MERS-COV in the Middle East, a one health concept approach

Abstract

The MERS-COV virus is a zoonotic coronavirus that emerged in 2012 in KSA and caused viral illness with a case fatality rate up to 35 %. Over a decade later, the virus is still evolving and circulating. The aim of this review is to discuss the current epidemiology of MERS-COV both in humans and animals, during and post the COVID-19 pandemic. We have found that MERS-COV is still evolving in camels with new lineages being detected in Saudi Arabia. Although the number of human cases has decreased, there is a gradual resurgence in the number of cases. Furthermore, many cases are being reported without exposure to camels and/or raw products, nor contact with known human cases. This necessitates global efforts in the surveillance of asymptomatic carriers in the community, role of unknown animal reservoirs in the virus spread if any, as well as extensive genomic surveillance of the virus. This is in order to unveil and assess the genetic changes that the virus is undergoing and their according effect on the viral fitness, tropism, and virulence. These efforts are crucial for potential future pandemic preparedness, understanding the modes of transmission, as well as drug and vaccine development for MERS-COV.

1. Introduction

The Middle East respiratory syndrome coronavirus (MERS-COV) is a zoonotic virus that was first detected in Saudi Arabia in a patient who died from pneumonia in Jeddah-2012 [1]. Later on, MERS-COV was reported from twenty-seven countries worldwide [2]. Compared to other respiratory viruses, the main concern with MERS-COV is its high fatality rate which goes up to 35 % [3]. This is in addition to the lack of approved anti-viral drugs and vaccines for treatment and prevention, respectively [4]. As of June 2025, up to 2627 laboratory confirmed cases of MERS-COV and 947 deaths have been reported worldwide, with the majority being observed from the Middle East, and specifically in Saudi Arabia [5]. MERS-COV causes a respiratory illness that ranges from an asymptomatic to a life-threatening disease [6]. Typical symptoms include cough, fever, sore throat, myalgia and shortness of breath [7]. Gastrointestinal symptoms such as vomiting, diarrhea as well as abdominal pain, may also show [8]. Severe form of the disease, on the other hand, is manifested as acute pneumonia, respiratory or multi-organ failure and death [9]. Predictors of poor prognosis include older age, weakened immune system, presence of underlying comorbidities such as diabetes, cancer, progressive lymphocytopenia, chronic renal or lung disease, in addition to low albumin level [10] [11] [7].

The MERS-COV is believed to originate from a zoonotic spillover from camels to humans [12]. Dromedary camels are considered a significant reservoir for the virus [13], with exposure to these latter being regarded as a significant risk factor for the acquisition of MERS-COV infection [14]. Active MERS infections have been detected in dromedaries in several continents, including Asia (including countries such as KSA, UAE, Oman, Jordan, Iraq, Qatar, Kuwait, and Pakistan), and Africa (including countries such as Morocco, Egypt, Nigeria, Kenya, Ethiopia and Burkina Faso) [15]. Evidence for the zoonotic spread include the close relationship between MERS-COV genomes isolated from both humans and camels [16]. More evidence is the detection of single nucleotide polymorphisms (SNPs) in humans, following their first identification in dromedaries [17]. In 2016, around one-fourth of the analyzed sequences of ORF3 in camels had the P86L and L17F variants. Thereafter, these two variants became dominant in humans from 2015 to 2019. It is worth mentioning that P86L and L17F were not detected before this date in humans, emphasizing accordingly the transmission route of MERS-COV between the two compartments. Another example, is the L23M variant of the N gene, detected in KSA in 2013. This variant was later identified in human samples, in 2016–2018 in KSA, as well as in South Korea [17].

Since the beginning of the COVID-19 pandemic, the number of reported MERS-COV cases have declined. This could be attributed in part to the implemented infection control measures in view of the pandemic; in addition to the probable decreased surveillance of this virus, and the priority given for the monitoring of SARS-COV-2 [18]. Although the circulation of MERS-COV has decreased in humans, this was not the case in camels. In addition, sporadic cases have resurged in humans in the last years, with many of them being reported without camel exposure; necessitating continuous surveillance and monitoring. The aim of this review is to summarize the recent findings of MERS-COV in terms of epidemiology, risk factors, and genomic characteristics, in the Middle Eastern countries during and post the COVID-19 pandemic (2019-up to date), in both humans and camels. Our attempt is to shed the light on the current situation of the MERS-COV in our region, in order to guide health authorities and research committees for the prevention and containment of future potential epidemics of this virus.

2. Epidemiology of MERS-COV in humans

From 2019 and up to date, human cases of MERS-COV have been reported in five Middle Eastern countries including: Jordan, Sultanate of Oman, Qatar, United Arab Emirates (UAE) and the Kingdom of Saudi Arabia (KSA) (Table 1).

Table 1.

Characteristics of MERS-COV human cases reported from 2019- up to date.

Country	Year	Number of Cases	Age (years)	Gender	Prognosis	Comorbidities	Direct/indirect camel exposure	Clinical outcome
Jordan	2019	1	27	M	Asymptomatic	Unknown	No	Recovered
UAE	2019	1	60	M	Symptomatic	Dyslipidemia, HTN, diabetes	Yes	Recovered
	2021	1	39	M	Symptomatic	No	Yes	Recovered
	2023	1	28	M	Symptomatic	No	No	Recovered
Qatar	2019	3	67	F	Symptomatic	yes**	No	Died
			50	M	Asymptomatic ¥	Yes**	No	Recovered
			32	Unknown	Asymptomatic ¥	No	No	Recovered
	2020	1	65	M	Symptomatic	CAD, HTN, diabetes	Yes	Unknown
	2022	2	50	M	Symptomatic	No	Yes	Recovered
			85	M	Symptomatic	Hypercholesterolemia, HTN, DM	Yes	Died
Sultanate of Oman	2019	13	43	F	Symptomatic	HTN	No	Died
			30	F	Symptomatic ¥	Yes**	No	Died
			39	F	Symptomatic ¥	Cardiomyopathy	No	Recovered
			59	F	Symptomatic	CKD, DM, HTN, IHD, HY	No	Recovered
			37	F	Symptomatic ¥	Unknown	No	Recovered
			77	F	Asymptomatic	DM, HTN, azheimer	No	Recovered
			65	F	Symptomatic	DM, HTN	No	Recovered
			61	F	Symptomatic	DM, HTN, dementia	No	Recovered
			31	F	Asymptomatic	No	No	Recovered
			63	M	Symptomatic	DM, IHD, CKD	Yes	Died
			68	M	Symptomatic	DM, HTN, CKD	No	Recovered
			30	M	Symptomatic	Asthma	No	Died
			48	M	Symptomatic	Cardiomyopathy	No	Died
	2022	1	34	M	Symptomatic	No	Yes	Unknown
	2023	1	60	M	Symptomatic	Yes**	No	Recovered
KSA	2019	203 ¶						(51) Recovered, (152) died
	2020	8	48	M	Symptomatic	No	Unknown	Died
			36	M	Symptomatic	No	Unknown	Recovered
			36	M	Symptomatic	No	Unknown	Died
			39	F	Symptomatic	No	Unknown	Recovered
			33	M	Symptomatic	No	Unknown	Recovered
			52	M	Asymptomatic	No	Unknown	Recovered
			69	F	Symptomatic	Diabetes	Unknown	Died
			42	M	Symptomatic	No	Unknown	Recovered
	2021	1	74	M	Symptomatic	HTN, BRH, renal disease	Yes	Recovered
	2022	4*	23	F	Symptomatic	Bechet disease	Unknown	Recovered
			68	M	Symptomatic	DM	Yes	Recovered
			53	M	Symptomatic	HTN, DM	Yes	Recovered
	Aug 2023- Feb 2024	4	59–93	(2) M & (2) F	Symptomatic	Yes**	(2) Yes, (2) no	(2) Recovered, (2) died
	Feb-24	1	32	M	Symptomatic	Yes**	Yes	Unknown
	Apr-24	3	56	M	Symptomatic	HTN, CRF	No	Died
			60	M	Symptomatic ¥	Heart disease	No	Recovered
			60	M	Symptomatic ¥	CRF, malignancy, liver disease	No	Recovered
	Sep-24	1	50–55	M	Symptomatic	Yes**	No	Recovered
	2025	9	(2) >65 & (7) 18–65	(5) M & (4) F	(4) Asymptomatic, & (5) Symptomatic (***)	Unknown	(1) Yes, (2) unknown	(7) Recovered, (2) died

¶ for this year no specific number on the different variables could be retrieved, ¥ = secondary cases, & = and, * = 1 was a citizen from 2022 Hajj season, ** = not mentioned specifically, (***) = 6/9 were secondary cases, BRH = Benign prostatic hyperplasia, HTN = hypertension, DM = diabetes mellitus, CKD = chronic kidney disease, IHD = ischemic heart disease, CRF = chronic renal failure, CAD = coronary artery disease, HY = hypothyroidism, Aug = August, Feb = February, Apr = April, Sep = September, M = male, F = female.

2.1. Middle East except KSA

From 2019 until now, only one case of MERS-COV in humans has been reported in Jordan, with this dating back to 2021. The case was detected as part of an ongoing nationwide one health project (2019–2025), aiming to the reduce the threat of avian influenza as well as MERS-COV and strengthening the capacity of the regional disease surveillance in the country [19]. The case was of a 27-year-old male with an asymptomatic MERS-COV infection. Camels living in close proximity to this case were also positive for MERS-COV. Phylogenetic analysis of partial spike sequence revealed that the human strain belongs to lineage B, and clusters with other strains originating from the Arabia peninsula; specifically, with up to 100 % and 99.79 % similarity to the Riyadh_1764_2015, and Florida/USA-2_Saudi Arabia_2014 strains, respectively [19].

In the UAE, three cases of MERS-COV in humans has been reported since 2019. The first one was a 60-year-old male from Abu Dhabi, who owned a dromedary camel farm and who presented with typical respiratory symptoms. The patient having several underlying conditions including dyslipidemia, hypertension and diabetes, was hospitalized and recovered later on, following the administration of appropriate treatment [20]. The second case was detected in 2021 from a 39 year old male without comorbidities, and that had recent camel exposure [21]. The third case was reported on July 10th, 2023, where a 28 year old male, (who had no recent travel outside UAE, nor recent contact with camels or their raw products), presented to the hospital with atypical symptoms including dysuria, vomiting and right flank pain. Although the patient had no comorbidities, their condition deteriorated and they were admitted to an intensive care unit (ICU) and put on mechanical ventilation. Later on the patient survived, and was discharged with no secondary cases being detected [22].

In late 2019, three cases of MERS-COV were reported to the world health organization (WHO) by Qatar. The first case was a 67 year old female with comorbidities, who passed away following infection. The patient had no history of travel outside Qatar, nor previous contact with camels or their raw products. Contact tracing revealed thereafter, two asymptomatic secondary cases [23]. In February 2020, another MERS-COV case with close contact history with camels was detected in the country. The patient was a 65 year old male, with coronary artery disease, hypertension and diabetes, who experienced severe form of the disease, and was admitted to the ICU [24]. In 2022, two additional MERS-COV cases with recent dromedary contact were reported, including one death. Unlike the survived case, the patient who died was an 85 year old male with several underlying medical conditions, including hypercholesterolemia, hypertension and diabetes mellitus [25]. The presence of underlying comorbidities is a significant risk factor for death and severe disease in MERS-COV infected patients [26]. In their study, Alaskar et al., found a 100 % mortality rate in a hematology/oncology MERS-COV infected patients, regardless of the disease status and/or age [27].

In the Sultanate of Oman, at the beginning of 2019, from mid-January to mid-February, 13 MERS-COV cases, with 4 deaths (31 % case fatality rate), were recorded, with septic shock and bronchopneumonia being the most common causes of death [28]. The majority of cases were young (less than 55 years old), and female, which is unlike what has been previously reported in other studies, where MERS-COV cases tend be predominantly detected in males of older ages (> 55 years). Hypertension, uncontrolled diabetes mellitus, and ischemic heart disease were the most common underlying comorbidities reported. Interestingly, four cases were household members with one of them having a recent history of camel contact. Other modes of transmission in these cases included community and nosocomial acquisition of MERS-COV [28]. According to Awaidy et al., nosocomial transmission could be attributed in part to delays in suspicion and/or case detection, and on another part, due to the lack of adherence to strict infection control measures, (such as the proper use of personal protective equipment [PPE]), as well as the lack of proper isolation facilities. It is worth mentioning that camels living in vicinity of cases who reported recent contact with them, were screened for MERS-COV and only one tested positive [29] [28]. After 2019, no more cases of MERS-COV have been reported in the Sultanate of Oman, until April 2022, where a 34-year-old male with no comorbidities and a recent contact with dromedaries, was detected. This patient experienced fever, hypotension, severe respiratory distress and was diagnosed with “clinical pneumonia with fluid”. Following the deterioration of his status, the patient was transferred to ICU and was put on mechanical ventilation [30], no more details were given regarding the death or survival of this case. Later on, in January 2023, the was notified of a positive case of MERS-COV. The patient had no known comorbidities and although he had no recent contact with camels, camel racing exercises were underway in the patient's residential area [31], suggesting a possible transmission.

2.2. Saudi Arabia

In the Kingdom of Saudi Arabia, several studies reported the detection of MERS-COV in the country, together with the demographic and clinical characteristics and mode of exposure [32] [33] [34] [35] [36]. According to WHO reports, 203 cases were identified in 2019, with 25 % fatality rate (51 deaths) [5]. This number started to drop until 2023, and then started to re-surge gradually from 2024, up to now. According to these reports, 68 % of the total number of cases from 2019 until June 2025 were considered primary cases [5]. In their study, Al-Ahmadi et al., found significant correlation between MERS-COV primary cases and the presence of surrounding camels in all provinces, regardless of direct/indirect exposure. This suggests the presence of an asymptomatic human carrier that contributes to the transmission of the virus in the human population; or less likely that there is an unknown animal host that is in contact with both humans and camels and is responsible for the transmission [33]. Human to human transmission (exposure to identified MERS-COV cases), being a health care provider and animal to human transmission (exposure to camels or their raw products), are all possible modes of MERS-COV spread, that have been all reported from Saudi Arabia [35]. Studies have shown that the percentage of MERS-COV positive health care workers ranges from 11.9 % to 15 % [37] [38]. Whether being a health care provider increases or decreases the risk of death is controversial. While one study found that health care workers have 2.4 increased odds of death compared to community subjects [38]; another has found that they have lower mortality rates [37] [39]. Looking at the relation of camel exposure with death risk, one study has found that exposure to camels and/or consumption of their raw products increases mortality risk in infected patients [38] [39]. On the other hand, another study found that these exposed infected patients are unlikely to die from MERS-COV infection [37]. It has been suggested that human-human transmission mediates the development of more virulent strains compared to animal – human transmission. [37].

Looking more deeply, in 2019, most of the reported cases in KSA were from Riyadh [35] [38]. Studies in the country revealed that most of the patients infected with MERS-COV had underlying conditions including diabetes, hypertension, and cardiovascular diseases [35]. Not surprisingly, in the majority of the studies, it was found that the presence of comorbidities increases the risk of death significantly [40] [38] [41]. This is except for one study, where MERS-COV patients with comorbidities were found to have higher odds of death compared to those without, however this difference was not statistically significant (35 % vs 23 %) [37]. Furthermore, one study also found that males have 1.5 increased risk of death compared to females [38]. This could be due to the fact that male gender dominates MERS-COV infections. The majority of patients during 2019 were more than 50 years old [35] [41]. For instance, one study found that patients being older than 65 years old was an independent risk factor for mortality [41]. Another study found that patients aged more than 60 years have 4.9 higher risk of death compared to those aged 16–30 years [38]. Moreover, Zhang et al., reported that delay in MERS-COV infection diagnosis is also an independent risk factor for death in MERS-COV subjects [41].

In 2020, Elhazmi et al., reported in their study, eight cases of ICU hospitalized SARS-COV-2 patients were co-infected with MERS-COV. The majority of the cases were male, obese, and had a mean age of 44.4 years old. Three patients had underlying conditions including heart failure and diabetes mellitus; one of which was on anti-platelet therapy. The mean length of a hospital and ICU stay was 21.1 and 10.9 days, respectively, with a mortality rate of 37.5 % (3 died). According to authors, co-infection was not associated with differences in laboratory data, symptoms, nor increased risk of death compared to mono-infection [42]. From the end of 2021 to October 2022, four cases of MERS-COV were reported in KSA, with zero deaths. Two were detected in Riyadh, 1 in Qassim, and 1 in the holy city of Makkah. All cases had underlying conditions and three had a recent history of contact with camels and/or their raw products [43]. During the same year, Assiri et al., reported the detection of one MERS-COV case in a citizen, in the holy city during the Hajj period [44]. On the following year, the Ministry of Health (MOH) in Saudi Arabia reported to the WHO four cases of MERS-COV that were detected between August 13th, 2023, and February 1st, 2024, in Riyadh, Qassim and the eastern region, to the WHO. The case fatality rate was 50 % with all of the cases having comorbidities. One of the four cases was a camel owner, and one had an indirect contact with camels as his relatives were also owners of camels [45]. During the same period, in Taif, one MERS-COV patient with comorbidities and camel exposure died. For instance, in the second quarter of 2023, for samples who test negative for SARS-COV-2 and Influenza, the MOH in Saudi Arabia, included MERS-COV in the “sentinel surveillance testing algorithm”; this was to increase the country's testing capacity of this virus [46]. In April 2024, three male cases with comorbidities including hypertension, chronic renal failure, malignancy, heart and liver disease were reported from Riyadh, all related to the same hospital. Two of the cases were secondary to the first Index case who died later on, and who had no recent history of exposure to known MERS-COV risk factors [46]. In September 2024, one further case was been reported in the Eastern region of the country, with no history of interaction with camels or their raw products [47]. Lastly in 2025, eleven MERS-COV cases have been reported from Saudi Arabia between the 1st March and 21th April 2025, with a mortality rate of 22.2 %. Eight of the cases were detected in Riyadh and one in Hail. Only one of the 9 cases had recent contact with camels. In Riyadh, 7 cases were a cluster related to a health care facility, (where the infection was identified in 6 health care workers through contact tracing) after the detection of one MERS-COV positive patient. Two of the health care personnel presented with mild symptoms, including nausea, vomiting, fatigue, and myalgia; whereas four were asymptomatic [48].

3. Epidemiology of MERS-COV in animals

As already mentioned, camels are being regarded as natural MERS-COV reservoirs, from which transmission to humans can occur. In the middle east, from 2019 and until now, MERS-COV in camels has been detected in Egypt, Jordan, Iraq, UAE and KSA (Fig. 1).

Fig. 1.

Distribution of reported MERS-COV infections in animals and humans in the middle east.

3.1. Middle East except KSA

From December 2019 to March 2020, and following multiple samplings, a study conducted in a close camel herd in Egypt, revealed that 35.2 % of the screened camels were consistently seropositive for MERS-COV and 14.8 % were both seropositive and seronegative at different sampling times. Adult camels had higher odds of being positive. Notably, MERS-COV RNA was not detected in any camel including the ones that probably seroconverted [49]. A plausible explanation could be that the virus is present in the camels' nasal area only for a short period of time, thus limiting its reliable identification during surveillance [49]. In Jordan, one study conducted in 2020, revealed the circulation of MERS-COV lineage B in camels residing in a private farm. Phylogenetic analysis of the partial spike gene showed that the circulating strains are closely related to the ones reported from camels and humans, in the Arabian peninsula [50]. In Iraq, Madhloom et al., reported the detection of MERS-COV RNA in the nasal samples (42 %) obtained from camels in the Wasit province in January–April 2023 [51]. During the same period, another study showed a 37.58 % seropositivity in camels from the same region, with increased odds in those aged more than 3 years old [52].

In the United Arab Emirates, in 2019, one study reported the detection of MERS-COV antibodies in Bactrian and hybrid camels, in a private collection in Dubai, where they are kept as hobby animals. Hybrid and Bactrian camels are occasionally used for racing together with dromedary camels, from which they could have acquired the virus [53]. During the same year, another study revealed 88 % seropositivity in a dromedary collection obtained from different sources, including desert wildlife reserves, national livestock markets and a private farm. MERS-COV RNA was detected in almost half of the nasal swabs of another group of dromedary samples collected in the same study. Notably, some positive MERS-COV RNA samples were seronegative, possibly indicating a recent viral infection [54]. Moreover, two interesting studies in the UAE explored the possibility of other animals, beside camels, being potential reservoirs and/or vectors for the transmission and spread of the MERS-COV virus. Weidinger et al., reported the detection of MERS-COV RNA in the nasal sample of a two-year-old sheep that lives in close proximity to a camel pen. 91.1 % of the camels living in the same market were seropositive and 35.6 % were positive for the MERS-COV RNA. It is worth mentioning here that seropositivity testing showed that the sheep lacked MERS-COV antibodies, suggesting either a spillover from nearby camels or recent infection [55]. Sequencing of the complete MERS-COV N gene from the sheep revealed the presence of the Clade B lineage. Phylogenetic analysis showed that the strain had more than 99 % similarity to reference sequences, and strains isolated from camels living in the nearby pen [55]. The other study explored the possibility of Hyalomma ticks as possible vectors for the transmission of MERS-COV. In this latter, it was found that 8 out of 242 tick pools tested positive for the MERS-COV RNA. N gene sequencing, revealed identical sequences between tick strains and their host camels; in addition, these were 99.6 % closely related to the ones detected in humans and camels in Saudi Arabia in the years 2015 to 2019. Given that all camels were seronegative for MERS-COV RNA, despite being more than 50 % positive in the nasal samples, contradicts the possibility of viremia, and thus ticks could be a vector for MERS-COV. Ticks could have acquired the virus when moving across the camels' nasal area [56]. The role of ticks as possible vectors for the transmission of MERS-COV should be however further explored in larger cohort studies.

3.2. Saudi Arabia

In the Kingdom of Saudi Arabia, several studies reported also the detection of MERS-COV RNA and antibodies in camels. The most recent one is a large study conducted from November 2023 to January 2024, in dromedary camel farms located in 6 different locations/cities over the kingdom. The overall rate of detection of the MERS-COV RNA was 38.9 % (217 out of 558), with this ranging from 16.2 % in Shaqra, to 53.7 % in Riyadh, to 70 % in Al Duwadimi region [57]. In 2019, one study revealed the detection of MERS-COV RNA (38.6 % prevalence) and antibodies (70.8 %) in slaughtered camels coming from different barns, farms and markets across Riyadh province. Spike gene sequencing analysis revealed a high level of similarity (98.99 %) among sequenced isolates. Phylogenetic analysis showed that these are 94 % similar to previously published MERS-COV strains from camels, with the least similarity being observed to a strain isolated in the UAE in 2016. In Saudi Arabia, MERS-COV RNA was also detected in the saliva, conjunctiva, breath and milk samples from camels [58] [59] [60]. Phylogenetic analysis using the N gene sequencing of saliva and breath samples revealed that these are closely related to previously isolated strains, in humans and camels, from the Arabia peninsula, especially KSA [58] [59]. In breath samples, partial S gene clustering revealed also close genetic relatedness to strains isolated in Al-Hufuf city in Saudi Arabia, as well as in Qatar and Jordan in 2015 [59].

4. Genomic analysis of MERS-COV in humans and animals

In humans, genomic analysis of MERS-COV strains, has been conducted only up to 2019 [61], and only in Saudi Arabia. For instance, using whole genome sequencing, one study revealed that two strains of MERS-COV isolated in 2019 belongs to the B3 lineage [62]. Genomic analysis, conducted in other studies, revealed the detection of the G198S variant in the nucleocapsid (N) gene from human samples in the country 2019 [17] [62]. Interestingly, this variant was previously detected in dromedary camels during 2015–2016 in Nigeria [17]. Other mutations identified in the N gene in MERS-COV strains of 2019 include: V178A, R292P, P7L, A300V, S391I [62]. During the same year, the following mutations has been also reported in the MERS-COV genomes of strains in the country: 31 amino acids longer version of the ORF-8B [17], V26L, S191P, S459T, T424I, Q1009L in the spike gene, V62F, G85D/P86F, P86L, in ORF3, and I147L, and A218S in ORF4b [62]. Indeed, the virus appears to evolve in crucial genomic parts that are involved in the host mediated immune responses.

In animals, non-targeted sequencing of MERS-COV samples from 6 different camels samples sites in Saudi Arabia from 2023 to 2024, revealed the formation of a “monophyletic clade apical to lineage B5” (B5–2023) [57]. Phylogenetic analysis showed the differentiation of five sub-lineages within the B5–2023, without geographical clustering. Compared to the closely related reference sequence that was previously detected in country in 2019, the B5–2023 clade have acquired more than 50 polymorphisms that includes: amino acid (aa) substitutions in the N terminal, aa deletions and substitutions in the spike protein, including the cathepsin cleavage site, as well as the receptor binding domain (RBD). In MERS-COV infected patients, the RBD is the most site targeted by neutralizing antibodies [63] [64]. For the cathepsin L cleavage site mutations, it has been suggested that these might affect the cleavage of the spike protein, in cells not expressing the transmembrane protease serine 2 [65] [57]. Therefore, the effect of these mutations on the viral fitness, tropism, cell entry, receptor affinity, in addition to immunity escape, should be further explored in future studies (see Outstanding questions). Indeed, it has been previously suggested that mutations in the MERS-COV spike protein can alter its receptor binding affinity, transmissibility, as well as host range. Several studies have found that amino acid variations in the receptor binding domain (RBD) of MERS-COV, such as T512I, L506F, and S746R increase both replication efficiency and binding affinity in the epithelial cells of the human airways [66]. Moreover, one study revealed that in the upper respiratory tract of humans, the adaptation of the MERS-COV virus is possible, following in vitro experiments [67]. Adaptive mutations might intensify the virus transmissibility, and/or spill over from animals to humans, making it accordingly a potential highly contagious pathogen in humans [66]. Nevertheless, this statement can't be conclusive for all mutations that occurs in the MERS-COV genome, including those occurring in the spike protein. For example, several studies have found that two RBD mutations: D510G, I529T that were previously reported from Korea, not only decreased the binding affinity of the virus towards the human receptor DPP4 [68,69]; but also decreased its virulence in vitro, manifested by less severe lung injury, less induction of inflammatory cytokines, and greater survival [70]. On the other hand, in the same study, spike proteins variants from the African isolates, were the virus is endemic in camel but not in humans, were still nearly fully virulent [70], suggesting and emphasizing thus that other factors including variations in MERS-COV accessory proteins [71], could play a role in the transmission dynamics of the virus at the animal-human interface, an area that should be further explored in future studies.

5. Conclusion and future perspectives

Altogether, this review highlighted essential phenomenon happening in the MERS-COV epidemiology during and after the COVID-19 pandemic: 1) the virus is still circulating and evolving in camels with variants and recombination events occurring “the B5-2023 lineage”, 2) the number of cases in humans have decreased during the pandemic but is resurging gradually since 2024. MERS-COV is still on the blue print list of priority pathogens according to the WHO [72]. Indeed, KSA are part of the WHO EMRO and Public Health Authority (PHA) perform active surveillance testing on MERS-CoV, as well as other respiratory viruses including SARS-CoV-2, RSV and Influenza, and submit regularly obtained results to the EMFLU platform [[73], [74]]. In order to prevent and be prepared for future pandemics, adoption of the “one health concept” is of paramount importance. Extensive genomic and serological surveillance should be conducted both in humans, animals and environment in different geographical areas, especially in countries where previous MERS-COV cases have been reported. Serological surveillance will unveil the silent transmission of this virus. Genomic surveillance, on the other hand, will shed the light on the mutations, and recombination events that are silently occurring in the viral genome, which might affect the virus transmissibility, adaptation, virulence, infectivity and tropism. Furthermore, genomic analysis will aid vaccine development efforts; this is in addition to guiding the WHO in their MERS-COV global risk assessment, in order to implement timely and appropriate actions accordingly. In another part, the role of non-camelid species, ticks and environment in the transmission of MERS-COV should be further elucidated (Fig. 2). In many studies, MERS-COV negative close herds are being reported to acquire new infections, the driver of which should be explored in order to determine unknown MERS-COV reservoirs/vector and limit its spread. Moreover, infection control measures in animals should be further enforced, including the use of PPE by camel owner/holders, especially when dealing with sick animals. This can prevent the displacement of camels without prior testing of active MERS-COV infection, and raise awareness of infection risk accompanied to the consumption of raw camel products including unpasteurized milk.

Fig. 2.

MERS-COV in the human animal interface.

CRediT authorship contribution statement

Iman Dandachi: Writing – original draft, Conceptualization. Waleed Aljabr: Writing – review & editing, Conceptualization.

Declaration of competing interest

The authors declare no conflict of interest.

Data availability

No data was used for the research described in the article.