public - ct7

2014 MERS-CoV Outbreak in Jeddah — A Link to Health Care Facilities

Ikwo K. Oboho, M.D., Sara M. Tomczyk, P.H.N., M.Sc., Ahmad M. Al-Asmari, M.D., Ayman A. Banjar, M.D., M.P.H., Hani Al-Mugti, M.D., Muhannad S. Aloraini, M.D., Khulud Z. Alkhaldi, M.D., Emad L. Almohammadi, M.D., Basem M. Alraddadi, M.D., Susan I. Gerber, M.D., David L. Swerdlow, M.D., John T. Watson, M.D., and Tariq A. Madani, M.D. Centers for Disease Control and Prevention (CDC) (I.K.O., S.M.T., S.I.G., D.L.S., J.T.W.) and the Epidemic Intelligence Service, CDC (I.K.O., S.M.T.), Atlanta; and the Ministry of Health (A.M.A.- A., A.A.B., K.Z.A., E.L.A., B.M.A., T.A.M.), the Community and Preventive Medicine Center, National Guard Health Affairs, Western Region, Ministry of National Guard (H.A.-M.), King Faisal Specialist Hospital and Research Center (B.M.A.), and the Department of Medicine, Faculty of Medicine, King Abdulaziz University (T.A.M.), Jeddah, and the Department of Family and Community Medicine, Faculty of Medicine, Al-Qas-sim University, Al-Qassim (M.S.A.) — all in Saudi Arabia.

Abstract

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

Address reprint requests to Dr. Madani at the Department of Medicine, King Abdulaziz University, P.O. Box 80215, Jeddah 21589, Saudi Arabia, or at [email protected]. Dr. Oboho and Ms. Tomczyk contributed equally to this article.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

HHS Public Access Author manuscript N Engl J Med. Author manuscript; available in PMC 2017 December 01.

Published in final edited form as: N Engl J Med. 2015 February 26; 372(9): 846–854. doi:10.1056/NEJMoa1408636.

A u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t

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.)

The Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging novel

betacoronavirus belonging to lineage C, is known to cause severe acute respiratory illness in

humans. From the time the disease was first identified in 2012, mortality among patients

with laboratory-confirmed infection has been reported to be approximately 30 to 40%.1,2 As

of this writing, cases have been linked to seven countries in or near the Arabian Peninsula,

and the majority of reported cases have been from Saudi Arabia.3,4

A zoonotic origin of MERS-CoV has been presumed on the basis of evidence to date. The

reservoir, mechanism of transmission, and risk factors for transmission resulting in primary

cases of infection remain elusive,5 although increasing evidence suggests that dromedary

camels may be able to transmit the virus to humans through close contact.6-8 Infected camels

may have mild, self-limited respiratory signs or inapparent infection.6,9 Primary cases of

MERS-CoV infection that are probably associated with zoonotic exposures have been

documented in community settings and can result in limited secondary transmission in

households.10 Secondary transmission in health care settings, which also has been

documented, has resulted in large outbreaks.11,12 Data on risk factors for transmission in

households and health care settings are lacking.

Beginning in mid-March 2014, an increase in reported cases of MERS-CoV infection in

Jeddah, Saudi Arabia, heightened international concern3,13 about the potential for global

transmission of this virus.14 Amid intense speculation regarding the cause of the sudden

increase in cases, several hypotheses emerged, including, either alone or in combination,

genomic changes resulting in increased transmissibility of the virus, an unidentified

seasonality component, an increase in testing to detect MERS-CoV infection, an increase in

primary cases in the community as a result of changes in contacts between humans and

potential animal reservoirs, an increase in cases because of sustained transmission in the

community (unrelated to health care exposures), and health care–associated amplification.

Subsequently, a laboratory-based study indicated that the outbreak was not associated with

changes in the virus, and the investigators postulated a predominance of human-to-human

transmission in Jeddah as an explanation.15

On May 10, 2014, the Saudi Arabian Ministry of Health, with assistance from the U.S.

Centers for Disease Control and Prevention (CDC), began an investigation to determine the

reasons for the increase in cases of MERS-CoV infection. Our primary objectives were to

identify the cause of the increase in reported cases by characterizing the possible sources of

exposure and to define the epidemiologic and clinical features of patients with the disease.

Because data are lacking regarding asymptomatic patients with MERS-CoV infection, our

secondary objective was to further characterize asymptomatic patients within our cohort.

Oboho et al. Page 2

N Engl J Med. Author manuscript; available in PMC 2017 December 01.

A u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t

Methods

Patients and Study Oversight

All patients from the Jeddah region who were reported to have laboratory-confirmed MERS-

CoV infection between January 1 and May 16, 2014, were identified. In Saudi Arabia,

before May 13, 2014, a person was considered to have a confirmed case of MERS-CoV

infection if there was laboratory confirmation of MERS-CoV infection on the basis of a

positive real-time reverse-tran-scriptase–polymerase-chain-reaction (RT-PCR) assay

targeting two genes — the E gene and open-reading frame gene 1a. Persons with confirmed

infection included reportedly asymptomatic persons who were identified by contact tracing,

post-exposure screening of health care personnel, or both. The case definition was revised on

May 13, 2014, after which a person with a confirmed case of MERS-CoV infection was

defined as a person with laboratory confirmation as noted above and clinical or radiologic

evidence consistent with the infection.16-18

In Saudi Arabia, real-time RT-PCR testing for MERS-CoV is performed at five Saudi

Arabian Ministry of Health regional laboratories, one of which is located in Jeddah. In

addition, at least three hospitals in Jeddah independently perform real-time RT-PCR testing

for MERS-CoV in hospitalized patients with suspected infection.

We obtained a list of patients with laboratory-confirmed MERS-CoV cases from the

Ministry of Health regional laboratory in Jeddah. We also obtained case information from

the Communicable Diseases Control Department of the Ministry of Health in Riyadh, the

Jeddah Health Affairs Directorate, and from local hospitals in Jeddah that were identified

through these two aforementioned sources as having patients with laboratory-confirmed

MERS-CoV infection.

Since this investigation was part of a public health response, it was not considered by the

CDC and the Saudi Arabian Ministry of Health to be research that was subject to review by

an institutional review board. Written informed consent was not required.

Possible Sources of Exposure

In order to identify possible sources of exposure among symptomatic patients, we first

categorized all patients according to health status (symptomatic or asymptomatic) and

employment status (health care personnel or not health care personnel) as coded by the

Ministry of Health or admitting hospitals. We then attempted to contact the symptomatic

patients who were not health care personnel at least four times by telephone. We obtained

oral informed consent from these patients, and we conducted telephone interviews in Arabic

or English. Proxies (i.e., the closest relative or friend) were interviewed if patients were

deceased. Interviews were conducted from May 12 through June 9, 2014. Patients or their

proxies were asked about demographic characteristics, occupation, underlying medical

conditions, the clinical course of the infection, and exposure.

In addition, available hospital medical records were reviewed to characterize potential

exposures and verify information obtained from telephone interviews. We categorized

patients according to whether they had worked at, been admitted to, or visited a health care

Oboho et al. Page 3

N Engl J Med. Author manuscript; available in PMC 2017 December 01.

A u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t

facility, as well as according to whether they reported contact with a patient with confirmed

MERS-CoV infection or someone admitted to the hospital with severe respiratory illness of

unknown cause during the 14 days before the onset of illness. These criteria addressed

potential secondary exposures as specified in the revised World Health Organization (WHO)

case–control protocol for assessment of potential risk factors for primary MERS-CoV

infection.19

In patients in whom secondary exposures were identified, we did not collect information

about primary exposure (e.g., contact with animals). The dates of onset of illness were

extracted from hospital charts, telephone interviews, or Ministry of Health case lists. For

patients in whom the date of onset of illness was unclear, we first used the date of onset of

MERS-CoV–related symptoms.

Next, if that date was not available, we used the date of clinical deterioration (e.g.,

admission to an intensive care unit [ICU]), and finally, if neither of those dates were

available, we used the date of testing for MERS-CoV. When information about exposure

before the onset of illness was available, we characterized admissions to a health care

facility according to the primary diagnosis and we characterized visits to a health care

facility according to type (emergency or outpatient visit, or visits to hospitalized friends or

family). Symptomatic patients who were not health care workers and who had none of the

aforementioned exposures were considered to be potential primary cases.

Signs and Symptoms in Patients Reported to Have Been Asymptomatic

We conducted a telephone survey from May 26 through June 8, 2014, of patients who had

been coded by the Ministry of Health and reported to the WHO as being asymptomatic. At

least four attempts were made to contact patients with available telephone numbers. We

obtained oral informed consent from these patients, and we conducted the telephone

interviews in Arabic or English.

We sought to determine whether, in fact, any of the following signs or symptoms had been

present during the 1 month before PCR testing to detect MERS-CoV (the period that was

consistent with the presumed duration of viral shedding)20: cough, shortness of breath,

rhinorrhea, sore throat, hemoptysis, fever, chills, muscle pain, abdominal pain, nausea,

vomiting, diarrhea, rash, fatigue, chest pain, headache, night sweats, or other symptoms. The

interview questions pertained to the patients’ demographic characteristics, occupation, and

underlying medical conditions, as well as the clinical course of the infection, the reason for

testing to detect MERS-CoV, and the history of defined symptoms. Patients were then

characterized according to the presence or absence of symptoms and, among patients who

were determined to have had symptoms, according to the type of symptoms.

Statistical Analysis

Descriptive analyses were performed for the following groups: all patients, all symptomatic

patients who were not health care personnel, and asymptomatic patients. Results were

reported as frequencies and proportions for categorical variables and as median values and

interquartile ranges for continuous variables. In addition, the chi-square test, Fisher's exact

test, and the F-test were used to compare prespecified subgroups of symptomatic patients

Oboho et al. Page 4

N Engl J Med. Author manuscript; available in PMC 2017 December 01.

A u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t

(those who were not available for the assessment of potential exposure to MERS-CoV vs.

those who were available for that assessment) and of asymptomatic patients (those who

responded to the telephone survey vs. those who did not respond). A P value of less than

0.05 was considered to indicate statistical significance. All analyses were conducted with the

use of SAS software, version 9.3 (SAS Institute).

Results

We identified 255 patients in Jeddah who had laboratory-confirmed MERS-CoV infection.

The median age was 45 years (interquartile range, 30 to 59). A total of 174 patients (68.2%)

were male, 78 (30.6%) were health care personnel, 140 (54.9%) were from Saudi Arabia, 93

(36.5%) were admitted to an ICU, and 93 died (case-fatality rate, 36.5%) (Table 1).

Figure 1 shows an epidemic curve according to the date of onset of illness in symptomatic

patients and according to the date of the test for MERS-CoV infection in asymptomatic

patients. Of the 255 patients, 64 (25.1%) were reported to be asymptomatic, of whom 41

(64%) were health care personnel (Fig. 2). Of the 191 symptomatic patients, 40 (20.9%)

were health care personnel. Among the 151 symptomatic patients who were not health care

personnel, the median age was 54 years (interquartile range, 37 to 64), 118 (78.1%) were

men, 100 (66.2%) were from Saudi Arabia, and 89 died (58.9%) (Table 1).

Of the 151 symptomatic patients who were not health care personnel, we obtained data on

130 (86.1%), by telephone interview (89 [58.9% ]), review of medical charts (122 [80.8% ]),

or both (81 [53.6% ]). The inability to reach a patient by telephone was attributable to a lack

of an available phone number or four unsuccessful calling attempts. Among the 130

symptomatic patients who were not health care personnel and who were called or had

medical charts reviewed, exposures before the onset of illness could be assessed in 112

(86.2%). Exposures before the onset of illness were not assessed in 18 patients owing to

insufficient medical history (Fig. 2). Patients who were contacted by telephone and for

whom potential exposures were assessed were significantly more likely to have been

admitted to an ICU than those for whom we could not assess exposure (P<0.001) (Table 1).

Otherwise, the characteristics that were evaluated were similar in the two groups.

Of the 112 patients with data that could be assessed, 109 (97.3%) had one or more of the

following types of secondary exposures during the 14 days before the onset of symptoms:

admission to a health care facility (37 patients [33.9% ]), visits to a health care facility as a

patient (68 patients [62.4% ]), contact with a patient who had confirmed MERS-CoV

infection (22 patients [20.2% ]), or contact with someone with a severe respiratory illness of

unknown cause (4 patients [3.7% ]) (Table 2). Only 3 of the 112 symptomatic patients who

were not health care personnel (2.7%) reported no secondary exposures. Overall, 98 patients

(87.5%) had exposure to a health care facility and 14 (12.5%) did not.

Among the 68 visits to a health care facility during the 14 days preceding the onset of

illness, 35 (51%) were related to renal dialysis. Eighteen patients visited family members or

friends in a health care facility, and 11 of these patients reported that this visitation was their

only health care–related exposure. Among the 37 admissions to a health care facility during

Oboho et al. Page 5

N Engl J Med. Author manuscript; available in PMC 2017 December 01.

A u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t

the 14 days preceding the onset of illness, the median interval between admission and the

onset of MERS-CoV symptoms was 11 days (interquartile range, 7 to 23).

Of the 64 patients who were originally identified as being asymptomatic, 33 (52%) were

available for the telephone survey. There were no significant differences in demographic

characteristics between the 33 patients who responded to the telephone survey and the 31

patients who did not respond. Table 3 lists the demographic characteristics of these patients,

reasons for testing, and symptoms reported. Of note, 73% of the patients were health care

personnel. Twenty-six of the 33 asymptomatic patients who were reached by telephone

(79%) reported at least one symptom in the month before testing, and 23 (70%) reported

more than one symptom. Unexpectedly, 12 of the 33 patients surveyed (36%) reported the

presence of signs and symptoms as the reason for MERS-CoV testing, even though they had

been identified as being asymptomatic (Table 3).

Discussion

The outbreak of MERS-CoV infections in Jeddah raised international concern and led to

widespread speculation regarding possible causes. We found that the marked increase in the

number of patients with MERS-CoV infection in Jeddah could be explained by secondary

human-to-human transmission and amplification in health care facilities, rather than by a

sudden increase in primary cases in the community. We determined that the vast majority of

patients with reported MERS-CoV infection in the Jeddah region from January 1 through

May 16, 2014, had potential exposure to other patients with MERS-CoV infection, mostly in

health care settings. We could not identify these exposures in 3 of 112 symptomatic patients

who were not health care personnel (2.7%) and who had data that could be assessed. Efforts

to identify risk factors for community transmission, including exposure to animals, are

ongoing in Saudi Arabia and were not part of this investigation. We provide a further

description of reportedly asymptomatic MERS-CoV patients, the majority of whom were

health care personnel in clinical settings. We were able to elicit a history of symptoms in a

majority of patients, and a substantial proportion reported the presence of symptoms as the

reason for testing for MERS-CoV infection. These findings warrant further investigation.

Our study had several limitations. On the basis of the epidemiology of MERS-CoV to date,

we considered the risk of MERS-CoV transmission to be higher in health care facilities than

in the community. We thus designated cases as being potentially health care–associated if we

could document an exposure to a health care setting or a patient with MERS-CoV infection

during the 14 days before the onset of illness.19 Given this, it is possible that among patients

with frequent visits to health care facilities, some cases that we designated as health care–

associated could have been primary cases. In addition, because MERS-CoV testing is

ordered at the discretion of the treating health care personnel, the decision to test could be

biased toward certain features such as access to health care, demographic characteristics, or

underlying disease. Second, for patients in whom the onset of illness was unclear, we used

the date of MERS-CoV testing, the date of clinical deterioration (e.g., admission to an ICU),

or the date of onset of MERS-CoV–related symptoms. Although the onset of illness was

unclear in a small number of patients, these patients had frequent health care–related

exposures that could have provided multiple opportunities for MERS-CoV transmission.

Oboho et al. Page 6

N Engl J Med. Author manuscript; available in PMC 2017 December 01.

A u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t

Third, some symptomatic patients were not reached by telephone, although assessed

variables indicated that these patients were similar to those who were reached (Table 1). In

addition, although medical histories were supplemented by hospital chart review in most

cases, poor recall may have limited the accuracy of some responses. Fourth, asymptomatic

patients were identified through a variety of methods (e.g., investigation of contacts and

screening of health care workers) and not through routine surveillance. Among health care

personnel, the decision to seek testing may have been influenced by knowledge or

perception of high-risk exposures. However, because we restricted our analysis of secondary

exposures to persons who were not health care personnel, this is unlikely to have affected

our results. Finally, no controls were enrolled for comparison with cases; therefore, we could

not assess the frequency of respiratory symptoms or exposure to health care facilities in this

population.

The large proportion of reported cases associated with exposure to health care facilities

highlights the importance of implementation of infection-control practices to limit

transmission. Our results show a wide range of clinical presentations associated with MERS-

CoV in various locations within health care facilities. These findings underscore the need to

strengthen infection prevention and control practices throughout health care facilities,

including early recognition and care of patients who are potentially infected with MERS-

CoV and who present with mild disease. Saudi Arabia has recently revised its Ministry of

Health MERS-CoV surveillance case definitions and infection-control guidance.18 This

revision has been accompanied by intensive efforts to improve case detection, testing, and

reporting. Efforts are ongoing to strengthen infection-control practices throughout Saudi

Arabia.

Acknowledgments

The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Supported by the Ministry of Health, Saudi Arabia, and the U.S. Centers for Disease Control and Prevention.

We thank the following persons who assisted with identifying patients, abstracting medical records, and reporting case data: Ministry of Health, Saudi Arabia: Dr. Banan M. Alamoudi, Dr. Ghadi F. Subahi, Dr. Maram Al Mohammadi, Dr. Mohammed S. Kutbi, Dr. Omima Shabouni, Dr. Ziad Bin-Saad, and Nahed Batarfi; King Fahd General Hospital: Dr. Imad A. Al-Jahdali, Dr. Mohammed A. Garout, Dr. Areej Bin-Sadiq, Dr. Kholoud Alsulaimani, Dr. Reham M. Gandeh, and Arwa A. Sebaih; King Faisal Specialist Hospital: Dr. Bakr Bin-Sadiq, Ms. Hanadi S. Al-Salmi, and Richard Sanvictores; King Abdulaziz General Hospital: Dr. Mohammad F. Al-Mobarak and Dr. Aisha Mutwalli; King Abdulaziz University Hospital: Dr. Nabeela A. Al-Abdullah and Dr. Anees Sindi; King Saud Hospital: Dr. Batool M.S. Ali and Dr. Dalya M. Atallah; Erfan Hospital: Dr. Azza Khattab; United Doctors Hospital: Dr. Nuha Mirza; Saudi German Hospital: Dr. Khaled Batterjee, Dr. Wael Alganaini, Dr. Jehan Ibrahim, Sally Barr, and Mostafa Nasar; International Medical Center: Dr. Mujahed Abbas and Dr. Raya Jabar; Fakeeh Hospital: Dr. Samar A. Badreddine; National Guard Hospital: Dr. Abdulhakeem Al-Thaqafi; Bakhsh Hospital: Suseela Koruthu; Al-Jedani Hospital: Dr. Ibrahim Hassan and Sally Diwa; Centers for Disease Control and Prevention: Dr. Rima Khabbaz, Dr. John Jernigan, Dr. Allison Arwady, Dr. Colin Basler, Dr. Andrew Geller, Dr. Concepcion Estivariz, and Dr. Glen Abedi. We also thank Miss Fadwa Mushtag for assistance with preparation of an earlier version of the manuscript.

References

1. The WHO MERS-CoV Research Group. State of knowledge and data gaps of Middle East respiratory syndrome coronavirus (MERS-CoV) in humans. PLOS Currents Outbreaks. 2013.

Oboho et al. Page 7

N Engl J Med. Author manuscript; available in PMC 2017 December 01.

A u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t

(http://currents.plos.org/outbreaks/article/state-of-knowledge-and-data-gaps-of-middle-east- respiratory-syndrome-coronavirus-mers-cov-in-humans-2)

2. Middle East respiratory syndrome coronavirus (MERS-CoV) — update. World Health Organization; Jun 11. 2014 (http://www.who.int/csr/don/2014_06_11_mers/en)

3. Middle East respiratory syndrome coronavirus (MERS-CoV) summary and literature update — as of 9 May 2014. World Health Organization; 2014. (http://www.who.int/csr/disease/ coronavirus_infections/MERS_CoV_Update_09_May_2014pdf?ua=1)

4. Middle East respiratory syndrome coronavirus (MERS-CoV) summary and literature update — as of 11 June 2014. World Health Organization; 2014. (http://www.who.int/csr/disease/ coronavirus_infections/MERS-CoV_summary_update_20140611.pdf)

5. WHO risk assessment: Middle East respiratory syndrome coronavirus. World Health Organization; Apr 24. 2014 (http://www.who.int/csr/disease/coronavirus_infections/ MERS_CoV_RA_20140424.pdf?ua=1)

6. Azhar EI, El-Kafrawy SA, Farraj SA, et al. Evidence for camel-to-human transmission of MERS coronavirus. N Engl J Med. 2014; 370:2499–505. [PubMed: 24896817]

7. Haagmans BL, Al Dhahiry SH, Re-usken CB, et al. Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect Dis. 2014; 14:140–5. [PubMed: 24355866]

8. Update on MERS-CoV transmission from animals to humans, and interim recommendations for at- risk groups. World Health Organization; Jun 13. 2014 (http://www.who.int/csr/disease/ coronavirus_infections/MERS_CoV_RA_20140613.pdf)

9. Middle East respiratory syndrome coronavirus summary and literature update — as of 27 March 2014. World Health Organization; 2014. (http://www.who.int/csr/disease/coronavirus_infections/ MERS_CoV_Update_27_March_2014.pdf?ua=1)

10. Memish ZA, Zumla AI, Al-Hakeem RF, Al-Rabeeah AA, Stephens GM. Family cluster of Middle East respiratory syndrome coronavirus infections. N Engl J Med. 2013; 368:2487–94. [PubMed: 23718156]

11. Assiri A, McGeer A, Perl TM, et al. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med. 2013; 369:4, 07–16.

12. Al-Abdallat MM, Payne DC, Alqasrawi S, et al. Hospital-associated outbreak of Middle East respiratory syndrome corona-virus: a serologic, epidemiologic, and clinical description. Clin Infect Dis. 2014; 59:1225–33. [PubMed: 24829216]

13. Gulland A. WHO voices concern over rising numbers of MERS-CoV cases. BMJ. 2014; 348:g2968. [PubMed: 24778282]

14. Soaring MERS cases cause pandemic jitters, but causes are unclear. Science Insider. 2014. (http:// news.sciencemag.org/health/2014/04/soaring-mers-cases-cause-pandemic-jitters-causes-are- unclear)

15. Drosten C, Muth D, Corman VM, et al. An observational, laboratory-based study of outbreaks of Middle East respiratory syndrome coronavirus in Jeddah and Riyadh, Kindom of Saudi Arabia. Clin Infect Dis. 2015; 60:369–77. [PubMed: 25323704]

16. Madani TA, Althaqafi AO, Alraddadi BM. Infect ion prevent ion and control guidelines for patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Saudi Med J. 2014; 35:897–913. [PubMed: 25129197]

17. Madani TA. Case definition and management of patients with MERS coronavirus in Saudi Arabia. Lancet Infect Dis. 2014; 14:911–3. [PubMed: 25253396]

18. Case definition and surveillance guidance for MERS-CoV testing in Saudi Arabia. Kingdom of Saudi Arabia Ministry of Health. May 13. 2014 (http://www.moh.gov.sa/en/CoronaNew/ Regulations/MoHCaseDefinitionMERSCoVVersionMay132014.pdf)

19. Case-control study to assess potential risk factors related to human illness caused by Middle East respiratory syndrome coronavirus (MERS-CoV). World Health Organization; Jul 15. 2014 (http:// www.who.int/csr/disease/coronavirusinfections/MERSCoVCaseControlStudyofExposures.pdf? ua=1)

Oboho et al. Page 8

N Engl J Med. Author manuscript; available in PMC 2017 December 01.

A u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t

20. Poissy J, Goffard A, Parmentier-Decrucq E, et al. Kinetics and pattern of viral excretion in biological specimens of two MERS-CoV cases. J Clin Virol. 2014; 61:275–8. [PubMed: 25073585]

Oboho et al. Page 9

N Engl J Med. Author manuscript; available in PMC 2017 December 01.

A u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t

Figure 1. Laboratory-Confirmed Cases of MERS-CoV Infection The date of onset of symptoms is shown for symptomatic patients, and the date of testing for

MERS-CoV is shown for asymptomatic patients.

Oboho et al. Page 10

N Engl J Med. Author manuscript; available in PMC 2017 December 01.

A u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t

Figure 2. Characteristics of Patients with Confirmed MERS-CoV Infection

Oboho et al. Page 11

N Engl J Med. Author manuscript; available in PMC 2017 December 01.

A u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t

A u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t

Oboho et al. Page 12

Ta b

le 1

C ha

ra ct

er is

ti cs

o f

A ll

P at

ie nt

s w

it h

L ab

or at

or y-

C on

fi rm

ed M

E R

S -C

oV I

nf ec

ti on

a nd

o f

S ym

pt om

at ic

P at

ie nt

s W

ho W

er e

N ot

H ea

lt h

C ar

e P

er so

nn el

.*

C h

ar ac

te ri

st ic

A ll

P at

ie n

ts w

it h

L

ab or

at or

y- C

on fi

rm ed

In

fe ct

io n

( N

= 2

55 )

S ym

p to

m at

ic P

at ie

n ts

W h

o W

er e

N ot

H ea

lt h

C ar

e P

er so

n n

el (

N =

1 51

)

A ll

P at

ie n

ts (

N =

1 51

) D

at a

N ot

A ss

es se

d (

N =

3 9)

D at

a A

ss es

se d

( N

= 1

12 )

n on

pr im

ar y

ca se

( N

= 1

09 )

P ot

en ti

al p

ri m

ar y

ca se

( N

= 3

)

A ge

— y

r

M

ed ia

n 45

54 53

54 55

In

te rq

ua rt

il e

ra ng

e† 30

-5 9

37 -6

4 30

-6 5

41 -6

4 49

-5 6

M al

e se

x —

n o.

( %

) 17

4 (6

8) 11

8 (7

8) 33

( 85

) 82

( 75

) 3

(1 00

)

S au

di A

ra bi

an —

n o.

( %

) 14

0 (5

5) 10

0 (6

6) 27

( 69

) 72

( 66

) 1

(3 3)

A dm

is si

on t

o in

te ns

iv e

ca re

u ni

t —

n o.

( %

)‡ 93

( 36

) 78

( 52

) 11

( 28

) 66

( 61

) 1

(3 3)

D ie

d —

n o.

( %

) 93

( 36

) 89

( 59

) 20

( 51

) 68

( 62

) 1

(3 3)

A sy

m pt

om at

ic —

n o.

( %

) 64

( 25

) N

A N

A N

A N

A

H ea

lt h

ca re

p er

so nn

el —

n o.

( %

) 78

( 31

) N

A N

A N

A N

A

* N A

d en

ot es

n ot

a pp

li ca

bl e.

† T he

r an

ge f

or a

ll p

at ie

nt s

w as

3 m

on th

s to

9 4

ye ar

s, f

or p

at ie

nt s

w it

h da

ta t

ha t

w er

e no

t as

se ss

ed 3

m on

th s

to 9

0 ye

ar s,

f or

n on

pr im

ar y

ca se

s 7

to 9

4 ye

ar s,

a nd

f or

p ot

en ti

al p

ri m

ar y

ca se

s 49

t o

56 y

ea rs

.

‡ P <

0. 00

1 by

t he

c hi

-s qu

ar e

te st

f or

t he

c om

pa ri

so n

of t

he g

ro up

o f

pa ti

en ts

w it

h da

ta t

ha t

w er

e no

t as

se ss

ed a

nd t

he g

ro up

o f

pa ti

en ts

w it

h da

ta t

ha t

w er

e as

se ss

ed .

N Engl J Med. Author manuscript; available in PMC 2017 December 01.

A u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t

Oboho et al. Page 13

Table 2

Types of Secondary Exposure to MERS-CoV in 109 Patients within 14 days before Onset of Symptoms.*

Source of Exposure No. of Patients (%)

Admission to a health care facility for treatment 37 (34)

Cardiopulmonary disease† 9 (8)

Surgery 5 (5)

Gastrointestinal disease‡ 4 (4)

Bloodstream infection 3 (3)

Endocrine disease 3 (3)

Neurologic disease 3 (3)

Cancer or immunosuppression 3 (3)

Skin and soft-tissue infection 3 (3)

Renal disease 2 (2)

Vascular disease 2 (2)

Outpatient visit to a health care facility for treatment 68 (62)

Emergency department

Cardiovascular disease 3 (3)

Gastrointestinal disease 3 (3)

Trauma 2 (2)

Outpatient facility

Renal dialysis 35 (32)

Endocrine disease 2 (2)

Cancer 2 (2)

Cardiovascular disease 1 (1)

Prenatal visit 1 (1)

General clinic visit 1 (1)

Visit to a patient at a health care facility 18 (17)

Potential case contact not related to exposure at a health care facility 26 (24)

Contact with a patient with a confirmed MERS-CoV infection 22 (20)

Contact with a person with a severe respiratory illness of unknown cause 4 (4)

* Patients may have had more than one type of exposure. No secondary exposures were detected in 3 of 112 symptomatic patients who were not

health care personnel (2.7%) and who had confirmed infection.

† Admissions related to the cardiopulmonary system included congestive heart failure, chronic obstructive pulmonary disease, cardiomyopathy,

myocardial infarction, mitral stenosis, chest pain, and hypotension.

‡ Admissions related to the gastrointestinal system included intestinal hemorrhage, perforated intestine, hepatic encephalopathy, and anorexia.

N Engl J Med. Author manuscript; available in PMC 2017 December 01.

A u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t A

u th

o r M

a n u scrip

t

Oboho et al. Page 14

Table 3

Demographic Characteristics, Reasons for Testing, and Signs and Symptoms Reported within 1 Month before

Testing among 33 Patients Initially Reported as Being Asymptomatic.

Characteristic All Patients R (N = 33) eported No Symptoms (N = 7) Reported Symptoms (N = 26)

Demographic characteristics and medical history

Age — yr

Median 35 29 36

Interquartile range* 27-51 28-37 26-52

Male sex — no. (%) 20 (61) 2 (29) 18 (69)

Saudi Arabian — no. (%) 14 (42) 3 (43) 11 (42)

Health care personnel — no. (%) 24 (73) 6 (86) 18 (69)

Underlying illness — no. (%) 14 (42) 1 (14) 13 (50)

Reason for test — no. (%)

Contact investigation 5 (15) 3 (43) 2 (8)

Screening of health care worker 15 (45) 4 (57) 11 (46)

Presence of signs and symptoms 12 (36) 0 12 (46)

Signs and symptoms — no. (%)

Fever 16 (48) NA 16 (62)

Cough 13 (39) NA 13 (50)

Shortness of breath 11 (33) NA 11 (42)

Fatigue 9 (27) NA 9 (35)

Nausea and vomiting 6 (18) NA 6 (23)

Rhinorrhea 5 (15) NA 5 (19)

Sore throat 5 (15) NA 5 (19)

Diarrhea 4 (12) NA 4 (15)

Chills 3 (9) NA 3 (12)

Muscle pain 3 (9) NA 3 (12)

Headache 3 (9) NA 3 (12)

Chest pain 2 (6) NA 2 (8)

Loss of appetite 2 (6) NA 2 (8)

Abdominal pain 1 (3) NA 1 (4)

Conjunctivitis 1 (3) NA 1 (4)

Night sweats 1 (3) NA 1 (4)

Rash 1 (3) NA 1 (4)

More than one sign or symptom 23 (70) NA 23 (88)

Fever, cough, and shortness of breath 7 (21) NA 7 (27)

* The range for all patients was 1 to 71 years, for patients who reported no symptoms 26 to 43 years, and for patients who reported symptoms 1 to

71 years.

N Engl J Med. Author manuscript; available in PMC 2017 December 01.