Middle East respiratory syndrome in Al Ahsa , Saudi Arabia , 2015-18 : a lingering epidemic

Corresponding Author Dr. Balaji Rama Naik; Infection Control Specialist, Infection Prevention and Control Administration. Directorate of Health Affairs, Al Ahsa, Ministry of Health, Saudi Arabia. E-mail: drbalajinaik@gmail.com

In total, 103 cases were reported during the study period with fever and cough as predominant presenting symptoms. The majority were male, >50 years old, and Saudi nationals. One third of patients had comorbid conditions (diabetes and cardiac predominantly). Occupation profiles of the patients varied, with camel owners and security personnel constituting 40% of the study population.
In conclusions, older age, nationality, extracorporeal membrane oxygenation (ECMO) treatment, and associated comorbid conditions were found to be probable risk factors for poor outcomes. The mortality rate (59%) was distinctly higher in patients aged >60 years. The study highlights probable risk factors for poor outcomes in MERS patients, and discusses scope for further intervention and better management.

Introduction
Middle East respiratory syndrome (MERS), caused by the MERS-Corona Virus (MERS-CoV), is one of the top 10 emerging diseases listed by the World Health Organization (WHO), based on case fatality rate and transmissibility. MERS has entered the human population because of human contact with infected dromedary camels. 1 Initial reports of MERS were published in 2012 from Saudi Arabia; research continues to improve scientific understanding of the virus. 1,2 Globally, outbreaks of MERS have been reported periodically; 3 smaller regional outbreaks occur, which can develop into epidemics. Understanding these variations in disease presentation will help prevent further outbreaks.
Here we describe socio-demographic features of MERS cases in Al Ahsa (population: 1.2 million; largest region in the eastern part of Saudi Arabia) from a fouryear (2015-2018) dataset. 4

Methods
Setting: Ministry of Health (MoH) and private health care facilities of Al Ahsa, the largest governorate in the eastern province of Saudi Arabia.

Study design
Descriptive study based on routinely collected program data. Data collected by Infection Control Administration and the Regional Center for Command and Control (CCC) of Al Ahsa region for 2015 to 2018 for all confirmed cases of MERS Co-V were used; all included MERS cases were treated in hospitals designated by the MoH. Data were extracted from the rapid response team (RRT) reports prepared by RRT members as and when the cases were notified.
The key variables included in the study were age, sex, nationality, history of contact with camels, extracorporeal membrane oxygenation (ECMO) treatment, comorbid conditions (Table I). Data were analyzed for socio-demographic characteristics, primary/ secondary status of the cases, presenting complaints, existing comorbidities, time delays during the course of management, presence of pneumonia on chest X-ray, history of contact with camels/ camel products, and patient outcome. The case definition for confirmed cases was as per MoH regulations. 5

Statistical Analysis
Data were analyzed using the EpiData analysis software (Version V2.2.2.185; EpiData Association, Odense, Denmark). Frequencies and proportions were calculated. Differences between groups were compared using Chi square tests and 95% confidence intervals (CIs). A p-value of <0.05 was considered as statistically significant.

Results
Over a four-year period (2015-2018), 103 confirmed MERS cases were reported. The majority (69%) were men, median age (inter quartile range -IQR) was 53 years (37.3-63.5), with a higher proportion (58%) of patients aged > 50years. The socio-demographic and clinical characteristics are shown in Table I. The median (IQR) duration from symptom onset to death and from admission to death was 16 days (6 to 22) and 17 days (8 to 26), respectively.
Bivariate analyses with death as outcome are shown in Table II. Among comorbidities, diabetes mellitus alone or in combination with other diseases was found in 47 (63%) out of 75 comorbid patients. Ischemic heart disease with or without other conditions was reported in 44% patients and hypertension was found in 66% patients. Thirteen patients were smokers and nine had renal issues. There were seven patients with multiple comorbidities. The overall death rate was 46%. Death rate among patients aged 60 years and above was 64% with the highest rate of 86% among patients aged more than 80 years. Of the 10 patients on ECMO, nine died during treatment. A high proportion (56%) of patients who died had a history of contact with camels, but the finding was statistically insignificant (p=0.14).

Discussion and Conclusion
The study highlights older age, nationality, ECMO treatment, and associated comorbid conditions as probable risk factors for poor outcomes. Excluding health care workers (21% of the cases), the majority of patients were elderly. The mortality rate was distinctly higher in patients aged >60 years in our study, compared to previous studies. 6 Systematic reviews have strongly linked associated comorbidities with poorer outcomes. 7 Male sex was not a risk factor for death, which was not in agreement with findings from other studies. 7 Though not statistically significant in our study, relationship between exposure to camels and MERS has been reported to be strong. Being a Saudi national was strongly associated with death, similar to Aleanizy et al. 8 Though the reasons for this association are yet unclear; cultural issues and the intimacy of the people with camels might be a plausible area of exploration (personal communication).
Our study has few limitations. It was out of scope to capture cultural and personal behavior of the patients. We did not analyze the extent and type of contact with camels or camel products, which may have impacted study outcomes.
The occupational profiles of the patients need exploration. More than 50% of patients who died were involved in occupations with close contact with camels, camel products, or probable MERS-infected patients. The list of job profiles can be considered in designing cost-effective interventions for prevention, early detection and timely management.
Ninety percent patients on ECMO died, in agreement with findings from a study by Al Ghamdi et al., 9 indicating that severity of illness at admission prognosticates poor outcomes irrespective of age. Overall mortality was higher in patients aged >60 years, but patients on ECMO were 41 years on average. There was no evidence of treatment delay in these cases. Patients with compromised lung capacity, ECMO treatment, the elderly, and those with associated comorbidities showed adverse outcomes as shown in other studies too. 10 Among patients who died, 90% had comorbidities, suggesting possible immunosuppressive state and susceptibility to infections. Information about the treatment modalities of the patients was not collected.
The above-mentioned risk factors need to be considered in patient management and necessary modifications adopted. A strong surveillance system for early identification of cases may help save lives. Infection control practices in hospitals need to be strengthened for early detection and effective management, to help prevent occurrence of cases among health care providers and further spread leading to nosocomial outbreaks.

Ethics approval
National program data were used in this study; no individual patient consents were obtained. Necessary approval for using the data was obtained from the Directorate of Health Affairs, Al Ahsa, Saudi Arabia.