The history and epidemiology of Middle East respiratory syndrome corona virus

The first cases of corona virus infection in Saudi Arabia, specifically Jeddah, were reported on June 13, 2012; after this outbreak, corona virus continued to spread overseas to many countries in Asia, Africa, Europe, and America [1–4]. During this outbreak, most cases occurred in Middle Eastern countries, including those in the Gulf region (Saudi Arabia, Qatar, United Arab Emirates, Oman, Bahrain, Kuwait, and Iraq), as well as Jordan, Syria, Lebanon, Palestine, and Egypt. These countries were considered to be at high risk for corona virus infection according to the European Centre for Disease Prevention and Control (ECDC). Thus, any person arriving from any of these countries should be screened at the airport before entering, particularly after several cases of infection were reported in European countries, including France and the United Kingdom [4–6].

The corona virus responsible for this outbreak was a novel virus that mainly affected adults. The transmission mechanism and potential treatment strategies were still unclear. Notably, although this virus initially appeared to only affect adults, cases have also been observed in pediatric patients. Thus, this novel, potentially fatal virus represented a substantial public health risk. In this review, we discuss the history, epidemiology, and molecular mechanisms of this novel virus, called the Middle East respiratory syndrome corona virus (MERS-CoV).

This study was scheduled and directed to be adhered to PRISMA standards of quality for reporting meta-analysis. We used PRISMA 2009 checklist in writing all parts of the article. It was a meta- analysis.

The median incubation period for MERS-CoV is 5.2–12 days, and adults are mostly affected. However, several pediatric cases have been reported in Saudi Arabia. The clinical presentation of MERS-CoV ranges from flu-like symptoms, i.e., fever and cough in 87% of patients, chills, rigor, rhinorrhea, myalgia, and fatigue, to more severe symptoms, including shortness of breath in 48% of patients and respiratory failure, resulting in the requirement for intubation and ventilation. Gastrointestinal symptoms, including nausea, vomiting, diarrhea, and abdominal pain, have also been reported in about 35% of cases, and acute renal failure necessitating hemodialysis has been seen. On physical examination, patients generally present with fever and pulmonary findings, such as rhonchi and crepitation. Laboratory investigation may revealed lymphopenia, thrombocytopenia, disseminated intravascular coagulation (DIC), and multi-organ failure, which can result in death. The CDC recommends collecting multiple specimens at different times from different sites; for example, samples should be collected from oropharyngeal and nasopharyngeal swabs, sputum, blood, and stool and rectal swabs, as well as the lower respiratory tract, which is most frequently positive for the virus.

Typically, samples will be processed by real-time reverse transcription (rRT)-PCR to analyze the following sequences: upstream of the E protein gene (upE), open reading frame 1b (ORF 1b), and open reading frame (ORF 1a), which is the most sensitive sequence for identification of the specific virus. RNA dependent RNA polymerase (RdRp) and N genes are also target sites in the MERS-CoV genome. To confirm the diagnosis, one of the following criteria must be present: (1) a positive PCR result for at least two different specific targets in the MERS-CoV genome or (2) one positive PCR result for a specific target on the MERS-CoV genome and an additional different PCR product confirming a known sequence of MERS-CoV. The algorithm for diagnosis is as follows: (A) upE-specific rRT-PCR – if positive, confirm with ORF 1a rRT-PCR analysis, and, if positive, the case is confirmed; (B) upE-specific rRT-PCR – if positive, confirm with sequencing of one of the two target sites (RdRp or N assay), and, if positive, the case is confirmed. False negative results can occur due to issues with specimen collection, including early or late collection or shipping/handling problems [16–23].

In June 13, 2012, the first reported case of MERS-CoV 1 occurred in Jeddah, Saudi Arabia. This outbreak resulted in many cases of infection, particularly among health care workers who were in direct contact with the patients, indicating that the virus could be transmitted from human to human via air droplets. This prompted strict contact precautions, such as isolation and the use of personal protective equipment, i.e., gloves, N 95-typemasks, and gowns. In Saudi Arabia, many cases of MERS-CoV were reported in almost all provinces, with Jeddah, Makka, Riyadh, and Al-Hassa being the most commonly affected cities. Additionally, many outbreaks were reported in hospitals, causing affected hospitals to close down and not to accept any infected patients. Most of the patients who died were immunocompromised, having conditions such as chronic renal failure, congestive heart failure, and diabetes or having recently received organ transplants (e.g., kidney transplants). After the initial outbreak in Saudi Arabia, MERS-CoV was reported in several other countries, including Qatar, Bahrain, Kuwait, Jordan, and Tunisia. According to the Minister of Health in Saudi Arabia, from June 13, 2012 until December 2015, a total of 1227 cases of MERS-CoV have been reported, with 728 recovered, one still under treatment, and 549 expired due to MERS-CoV-related symptoms. The Minister of Health, primary healthcare facilities, and public health officials immediately sought to educate the population in Saudi Arabia through internet, lectures, and brochures and continued to carefully record each new case in order to improve knowledge and therapeutic strategies for this virus. The latest report from the WHO on December 7, 2015 showed that MERS-COV has been identified in 26 countries, with 1621 confirmed cases and 584 deaths globally. Notably, the highest numbers of both reported cases and deaths have been in the Saudi Arabia [1, 2, 24, 25].

The main treatment strategy for typical corona virus infection is supportive therapy, in deeding administration of antipyretics and analgesics, maintenance of hydration, respiratory support by either mechanical ventilation or extracorporeal membrane oxygenation (ECMO), and treatment with antibiotics in the case of bacterial super infections. However, such treatments may not be sufficient for MERS-CoV infections, which may be more severe. Ribavirin and interferon alpha have been shown to have synergistic effects and are more beneficial when started early. Additionally, mycophenolic acid has been shown to be efficacious and can be used as a monotherapy; however, initial clinical trials included few patients, and further studies are necessary [44–49]. Although several companies are attempting to develop MERS-CoV vaccines, none are available yet. Improving our understanding of viral antibodies will facilitate the design of appropriate and efficacious vaccines.

MERS-CoV is a lethal zoonotic virus that originated in the Middle East. The main source of transmission, as has been shown in several studies, is through camels. Therapies are still under development and include ribavirin a, interferon alpha, and mycophenolic acid. Further studies are underway to develop an effective vaccine for MERS-CoV aiming to reduce the incidence and mortality rate of infection with this virus.