J. Microbiol. Infect. Dis., (2024), Vol. 14(4): 158–164

Review Article

10.5455/JMID.20240828072847

Middle East respiratory syndrome coronavirus (MERS-CoV): Virology, clinical features, epidemiology, and prevention

Mariyam Luba Abdulla¹, Kannan Subbaram^1*, Razana Faiz¹, Zeba Un Naher¹, Punya Laxmi Manandhar¹, Sheeza Ali¹, Sina Salajegheh Tazerji², and Phelipe Magalhães Duarte³

¹SSchool of Medicine, The Maldives National University, Malé, Maldives, 20371.

²Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, 1477893855, Iran

³Postgraduate Program in Animal Bioscience, Federal Rural University of Pernambuco (UFRPE), Recife, Pernambuco, Brazil, 52171-900

*Corresponding Author: Dr. Kannan Subbaram, MSc., PhD., School of Medicine, The Maldives National University, Malé, Maldives. Email: kannan.subbaram [at] mnu.edu.mv

Submitted: 28/08/2024 Accepted: 05/12/2024 Published: 31/12/2024

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ABSTRACT

Background: Middle East respiratory syndrome (MERS) is caused by the virus called Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV belongs to the viral family of Coronaviridae of the genus beta Coronavirus.

Aim: The aim of this article is to bring the recent developments on the virology, clinical features, epidemiology, and prevention of MERS-CoV. Review of the literature was conducted on MERS-CoV, its past and present outbreaks, its relationship with SARS-CoV-2, virology, clinical features, complications, mortality rate, epidemiology, treatment, and prevention.

Methods: The literature search was performed between January 2010 and November 2024. The article listed in Google Scholar, Scopus, Web of Sciences, Embase, and Hinari were used for this study.

Results: During this study we observed many interesting findings. This virus contains a single-stranded, non-segmented positive-sense RNA genome of around 30 kb. Their morphological structures include a bilayer lipoprotein envelope with glycoprotein spikes on the surface, surrounding the capsid containing the genome. It has several structural proteins, such as the protein envelope (E) protein and the spike (S) protein. This virus is genetically related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. We would like to conclude that MERS-CoV was identified in dromedary camels, and these camels acted as a source for transmission of the virus to humans as zoonosis. There were many cases of hospital (nosocomial) MERS outbreaks that have also been documented in Saudi Arabia. The clinical spectrum of MERS-CoV ranges from asymptomatic or mild respiratory illness to severe respiratory failure and multi-organ dysfunction. The case fatality rate of MERS-CoV was 36%, much higher than COVID-19.

Conclusion: The future perspective of this study recommends that more detailed research to be carried out on molecular aspects, virulence, and the development of effective antiviral agents to counter MERS-CoV future outbreaks.

Keywords: MERS-CoV, Middle East respiratory syndrome, dromedary camels, mortality, pathogenesis, epidemiology, coronavirus.

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INTRODUCTION

Middle East respiratory syndrome (MERS) is a respiratory disease caused by a coronavirus (CoV) known as MERS-CoV. MERS-CoV contains positive-sense single-stranded (ss) RNA as the genome. MERS is highly prevalent in dromedary camels (Camelus dromedarius) in the Arabian Peninsula (Subbaram and Ali, 2020). In the year 2012, the first human case of MERS was reported from Saudi Arabia (Zaki et al., 2012). Since then, there were many MERS cases have been reported from Saudi Arabia and other Gulf countries. The virus MERS-CoV can be transmitted from camels to humans as zoonosis (Hijawi et al., 2013). There were several cases of human-to-human transmission were also documented. There were cases of nosocomial transmission were noticed in MERS in the hospitals of Saudi Arabia. The clinical features of MERS include fever, cough, and severe respiratory distress leading to pneumonia. Many patients also exhibited complications like encephalitis/meningitis, acute renal failure, and endocarditis. The mortality rate of MERS is around 35%, which is very much higher than COVID-19. By July of 2013, 90 cases and 45 deaths had been identified globally, of which 70 cases were from Saudi Arabia. A notable outbreak occurred between March and May of 2014 in Jeddah, Saudi Arabia, where 255 were confirmed with infection and 93 died (Assiri et al., 2013a). The biggest outbreak outside the Middle East happened in South Korea in 2015, with the index patient being one who had traveled to several countries in the Middle East and then subsequently visited four different healthcare facilities in South Korea (Park et al., 2015). A total of 186 patients were confirmed to be infected and 36 died in this outbreak. Eight confirmed cases and five deaths were reported in Saudi Arabia between September 2022 and February 2024 (Memish et al., 2014). Among these cases, five had come into direct or indirect contact with dromedary camels. The most recent outbreak was reported by the World Health Organization in May of 2024, three new cases and one death in April of 2024. All three have been linked to the same hospital in the Riyadh (Assiri et al., 2013b).

Past and Current Middle East Respiratory Syndrome (MERS) Outbreak

MERS-CoV was initially isolated from a patient in Jeddah, Saudi Arabia, in September of 2012 (Zaki et al., 2012). However, the first reported cases occurred in a hospital in Zarqa City of Jordan in April of the same year. Retrospective analysis of the stored sputum of the outbreak, which initially had inconclusive laboratory results, later confirmed the diagnosis of the virus in two patients. The outbreak of acute respiratory illness had affected 11 people, among which one died (Zaki et al., 2012). By July of 2013, 90 cases and 45 deaths had been identified globally (Park et al., 2015), of which 70 cases were from Saudi Arabia. All the cases had been linked directly or indirectly to Saudi Arabia, Jordan, Qatar, and the United Arab Emirates (Assiri, Al-Tawfiq, et al., 2013). The Al-Hasa outbreak of April 2013 involved 23 confirmed cases (Park et al., 2015).

A notable outbreak occurred between March and May of 2014 in Jeddah, Saudi Arabia, where 255 were confirmed with infection and 93 died (Memish et al., 2014). The biggest outbreak outside the Middle East happened in South Korea in 2015, with the index patient being one who had traveled to several countries in the Middle East and then subsequently visited four different healthcare facilities in South Korea. A total of 186 patients were confirmed to be infected and 36 died in this outbreak (Assiri, McGeer, et al., 2013, Oboho et al., 2015). Eight confirmed cases and five deaths were reported in Saudi Arabia between September 2022 and February 2024. Among these cases, five had come into direct or indirect contact with dromedary camels (Middle East Respiratory Syndrome Coronavirus Outbreak in the Republic of Korea, 2015, Middle East Respiratory Syndrome Coronavirus (MERS-CoV)- Kingdom of Saudi Arabia). The most recent outbreak was reported by the World Health Organization in May of 2024. Three new cases and one death in April of 2024. All three have been linked to the same hospital in the Riyadh (Middle East Respiratory Syndrome Coronavirus). Figure 1 reveals the number of laboratory-confirmed cases of MERS-CoV by geographical regions across the globe.

Fig. 1. Based on the number of laboratory-confirmed cases of MERS-CoV by region (MERS Coronavirus). (As of March 2024).

Relationship of MERS-CoV with SARS-CoV-2

Both MERS-CoV and SARS-CoV-2 are from the Coronaviridae family of coronavirus. They have similar morphology, but they do have numerous structural differences, such as the hemagglutinin and acetyl esterase membrane proteins that are present in MERS-CoV, but not in SARS-CoV-2 (Middle East respiratory syndrome coronavirus-Kingdom of Saudi Arabia, 2024). Genomic analysis shows 65%–68% relation between MERS-CoV and SARS-CoV-2 (Kannan et al., 2020). Phylogenetic tree analysis suggests that even though SARS-CoV-2 and MERS-CoV are related, MERS-CoV has evolved as an entirely different lineage. Both have been shown to cause severe respiratory illness with fever and shortness of breath and cause mortality. Shortness of breath appeared to be less common in SARS-CoV-2 (17%) compared to MERS-CoV (51%). Mortality rate was also higher in MERS-CoV (36%) compared to SARS-CoV-2 (5.6%) (Pormohammad et al., 2020).

Virology of MERS-CoV

The MERS-CoV is classified under the family of Coronaviridae and under the genus β coronavirus (Mohd et al., 2016). It contains a single-stranded, non-segmented positive-sense RNA genome of around 30 kb (Middle East Respiratory Syndrome / MERS | CDC Yellow Book 2024) (Fehr and Perlman, 2015, Woo et al., 2010, Beigel et al., 2018). Their morphological structures include a bilayer lipoprotein envelope with glycoprotein spikes on the surface, surrounding the capsid containing the genome (Subbaram and Ali 2020). It has several structural proteins such as protein envelope (E) protein and the spike (S) protein. There proteins play vital roles in its virulence, where the E protein is responsible for attaching to host receptors and S protein is responsible for fusing and entering into respiratory epithelial cells. There are also other two proteins present in the virus: they are membrane (M) glycoprotein and nucleocapsid (N) phosphoprotein. M protein is responsible for attachment and initiation of virus entry and N protein plays a vital role in the replication and protection of viral genome (Figure 2). The virus also consists of polyprotein AB and nonstructural proteins (NSPs). The viral polyprotein AB and NSPs play a crucial role in the biosynthesis and assembly, release, and thereby increasing pathogenesis of MERS-CoV. These two proteins contribute to producing important enzymes for viral replication. The cellular receptors for MERS-CoV are angiotensin-converting enzyme 2 and dipeptidyl peptidase 4 (DPP4) (Durai et al., 2015).

Fig. 2. Molecular morphology of MERS-CoV. (Photo courtesy Dr Ian M Mackay, PhD).

Clinical Features of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection

The clinical spectrum of MERS-CoV ranges from asymptomatic or mild respiratory illness to severe respiratory failure and multi-organ dysfunction (Hijawi et al., 2013). Most affected patients are adults with a mean age of 56 years. The incubation period ranges from 2 to 14 days, with the median incubation period being slightly over 5 days (Middle East Respiratory Syndrome / MERS | polyCDC Yellow Book 2024). The most characteristic features of MERS-CoV are high fever, cough, and dyspnea (Al-Tawfiq and Memish 2024 Jan 1, Subbaram et al., 2017, Middle East Respiratory Syndrome / MERS | CDC Yellow Book 2024, Al-Tawfiq and Memish 2024 Jan 1). Other non-specific illnesses include abdominal pain, nausea, vomiting, chills, myalgias, headache, and sore throat (Middle East Respiratory Syndrome / MERS | CDC Yellow Book 2024). Chest radiographs show variable but nonspecific changes (Hijawi et al., 2013, Middle East Respiratory Syndrome / MERS | CDC Yellow Book 2024).

Complications of Middle East respiratory Syndrome Coronavirus (MERS-CoV)

These symptoms have been recorded to progress to pneumonia (Alenazi and Arabi 2019). Severe respiratory compromise is the most common complication. Other life-threatening complications include acute renal injury, hypovolemic shock, and cardiovascular collapse (Middle East Respiratory Syndrome / MERS | CDC Yellow Book 2024). One study indicates the likelihood that MERS-CoV may be a prothrombotic disease with reports of venous thromboembolic events such as pulmonary embolism and deep vein thrombosis (Al Raizah et al., 2021). Acute kidney injury was found in one fourth of the study sample in a study done in Korea, even though an exact causative relationship is not established (Cha et al., 2015). Other coronavirus infections have been shown to manifest with neurological complications such as encephalopathy, encephalitis, and meningitis, and similar cases have been seen in those with MERS-CoV as well (Alshebri et al., 2020 Oct 16) (Figure 3).

Fig. 3. Pathological changes and dissemination after MERS-CoV infection (developed using Canva).

Mortality Rate of MERS-CoV Since its Discovery

Between 2012 and May of 2024, 941 deaths have been reported from globally from 2613 cases (Middle East Respiratory Syndrome Coronavirus). This makes the case fatality rate of MERS-CoV to 36%. It is believed that this value may be an overestimation as it is based only on laboratory-confirmed cases and milder cases might not be reported. Among these deaths, 91% are from Saudi Arabia. Higher mortality rates have been observed in patients who are of male sex, older age, immunocompromised, or have underlying illnesses such as diabetes mellitus, renal disease, respiratory disease, heart disease, and hypertension (Middle East Respiratory Syndrome / MERS | CDC Yellow Book 2024, Matsuyama et al., 2016).

Epidemiology of MERS-CoV

Since 2012 to May of 2024, there were 2613 cases have been reported from 27 countries. Among this 84% of cases are from Saudi Arabia (Middle East Respiratory Syndrome Coronavirus). All cases have been linked directly or indirectly to the Arabian Peninsula and parts of Africa (Peiris and Perlman, 2022).

Dromedary camels appear to the primary animal host for the virus (MERS Coronavirus, 2024), and camel-to-human transmission has been demonstrated (Azhar et al., 2014; Ramadan and Shaib, 2019). Human-to-human transmission has also been demonstrated in many epidemiological studies, with a tendency for nosocomial infections, as understood by the multiple outbreaks in health care facilities (Al-Tawfiq and Memish 2024 Jan 1). The spread of MERS-CoV internationally to countries that do not have dromedary camels can also be attributed to interhuman transmissions. As the virus has tropism for respiratory epithelia, sneezing and coughing seem to be the mode of transmission in both camel-to-human and human-to-human transmission (Arabi et al., 2018). Seasonal increase in cases have been noted between April and June, hypothesized to be due to the camel birthing season, where younger camels are more prone to infection.

Treatment for MERS

According to WHO, there is currently no specific or definitive treatment for MERS-CoV, but they are in the stages of development. Supportive care and monitoring of clinical parameters is the mainstay of management as of now (Al-Tawfiq and Memish 2024 Jan 1, Middle East Respiratory Syndrome Coronavirus). One randomized controlled trial, termed the MIRACLE trial (MERS-CoV Infection treated with a combination of Lopinavir/ritonavir and Interferon-β1b), tested the combination of lopinavir, ritonavir, and interferon-β1b with a successful reduction in 90-day mortality (Arabi et al., 2018). Another study tested human polyclonal IgG antibody (SAB-301) infusions, which appeared to be safe in healthy individuals (Beigel et al., 2018). The drugs mentioned above are undergoing clinical trial for treatment in humans.

Prevention of MERS

At the current time, there is no vaccine or preventive therapies for MERS-CoV (Middle East Respiratory Syndrome Coronavirus, Middle East Respiratory Syndrome / MERS | CDC Yellow Book 2024). However, many preventive practices have been advised by WHO and CDC. All standard contact and airborne infection precautions such as frequent handwashing, avoiding touching the eyes, noses, and mouths, and avoiding contact with sick people is recommended. These practices should be applied especially before and after touching animals (Middle East Respiratory Syndrome Coronavirus). WHO also recommends against consuming raw camel milk, camel urine, and eating meat that is not properly cooked. In-hospital surveillance is strictly recommended due to the tendency for nosocomial transmission and outbreaks (Middle East Respiratory Syndrome / MERS | CDC Yellow Book 2024). There are research going on to develop effective vaccine against MERS-CoV.

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CONCLUSIONS

The MERS-CoV is a virus that can cause life-threatening complications and with a high mortality rate. As diagnosed cases of the virus continue to be found, emphasis needs to be put on further studies into its epidemiology, prevention, and treatment, as well as public awareness. The importance of surveillance and early detection, especially in in-patient settings among those who have high-risk factors such as old age and multiple comorbidities is to be highlighted. Epidemiological studies in larger populations may help detect asymptomatic and mild cases of MERS-CoV, leading us to more accurate values for case fatality rates. The successful development of vaccines and definite pharmacological therapy can become a beacon of hope for the devastating outcomes of this infection. Most importantly, public awareness programs especially in regions with increased cases and endemic dromedary camels, can strengthen preventive measures such as frequent hand-washing and avoiding improper consumption of camel milk and meat.

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FUNDING

None declared.

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CONFLICT OF INTEREST

None declared.

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