Signa Vitae. 2022; 18(4): 68-74. doi: 10.22514/sv.2021.251
Original Research

Epidemiological characteristics and initial clinical presentation of patients with laboratory-confirmed MERS-CoV infection in an emergency department

Zohair Al Aseri1,*,, Jaffar A. Al-Tawfiq2,3,4, Mohammed Alnakhli5, Abdullah AlNooh5, Abdulaziz Alnassar5, Salah Alkhalid5, Abdulaziz Al Dughayman5, Tariq Wani6, Abdulkarim Alhetheel7, Mazin Barry8

1Departments of Emergency Medicine and Critical Care, College of Medicine, King Saud University, 11472 Riyadh, Saudi Arabia

2Specialty Internal Medicine and Quality Department, Johns Hopkins Aramco Healthcare, 31311 Dhahran, Saudi Arabia

3Infectious Disease Division, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA

4Infectious Disease Division, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

5Clinical Sciences Department, College of Medicine, Dar Al Uloom University, 13314 Riyadh, Saudi Arabia

6Research Center, King Fahad Medical City, 11525 Riyadh, Saudi Arabia

7Department of Pathology and Laboratory Medicine, College of Medicine, King Saud University, 11472 Riyadh, Saudi Arabia

8Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, King Saud University, 11472 Riyadh, Saudi Arabia

*Corresponding Author(s):zohairalaseri@yahoo.com; zalaseri@ksu.edu.sa (Zohair Al Aseri)

History Submitted: 13 September 2021 | Accepted: 25 November 2021 | Published: 08 July 2022
Copyright:  ©2022  The Author(s). Published by MRE Press.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).

Collapse table of contents

Abstract

Emergency departments have been implicated as a source of index cases of the Middle East Respiratory Syndrome (MERS) coronavirus infection. We describe the epidemiological characteristics and initial clinical presentation of patients with Middle East respiratory syndrome coronavirus infection in an emergency department at a hospital in Riyadh, in the Kingdom of Saudi Arabia. The records of all patients presenting to the emergency department who tested positive for Middle East respiratory syndrome coronavirus infection on real-time reverse transcriptase polymerase chain reaction testing from April 2014 to November 2019 were reviewed, and the outcomes were assessed. The clinical presentations and outcomes were compared according to sex. A total of 68 patients with Middle East respiratory syndrome coronavirus infection were identified, of whom 40 (58.8%) were female, and 28 (41.2%) were male. The mean age was 50.7 (standard deviation: 16.4) years, and female patients were younger (44.7 ± 13.1 years) than male patients (59.4 ± 16.9 years). Nineteen of the 68 patients (27.9%) were asymptomatic of whom the majority (16/19, 84%) were female (p = 0.012). The most common symptoms were fever (n = 29, 42.6%), cough (n = 25, 36.8%), upper respiratory tract infection (n = 23, 33.8%), and pneumonia (n = 15, 22.1%). Pneumonia, diarrhea, dyspnea, and vomiting/diarrhea were more common among male patients. Male patients were more likely than female patients to require hospital admission (78.6% vs. 30.0%), intensive care unit admission (64.3% vs. 15.0%), and invasive mechanical ventilation (32.1% vs. 10.0%). The most common presentation of Middle East respiratory syndrome coronavirus infection in this cohort was asymptomatic infection. A high proportion of asymptomatic infections has not been reported previously. The study did not identify typical clinical features of MERS patients. Male patients tended to develop more severe disease than female patients. A larger study is needed to confirm these findings.

Keywords:MERS-CoV;Emergency department;Clinical presentation;Outbreak
PDF(201.71 kB)|EndNote (RIS)|BibTeX|RefMan|RefWorks

Cite this article

Zohair Al Aseri, Jaffar A. Al-Tawfiq, Mohammed Alnakhli, Abdullah AlNooh, Abdulaziz Alnassar, Salah Alkhalid, Abdulaziz Al Dughayman, Tariq Wani, Abdulkarim Alhetheel, Mazin Barry. Epidemiological characteristics and initial clinical presentation of patients with laboratory-confirmed MERS-CoV infection in an emergency department. Signa Vitae. 2022; 18(4): 68-74. doi: 10.22514/sv.2021.251

1. Introduction

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first described in the Kingdom of Saudi Arabia (KSA) in 2012 in a man with severe pneumonia [1]. Subsequently, it spread to 27 countries. By the end of June 2021, 2574 laboratory-confirmed cases, and 886 deaths, have been reported, with a case fatality ratio (CFR) of 34.4%. Most cases (n = 2174) occurred in KSA, including 808 deaths (CFR: 37.2%) [2]. MERS-CoV infection has a wide spectrum of presentations, ranging from asymptomatic to acute respiratory distress syndrome [3, 4]. However, there are currently no specific treatments or vaccines for MERS-CoV infection, and the virus is included in the World Health Organization (WHO) Research and Development Blueprint priority list because it poses a high public health risk [5].

The main hallmark of Middle East respiratory syndrome (MERS) is healthcare-associated outbreaks, most of which have occurred in KSA and South Korea [6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27]. Emergency departments have been implicated as the initial source of the index cases in several such outbreaks [23]. Although various MERS outbreaks are well described, limited data on patients’ initial presentation in the emergency department are available. This information is vital for the early detection of the disease and to help prevent future outbreaks.

This study aimed to describe the epidemiological characteristics and initial clinical presentation of patients with laboratory-confirmed MERS-CoV infection admitted to an emergency department at a tertiary care university hospital in Riyadh, KSA over a 5-year period. We also compared presentations and outcomes according to sex.

2. Materials and methods

2.1 Study site and study population

This study was conducted at a university hospital in Riyadh, KSA after approval by the institutional review board and ethics committee. In this study, we included MERS-CoV infected patients who were seen in the emergency department between April 2014 and November 2019. All patients who met the clinical criteria for the definition of MERS, with MERS-CoV infection confirmed by polymerase chain reaction (PCR) testing of either a nasopharyngeal swab or lower respiratory tract specimen, were included in the study. Patient demographics and clinical data were obtained from electronic health records within the hospital system and manually from the medical records department.

2.2 Detection of MERS-CoV using reverse transcription polymerase chain reaction

MERS-CoV RNA was detected from nasopharyngeal swabs stored in a sample collection tube containing 3 mL of the viral transport medium (Copan, Brescia, Italy) as previously described [28]. The total RNA was extracted from 400 μL of sample using a MagNA Pure Compact nucleic acid isolation kit I (Roche Diagnostics, Indianapolis, IN) and tested using the MagNA Pure LC system (Roche Applied Science, Indianapolis, IN). The extracted RNA was then eluted in 50 μL of elution buffer. Next, RNA (10 μL) was reverse transcribed to cDNA using random primers. The cDNA was amplified and screened for the MERS-CoV upstream of the E gene (UpE) and the open-reading frame gene 1a (Orf1a) genes using the primers and probes of the RealStar MERS-CoV RT-PCR kit (Altona Diagnostics, Hamburg, Germany) and Rotor-Gene Q system (Qiagen, Santa Clarita, CA). A patient was considered positive if both the UpE and Orf1a genes were detected.

2.3 Statistical analyses

SPSS software (version 21.0; IBM Corp., Armonk, NY, USA) was used for data analysis. Categorical data were reported as frequencies and percentages, and continuous data were reported as the mean and standard deviation (mean ±SD). A 95% confidence interval (CI) was used to draw statistical inferences. The Kolmogorov–Smirnov test based on patient sex confirmed that age, oxygen saturation, systolic blood pressure, and respiratory rate showed a skewed distribution. Similarly, oxygen saturation, systolic blood pressure, and respiratory rate showed skewed distributions according to survival status. Inter-group comparisons of the variables with a skewed distribution were performed using the Mann–Whitney U test, whereas normally distributed data were compared using Student’s t-test. The chi-square test was used to measure the associations between categorical variables and the underlying dependent variables. All significantly associated variables in the univariate analysis were included for backward stepwise multivariable logistic regression analysis. Results were presented as adjusted odds ratios with 95% CIs.

3. Results

A total of 68 patients were admitted to the emergency department with MERS-CoV-2 infection during the study period, of whom 40 (58.8%) were female and 28 (41.2%) were male (Table 1). Most of the male patients (64.3%) were Saudi nationals, whereas most of the female patients (67.5%) were non-Saudi nationals (p < 0.001). The mean age of the female patients was 44.7 ± 13.1 years; 57.5% were aged 31–50 years. The mean age of the male patients was 59.4 ± 16.9 years; 50.0% were aged >60 years (p = 0.005). A history of contact with another MERS case was more common in female patients (42.5%) than in male patients (17.9%). Flu-like symptoms were more common in female patients than in male patients (p = 0.002) (Table 1).

Table 1.Socio-demographic characteristics of patients with MERS-CoV–positive patients infection stratified by sex (n = 68).
CharacteristicsFemaleMaleTotalp value
(n = 40, 58.8%)(n = 28, 41.2%)(n = 68)
Nationality<0.001
Saudi national11 (27.5)18 (64.3)29 (42.6)
Non-national27 (67.5)5 (17.9)32 (47.1)
Unknown2 (5.0)5 (17.9)7 (10.3)
Age, mean ± SD [range], (years)44.7 ± 13.1 [25–75]59.4 ± 16.9 [22–88]50.7 ± 16.4 [22–88]0.005
≤304 (10.0)2 (7.1)6 (8.8)
31–4015 (37.5)2 (7.1)17 (25.0)
41–508 (20.0)3 (10.7)11 (16.2)
51–607 (17.5)7 (25.0)14 (20.6)
61–704 (10.0)5 (17.9)9 (13.2)
>702 (5.0)9 (32.1)11 (16.2)
Diagnosis0.002
Exposure to other MERS cases17 (42.5)5 (17.9)22 (32.4)
Flu-like symptoms8 (20.0)2 (7.1)10 (14.7)
Pneumonia1 (2.5)7 (25.0)8 (11.8)
Testing14 (35.0)14 (50.0)28 (41.1)
Data are presented as n (%) unless otherwise specified.

The clinical characteristics of the patients included fever (n = 29, 42.6%), cough (n = 25, 36.8%), upper respiratory tract symptoms (n = 23, 33.8%), dyspnea (n = 14, 50%), vomiting and diarrhea (n = 8, 28.6%), and pneumonia (n = 11, 39.3%) (Table 2). There were significantly more asymptomatic cases in female patients (n = 16, 40%) than in male patients (n = 3, 10.7%). The incidence of cough (n = 25, 36.8%) and upper respiratory infection (n = 23, 33.8%), which did not differ significantly according to sex.

Table 2.Clinical characteristics of patients with MERS-CoV infection stratified by sex (n = 68).
CharacteristicsFemaleMaleTotalp value
(n = 40, 58.8%)(n = 28, 41.2%)(n = 68)
Fever10 (25.0)19 (67.9)29 (42.6)0.001
Cough14 (35.0)11 (39.3)25 (36.8)0.801
Sputum6 (15.0)5 (17.9)11 (16.2)0.753
Hemoptysis0 (0.0)0 (0.0)0 (0.0)1.000
Dyspnea5 (12.5)14 (50.0)19 (27.9)0.001
Fatigue4 (10.0)6 (21.4)10 (14.7)0.190
Myalgia/arthralgia4 (10.0)5 (17.9)9 (13.2)0.471
Abdominal pain6 (15.0)3 (10.7)9 (13.2)0.727
Vomiting/diarrhea3 (7.5)8 (28.6)11 (16.2)0.041
Headache1 (2.5)3 (10.7)4 (5.9)0.298
Confusion1 (2.5)3 (10.7)4 (5.9)0.298
Asymptomatic16 (40.0)3 (10.7)19 (27.9)0.012
Upper respiratory infection12 (30.0)11 (39.3)23 (33.8)0.462
Pneumonia4 (10.0)11 (39.3)15 (22.1)0.007
Data are presented as n (%).

More than 50% of patients had a medical history of chronic kidney disease (CKD), diabetes mellitus, hypertension, respiratory illness (asthma, pneumonia), or other chronic disease (Table 3). CKD was the only condition that differed significantly according to sex and was significantly more common in males (n = 6, 21.4% vs. n = 0, 0%; p = 0.003). Cardiac disease was observed in 14 (21.2%) patients and was significantly higher in male patients (37.0%) than in female patients (10.3%). The incidence of other chronic diseases was very low and, thereby, did not show any significant difference between both sexes.

Table 3.Medical history of patients with MERS-CoV infection, stratified by sex (n= 68).
CharacteristicsFemaleMaleTotalp value
(n = 40, 58.8%)(n = 28, 41.2%)(n = 68)
Chronic kidney disease0 (0.0)6 (21.4)6 (8.8)0.003
Diabetes mellitus6 (15.0)6 (21.4)12 (17.6)0.532
Hypertension7 (17.5)4 (14.3)11 (16.2)>0.999
Respiratory tract infections (asthma, pneumonia)6 (15.0)4 (14.3)10 (14.7)>0.999
Other chronic medical conditions6 (15.0)1 (3.6)7 (10.3)0.226
Any chronic medical condition18 (45.0)16 (57.1)34 (50.0)0.460
Data are presented as n (%).

Of all patients, 50% required admission, 35.3% needed ICU, and 19.1% needed assisted ventilation (Table 4). There was a difference between male patients and female patients in terms of the need for ventilation and hospital and ICU admission (Table 4).

Table 4.In-hospital evaluation of patients with MERS-CoV infection, stratified by sex (n = 68).
CharacteristicFemaleMaleTotalp value
(n = 40, 58.8%)(n = 28, 41.2%)(n = 68)
Radiology evaluation
Done11 (27.5)16 (57.1)27 (39.7)0.014
Normal6 (15.0)2 (7.1)8 (11.8)0.003
Unilateral infiltration1 (2.5)6 (21.4)7 (10.3)0.013
Bilateral infiltration4 (10.0)8 (28.6)12 (17.6)0.048
Required hospital admission12 (30.0)22 (78.6)34 (50.0)<0.001
Required intensive unit care6 (15.0)18 (64.3)24 (35.3)<0.001
Required assisted ventilation4 (10.0)9 (32.1)13 (19.1)0.030
Acute lung injury/acute respiratory distress syndrome2 (5.0)4 (14.3)6 (8.8)0.220
Acute kidney injury1 (2.5)5 (17.9)6 (8.8)0.074
Liver dysfunction1 (2.5)2 (7.1)3 (4.4)0.564
Rhabdomyolysis0 (0.0)0 (0.0)0 (0.0)>0.999
Pneumothorax0 (0.0)1 (3.6)1 (1.5)0.412
Arrhythmias1 (2.5)3 (10.7)4 (5.9)0.298
Disseminated intravascular coagulation0 (0.0)0 (0.0)0 (0.0)>0.999
Seizures0 (0.0)0 (0.0)0 (0.0)>0.999
Cardiac disease4 (10.3)10 (37.0)14 (21.2)0.014
Final outcome0.179
Survived36 (90.0)21 (75.0)57 (83.8)
Died in hospital4 (10.0)7 (25.0)11 (16.2)
Data are presented as n (%).

The mean oxygen saturation in male patients (93.6 ± 7%) was significantly lower than in female patients (97.6 ± 3.7%). However, differences in heart rate, systolic blood pressure, diastolic blood pressure, and respiratory rate were not significantly different between the sexes (Table 5).

Table 5.Vital signs of patients with MERS-CoV infection, stratified by sex (n = 68).
CharacteristicFemaleMaleTotalp value
(n = 40, 58.8%)(n = 28, 41.2%)(n = 68)
Oxygen saturation (%)97.6 ± 3.7 [83–100]93.6 ± 7 [65–100]95.9 ± 5.6 [65–100]0.004
Heart rate (beats/min)88.1 ± 15.2 [57–117]87.5 ± 16 [60–120]87.9 ± 15.4 [57–120]0.876
Systolic blood pressure (mmHg)129.7 ± 19.7 [100–177]131.2 ± 25.1 [63–189]130.3 ± 21.8 [63–189]0.798
Diastolic blood pressure (mmHg)71.5 ± 10.4 [45–95]68.7 ± 12.4 [43–88]70.4 ± 11.2 [43–95]0.319
Respiratory rate (breaths/min)20.2 ± 4 [16–40]22 ± 6.9 [16–46]20.9 ± 5.4 [16–46]0.213
Data are presented as mean ± SD [range].

Compared with female patients, male patients were more likely to have unilateral (21.4%) and bilateral (28.6%) infiltrations (Table 6). Male patients were also significantly more likely to be admitted to hospital (78.6% vs. 30.0%), or the ICU (64.3% vs. 15.0%), and to need assisted ventilation (32.1% vs. 10.0%) (Table 6). The survival rate was higher in female patients (n = 36, 90%) than in male patients (n = 21, 75%); however, this difference was not statistically significant.

Table 6.Multivariable logistic regression analysis of sex-dependent variables.
VariablesDescriptionOR [95% CI]p value
Step 1NationalitySaudi nationalReference0.132
Non-national0.04 [0–3.51]0.158
Unknown21.15 [0.57–784]0.098
DiagnosisExposureReference0.435
Flu-like symptoms0.77 [0.03–17.26]0.867
Pneumonia0.01 [0–39.55]0.279
Routine testing0.34 [0.01–7.82]0.999
Unrelated0 [0–2.97]0.092
SymptomFever0.03 [0–3.43]0.145
Dyspnea4.67 [0.22–97.39]0.320
Vomiting/diarrhea8.21 [0.12–580]0.332
Asymptomatic0.02 [0–2.92]0.121
Medical historyChronic kidney disease21.82 [1.16–409.25]0.999
Radiological evaluation0.47 [0.02–8.84]0.611
Hospital admission18.26 [0.09–3730]0.284
Need for intensive care unit care76.63 [0.22–26500]0.146
Assisted ventilation0.24 [0–12]0.473
Cardiac disease2.31 [0.18–28.98]0.515
Outcome (died)0.04 [0–2.13]0.114
Age (year)1.1 [0.99–1.21]0.075
Oxygen saturation (%)0.98 [0.92–1.04]0.471
Step 12Asymptomatic0.19 [0.04–0.96]0.045
Cardiac disease5.89 [1.09–31.74]0.039
Age (year)1.09 [1.04–1.14]0.001
Oxygen saturation (%)0.95 [0.93–0.98]<0.001
OR, odds ratio; CI, confidence interval.

In the logistic regression analysis comparing male and female patients, male patients were significant less likely to have asymptomatic disease (odds ratio [OR]: 0.19, 95% CI: 0.04–0.96), and similarly low levels of oxygen saturation in patients were predicted (0.95, 95% CI: 0.93–0.98). However, male patients had a significantly greater risk of cardiac disease (OR: 5.89, 95% CI: 1.09–31.74), and the male patients were significantly older (OR: 1.09, 95% CI: 1.04–1.14).

4. Discussion

In this study, we evaluated the epidemiological characteristics and initial clinical presentations of patients with laboratory-confirmed MERS-CoV infection admitted to an emergency department of a tertiary hospital in KSA. In this study, 58.8% of the cases were among females and 41.2% were males. This finding is dissimilar from the initial studies. The initial cases of MERS-CoV were thought to have male predominance, with a male-to-female ratio of 2.8–3.3 to 1 [28, 29]. The initial male predominance was related to the nature of the MERS-CoV outbreaks. However, a study describing the largest outbreak of MERS-CoV outside KSA, i.e., in the Republic of Korea, also showed a male predominance [30]. Multiple hypotheses were proposed, including differences in terms of sex, gender roles, social paradigms, culture, and behavioral attributes [31].

In this study, 19 (27%) of the included patients were asymptomatic. The occurrence of asymptomatic patients with MERS-CoV infection is well known. Initial outbreaks of MERS-CoV have been characterized by severe clinical cases [7, 32]. However, the occurrence of asymptomatic cases was also well established. In a study conducted from April 2013 to October 2013, 12.5% of 144 PCR laboratory-confirmed cases were asymptomatic, and this percentage increased to 25.1% among 255 confirmed cases in 2014 [33]. The average prevalence of asymptomatic MERS cases was 9.8% according to previous studies [33, 34]. There was also a variation in the prevalence of asymptomatic patients among different age groups, with higher rates, ranging from 41.9% to 81.8%, reported among children [33]. The contribution of asymptomatic patients to the transmission of MERS-CoV infection has been investigated [33, 35, 36, 37, 38, 39]. In addition, controlling asymptomatic transmission is challenging.

Interestingly, we found that asymptomatic cases were more common among female patients (40%) than among male patients (10.7%). This difference might be secondary to physiological differences or related to the sample size. The most prevalent symptoms of MERS-CoV infection on presentation include non-specific symptoms such as cough and dyspnea [25, 27, 28, 40]. In this study, the prevalence of dyspnea, pneumonia, and fever were more common among male patients than among female patients. To our knowledge, no study has yet described the differences between male and female patients with MERS-CoV infection. Previous studies have noted that 33% of patients with MERS experienced vomiting and diarrhea [7, 23, 27, 28, 40, 41, 42]. In this study, these symptoms were present in 16.2% of patients, with a sex-based difference (males: 28.6%, females: 7.5%). In another study, 62.5% of ICU patients were male, and 37.5% were female [43]. The need for ICU admission and mechanical ventilation was observed in 44.4% and approximately 25–100% of patients, depending on the study population [44]. The need for ICU admission was noted in 35.3% of all patients and was more common among male patients (64.3%) than among female patients (15%). Previous studies have reported that those with severe disease tend to have respiratory failure, acute kidney disease, acute liver injury, and cardiac arrhythmias [7, 27, 41, 45]. The rate of death was associated with the presence of comorbidities (RR = 3), male sex (RR = 1.6), occupational camel exposure (RR = 1.6), and raw milk consumption (RR = 1.5) [46]. In this study, we revealed the differences in presentations and outcomes of MERS-CoV among male and female patients. Such disparities in outcomes and presentations have also been noted among COVID-19 patients, especially among those of different races and nationalities [47, 48, 49].

This study had a few limitations. First, we only analyzed a small sample size limited from a single center. However, the length of the study period was a strength of this study. Second, we did not further evaluate all risk factors pertinent to exposure and the exact source of infection. We also did not have data on the duration of symptoms prior to the presentation, and there was no further analysis of the virus to examine its phylogenetic evolution. In addition, since most of the females were non-Saudi nationals and males were Saudi nationals, the comparison between males and females might be influenced by the nationality. Despite these limitations, this study provided valuable information, especially sex-based differences among MERS patients.

5. Conclusions

The most common symptoms among the diagnosed patients were fever, cough, and dyspnea. The study did not identify typical clinical features of MERS patients. The need for ICU admission and mechanical ventilation were more common among male patients. This study also showed a high rate of asymptomatic cases. Further studies are needed to explore the differences in MERS-CoV presentations and outcomes among different sexes and elucidate the underlying reasons for these differences.

Author contributions

ZAA—designed the study, wrote original draft, reviewed, supervised, and edited; JAAT—wrote original draft, reviewed and edited and corrected English; MA, AAIN, AAln, SA, and AAD—designed the study and data collection and wrote original draft; TW—designed the study, reviewed and edited the result and statistical analysis; AAlh—design and wrote the method; MB—wrote original draft, reviewed and edited and corrected English.

Ethics approval and consent to participate

The study was approved by the intuitional review board of college of medicine and King Khalid University Hospital (approval No. E-17-2369). The need for informed consent has been waived owing to its retrospective nature.

Acknowledgment

This work was supported by the College of Medicine Research Center, Deanship of Scientific Research, King Saud University, Riyadh, Saudi Arabia. We also would like to express our gratitude to all those who helped us during the writing of this manuscript, and all the peer reviewers for their opinions and suggestions.

Funding

This research received no external funding.

Conflict of interest

The authors declare no conflict of interest.

References

Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus ADME, Fouchier RAM. Isolation of a Novel Coronavirus from a Man with Pneumonia in Saudi Arabia. New England Journal of Medicine. 2012; 367: 1814–1820.

[Google Scholar]

World Health Organization Regional Office for the Eastern Mediterranean. Homepage on the Internet. 2021. Available at: http://www.emro.who.int/health-topics/mers-cov/mers-outbreaks.html (Accessed: 1 May 2021).

[Google Scholar]

Al-Tawfiq JA, Memish ZA. Middle East respiratory syndrome coronavirus: transmission and phylogenetic evolution. Trends in Microbiology. 2014; 22: 573–579.

[Google Scholar]

Al-Tawfiq JA, Memish ZA. Middle East Respiratory Syndrome Coronavirus and Severe Acute Respiratory Syndrome Coronavirus. Seminars in Respiratory and Critical Care Medicine. 2020; 41: 568–578.

[Google Scholar]

World Health Organization. Homepage on the Internet. 2021. Available at: https://www.who.int/activities/prioritizing-diseases-for-research-and-development-in-emergency-contexts (Accessed: 1 May 2021).

[Google Scholar]

Drosten C, Muth D, Corman VM, Hussain R, Al Masri M, HajOmar W, et al. An Observational, Laboratory-Based Study of Outbreaks of Middle East Respiratory Syndrome Coronavirus in Jeddah and Riyadh, Kingdom of Saudi Arabia, 2014. Clinical Infectious Diseases. 2015; 60: 369–377.

[Google Scholar]

Assiri A, McGeer A, Perl TM, Price CS, Al Rabeeah AA, Cummings DAT, et al. Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus. New England Journal of Medicine. 2013; 369: 407–416.

[Google Scholar]

Memish ZA, Al-Tawfiq JA, Alhakeem RF, Assiri A, Alharby KD, Almahallawi MS, et al. Middle East respiratory syndrome coronavirus (MERS-CoV): a cluster analysis with implications for global management of suspected cases. Travel Medicine and Infectious Disease. 2015; 13: 311–314.

[Google Scholar]

El Bushra HE, Abdalla MN, Al Arbash H, Alshayeb Z, Al-Ali S, Latif ZA, et al. An outbreak of Middle East Respiratory Syndrome (MERS) due to coronavirus in Al-Ahssa Region, Saudi Arabia, 2015. Eastern Mediterranean Health Journal. 2016; 22: 468–475.

[Google Scholar]

Balkhy HH, Alenazi TH, Alshamrani MM, Baffoe-Bonnie H, Al-Abdely HM, El-Saed A, et al. Notes from the Field: Nosocomial Outbreak of Middle East Respiratory Syndrome in a Large Tertiary Care Hospital—Riyadh, Saudi Arabia, 2015. MMWR. Morbidity and Mortality Weekly Report. 2016; 65: 163–164.

[Google Scholar]

Balkhy HH, Alenazi TH, Alshamrani MM, Baffoe-Bonnie H, Arabi Y, Hijazi R, et al. Description of a Hospital Outbreak of Middle East Respiratory Syndrome in a Large Tertiary Care Hospital in Saudi Arabia. Infection Control & Hospital Epidemiology. 2016; 37: 1147–1155.

[Google Scholar]

Assiri AM, Biggs HM, Abedi GR, Lu X, Bin Saeed A, Abdalla O, et al. Increase in Middle East Respiratory Syndrome-Coronavirus Cases in Saudi Arabia Linked to Hospital Outbreak with Continued Circulation of Recombinant Virus, July 1-August 31, 2015. Open Forum Infectious Diseases. 2016; 3: ofw165.

[Google Scholar]

Nazer RI. Outbreak of Middle East Respiratory Syndrome-Coronavirus Causes High Fatality after Cardiac Operations. The Annals of Thoracic Surgery. 2017; 104: e127–e129.

[Google Scholar]

Assiri A, Abedi GR, Bin Saeed AA, Abdalla MA, al-Masry M, Choudhry AJ, et al. Multifacility Outbreak of Middle East Respiratory Syndrome in Taif, Saudi Arabia. Emerging Infectious Diseases. 2016; 22: 32–40.

[Google Scholar]

Hunter JC, Nguyen D, Aden B, Al Bandar Z, Al Dhaheri W, Abu Elkheir K, et al. Transmission of Middle East Respiratory Syndrome Coronavirus Infections in Healthcare Settings, Abu Dhabi. Emerging Infectious Diseases. 2016; 22: 647–656.

[Google Scholar]

Cauchemez S, Van Kerkhove MD, Riley S, Donnelly CA, Fraser C, Ferguson NM. Transmission scenarios for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and how to tell them apart. Euro Surveillance. 2013; 18: 20503.

[Google Scholar]

Cauchemez S, Fraser C, Van Kerkhove MD, Donnelly CA, Riley S, Rambaut A, et al. Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility. The Lancet. Infectious Diseases. 2014; 14: 50–56.

[Google Scholar]

Al-Abdallat MM, Payne DC, Alqasrawi S, Rha B, Tohme RA, Abedi GR, et al. Hospital-associated outbreak of Middle East respiratory syndrome coronavirus: a serologic, epidemiologic, and clinical description. Clinical Infectious Diseases. 2014; 59: 1225–1233.

[Google Scholar]

Chowell G, Abdirizak F, Lee S, Lee J, Jung E, Nishiura H, et al. Transmission characteristics of MERS and SARS in the healthcare setting: a comparative study. BMC Medicine. 2015; 13: 210.

[Google Scholar]

Barry M, Phan MV, Akkielah L, Al-Majed F, Alhetheel A, Somily A, et al. Nosocomial outbreak of the Middle East Respiratory Syndrome coronavirus: a phylogenetic, epidemiological, clinical and infection control analysis. Travel Medicine and Infectious Disease. 2020; 37: 101807.

[Google Scholar]

Hijawi B, Abdallat M, Sayaydeh A, Alqasrawi S, Haddadin A, Jaarour N, et al. Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation. Eastern Mediterranean Health Journal. 2013; 19: S12–S18.

[Google Scholar]

Al-Tawfiq JA, Memish ZA. Drivers of MERS-CoV transmission: what do we know? Expert Review of Respiratory Medicine. 2016; 10: 331–338.

[Google Scholar]

Oboho IK, Tomczyk SM, Al-Asmari AM, Banjar AA, Al-Mugti H, Aloraini MS, et al. 2014 MERS-CoV outbreak in Jeddah–a link to health care facilities. The New England Journal of Medicine. 2015; 372: 846–854.

[Google Scholar]

Alraddadi B, Bawareth N, Omar H, Alsalmi H, Alshukairi A, Qushmaq I, et al. Patient characteristics infected with Middle East respiratory syndrome coronavirus infection in a tertiary hospital. Annals of Thoracic Medicine. 2016; 11: 128–131.

[Google Scholar]

Fagbo SF, Skakni L, Chu DKW, Garbati MA, Joseph M, Peiris M, et al. Molecular Epidemiology of Hospital Outbreak of Middle East Respiratory Syndrome, Riyadh, Saudi Arabia, 2014. Emerging Infectious Diseases. 2015; 21: 1981–1988.

[Google Scholar]

Almekhlafi GA, Albarrak MM, Mandourah Y, Hassan S, Alwan A, Abudayah A, et al. Presentation and outcome of Middle East respiratory syndrome in Saudi intensive care unit patients. Critical Care. 2016; 20: 123.

[Google Scholar]

Saad M, Omrani AS, Baig K, Bahloul A, Elzein F, Matin MA, et al. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. International Journal of Infectious Diseases. 2014; 29: 301–306.

[Google Scholar]

Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, Al-Rabiah FA, Al-Hajjar S, Al-Barrak A, et al. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. The Lancet. Infectious Diseases. 2013; 13: 752–761.

[Google Scholar]

Al-Tawfiq JA, Assiri A, Memish ZA. Middle East respiratory syndrome novel corona MERS-CoV infection. Epidemiology and outcome update. Saudi Medical Journal. 2013; 34: 991–994.

[Google Scholar]

Jansen A, Chiew M, Konings F, Lee C, Ailan L. Sex matters - a preliminary analysis of Middle East respiratory syndrome in the Republic of Korea, 2015. Western Pacific Surveillance and Response Journal. 2015; 6: 68–71.

[Google Scholar]

Ali MA. Gender dynamics and socio-cultural determinants of Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia. University of Toronto Medical Journal. 2017; 94: 32–37.

[Google Scholar]

Al-Tawfiq JA, Perl TM. Middle East respiratory syndrome coronavirus in healthcare settings. Current Opinion in Infectious Diseases. 2015; 28: 392–396.

[Google Scholar]

Al-Tawfiq JA, Gautret P. Asymptomatic Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection: Extent and implications for infection control: a systematic review. Travel Medicine and Infectious Disease. 2019; 27: 27–32.

[Google Scholar]

Al-Tawfiq JA. Asymptomatic coronavirus infection: MERS-CoV and SARS-CoV-2 (COVID-19). Travel Medicine and Infectious Disease. 2020; 35: 101608.

[Google Scholar]

Al-Tawfiq JA, Auwaerter PG. Healthcare-associated infections: the hallmark of Middle East respiratory syndrome coronavirus with review of the literature. Journal of Hospital Infection. 2019; 101: 20–29.

[Google Scholar]

Al-Gethamy M, Corman VM, Hussain R, Al-Tawfiq JA, Drosten C, Memish ZA. A case of long-term excretion and subclinical infection with Middle East respiratory syndrome coronavirus in a healthcare worker. Clinical Infectious Diseases. 2015; 60: 973–974.

[Google Scholar]

Al-Abdely HM, Midgley CM, Alkhamis AM, Abedi GR, Tamin A, Binder AM, et al. Infectious MERS-CoV Isolated from a Mildly Ill Patient, Saudi Arabia. Open Forum Infectious Diseases. 2018; 5: ofy111.

[Google Scholar]

Corman VM, Albarrak AM, Omrani AS, Albarrak MM, Farah ME, Almasri M, et al. Viral Shedding and Antibody Response in 37 Patients with Middle East Respiratory Syndrome Coronavirus Infection. Clinical Infectious Diseases. 2016; 62: 477–483.

[Google Scholar]

Memish ZA, Assiri AM, Al-Tawfiq JA. Middle East respiratory syndrome coronavirus (MERS-CoV) viral shedding in the respiratory tract: an observational analysis with infection control implications. International Journal of Infectious Diseases. 2014; 29: 307–308.

[Google Scholar]

Al-Tawfiq JA, Hinedi K, Ghandour J, Khairalla H, Musleh S, Ujayli A, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clinical Infectious Diseases. 2014; 59: 160–165.

[Google Scholar]

Arabi YM, Arifi AA, Balkhy HH, Najm H, Aldawood AS, Ghabashi A, et al. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Annals of Internal Medicine. 2014; 160: 389–397.

[Google Scholar]

Shalhoub S, Farahat F, Al-Jiffri A, Simhairi R, Shamma O, Siddiqi N, et al. IFN-α2a or IFN-β1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. The Journal of Antimicrobial Chemotherapy. 2015; 70: 2129–2132.

[Google Scholar]

Halim AA, Alsayed B, Embarak S, Yaseen T, Dabbous S. Clinical characteristics and outcome of ICU admitted MERS corona virus infected patients. Egyptian Journal of Chest Diseases and Tuberculosis. 2016; 65: 81–87.

[Google Scholar]

Matsuyama R, Nishiura H, Kutsuna S, Hayakawa K, Ohmagari N. Clinical determinants of the severity of Middle East respiratory syndrome (MERS): a systematic review and meta-analysis. BMC Public Health. 2016; 16: 1203.

[Google Scholar]

Al-Hameed F, Wahla AS, Siddiqui S, Ghabashi A, Al-Shomrani M, Al-Thaqafi A, et al. Characteristics and Outcomes of Middle East Respiratory Syndrome Coronavirus Patients Admitted to an Intensive Care Unit in Jeddah, Saudi Arabia. Journal of Intensive Care Medicine. 2016; 31: 344–348.

[Google Scholar]

Rahman A, Sarkar A. Risk Factors for Fatal Middle East Respiratory Syndrome Coronavirus Infections in Saudi Arabia: Analysis of the who Line List, 2013–2018. American Journal of Public Health. 2019; 109: 1288–1293.

[Google Scholar]

Tirupathi R, Muradova V, Shekhar R, Salim SA, Al-Tawfiq JA, Palabindala V. COVID-19 disparity among racial and ethnic minorities in the us: a cross sectional analysis. Travel Medicine and Infectious Disease. 2020; 38: 101904.

[Google Scholar]

Al-Tawfiq JA, Leonardi R, Fasoli G, Rigamonti D. Prevalence and fatality rates of COVID-19: what are the reasons for the wide variations worldwide? Travel Medicine and Infectious Disease. 2020; 35: 101711.

[Google Scholar]

Rigamonti D. Coronavirus Disease Mortality: Understanding Regional Differences. To be published in Erciyes Medical Journal. 2021. (Preprint)

[Google Scholar]