentially contaminated environment without direct contact with the index case. The main risk factor for transmission of MERS-CoV was the location of exposure.
INTERPRETATION: Our results showed increased transmission potential of MERS-CoV from a single patient in an overcrowded emergency room and provide compelling evidence that health-care facilities worldwide need to be prepared for emerging infectious diseases.
FUNDING: None.
Copyright © 2016 Elsevier Ltd. All rights reserved.
Myoung-Don Oh, Wan Beom Park, Pyoeng Gyun Choe, Su-Jin Choi, Jong-Il Kim, Jeesoo Chae, Sung Sup Park, Eui-Chong Kim, Hong Sang Oh, Eun Jung Kim, Eun Young Nam, Sun Hee Na, Dong Ki Kim, Sang-Min Lee, Kyoung-Ho Song, Ji Hwan Bang, Eu Suk Kim, Hong Bin Kim, Sang Won Park, Nam Joong Kim
Viral Load Kinetics of MERS Coronavirus Infection.
N Engl J Med. 2016 Sep 29;375(13):1303-5. doi: 10.1056/NEJMc1511695.
Abstract/Text
WPRO. Case of imported MERS reported in Republic of Korea. Available from: https://www.who.int/westernpacific/news/detail/09-09-2018-case-of-imported-mers-reported-in-republic-of-korea#
Moran Ki
2015 MERS outbreak in Korea: hospital-to-hospital transmission.
Epidemiol Health. 2015;37:e2015033. doi: 10.4178/epih/e2015033. Epub 2015 Jul 21.
Abstract/Text
The distinct characteristic of the Middle East Respiratory Syndrome (MERS) outbreak in South Korea is that it not only involves intra-hospital transmission, but it also involves hospital-to-hospital transmission. It has been the largest MERS outbreak outside the Middle East, with 186 confirmed cases and, among them, 36 fatal cases as of July 26, 2015. All confirmed cases are suspected to be hospital-acquired infections except one case of household transmission and two cases still undergoing examination. The Korean health care system has been the major factor shaping the unique characteristics of the outbreak. Taking this as an opportunity, the Korean government should carefully assess the fundamental problems of the vulnerability to hospital infection and make short- as well as long-term plans for countermeasures. In addition, it is hoped that this journal, Epidemiology and Health, becomes a place where various topics regarding MERS can be discussed and shared.
Kyung Min Kim, Moran Ki, Sung-Il Cho, Minki Sung, Jin Kwan Hong, Hae-Kwan Cheong, Jong-Hun Kim, Sang-Eun Lee, Changhwan Lee, Keon-Joo Lee, Yong-Shik Park, Seung Woo Kim, Bo Youl Choi
Epidemiologic features of the first MERS outbreak in Korea: focus on Pyeongtaek St. Mary's Hospital.
Epidemiol Health. 2015;37:e2015041. doi: 10.4178/epih/e2015041. Epub 2015 Sep 17.
Abstract/Text
OBJECTIVES: This study investigated the epidemiologic features of the confirmed cases of Middle East Respiratory Syndrome (MERS) in Pyeongtaek St. Mary's Hospital, where the outbreak first began, in order to identify lessons relevant for the prevention and control of future outbreaks.
METHODS: The patients' clinical symptoms and test results were collected from their medical records. The caregivers of patients were identified by phone calls.
RESULTS: After patient zero (case #1) was admitted to Pyeongtaek St. Mary's Hospital (May 15-May 17), an outbreak occurred, with 36 cases between May 18 and June 4, 2015. Six patients died (fatality rate, 16.7%). Twenty-six cases occurred in the first-generation, and 10 in the second-generation. The median incubation period was five days, while the median period from symptom onset to death was 12.5 days. While the total attack rate was 3.9%, the attack rate among inpatients was 7.6%, and the inpatients on the eighth floor, where patient zero was hospitalized, had an 18.6% attack rate. In contrast, caregivers and medical staff showed attack rates of 3.3% and 1.1%, respectively.
CONCLUSIONS: The attack rates were higher than those of the previous outbreaks in other countries. The outbreak spread beyond Pyeongtaek St. Mary's Hospital when four of the patients were moved to other hospitals without appropriate quarantine. The best method of preventing future outbreaks is to overcome the vulnerabilities observed in this outbreak, such as ward crowding, patient migration without appropriate data sharing, and the lack of an initial broad quarantine.
K H Kim, T E Tandi, J W Choi, J M Moon, M S Kim
Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health implications.
J Hosp Infect. 2017 Feb;95(2):207-213. doi: 10.1016/j.jhin.2016.10.008. Epub 2016 Oct 14.
Abstract/Text
BACKGROUND: Since the first case of Middle East respiratory syndrome coronavirus (MERS-CoV) in South Korea was reported on 20th May 2015, there have been 186 confirmed cases, 38 deaths and 16,752 suspected cases. Previously published research on South Korea's MERS outbreak was limited to the early stages, when few data were available. Now that the outbreak has ended, albeit unofficially, a more comprehensive review is appropriate.
METHODS: Data were obtained through the MERS portal by the Ministry for Health and Welfare (MOHW) and Korea Centres for Disease Control and Prevention, press releases by MOHW, and reports by the MERS Policy Committee of the Korean Medical Association. Cases were analysed for general characteristics, exposure source, timeline and infection generation. Sex, age and underlying diseases were analysed for the 38 deaths.
FINDINGS: Beginning with the index case that infected 28 others, an in-depth analysis was conducted. The average age was 55 years, which was a little higher than the global average of 50 years. As in most other countries, more men than women were affected. The case fatality rate was 19.9%, which was lower than the global rate of 38.7% and the rate in Saudi Arabia (36.5%). In total, 184 patients were infected nosocomially and there were no community-acquired infections. The main underlying diseases were respiratory diseases, cancer and hypertension. The main contributors to the outbreak were late diagnosis, quarantine failure of 'super spreaders', familial care-giving and visiting, non-disclosure by patients, poor communication by the South Korean Government, inadequate hospital infection management, and 'doctor shopping'. The outbreak was entirely nosocomial, and was largely attributable to infection management and policy failures, rather than biomedical factors.
Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
Yaseen M Arabi, Hanan H Balkhy, Frederick G Hayden, Abderrezak Bouchama, Thomas Luke, J Kenneth Baillie, Awad Al-Omari, Ali H Hajeer, Mikiko Senga, Mark R Denison, Jonathan S Nguyen-Van-Tam, Nahoko Shindo, Alison Bermingham, James D Chappell, Maria D Van Kerkhove, Robert A Fowler
Middle East Respiratory Syndrome.
N Engl J Med. 2017 Feb 9;376(6):584-594. doi: 10.1056/NEJMsr1408795.
Abstract/Text
Abdullah Assiri, Allison McGeer, Trish M Perl, Connie S Price, Abdullah A Al Rabeeah, Derek A T Cummings, Zaki N Alabdullatif, Maher Assad, Abdulmohsen Almulhim, Hatem Makhdoom, Hossam Madani, Rafat Alhakeem, Jaffar A Al-Tawfiq, Matthew Cotten, Simon J Watson, Paul Kellam, Alimuddin I Zumla, Ziad A Memish, KSA MERS-CoV Investigation Team
Hospital outbreak of Middle East respiratory syndrome coronavirus.
N Engl J Med. 2013 Aug 1;369(5):407-16. doi: 10.1056/NEJMoa1306742. Epub 2013 Jun 19.
Abstract/Text
BACKGROUND: In September 2012, the World Health Organization reported the first cases of pneumonia caused by the novel Middle East respiratory syndrome coronavirus (MERS-CoV). We describe a cluster of health care-acquired MERS-CoV infections.
METHODS: Medical records were reviewed for clinical and demographic information and determination of potential contacts and exposures. Case patients and contacts were interviewed. The incubation period and serial interval (the time between the successive onset of symptoms in a chain of transmission) were estimated. Viral RNA was sequenced.
RESULTS: Between April 1 and May 23, 2013, a total of 23 cases of MERS-CoV infection were reported in the eastern province of Saudi Arabia. Symptoms included fever in 20 patients (87%), cough in 20 (87%), shortness of breath in 11 (48%), and gastrointestinal symptoms in 8 (35%); 20 patients (87%) presented with abnormal chest radiographs. As of June 12, a total of 15 patients (65%) had died, 6 (26%) had recovered, and 2 (9%) remained hospitalized. The median incubation period was 5.2 days (95% confidence interval [CI], 1.9 to 14.7), and the serial interval was 7.6 days (95% CI, 2.5 to 23.1). A total of 21 of the 23 cases were acquired by person-to-person transmission in hemodialysis units, intensive care units, or in-patient units in three different health care facilities. Sequencing data from four isolates revealed a single monophyletic clade. Among 217 household contacts and more than 200 health care worker contacts whom we identified, MERS-CoV infection developed in 5 family members (3 with laboratory-confirmed cases) and in 2 health care workers (both with laboratory-confirmed cases).
CONCLUSIONS: Person-to-person transmission of MERS-CoV can occur in health care settings and may be associated with considerable morbidity. Surveillance and infection-control measures are critical to a global public health response.
Ziad A Memish, Jaffar A Al-Tawfiq, Hatem Q Makhdoom, Abdullah Assiri, Raafat F Alhakeem, Ali Albarrak, Sarah Alsubaie, Abdullah A Al-Rabeeah, Waleed H Hajomar, Raheela Hussain, Ali M Kheyami, Abdullah Almutairi, Esam I Azhar, Christian Drosten, Simon J Watson, Paul Kellam, Matthew Cotten, Alimuddin Zumla
Respiratory tract samples, viral load, and genome fraction yield in patients with Middle East respiratory syndrome.
J Infect Dis. 2014 Nov 15;210(10):1590-4. doi: 10.1093/infdis/jiu292. Epub 2014 May 15.
Abstract/Text
BACKGROUND: Analysis of clinical samples from patients with new viral infections is critical to confirm the diagnosis, to specify the viral load, and to sequence data necessary for characterizing the viral kinetics, transmission, and evolution. We analyzed samples from 112 patients infected with the recently discovered Middle East respiratory syndrome coronavirus (MERS-CoV).
METHODS: Respiratory tract samples from cases of MERS-CoV infection confirmed by polymerase chain reaction (PCR) were investigated to determine the MERS-CoV load and fraction of the MERS-CoV genome. These values were analyzed to determine associations with clinical sample type.
RESULTS: Samples from 112 individuals in which MERS-CoV was detected by PCR were analyzed, of which 13 were sputum samples, 64 were nasopharyngeal swab specimens, 30 were tracheal aspirates, and 3 were bronchoalveolar lavage specimens; 2 samples were of unknown origin. Tracheal aspirates yielded significantly higher MERS-CoV loads, compared with nasopharyngeal swab specimens (P = .005) and sputum specimens (P = .0001). Tracheal aspirates had viral loads similar to those in bronchoalveolar lavage samples (P = .3079). Bronchoalveolar lavage samples and tracheal aspirates had significantly higher genome fraction than nasopharyngeal swab specimens (P = .0095 and P = .0002, respectively) and sputum samples (P = .0009 and P = .0001, respectively). The genome yield from tracheal aspirates and bronchoalveolar lavage samples were similar (P = .1174).
CONCLUSIONS: Lower respiratory tract samples yield significantly higher MERS-CoV loads and genome fractions than upper respiratory tract samples.
© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Jaffar A Al-Tawfiq, Kareem Hinedi, Jihad Ghandour, Hanan Khairalla, Samir Musleh, Alaa Ujayli, Ziad A Memish
Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients.
Clin Infect Dis. 2014 Jul 15;59(2):160-5. doi: 10.1093/cid/ciu226. Epub 2014 Apr 9.
Abstract/Text
BACKGROUND: There is a paucity of data regarding the differentiating characteristics of patients with laboratory-confirmed and those negative for Middle East respiratory syndrome coronavirus (MERS-CoV).
METHODS: This is a hospital-based case-control study comparing MERS-CoV-positive patients (cases) with MERS-CoV-negative controls.
RESULTS: A total of 17 case patients and 82 controls with a mean age of 60.7 years and 57 years, respectively (P = .553), were included. No statistical differences were observed in relation to sex, the presence of a fever or cough, and the presence of a single or multilobar infiltrate on chest radiography. The case patients were more likely to be overweight than the control group (mean body mass index, 32 vs 27.8; P = .035), to have diabetes mellitus (87% vs 47%; odds ratio [OR], 7.24; P = .015), and to have end-stage renal disease (33% vs 7%; OR, 7; P = .012). At the time of admission, tachypnea (27% vs 60%; OR, 0.24; P = .031) and respiratory distress (15% vs 51%; OR, 0.15; P = .012) were less frequent among case patients. MERS-CoV patients were more likely to have a normal white blood cell count than the control group (82% vs 52%; OR, 4.33; P = .029). Admission chest radiography with interstitial infiltrates was more frequent in case patients than in controls (67% vs 20%; OR, 8.13; P = .001). Case patients were more likely to be admitted to the intensive care unit (53% vs 20%; OR, 4.65; P = .025) and to have a high mortality rate (76% vs 15%; OR, 18.96; P < .001).
CONCLUSIONS: Few clinical predictors could enhance the ability to predict which patients with pneumonia would have MERS-CoV. However, further prospective analysis and matched case-control studies may shed light on other predictors of infection.
© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Jacqui Wise
Patient with new strain of coronavirus is treated in intensive care at London hospital.
BMJ. 2012 Sep 24;345:e6455. doi: 10.1136/bmj.e6455. Epub 2012 Sep 24.
Abstract/Text
Abdullah Assiri, Jaffar A Al-Tawfiq, Abdullah A Al-Rabeeah, Fahad A Al-Rabiah, Sami Al-Hajjar, Ali Al-Barrak, Hesham Flemban, Wafa N Al-Nassir, Hanan H Balkhy, Rafat F Al-Hakeem, Hatem Q Makhdoom, Alimuddin I Zumla, Ziad A Memish
Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study.
Lancet Infect Dis. 2013 Sep;13(9):752-61. doi: 10.1016/S1473-3099(13)70204-4. Epub 2013 Jul 26.
Abstract/Text
BACKGROUND: Middle East respiratory syndrome (MERS) is a new human disease caused by a novel coronavirus (CoV). Clinical data on MERS-CoV infections are scarce. We report epidemiological, demographic, clinical, and laboratory characteristics of 47 cases of MERS-CoV infections, identify knowledge gaps, and define research priorities.
METHODS: We abstracted and analysed epidemiological, demographic, clinical, and laboratory data from confirmed cases of sporadic, household, community, and health-care-associated MERS-CoV infections reported from Saudi Arabia between Sept 1, 2012, and June 15, 2013. Cases were confirmed as having MERS-CoV by real-time RT-PCR.
FINDINGS: 47 individuals (46 adults, one child) with laboratory-confirmed MERS-CoV disease were identified; 36 (77%) were male (male:female ratio 3·3:1). 28 patients died, a 60% case-fatality rate. The case-fatality rate rose with increasing age. Only two of the 47 cases were previously healthy; most patients (45 [96%]) had underlying comorbid medical disorders, including diabetes (32 [68%]), hypertension (16 [34%]), chronic cardiac disease (13 [28%]), and chronic renal disease (23 [49%]). Common symptoms at presentation were fever (46 [98%]), fever with chills or rigors (41 [87%]), cough (39 [83%]), shortness of breath (34 [72%]), and myalgia (15 [32%]). Gastrointestinal symptoms were also frequent, including diarrhoea (12 [26%]), vomiting (ten [21%]), and abdominal pain (eight [17%]). All patients had abnormal findings on chest radiography, ranging from subtle to extensive unilateral and bilateral abnormalities. Laboratory analyses showed raised concentrations of lactate dehydrogenase (23 [49%]) and aspartate aminotransferase (seven [15%]) and thrombocytopenia (17 [36%]) and lymphopenia (16 [34%]).
INTERPRETATION: Disease caused by MERS-CoV presents with a wide range of clinical manifestations and is associated with substantial mortality in admitted patients who have medical comorbidities. Major gaps in our knowledge of the epidemiology, community prevalence, and clinical spectrum of infection and disease need urgent definition.
FUNDING: None.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Maimuna S Majumder, Sheryl A Kluberg, Sumiko R Mekaru, John S Brownstein
Mortality Risk Factors for Middle East Respiratory Syndrome Outbreak, South Korea, 2015.
Emerg Infect Dis. 2015 Nov;21(11):2088-90. doi: 10.3201/eid2111.151231.
Abstract/Text
As of July 15, 2015, the South Korean Ministry of Health and Welfare had reported 186 case-patients with Middle East respiratory syndrome in South Korea. For 159 case-patients with known outcomes and complete case histories, we found that older age and preexisting concurrent health conditions were risk factors for death.
Ali S Omrani, Mustafa M Saad, Kamran Baig, Abdelkarim Bahloul, Mohammed Abdul-Matin, Amal Y Alaidaroos, Ghaleb A Almakhlafi, Mohammed M Albarrak, Ziad A Memish, Ali M Albarrak
Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study.
Lancet Infect Dis. 2014 Nov;14(11):1090-5. doi: 10.1016/S1473-3099(14)70920-X. Epub 2014 Sep 29.
Abstract/Text
BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with high mortality and has no approved antiviral therapy. We aimed to compare ribavirin and interferon alfa-2a treatment for patients with severe MERS-CoV infection with a supportive therapy only.
METHODS: In this retrospective cohort study, we included adults (aged ≥16 years) with laboratory-confirmed MERS-CoV infection and pneumonia needing ventilation support, diagnosed between Oct 23, 2012, and May 1, 2014, at the Prince Sultan Military Medical City (Riyadh, Saudi Arabia). All patients received appropriate supportive care and regular clinical and laboratory monitoring, but patients diagnosed after Sept 16, 2013, were also given oral ribavirin (dose based on calculated creatinine clearance, for 8-10 days) and subcutaneous pegylated interferon alfa-2a (180 μg per week for 2 weeks). The primary endpoint was 14-day and 28-day survival from the date of MERS-CoV infection diagnosis. We used χ(2) and Fischer's exact test to analyse categorical variables and the t test to analyse continuous variables.
FINDINGS: We analysed 20 patients who received ribavirin and interferon (treatment group; initiated a median of 3 days [range 0-8] after diagnosis) and 24 who did not (comparator group). Baseline clinical and laboratory characteristics were similar between groups, apart from baseline absolute neutrophil count, which was significantly lower in the comparator group (5·88 × 10(9)/L [SD 3·95] vs 9·88 × 10(9)/L [6·63]; p=0·023). 14 (70%) of 20 patients in the treatment group had survived after 14 days, compared with seven (29%) of 24 in the comparator group (p=0·004). After 28 days, six (30%) of 20 and four (17%) of 24, respectively, had survived (p=0·54). Adverse effects were similar between groups, apart from reduction in haemoglobin, which was significantly greater in the treatment group than in the comparator group (4·32 g/L [SD 2·47] vs 2·14 g/L [1·90]; p=0·002).
INTERPRETATION: In patients with severe MERS-CoV infection, ribavirin and interferon alfa-2a therapy is associated with significantly improved survival at 14 days, but not at 28 days. Further assessment in appropriately designed randomised trials is recommended.
FUNDING: None.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Jaffar A Al-Tawfiq, Hisham Momattin, Jean Dib, Ziad A Memish
Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study.
Int J Infect Dis. 2014 Mar;20:42-6. doi: 10.1016/j.ijid.2013.12.003. Epub 2014 Jan 6.
Abstract/Text
BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) has been reported to have a high case-fatality rate. Currently, there is no specific therapy or vaccine with proven effectiveness for MERS-CoV infections.
METHODS: A combination of ribavirin and interferon therapy was used for the treatment of five MERS-CoV-positive patients. We reviewed the therapeutic schedule and the outcome of these patients.
RESULTS: All patients were critically ill with acute respiratory distress syndrome treated with adjunctive corticosteroids and were on mechanical ventilation at the time of initiation of therapy. The median time from admission to therapy with ribavirin and interferon was 19 (range 10-22) days. None of the patients responded to the supportive or therapeutic interventions and all died of their illness.
CONCLUSIONS: While ribavirin and interferon may be effective in some patients, our practical experience suggests that critically ill patients with multiple comorbidities who are diagnosed late in the course of their illness may not benefit from combination antiviral therapy as preclinical data suggest. There is clearly an urgent need for a novel effective antiviral therapy for this emerging global threat.
Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Minal Kapoor, Kimberly Pringle, Alan Kumar, Stephanie Dearth, Lixia Liu, Judith Lovchik, Omar Perez, Pam Pontones, Shawn Richards, Jaime Yeadon-Fagbohun, Lucy Breakwell, Nora Chea, Nicole J Cohen, Eileen Schneider, Dean Erdman, Lia Haynes, Mark Pallansch, Ying Tao, Suxiang Tong, Susan Gerber, David Swerdlow, Daniel R Feikin
Clinical and laboratory findings of the first imported case of Middle East respiratory syndrome coronavirus to the United States.
Clin Infect Dis. 2014 Dec 1;59(11):1511-8. doi: 10.1093/cid/ciu635. Epub 2014 Aug 6.
Abstract/Text
BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) was discovered September 2012 in the Kingdom of Saudi Arabia (KSA). The first US case of MERS-CoV was confirmed on 2 May 2014.
METHODS: We summarize the clinical symptoms and signs, laboratory and radiologic findings, and MERS-CoV-specific tests.
RESULTS: The patient is a 65-year-old physician who worked in a hospital in KSA where MERS-CoV patients were treated. His illness onset included malaise, myalgias, and low-grade fever. He flew to the United States on day of illness (DOI) 7. His first respiratory symptom, a dry cough, developed on DOI 10. On DOI 11, he presented to an Indiana hospital as dyspneic, hypoxic, and with a right lower lobe infiltrate on chest radiography. On DOI 12, his serum tested positive by real-time reverse transcription polymerase chain reaction (rRT-PCR) for MERS-CoV and showed high MERS-CoV antibody titers, whereas his nasopharyngeal swab was rRT-PCR negative. Expectorated sputum was rRT-PCR positive the following day, with a high viral load (5.31 × 10(6) copies/mL). He was treated with antibiotics, intravenous immunoglobulin, and oxygen by nasal cannula. He was discharged on DOI 22. The genome sequence was similar (>99%) to other known MERS-CoV sequences, clustering with those from KSA from June to July 2013.
CONCLUSIONS: This patient had a prolonged nonspecific prodromal illness before developing respiratory symptoms. Both sera and sputum were rRT-PCR positive when nasopharyngeal specimens were negative. US clinicians must be vigilant for MERS-CoV in patients with febrile and/or respiratory illness with recent travel to the Arabian Peninsula, especially among healthcare workers.
Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Karuppiah Muthumani, Darryl Falzarano, Emma L Reuschel, Colleen Tingey, Seleeke Flingai, Daniel O Villarreal, Megan Wise, Ami Patel, Abdullah Izmirly, Abdulelah Aljuaid, Alecia M Seliga, Geoff Soule, Matthew Morrow, Kimberly A Kraynyak, Amir S Khan, Dana P Scott, Friederike Feldmann, Rachel LaCasse, Kimberly Meade-White, Atsushi Okumura, Kenneth E Ugen, Niranjan Y Sardesai, J Joseph Kim, Gary Kobinger, Heinz Feldmann, David B Weiner
A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates.
Sci Transl Med. 2015 Aug 19;7(301):301ra132. doi: 10.1126/scitranslmed.aac7462.
Abstract/Text
First identified in 2012, Middle East respiratory syndrome (MERS) is caused by an emerging human coronavirus, which is distinct from the severe acute respiratory syndrome coronavirus (SARS-CoV), and represents a novel member of the lineage C betacoronoviruses. Since its identification, MERS coronavirus (MERS-CoV) has been linked to more than 1372 infections manifesting with severe morbidity and, often, mortality (about 495 deaths) in the Arabian Peninsula, Europe, and, most recently, the United States. Human-to-human transmission has been documented, with nosocomial transmission appearing to be an important route of infection. The recent increase in cases of MERS in the Middle East coupled with the lack of approved antiviral therapies or vaccines to treat or prevent this infection are causes for concern. We report on the development of a synthetic DNA vaccine against MERS-CoV. An optimized DNA vaccine encoding the MERS spike protein induced potent cellular immunity and antigen-specific neutralizing antibodies in mice, macaques, and camels. Vaccinated rhesus macaques seroconverted rapidly and exhibited high levels of virus-neutralizing activity. Upon MERS viral challenge, all of the monkeys in the control-vaccinated group developed characteristic disease, including pneumonia. Vaccinated macaques were protected and failed to demonstrate any clinical or radiographic signs of pneumonia. These studies demonstrate that a consensus MERS spike protein synthetic DNA vaccine can induce protective responses against viral challenge, indicating that this strategy may have value as a possible vaccine modality against this emerging pathogen.
Copyright © 2015, American Association for the Advancement of Science.
Matthew Cotten, Simon J Watson, Paul Kellam, Abdullah A Al-Rabeeah, Hatem Q Makhdoom, Abdullah Assiri, Jaffar A Al-Tawfiq, Rafat F Alhakeem, Hossam Madani, Fahad A AlRabiah, Sami Al Hajjar, Wafa N Al-nassir, Ali Albarrak, Hesham Flemban, Hanan H Balkhy, Sarah Alsubaie, Anne L Palser, Astrid Gall, Rachael Bashford-Rogers, Andrew Rambaut, Alimuddin I Zumla, Ziad A Memish
Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study.
Lancet. 2013 Dec 14;382(9909):1993-2002. doi: 10.1016/S0140-6736(13)61887-5. Epub 2013 Sep 20.
Abstract/Text
BACKGROUND: Since June, 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has, worldwide, caused 104 infections in people including 49 deaths, with 82 cases and 41 deaths reported from Saudi Arabia. In addition to confirming diagnosis, we generated the MERS-CoV genomic sequences obtained directly from patient samples to provide important information on MERS-CoV transmission, evolution, and origin.
METHODS: Full genome deep sequencing was done on nucleic acid extracted directly from PCR-confirmed clinical samples. Viral genomes were obtained from 21 MERS cases of which 13 had 100%, four 85-95%, and four 30-50% genome coverage. Phylogenetic analysis of the 21 sequences, combined with nine published MERS-CoV genomes, was done.
FINDINGS: Three distinct MERS-CoV genotypes were identified in Riyadh. Phylogeographic analyses suggest the MERS-CoV zoonotic reservoir is geographically disperse. Selection analysis of the MERS-CoV genomes reveals the expected accumulation of genetic diversity including changes in the S protein. The genetic diversity in the Al-Hasa cluster suggests that the hospital outbreak might have had more than one virus introduction.
INTERPRETATION: We present the largest number of MERS-CoV genomes (21) described so far. MERS-CoV full genome sequences provide greater detail in tracking transmission. Multiple introductions of MERS-CoV are identified and suggest lower R0 values. Transmission within Saudi Arabia is consistent with either movement of an animal reservoir, animal products, or movement of infected people. Further definition of the exposures responsible for the sporadic introductions of MERS-CoV into human populations is urgently needed.
FUNDING: Saudi Arabian Ministry of Health, Wellcome Trust, European Community, and National Institute of Health Research University College London Hospitals Biomedical Research Centre.
Copyright © 2013 Cotten et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by Elsevier Ltd. All rights reserved.
David S Hui
Tracking the transmission and evolution of MERS-CoV.
Lancet. 2013 Dec 14;382(9909):1962-4. doi: 10.1016/S0140-6736(13)61955-8. Epub 2013 Sep 20.
Abstract/Text
Ali M Zaki, Sander van Boheemen, Theo M Bestebroer, Albert D M E Osterhaus, Ron A M Fouchier
Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.
N Engl J Med. 2012 Nov 8;367(19):1814-20. doi: 10.1056/NEJMoa1211721. Epub 2012 Oct 17.
Abstract/Text
A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
B Hijawi, M Abdallat, A Sayaydeh, S Alqasrawi, A Haddadin, N Jaarour, S Alsheikh, T Alsanouri
Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation.
East Mediterr Health J. 2013;19 Suppl 1:S12-8.
Abstract/Text
In April 2012, an outbreak of acute respiratory illness occurred in a public hospital in Zarqa city, in Jordan; 8 health care workers were among the 11 people affected, 1 of who later died. The cause of the outbreak was unknown at the time and an epidemiological investigation including laboratory testing carried out immediately afterthe outbreak was inconclusive. Following the discovery of novel coronavirus infection (nCoV) in the Arabian peninsula in September 2012, stored respiratory and serum samples of patients from this outbreak were retested and the diagnosis of nCoV was confirmed in 2 deceased patients. This paper describes the epidemiological findings of retrospective investigation carried out in November 2012 and highlights the likelihood of nosocomial transmission of nCoV infection in a health-care setting. A total of 2 laboratory-confirmed and 11 probable cases were identified from this outbreak of whom 10 were HCWs and 2 were family members of cases.
Stephanie R Bialek, Donna Allen, Francisco Alvarado-Ramy, Ray Arthur, Arunmozhi Balajee, David Bell, Susan Best, Carina Blackmore, Lucy Breakwell, Andrew Cannons, Clive Brown, Martin Cetron, Nora Chea, Christina Chommanard, Nicole Cohen, Craig Conover, Antonio Crespo, Jeanean Creviston, Aaron T Curns, Rebecca Dahl, Stephanie Dearth, Alfred DeMaria, Fred Echols, Dean D Erdman, Daniel Feikin, Mabel Frias, Susan I Gerber, Reena Gulati, Christa Hale, Lia M Haynes, Lea Heberlein-Larson, Kelly Holton, Kashef Ijaz, Minal Kapoor, Katrin Kohl, David T Kuhar, Alan M Kumar, Marianne Kundich, Susan Lippold, Lixia Liu, Judith C Lovchik, Larry Madoff, Sandra Martell, Sarah Matthews, Jessica Moore, Linda R Murray, Shauna Onofrey, Mark A Pallansch, Nicki Pesik, Huong Pham, Satish Pillai, Pam Pontones, Kimberly Pringle, Scott Pritchard, Sonja Rasmussen, Shawn Richards, Michelle Sandoval, Eileen Schneider, Anne Schuchat, Kristine Sheedy, Kevin Sherin, David L Swerdlow, Jordan W Tappero, Michael O Vernon, Sharon Watkins, John Watson, Centers for Disease Control and Prevention (CDC)
First confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in the United States, updated information on the epidemiology of MERS-CoV infection, and guidance for the public, clinicians, and public health authorities - May 2014.
MMWR Morb Mortal Wkly Rep. 2014 May 16;63(19):431-6.
Abstract/Text
Since mid-March 2014, the frequency with which cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported has increased, with the majority of recent cases reported from Saudi Arabia and United Arab Emirates (UAE). In addition, the frequency with which travel-associated MERS cases have been reported and the number of countries that have reported them to the World Health Organization (WHO) have also increased. The first case of MERS in the United States, identified in a traveler recently returned from Saudi Arabia, was reported to CDC by the Indiana State Department of Health on May 1, 2014, and confirmed by CDC on May 2. A second imported case of MERS in the United States, identified in a traveler from Saudi Arabia having no connection with the first case, was reported to CDC by the Florida Department of Health on May 11, 2014. The purpose of this report is to alert clinicians, health officials, and others to increase awareness of the need to consider MERS-CoV infection in persons who have recently traveled from countries in or near the Arabian Peninsula. This report summarizes recent epidemiologic information, provides preliminary descriptions of the cases reported from Indiana and Florida, and updates CDC guidance about patient evaluation, home care and isolation, specimen collection, and travel as of May 13, 2014.
Daniel K W Chu, Leo L M Poon, Mokhtar M Gomaa, Mahmoud M Shehata, Ranawaka A P M Perera, Dina Abu Zeid, Amira S El Rifay, Lewis Y Siu, Yi Guan, Richard J Webby, Mohamed A Ali, Malik Peiris, Ghazi Kayali
MERS coronaviruses in dromedary camels, Egypt.
Emerg Infect Dis. 2014 Jun;20(6):1049-53. doi: 10.3201/eid2006.140299.
Abstract/Text
We identified the near-full-genome sequence (29,908 nt, >99%) of Middle East respiratory syndrome coronavirus (MERS-CoV) from a nasal swab specimen from a dromedary camel in Egypt. We found that viruses genetically very similar to human MERS-CoV are infecting dromedaries beyond the Arabian Peninsula, where human MERS-CoV infections have not yet been detected.
Thomas Briese, Nischay Mishra, Komal Jain, Iyad S Zalmout, Omar J Jabado, William B Karesh, Peter Daszak, Osama B Mohammed, Abdulaziz N Alagaili, W Ian Lipkin
Middle East respiratory syndrome coronavirus quasispecies that include homologues of human isolates revealed through whole-genome analysis and virus cultured from dromedary camels in Saudi Arabia.
MBio. 2014 Apr 29;5(3):e01146-14. doi: 10.1128/mBio.01146-14. Epub 2014 Apr 29.
Abstract/Text
ABSTRACT Complete Middle East respiratory syndrome coronavirus (MERS-CoV) genome sequences were obtained from nasal swabs of dromedary camels sampled in the Kingdom of Saudi Arabia through direct analysis of nucleic acid extracts or following virus isolation in cell culture. Consensus dromedary MERS-CoV genome sequences were the same with either template source and identical to published human MERS-CoV sequences. However, in contrast to individual human cases, where only clonal genomic sequences are reported, detailed population analyses revealed the presence of more than one genomic variant in individual dromedaries. If humans are truly infected only with clonal virus populations, we must entertain a model for interspecies transmission of MERS-CoV wherein only specific genotypes are capable of passing bottleneck selection. IMPORTANCE In most cases of Middle East respiratory syndrome (MERS), the route for human infection with the causative agent, MERS coronavirus (MERS-CoV), is unknown. Antibodies to and viral nucleic acids of MERS-CoV have been found in dromedaries, suggesting the possibility that they may serve as a reservoir or vector for human infection. However, neither whole viral genomic sequence nor infectious virus has been isolated from dromedaries or other animals in Saudi Arabia. Here, we report recovery of MERS-CoV from nasal swabs of dromedaries, demonstrate that MERS-CoV whole-genome consensus sequences from dromedaries and humans are indistinguishable, and show that dromedaries can be simultaneously infected with more than one MERS-CoV. Together with data indicating widespread dromedary infection in the Kingdom of Saudi Arabia, these findings support the plausibility of a role for dromedaries in human infection.
Maged G Hemida, Daniel K W Chu, Leo L M Poon, Ranawaka A P M Perera, Mohammad A Alhammadi, Hoi-Yee Ng, Lewis Y Siu, Yi Guan, Abdelmohsen Alnaeem, Malik Peiris
MERS coronavirus in dromedary camel herd, Saudi Arabia.
Emerg Infect Dis. 2014 Jul;20(7):1231-4. doi: 10.3201/eid2007.140571.
Abstract/Text
A prospective study of a dromedary camel herd during the 2013-14 calving season showed Middle East respiratory syndrome coronavirus infection of calves and adults. Virus was isolated from the nose and feces but more frequently from the nose. Preexisting neutralizing antibody did not appear to protect against infection.
V Stalin Raj, Elmoubasher A B A Farag, Chantal B E M Reusken, Mart M Lamers, Suzan D Pas, Jolanda Voermans, Saskia L Smits, Albert D M E Osterhaus, Naema Al-Mawlawi, Hamad E Al-Romaihi, Mohd M AlHajri, Ahmed M El-Sayed, Khaled A Mohran, Hazem Ghobashy, Farhoud Alhajri, Mohamed Al-Thani, Salih A Al-Marri, Mamdouh M El-Maghraby, Marion P G Koopmans, Bart L Haagmans
Isolation of MERS coronavirus from a dromedary camel, Qatar, 2014.
Emerg Infect Dis. 2014 Aug;20(8):1339-42. doi: 10.3201/eid2008.140663.
Abstract/Text
We obtained the full genome of Middle East respiratory syndrome coronavirus (MERS-CoV) from a camel in Qatar. This virus is highly similar to the human England/Qatar 1 virus isolated in 2012. The MERS-CoV from the camel efficiently replicated in human cells, providing further evidence for the zoonotic potential of MERS-CoV from camels.
Matthew Cotten, Simon J Watson, Alimuddin I Zumla, Hatem Q Makhdoom, Anne L Palser, Swee Hoe Ong, Abdullah A Al Rabeeah, Rafat F Alhakeem, Abdullah Assiri, Jaffar A Al-Tawfiq, Ali Albarrak, Mazin Barry, Atef Shibl, Fahad A Alrabiah, Sami Hajjar, Hanan H Balkhy, Hesham Flemban, Andrew Rambaut, Paul Kellam, Ziad A Memish
Spread, circulation, and evolution of the Middle East respiratory syndrome coronavirus.
MBio. 2014 Feb 18;5(1). doi: 10.1128/mBio.01062-13. Epub 2014 Feb 18.
Abstract/Text
UNLABELLED: The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) in 2012 and, to date, has been identified in 180 cases with 43% mortality. In this study, we have determined the MERS-CoV evolutionary rate, documented genetic variants of the virus and their distribution throughout the Arabian peninsula, and identified the genome positions under positive selection, important features for monitoring adaptation of MERS-CoV to human transmission and for identifying the source of infections. Respiratory samples from confirmed KSA MERS cases from May to September 2013 were subjected to whole-genome deep sequencing, and 32 complete or partial sequences (20 were ≥ 99% complete, 7 were 50 to 94% complete, and 5 were 27 to 50% complete) were obtained, bringing the total available MERS-CoV genomic sequences to 65. An evolutionary rate of 1.12 × 10(-3) substitutions per site per year (95% credible interval [95% CI], 8.76 × 10(-4); 1.37 × 10(-3)) was estimated, bringing the time to most recent common ancestor to March 2012 (95% CI, December 2011; June 2012). Only one MERS-CoV codon, spike 1020, located in a domain required for cell entry, is under strong positive selection. Four KSA MERS-CoV phylogenetic clades were found, with 3 clades apparently no longer contributing to current cases. The size of the population infected with MERS-CoV showed a gradual increase to June 2013, followed by a decline, possibly due to increased surveillance and infection control measures combined with a basic reproduction number (R0) for the virus that is less than 1.
IMPORTANCE: MERS-CoV adaptation toward higher rates of sustained human-to-human transmission appears not to have occurred yet. While MERS-CoV transmission currently appears weak, careful monitoring of changes in MERS-CoV genomes and of the MERS epidemic should be maintained. The observation of phylogenetically related MERS-CoV in geographically diverse locations must be taken into account in efforts to identify the animal source and transmission of the virus.
Chantal B E M Reusken, Lilia Messadi, Ashenafi Feyisa, Hussaini Ularamu, Gert-Jan Godeke, Agom Danmarwa, Fufa Dawo, Mohamed Jemli, Simenew Melaku, David Shamaki, Yusuf Woma, Yiltawe Wungak, Endrias Zewdu Gebremedhin, Ilse Zutt, Berend-Jan Bosch, Bart L Haagmans, Marion P G Koopmans
Geographic distribution of MERS coronavirus among dromedary camels, Africa.
Emerg Infect Dis. 2014 Aug;20(8):1370-4. doi: 10.3201/eid2008.140590.
Abstract/Text
We found serologic evidence for the circulation of Middle East respiratory syndrome coronavirus among dromedary camels in Nigeria, Tunisia, and Ethiopia. Circulation of the virus among dromedaries across broad areas of Africa may indicate that this disease is currently underdiagnosed in humans outside the Arabian Peninsula.
Benjamin Meyer, Marcel A Müller, Victor M Corman, Chantal B E M Reusken, Daniel Ritz, Gert-Jan Godeke, Erik Lattwein, Stephan Kallies, Artem Siemens, Janko van Beek, Jan F Drexler, Doreen Muth, Berend-Jan Bosch, Ulrich Wernery, Marion P G Koopmans, Renate Wernery, Christian Drosten
Antibodies against MERS coronavirus in dromedary camels, United Arab Emirates, 2003 and 2013.
Emerg Infect Dis. 2014 Apr;20(4):552-9. doi: 10.3201/eid2004.131746.
Abstract/Text
Middle East respiratory syndrome coronavirus (MERS-CoV) has caused an ongoing outbreak of severe acute respiratory tract infection in humans in the Arabian Peninsula since 2012. Dromedary camels have been implicated as possible viral reservoirs. We used serologic assays to analyze 651 dromedary camel serum samples from the United Arab Emirates; 151 of 651 samples were obtained in 2003, well before onset of the current epidemic, and 500 serum samples were obtained in 2013. Recombinant spike protein-specific immunofluorescence and virus neutralization tests enabled clear discrimination between MERS-CoV and bovine CoV infections. Most (632/651, 97.1%) camels had antibodies against MERS-CoV. This result included all 151 serum samples obtained in 2003. Most (389/651, 59.8%) serum samples had MERS-CoV-neutralizing antibody titers >1,280. Dromedary camels from the United Arab Emirates were infected at high rates with MERS-CoV or a closely related, probably conspecific, virus long before the first human MERS cases.
Victor M Corman, Joerg Jores, Benjamin Meyer, Mario Younan, Anne Liljander, Mohammed Y Said, Ilona Gluecks, Erik Lattwein, Berend-Jan Bosch, Jan Felix Drexler, Set Bornstein, Christian Drosten, Marcel A Müller
Antibodies against MERS coronavirus in dromedary camels, Kenya, 1992-2013.
Emerg Infect Dis. 2014 Aug;20(8):1319-22. doi: 10.3201/eid2008.140596.
Abstract/Text
Dromedary camels are a putative source for human infections with Middle East respiratory syndrome coronavirus. We showed that camels sampled in different regions in Kenya during 1992-2013 have antibodies against this virus. High densities of camel populations correlated with increased seropositivity and might be a factor in predicting long-term virus maintenance.
Mohamed Ali, Rabeh El-Shesheny, Ahmed Kandeil, Mahmoud Shehata, Basma Elsokary, Mokhtar Gomaa, Naglaa Hassan, Ahmed El Sayed, Ahmed El-Taweel, Heba Sobhy, Folorunso Oludayo Fasina, Gwenaelle Dauphin, Ihab El Masry, Abebe Wossene Wolde, Peter Daszak, Maureen Miller, Sophie VonDobschuetz, Subhash Morzaria, Juan Lubroth, Yilma Jobre Makonnen
Cross-sectional surveillance of Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels and other mammals in Egypt, August 2015 to January 2016.
Euro Surveill. 2017 Mar 16;22(11). doi: 10.2807/1560-7917.ES.2017.22.11.30487.
Abstract/Text
A cross-sectional study was conducted in Egypt to determine the prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) in imported and resident camels and bats, as well as to assess possible transmission of the virus to domestic ruminants and equines. A total of 1,031 sera, 1,078 nasal swabs, 13 rectal swabs, and 38 milk samples were collected from 1,078 camels in different types of sites. In addition, 145 domestic animals and 109 bats were sampled. Overall, of 1,031 serologically-tested camels, 871 (84.5%) had MERS-CoV neutralising antibodies. Seroprevalence was significantly higher in imported (614/692; 88.7%) than resident camels (257/339; 5.8%) (p < 0.05). Camels from Sudan (543/594; 91.4%) had a higher seroprevalence than those from East Africa (71/98; 72.4%) (p < 0.05). Sampling site and age were also associated with MERS-CoV seroprevalence (p < 0.05). All tested samples from domestic animals and bats were negative for MERS-CoV antibodies except one sheep sample which showed a 1:640 titre. Of 1,078 camels, 41 (3.8%) were positive for MERS-CoV genetic material. Sequences obtained were not found to cluster with clade A or B MERS-CoV sequences and were genetically diverse. The presence of neutralising antibodies in one sheep apparently in contact with seropositive camels calls for further studies on domestic animals in contact with camels.
This article is copyright of The Authors, 2017.
Carlos Gutiérrez, María Teresa Tejedor-Junco, Margarita González, Erik Lattwein, Stefanie Renneker
Presence of antibodies but no evidence for circulation of MERS-CoV in dromedaries on the Canary Islands, 2015.
Euro Surveill. 2015;20(37). doi: 10.2807/1560-7917.ES.2015.20.37.30019.
Abstract/Text
In 2012, a new betacoronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), was identified in humans. Several studies confirmed dromedary camels to be a potential reservoir and a source for human infection. Camels located on the Canary Islands were included in those studies and ca 10% of them were positive for MERS-CoV-specific antibodies. However, these findings could not be correctly interpreted because epidemiological information was not provided. Thus, further investigations were necessary to clarify these results. A total of 170 camels were investigated in this survey, of which seven (4.1%) were seropositive by ELISA. Epidemiological information revealed that all seropositive camels had been imported from Africa 20 or more years prior. We conclude that seropositive camels had contact with MERS-CoV in Africa and that there is no shedding of the virus among camels or people around the farms on the Canary Islands. However, the presence of antibodies in the camel herds should be monitored.
Muhammad Saqib, Andrea Sieberg, Muhammad Hammad Hussain, Muhammad Khalid Mansoor, Ali Zohaib, Erik Lattwein, Marcel Alexander Müller, Christian Drosten, Victor Max Corman
Serologic Evidence for MERS-CoV Infection in Dromedary Camels, Punjab, Pakistan, 2012-2015.
Emerg Infect Dis. 2017 Mar;23(3):550-551. doi: 10.3201/eid2303.161285.
Abstract/Text
Dromedary camels from Africa and Arabia are an established source for zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) infection among humans. In Pakistan, we found specific neutralizing antibodies in samples from 39.5% of 565 dromedaries, documenting significant expansion of the enzootic range of MERS-CoV to Asia.
Ulrich Wernery, Victor M Corman, Emily Y M Wong, Alan K L Tsang, Doreen Muth, Susanna K P Lau, Kamal Khazanehdari, Florian Zirkel, Mansoor Ali, Peter Nagy, Jutka Juhasz, Renate Wernery, Sunitha Joseph, Ginu Syriac, Shyna K Elizabeth, Nissy Annie Georgy Patteril, Patrick C Y Woo, Christian Drosten
Acute middle East respiratory syndrome coronavirus infection in livestock Dromedaries, Dubai, 2014.
Emerg Infect Dis. 2015 Jun;21(6):1019-22. doi: 10.3201/eid2106.150038.
Abstract/Text
Camels carry Middle East respiratory syndrome coronavirus, but little is known about infection age or prevalence. We studied >800 dromedaries of all ages and 15 mother-calf pairs. This syndrome constitutes an acute, epidemic, and time-limited infection in camels <4 years of age, particularly calves. Delayed social separation of calves might reduce human infection risk.
Danielle R Adney, Neeltje van Doremalen, Vienna R Brown, Trenton Bushmaker, Dana Scott, Emmie de Wit, Richard A Bowen, Vincent J Munster
Replication and shedding of MERS-CoV in upper respiratory tract of inoculated dromedary camels.
Emerg Infect Dis. 2014 Dec;20(12):1999-2005. doi: 10.3201/eid2012.141280.
Abstract/Text
In 2012, a novel coronavirus associated with severe respiratory disease in humans emerged in the Middle East. Epidemiologic investigations identified dromedary camels as the likely source of zoonotic transmission of Middle East respiratory syndrome coronavirus (MERS-CoV). Here we provide experimental support for camels as a reservoir for MERS-CoV. We inoculated 3 adult camels with a human isolate of MERS-CoV and a transient, primarily upper respiratory tract infection developed in each of the 3 animals. Clinical signs of the MERS-CoV infection were benign, but each of the camels shed large quantities of virus from the upper respiratory tract. We detected infectious virus in nasal secretions through 7 days postinoculation, and viral RNA up to 35 days postinoculation. The pattern of shedding and propensity for the upper respiratory tract infection in dromedary camels may help explain the lack of systemic illness among naturally infected camels and the means of efficient camel-to-camel and camel-to-human transmission.
Absence of MERS-CoV antibodies in feral camels in Australia: Implications for the pathogen’s origin and spread - PubMed [Internet]. [cited 2022 May 9]. Available from: https://pubmed.ncbi.nlm.nih.gov/28616468/
Kazuya Shirato, Akinori Azumano, Tatsuko Nakao, Daisuke Hagihara, Manabu Ishida, Kanji Tamai, Kouji Yamazaki, Miyuki Kawase, Yoshiharu Okamoto, Shigehisa Kawakami, Naonori Okada, Kazuko Fukushima, Kensuke Nakajima, Shutoku Matsuyama
Middle East respiratory syndrome coronavirus infection not found in camels in Japan.
Jpn J Infect Dis. 2015;68(3):256-8. doi: 10.7883/yoken.JJID.2015.094.
Abstract/Text
Chantal B E M Reusken, Bart L Haagmans, Marcel A Müller, Carlos Gutierrez, Gert-Jan Godeke, Benjamin Meyer, Doreen Muth, V Stalin Raj, Laura Smits-De Vries, Victor M Corman, Jan-Felix Drexler, Saskia L Smits, Yasmin E El Tahir, Rita De Sousa, Janko van Beek, Norbert Nowotny, Kees van Maanen, Ezequiel Hidalgo-Hermoso, Berend-Jan Bosch, Peter Rottier, Albert Osterhaus, Christian Gortázar-Schmidt, Christian Drosten, Marion P G Koopmans
Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study.
Lancet Infect Dis. 2013 Oct;13(10):859-66. doi: 10.1016/S1473-3099(13)70164-6. Epub 2013 Aug 9.
Abstract/Text
BACKGROUND: A new betacoronavirus-Middle East respiratory syndrome coronavirus (MERS-CoV)-has been identified in patients with severe acute respiratory infection. Although related viruses infect bats, molecular clock analyses have been unable to identify direct ancestors of MERS-CoV. Anecdotal exposure histories suggest that patients had been in contact with dromedary camels or goats. We investigated possible animal reservoirs of MERS-CoV by assessing specific serum antibodies in livestock.
METHODS: We took sera from animals in the Middle East (Oman) and from elsewhere (Spain, Netherlands, Chile). Cattle (n=80), sheep (n=40), goats (n=40), dromedary camels (n=155), and various other camelid species (n=34) were tested for specific serum IgG by protein microarray using the receptor-binding S1 subunits of spike proteins of MERS-CoV, severe acute respiratory syndrome coronavirus, and human coronavirus OC43. Results were confirmed by virus neutralisation tests for MERS-CoV and bovine coronavirus.
FINDINGS: 50 of 50 (100%) sera from Omani camels and 15 of 105 (14%) from Spanish camels had protein-specific antibodies against MERS-CoV spike. Sera from European sheep, goats, cattle, and other camelids had no such antibodies. MERS-CoV neutralising antibody titres varied between 1/320 and 1/2560 for the Omani camel sera and between 1/20 and 1/320 for the Spanish camel sera. There was no evidence for cross-neutralisation by bovine coronavirus antibodies.
INTERPRETATION: MERS-CoV or a related virus has infected camel populations. Both titres and seroprevalences in sera from different locations in Oman suggest widespread infection.
FUNDING: European Union, European Centre For Disease Prevention and Control, Deutsche Forschungsgemeinschaft.
Copyright © 2013 Elsevier Ltd. All rights reserved.
The Lancet Infectious Diseases
Need for global cooperation in control of MERS-CoV.
Lancet Infect Dis. 2013 Aug;13(8):639. doi: 10.1016/S1473-3099(13)70205-6.
Abstract/Text
M G Hemida, R A Perera, P Wang, M A Alhammadi, L Y Siu, M Li, L L Poon, L Saif, A Alnaeem, M Peiris
Middle East Respiratory Syndrome (MERS) coronavirus seroprevalence in domestic livestock in Saudi Arabia, 2010 to 2013.
Euro Surveill. 2013 Dec 12;18(50):20659. Epub 2013 Dec 12.
Abstract/Text
In Saudi Arabia, including regions of Riyadh and Al Ahsa, pseudoparticle neutralisation (ppNT) and microneutralisation (MNT) tests detected no antibodies to Middle East Respiratory Syndrome coronavirus (MERS-CoV) in sheep (n= 100), goats (n= 45), cattle (n= 50) and chickens (n= 240). Dromedary camels however, had a high prevalence of MERS-CoV antibodies. Bovine coronavirus (BCoV) infected sera from cattle had no cross-reactivity in MERS-CoV ppNT or MNT, while many dromedary camels’ sera reacted to both BCoV and MERS-CoV. Some nevertheless displayed specific serologic reaction profiles to MERS-CoV.
Esam I Azhar, Sherif A El-Kafrawy, Suha A Farraj, Ahmed M Hassan, Muneera S Al-Saeed, Anwar M Hashem, Tariq A Madani
Evidence for camel-to-human transmission of MERS coronavirus.
N Engl J Med. 2014 Jun 26;370(26):2499-505. doi: 10.1056/NEJMoa1401505. Epub 2014 Jun 4.
Abstract/Text
We describe the isolation and sequencing of Middle East respiratory syndrome coronavirus (MERS-CoV) obtained from a dromedary camel and from a patient who died of laboratory-confirmed MERS-CoV infection after close contact with camels that had rhinorrhea. Nasal swabs collected from the patient and from one of his nine camels were positive for MERS-CoV RNA. In addition, MERS-CoV was isolated from the patient and the camel. The full genome sequences of the two isolates were identical. Serologic data indicated that MERS-CoV was circulating in the camels but not in the patient before the human infection occurred. These data suggest that this fatal case of human MERS-CoV infection was transmitted through close contact with an infected camel.
Marcel A Müller, Benjamin Meyer, Victor M Corman, Malak Al-Masri, Abdulhafeez Turkestani, Daniel Ritz, Andrea Sieberg, Souhaib Aldabbagh, Berend-J Bosch, Erik Lattwein, Raafat F Alhakeem, Abdullah M Assiri, Ali M Albarrak, Ali M Al-Shangiti, Jaffar A Al-Tawfiq, Paul Wikramaratna, Abdullah A Alrabeeah, Christian Drosten, Ziad A Memish
Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study.
Lancet Infect Dis. 2015 May;15(5):559-64. doi: 10.1016/S1473-3099(15)70090-3. Epub 2015 Apr 8.
Abstract/Text
BACKGROUND: Scientific evidence suggests that dromedary camels are the intermediary host for the Middle East respiratory syndrome coronavirus (MERS-CoV). However, the actual number of infections in people who have had contact with camels is unknown and most index patients cannot recall any such contact. We aimed to do a nationwide serosurvey in Saudi Arabia to establish the prevalence of MERS-CoV antibodies, both in the general population and in populations of individuals who have maximum exposure to camels.
METHODS: In the cross-sectional serosurvey, we tested human serum samples obtained from healthy individuals older than 15 years who attended primary health-care centres or participated in a national burden-of-disease study in all 13 provinces of Saudi Arabia. Additionally, we tested serum samples from shepherds and abattoir workers with occupational exposure to camels. Samples were screened by recombinant ELISA and MERS-CoV seropositivity was confirmed by recombinant immunofluorescence and plaque reduction neutralisation tests. We used two-tailed Mann Whitney U exact tests, χ(2), and Fisher's exact tests to analyse the data.
FINDINGS: Between Dec 1, 2012, and Dec 1, 2013, we obtained individual serum samples from 10,009 individuals. Anti-MERS-CoV antibodies were confirmed in 15 (0·15%; 95% CI 0·09-0·24) of 10,009 people in six of the 13 provinces. The mean age of seropositive individuals was significantly younger than that of patients with reported, laboratory-confirmed, primary Middle Eastern respiratory syndrome (43·5 years [SD 17·3] vs 53·8 years [17·5]; p=0·008). Men had a higher antibody prevalence than did women (11 [0·25%] of 4341 vs two [0·05%] of 4378; p=0·028) and antibody prevalence was significantly higher in central versus coastal provinces (14 [0·26%] of 5479 vs one [0·02%] of 4529; p=0·003). Compared with the general population, seroprevalence of MERS-CoV antibodies was significantly increased by 15 times in shepherds (two [2·3%] of 87, p=0·0004) and by 23 times in slaughterhouse workers (five [3·6%] of 140; p<0·0001).
INTERPRETATION: Seroprevalence of MERS-CoV antibodies was significantly higher in camel-exposed individuals than in the general population. By simple multiplication, a projected 44,951 (95% CI 26,971-71,922) individuals older than 15 years might be seropositive for MERS-CoV in Saudi Arabia. These individuals might be the source of infection for patients with confirmed MERS who had no previous exposure to camels.
FUNDING: European Union, German Centre for Infection Research, Federal Ministry of Education and Research, German Research Council, and Ministry of Health of Saudi Arabia.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Anne Liljander, Benjamin Meyer, Joerg Jores, Marcel A Müller, Erik Lattwein, Ian Njeru, Bernard Bett, Christian Drosten, Victor Max Corman
MERS-CoV Antibodies in Humans, Africa, 2013-2014.
Emerg Infect Dis. 2016 Jun;22(6):1086-9. doi: 10.3201/eid2206.160064. Epub 2016 Jun 15.
Abstract/Text
Dromedaries in Africa and elsewhere carry the Middle East respiratory syndrome coronavirus (MERS-CoV). To search for evidence of autochthonous MERS-CoV infection in humans, we tested archived serum from livestock handlers in Kenya for MERS-CoV antibodies. Serologic evidence of infection was confirmed for 2 persons sampled in 2013 and 2014.
Yoon-Seok Chung, Jeong Min Kim, Heui Man Kim, Kye Ryeong Park, Anna Lee, Nam-Joo Lee, Mi-Seon Kim, Jun Sub Kim, Chi-Kyeong Kim, Jae In Lee, Chun Kang
Genetic Characterization of Middle East Respiratory Syndrome Coronavirus, South Korea, 2018.
Emerg Infect Dis. 2019 May 17;25(5). doi: 10.3201/eid2505.181534. Epub 2019 May 17.
Abstract/Text
We evaluated genetic variation in Middle East respiratory syndrome coronavirus (MERS-CoV) imported to South Korea in 2018 using specimens from a patient and isolates from infected Caco-2 cells. The MERS-CoV strain in this study was genetically similar to a strain isolated in Riyadh, Saudi Arabia, in 2017.
WHO. MERS-CoV Global Summary and risk assessment. Available from: http://www.who.int/emergencies/mers-cov/mers-summary-2016.pdf?ua=1
WHO. Middle East respiratory syndrome coronavirus (MERS-CoV) Fact sheet. Updated May 2017. Available from: http://who.int/mediacentre/factsheets/mers-cov/en/
[http://web.b.ebscohost.com/dynamed/detail?sid=1cd60444-6914-4ee0-a874-501b23b2b978%40sessionmgr115&vid=6&hid=107&bdata=Jmxhbmc9amEmc2l0ZT1keW5hbWVkLWxpdmUmc2NvcGU9c2l0ZQ%3d%3d#db=dme&AN=902618 Middle East respiratory syndrome coronavirus (MERS-CoV). Dyna.
Basem M Alraddadi, John T Watson, Abdulatif Almarashi, Glen R Abedi, Amal Turkistani, Musallam Sadran, Abeer Housa, Mohammad A Almazroa, Naif Alraihan, Ayman Banjar, Eman Albalawi, Hanan Alhindi, Abdul Jamil Choudhry, Jonathan G Meiman, Magdalena Paczkowski, Aaron Curns, Anthony Mounts, Daniel R Feikin, Nina Marano, David L Swerdlow, Susan I Gerber, Rana Hajjeh, Tariq A Madani
Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Illness in Humans, Saudi Arabia, 2014.
Emerg Infect Dis. 2016 Jan;22(1):49-55. doi: 10.3201/eid2201.151340.
Abstract/Text
Risk factors for primary Middle East respiratory syndrome coronavirus (MERS-CoV) illness in humans are incompletely understood. We identified all primary MERS-CoV cases reported in Saudi Arabia during March-November 2014 by excluding those with history of exposure to other cases of MERS-CoV or acute respiratory illness of unknown cause or exposure to healthcare settings within 14 days before illness onset. Using a case-control design, we assessed differences in underlying medical conditions and environmental exposures among primary case-patients and 2-4 controls matched by age, sex, and neighborhood. Using multivariable analysis, we found that direct exposure to dromedary camels during the 2 weeks before illness onset, as well as diabetes mellitus, heart disease, and smoking, were each independently associated with MERS-CoV illness. Further investigation is needed to better understand animal-to-human transmission of MERS-CoV.
Reina S Sikkema, Elmoubasher A B A Farag, Sayed Himatt, Adel K Ibrahim, Hamad Al-Romaihi, Salih A Al-Marri, Mohamed Al-Thani, Ahmed M El-Sayed, Mohammed Al-Hajri, Bart L Haagmans, Marion P G Koopmans, Chantal B E M Reusken
Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Infection in Camel Workers in Qatar During 2013-2014: A Case-Control Study.
J Infect Dis. 2017 Jun 1;215(11):1702-1705. doi: 10.1093/infdis/jix174.
Abstract/Text
The transmission routes and risk factors for zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) infections are still unknown. We used the World Health Organization questionnaire for MERS-CoV case-control studies to assess risk factors for human MERS-CoV seropositivity at a farm complex in Qatar. Nine camel workers with MERS-CoV antibodies and 43 workers without antibodies were included. Some camel-related activities may pose a higher risk of MERS-CoV infection, as may cross-border movements of camels, poor hand hygiene, and overnight hospital stays with respiratory complaints. The risk factors identified in this study can be used to develop infection prevention and control measures for human MERS-CoV infections.
© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Simon Cauchemez, Christophe Fraser, Maria D Van Kerkhove, Christl A Donnelly, Steven Riley, Andrew Rambaut, Vincent Enouf, Sylvie van der Werf, Neil M Ferguson
Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility.
Lancet Infect Dis. 2014 Jan;14(1):50-6. doi: 10.1016/S1473-3099(13)70304-9. Epub 2013 Nov 13.
Abstract/Text
BACKGROUND: The novel Middle East respiratory syndrome coronavirus (MERS-CoV) had, as of Aug 8, 2013, caused 111 virologically confirmed or probable human cases of infection worldwide. We analysed epidemiological and genetic data to assess the extent of human infection, the performance of case detection, and the transmission potential of MERS-CoV with and without control measures.
METHODS: We assembled a comprehensive database of all confirmed and probable cases from public sources and estimated the incubation period and generation time from case cluster data. Using data of numbers of visitors to the Middle East and their duration of stay, we estimated the number of symptomatic cases in the Middle East. We did independent analyses, looking at the growth in incident clusters, the growth in viral population, the reproduction number of cluster index cases, and cluster sizes to characterise the dynamical properties of the epidemic and the transmission scenario.
FINDINGS: The estimated number of symptomatic cases up to Aug 8, 2013, is 940 (95% CI 290-2200), indicating that at least 62% of human symptomatic cases have not been detected. We find that the case-fatality ratio of primary cases detected via routine surveillance (74%; 95% CI 49-91) is biased upwards because of detection bias; the case-fatality ratio of secondary cases was 20% (7-42). Detection of milder cases (or clinical management) seemed to have improved in recent months. Analysis of human clusters indicated that chains of transmission were not self-sustaining when infection control was implemented, but that R in the absence of controls was in the range 0·8-1·3. Three independent data sources provide evidence that R cannot be much above 1, with an upper bound of 1·2-1·5.
INTERPRETATION: By showing that a slowly growing epidemic is underway either in human beings or in an animal reservoir, quantification of uncertainty in transmissibility estimates, and provision of the first estimates of the scale of the epidemic and extent of case detection biases, we provide valuable information for more informed risk assessment.
FUNDING: Medical Research Council, Bill & Melinda Gates Foundation, EU FP7, and National Institute of General Medical Sciences.
Copyright © 2014 Cauchemez et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.
Romulus Breban, Julien Riou, Arnaud Fontanet
Interhuman transmissibility of Middle East respiratory syndrome coronavirus: estimation of pandemic risk.
Lancet. 2013 Aug 24;382(9893):694-9. doi: 10.1016/S0140-6736(13)61492-0. Epub 2013 Jul 5.
Abstract/Text
BACKGROUND: The new Middle East respiratory syndrome coronavirus (MERS-CoV) infection shares many clinical, epidemiological, and virological similarities with that of severe acute respiratory syndrome (SARS)-CoV. We aimed to estimate virus transmissibility and the epidemic potential of MERS-CoV, and to compare the results with similar findings obtained for prepandemic SARS.
METHODS: We retrieved data for MERS-CoV clusters from the WHO summary and subsequent reports, and published descriptions of cases, and took into account 55 of the 64 laboratory-confirmed cases of MERS-CoV reported as of June 21, 2013, excluding cases notified in the previous 2 weeks. To assess the interhuman transmissibility of MERS-CoV, we used Bayesian analysis to estimate the basic reproduction number (R0) and compared it to that of prepandemic SARS. We considered two scenarios, depending on the interpretation of the MERS-CoV cluster-size data.
RESULTS: With our most pessimistic scenario (scenario 2), we estimated MERS-CoV R0 to be 0·69 (95% CI 0·50-0·92); by contrast, the R0 for prepandemic SARS-CoV was 0·80 (0·54-1·13). Our optimistic scenario (scenario 1) yielded a MERS-CoV R0 of 0·60 (0·42-0·80). Because of recent implementation of effective contact tracing and isolation procedures, further MERS-CoV transmission data might no longer describe an entire cluster, but only secondary infections directly caused by the index patient. Hence, we calculated that, under scenario 2, eight or more secondary infections caused by the next index patient would translate into a 5% or higher chance that the revised MERS-CoV R0 would exceed 1--ie, that MERS-CoV might have pandemic potential.
INTERPRETATION: Our analysis suggests that MERS-CoV does not yet have pandemic potential. We recommend enhanced surveillance, active contact tracing, and vigorous searches for the MERS-CoV animal hosts and transmission routes to human beings.
FUNDING: Agence Nationale de la Recherche (Labex Integrative Biology of Emerging Infectious Diseases), and the European Community's Seventh Framework Programme project PREDEMICS.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Ikwo K Oboho, Sara M Tomczyk, Ahmad M Al-Asmari, Ayman A Banjar, Hani Al-Mugti, Muhannad S Aloraini, Khulud Z Alkhaldi, Emad L Almohammadi, Basem M Alraddadi, Susan I Gerber, David L Swerdlow, John T Watson, Tariq A Madani
2014 MERS-CoV outbreak in Jeddah--a link to health care facilities.
N Engl J Med. 2015 Feb 26;372(9):846-54. doi: 10.1056/NEJMoa1408636.
Abstract/Text
BACKGROUND: A marked increase in the number of cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred in Jeddah, Saudi Arabia, in early 2014. We evaluated patients with MERS-CoV infection in Jeddah to explore reasons for this increase and to assess the epidemiologic and clinical features of this disease.
METHODS: We identified all cases of laboratory-confirmed MERS-CoV infection in Jeddah that were reported to the Saudi Arabian Ministry of Health from January 1 through May 16, 2014. We conducted telephone interviews with symptomatic patients who were not health care personnel, and we reviewed hospital records. We identified patients who were reported as being asymptomatic and interviewed them regarding a history of symptoms in the month before testing. Descriptive analyses were performed.
RESULTS: Of 255 patients with laboratory-confirmed MERS-CoV infection, 93 died (case fatality rate, 36.5%). The median age of all patients was 45 years (interquartile range, 30 to 59), and 174 patients (68.2%) were male. A total of 64 patients (25.1%) were reported to be asymptomatic. Of the 191 symptomatic patients, 40 (20.9%) were health care personnel. Among the 151 symptomatic patients who were not health care personnel, 112 (74.2%) had data that could be assessed, and 109 (97.3%) of these patients had had contact with a health care facility, a person with a confirmed case of MERS-CoV infection, or someone with severe respiratory illness in the 14 days before the onset of illness. The remaining 3 patients (2.7%) reported no such contacts. Of the 64 patients who had been reported as asymptomatic, 33 (52%) were interviewed, and 26 of these 33 (79%) reported at least one symptom that was consistent with a viral respiratory illness.
CONCLUSIONS: The majority of patients in the Jeddah MERS-CoV outbreak had contact with a health care facility, other patients, or both. This highlights the role of health care-associated transmission. (Supported by the Ministry of Health, Saudi Arabia, and by the U.S. Centers for Disease Control and Prevention.).
Christian Drosten, Benjamin Meyer, Marcel A Müller, Victor M Corman, Malak Al-Masri, Raheela Hossain, Hosam Madani, Andrea Sieberg, Berend Jan Bosch, Erik Lattwein, Raafat F Alhakeem, Abdullah M Assiri, Waleed Hajomar, Ali M Albarrak, Jaffar A Al-Tawfiq, Alimuddin I Zumla, Ziad A Memish
Transmission of MERS-coronavirus in household contacts.
N Engl J Med. 2014 Aug 28;371(9):828-35. doi: 10.1056/NEJMoa1405858.
Abstract/Text
BACKGROUND: Strategies to contain the Middle East respiratory syndrome coronavirus (MERS-CoV) depend on knowledge of the rate of human-to-human transmission, including subclinical infections. A lack of serologic tools has hindered targeted studies of transmission.
METHODS: We studied 26 index patients with MERS-CoV infection and their 280 household contacts. The median time from the onset of symptoms in index patients to the latest blood sampling in contact patients was 17.5 days (range, 5 to 216; mean, 34.4). Probable cases of secondary transmission were identified on the basis of reactivity in two reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays with independent RNA extraction from throat swabs or reactivity on enzyme-linked immunosorbent assay against MERS-CoV S1 antigen, supported by reactivity on recombinant S-protein immunofluorescence and demonstration of neutralization of more than 50% of the infectious virus seed dose on plaque-reduction neutralization testing.
RESULTS: Among the 280 household contacts of the 26 index patients, there were 12 probable cases of secondary transmission (4%; 95% confidence interval, 2 to 7). Of these cases, 7 were identified by means of RT-PCR, all in samples obtained within 14 days after the onset of symptoms in index patients, and 5 were identified by means of serologic analysis, all in samples obtained 13 days or more after symptom onset in index patients. Probable cases of secondary transmission occurred in 6 of 26 clusters (23%). Serologic results in contacts who were sampled 13 days or more after exposure were similar to overall study results for combined RT-PCR and serologic testing.
CONCLUSIONS: The rate of secondary transmission among household contacts of patients with MERS-CoV infection has been approximately 5%. Our data provide insight into the rate of subclinical transmission of MERS-CoV in the home.
Ziad A Memish, Alimuddin I Zumla, Rafat F Al-Hakeem, Abdullah A Al-Rabeeah, Gwen M Stephens
Family cluster of Middle East respiratory syndrome coronavirus infections.
N Engl J Med. 2013 Jun 27;368(26):2487-94. doi: 10.1056/NEJMoa1303729. Epub 2013 May 29.
Abstract/Text
A human coronavirus, called the Middle East respiratory syndrome coronavirus (MERS-CoV), was first identified in September 2012 in samples obtained from a Saudi Arabian businessman who died from acute respiratory failure. Since then, 49 cases of infections caused by MERS-CoV (previously called a novel coronavirus) with 26 deaths have been reported to date. In this report, we describe a family case cluster of MERS-CoV infection, including the clinical presentation, treatment outcomes, and household relationships of three young men who became ill with MERS-CoV infection after the hospitalization of an elderly male relative, who died of the disease. Twenty-four other family members living in the same household and 124 attending staff members at the hospitals did not become ill. MERS-CoV infection may cause a spectrum of clinical illness. Although an animal reservoir is suspected, none has been discovered. Meanwhile, global concern rests on the ability of MERS-CoV to cause major illness in close contacts of patients.
