Respiratory #infections due to #human common cold #coronaviruses, #SARS-CoV, #MERS-CoV, and SARS-CoV-2: #epidemiology, #pathogenesis, clinical features, diagnostics, therapeutics, and vaccine landscapes

 

Summary

Over the past half-century, perceptions of human coronaviruses have evolved from their initial characterisation as causes of the common cold to recognition of their capacity to trigger severe disease and global epidemics. The emergence of three zoonotic coronaviruses—severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002, Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, and SARS-CoV-2 in 2019, has had profound health, economic, and societal consequences and continues to influence global epidemic-preparedness strategies. All three viruses remain on the WHO Blueprint of priority pathogens for research and development. This Review summarises current knowledge on human coronaviruses, drawing lessons from the past 25 years of epidemic outbreaks. The shared and divergent features of SARS-CoV, MERS-CoV, and SARS-CoV-2, including their origins, evolution, transmission determinants, zoonotic transmission, viral entry pathways, pathogenesis, spectrum of clinical manifestations, long-term sequelae, and case-fatality profiles are highlighted. The full range of clinical manifestations, from asymptomatic or atypical presentations to severe acute respiratory and multisystem disease, are outlined together with risk factors for progression and populations with the greatest susceptibility. Diagnostic approaches, including molecular assays, antigen-based tests, and imaging modalities are described alongside current therapeutics, antiviral strategies, immunomodulators, supportive care principles, and evidence from clinical trials. Advances in diagnostics, vaccines, therapeutics, and infection-control practices are examined together with persistent challenges in early recognition, particularly in resource-limited settings. Strengthening multinational clinical trial capacity, leveraging digital innovations, and embedding One Health approaches are essential to mitigating spillover risks and improving global readiness. We review the latest data, identify gaps and opportunities, and outline forward-looking strategies to anticipate and prepare for the threat of future coronaviruses, and other existing or new respiratory pathogens with epidemic potential. Clinicians and other health-care workers play a central role in detecting and reporting possible lethal coronavirus infection including atypical presentations, enabling rapid, coordinated infection control and management responses.

Source: 

Link: https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(26)00049-4/abstract?rss=yes

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Operational #zoonotic #containment of #MERS #coronavirus in #Saudi Arabia: An implementation-oriented #OneHealth genomic #framework

 

Abstract

Background and Aim: 

Middle East respiratory syndrome coronavirus (MERS-CoV) remains a persistent zoonotic threat more than a decade after its first detection, with Saudi Arabia continuing to be the global epicenter of human infections and the main reservoir interface through dromedary camels. Despite ongoing surveillance, advances in molecular diagnostics, and research on vaccines and therapeutics, sporadic zoonotic spillovers and healthcare-associated outbreaks still occur, showing that current prevention strategies are still not enough. This review compiles current evidence from epidemiological studies, camel reservoir research, genomic monitoring, and public health reports published between 2012 and April 2025 to identify the key gaps preventing effective containment. Special focus is given to recent genomic discoveries, including post-2022 clade B sublineages, recombination events, and spike protein changes that might affect transmission and the effectiveness of countermeasures. Available data suggest that MERS-CoV epidemiology is driven by repeated camel-to-human transmission, followed by occasional amplification in healthcare settings rather than sustained community spread. High seroprevalence and frequent detection of viral RNA in juvenile camels, seasonal gathering in markets, and extensive animal movement networks contribute to ongoing viral circulation at the animal–human interface. Genomic studies consistently show close phylogenetic relationships between camel and human isolates, confirming recurrent zoonotic transmissions. However, fragmented surveillance systems, delayed genomic data integration, inconsistent biosecurity practices, and limited field evidence for camel vaccination pose major barriers to control. Additionally, hospital outbreaks continue to occur due to delayed diagnosis, overcrowding, and incomplete adherence to infection-prevention protocols, underscoring the need for improved clinical preparedness. Based on the integrated synthesis of epidemiological, veterinary, and genomic evidence, this review proposes an implementation-focused One Health genomic framework tailored to the Saudi context. The proposed roadmap highlights real-time connection of human and camel surveillance, expands genomic sequencing capacity, targets vaccination strategies in camels and high-risk human populations, standardizes biosecurity measures in markets and abattoirs, and strengthens infection control systems in healthcare facilities. Alignment with national governance structures and Saudi Vision 2030 offers a practical pathway for coordinated multi-sectoral action. This review concludes that MERS-CoV is unlikely to be eradicated soon, but it can be effectively managed through a genomics-enabled, operational One Health approach that combines surveillance, vaccination, clinical preparedness, and policy coordination. The model outlined here provides a scalable way to reduce zoonotic spillover risk and strengthen readiness against future coronavirus and emerging zoonotic threats. 

Source: 

Link: https://veterinaryworld.org/Vol.19/March-2026/29.php

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Detection of a #Merbecovirus with potential #ACE2 usage in #France

 

ABSTRACT

A novel Merbecovirus, designated Cam-2023, has been identified in Pipistrellus pipistrellus in France through non-invasive surveillance. Phylogenetic analysis demonstrates that Cam-2023 belongs to a Merbecovirus clade previously associated with ACE2 usage in closely related viruses detected in the Netherlands and Russia. While the receptor usage of Cam-2023 remains to be functionally validated, sequence similarities within the Spike protein, particularly the receptor-binding domain, suggest a putative association with a Merbecovirus clade previously associated with ACE2 usage. This discovery broadens the known host diversity of this lineage and extends its geographical range to Western Europe. Our findings highlight the importance of continuous surveillance in European bat populations to better characterize the distribution and zoonotic potential of such high-risk coronaviruses.

Source: 

Link: https://www.tandfonline.com/doi/full/10.1080/22221751.2026.2651469

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A natural five-amino-acid insert at the S2’ #cleavage site of #MERS-CoV #spike enhances viral membrane fusion

 

Highlights

• A novel 5-aa insert, TSGVF, is present at the S2’ cleavage site of the spike protein of MERS-CoV from dromedary camels.

• Pseudovirus-based entry assays showed that the TSGVF insert increases viral entry efficiency in different human cells.

• Pseudovirus with TSGVF insert at the S2’ cleavage site showed strong resistance to TMPRSS2 inhibitor.

• The natural occurrence of TSGVF insert at the spike S2’ cleavage site enhances viral membrane fusion and syncytia formation.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S1995820X26000611?via%3Dihub

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Q1020R in the #spike proteins of #MERS-CoV from Arabian #camels confers resistance against soluble #human #DPP4

 

ABSTRACT

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a pre-pandemic coronavirus that is transmitted from camels, the natural reservoir, to humans and can cause severe disease. MERS cases have been documented in Arabia but not Africa, although the virus is circulating in both Arabian and African camels. Further, evidence has been provided that viruses in African camels might have a reduced capacity to cause disease. However, the underlying determinants are incompletely understood. Here, employing pseudotyped particles as model systems for MERS-CoV entry into cells, we compared cell entry of viruses from African and Arabian camels and its inhibition. We show that viruses found in Arabian camels and recent human cases are less susceptible to inhibition by human soluble DPP4 (sDPP4) than viruses from African camels, although both enter human cells efficiently and are comparably sensitive to inhibition by interferon-induced transmembrane (IFITM) proteins and neutralizing antibodies. Furthermore, relative resistance to sDPP4 was linked to mutation Q1020R, present in the spike proteins of recent Arabian but not African viruses. Finally, indirect evidence was obtained that sDPP4 in human plasma can inhibit MERS-CoV cell entry. These results support the concept that soluble DPP4 might constitute a natural barrier against human infection that is more efficiently overcome by viruses currently circulating in Arabian camels than those in African camels.

Source: 

Link: https://journals.asm.org/doi/10.1128/jvi.00282-26

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Clade C #MERS-CoV #camel #strains vary in #protease utilization during viral entry

 

Significance

Clade A/B Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreaks have caused over 957 deaths since the first spillover in 2012; meanwhile, Clade C strains have been found in camels across Africa but have not yet been reported to cause outbreaks. Investigating why these viruses do not successfully transmit to humans will be key to understanding the pandemic potential of the African MERS-CoV camel reservoir. Our study indicates that clade C viruses exhibit less spike cleavage and that East African clade C isolates are less able to utilize the TMPRSS2 for viral entry of both human cell lines and primary nasal cells. Differences in viral entry pathways could alter cellular and organ tropism and contribute to differential pandemic potential.

Abstract

Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a lethal pathogen with pandemic potential. Clade A and B MERS-CoV viruses have caused outbreaks in the Middle East since 2012 when they initially spilled over from camels to humans. Clade C viruses, however, are only found in camels across Africa and the spillover potential of these viruses seems to be lower than for clade A/B strains but remains to be fully understood. Here, we report that clade C spikes are less well-cleaved at the S1/S2 boundary than clade A or B viral spikes and that most clade C spikes induce reduced syncytium formation. Additionally, we demonstrate that several East African clade C strains are less able to utilize the TMPRSS2-mediated pathway for viral entry in both cell lines and primary nasal epithelial cultures. We map the molecular basis of this reduced TMPRSS2 usage to the N-terminal domain and subdomain 2 of East African clade C MERS-CoV. We suggest that reduced usage of the TMPRSS2-mediated entry pathway may underlie the reduced replication of East African clade C strains in humans, while the reduced replication of West African strains remains to be further investigated. Altered protease usage may contribute to differential tropism of East African clade C strains and indicate geographically distinct selection pressures on spike between MERS-CoV strains circulating in camels.

Source: 

Link: https://www.pnas.org/doi/10.1073/pnas.2525313123

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Characterisation of Naturally Occurring #MERS-CoV #Spike #Mutations and Their Impact on #Fusion and Neutralisation

 

Abstract

In this study, the phenotypic consequences of naturally occurring single nucleotide polymorphisms (SNPs) in the Middle East respiratory syndrome coronavirus (MERS-CoV) Spike protein were investigated. The impact of Spike mutations on the syncytia formation and neutralisation of contemporary MERS-CoV strains is not currently well understood. Mutations were identified by aligning 584 MERS-CoV Spike sequences from either human clinical isolates collected between 2012 and 2024 or from a clinical isolate that had been passaged in human cells. Fifteen SNPs of interest occurring in the N-terminal domain (NTD), receptor binding domain (RBD) and adjacent to the S1/S2 cleavage site were selected for further characterisation based on their location in the Spike protein, frequency and identification in previous studies. A contemporary clade B, lineage 5 wildtype Spike sequence, obtained from a human MERS-CoV clinical isolate, was used as the backbone in this study. The mutations of interest were introduced to the wildtype backbone to generate Spike variants. Spike variants were characterised via cell–cell fusion assays, and a lentiviral pseudotyping system was used to investigate the impact of these Spike mutations on neutralisation. The I529T, E536K and L745F mutations were shown to increase fusion and syncytia formation. The L411F, T424I, L506F, L745F and T746K mutations were found to increase resistance to neutralisation by pooled patient sera. This study has identified novel naturally occurring Spike mutations that resulted in phenotypic differences in the syncytia formation and neutralisation of contemporary MERS-CoV strains. Continued investigation of the phenotypic consequences of MERS-CoV Spike mutations is essential for assessing the risk to public health, especially given the pandemic potential of this virus.

Source: 

Link: https://www.mdpi.com/1999-4915/18/3/377

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Middle east respiratory syndrome coronavirus (#MERS-CoV): An underestimated #betacoronavirus with #pandemic potential

 

Highlights

• MERS-CoV remains an endemic camel-associated betacoronavirus with ongoing zoonotic spillover.

• Viral evolution shows three major clades with lineage B predominance and documented recombination.

• DPP4-mediated entry, immune suppression, and T-cell apoptosis drive severe disease and high fatality.

• Diagnosis relies primarily on rRT-PCR, while treatments and vaccines remain experimental.

• Strengthened One-Health surveillance, IPC, and genomic monitoring are essential for pandemic preparedness.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic beta coronavirus identified in 2012 that circulates in dromedary camels and occasionally infects humans. Although community spread is limited, the disease shows a high case fatality rate near 36 percent and has caused hospital outbreaks such as the 2015 South Korea event. The viral spike binds the DPP4 (CD26) receptor, enabling entry into airway epithelial and selected immune cells, while accessory proteins suppress early innate immunity. Genetic studies indicate continuing evolution with clades A, B, and C across the Arabian Peninsula and Africa. Human infection is linked to camel contact, farm exposure, or raw camel products, with secondary spread mainly in healthcare settings. Diagnosis uses rRT-PCR and serology; treatment is supportive, and vaccines and antivirals are under study. A One Health approach is vital for surveillance, early detection, and control.

Source: Diagnostic Microbiology and Infectious Disease, https://www.sciencedirect.com/journal/diagnostic-microbiology-and-infectious-disease

Link: https://doi.org/10.1016/j.diagmicrobio.2026.117367

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#MERS #Coronavirus–Specific T-Cell Responses in Dromedary #Camel #Abattoir #Workers in #Nigeria Suggests Frequent Zoonotic #Spillover

 

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is assessed to have high pandemic risk, and dromedary camels are the source of zoonotic spillover. More than 75% of MERS-CoV–infected dromedary camels are found in Africa, but no zoonotic disease has been reported from Africa where there is little awareness of MERS-CoV as a potential cause of respiratory disease. Antibody responses are a poor indicator of mild infection. We found that 47 of 60 (78%) dromedary camel abattoir workers in Kano, Nigeria, had MERS-CoV–specific T-cell responses while none of 18 controls did, suggesting that zoonotic infection is common in camel-exposed individuals in Africa.

Source: 

Link: https://academic.oup.com/jid/advance-article-abstract/doi/10.1093/infdis/jiag095/8504072?redirectedFrom=fulltext

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Unveiling the #epitope #repertoires and protective roles of #MERS-CoV-specific T cells in mice

 

Highlights

• MERS-CoV structural proteins and ORFs potently induce T cell responses in mice

• MERS-CoV-specific T cell epitope repertoires are identified in C57BL/6 and BALB/c mice

• Airway ORF4b208-CD4+ and ORF5167-CD8+ T cells are optimal effector T cells

• ORF4b208 and ORF5167-specific T cells protect mice against MERS-CoV infection

Summary

Since its initial emergence in 2012, MERS-CoV has remained endemic and a global health threat. While accessory proteins (ORFs) are known for immune evasion, their role in adaptive immunity is unexplored. This study systematically investigated T cell responses against MERS-CoV ORFs. We mapped epitope repertoires targeting structural proteins and ORFs in C57BL/6 and BALB/c mice, revealing that ORFs potently induced virus-specific T cells. Notably, ORF5 induced the dominant CD8+ T cell responses in BALB/c mice. Further analysis revealed that ORF4b208-specific CD4+ and ORF5167-specific CD8+ T cells in the respiratory tract exhibited polyfunctional cytokine profiles, high antigen sensitivity, and potent in vivo cytotoxicity. These specific T cells played protective roles during MERS-CoV infection by promoting viral clearance. Collectively, this study identified MERS-CoV-specific T cell epitopes and elucidated the roles of ORF4b- and ORF5-specific T cells, enhancing our understanding of anti-MERS-CoV T cell responses and advancing vaccine design strategies against MERS-CoV.

Source: 

Link: https://www.cell.com/cell-reports/fulltext/S2211-1247(26)00121-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS221112472600121X%3Fshowall%3Dtrue

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Decoding #antibody response to #MERS-CoV in wild dromedary #camels

 

Significance

Middle East respiratory syndrome coronavirus (MERS-CoV) remains the most lethal human coronavirus, with continued zoonotic transmission from wild naturally infected dromedary camels, posing a persistent risk of spillover to humans. Despite this ongoing threat, no specific antiviral treatment has been approved. In this study, we characterize the antibody response to MERS-CoV in naturally infected dromedaries, the primary animal reservoir, and identify a panel of nanobodies (Nbs) exhibiting potent neutralizing activity. These Nbs recognize a previously unreported binding and neutralizing site on the virus spike receptor-binding domain (RBD). Their distinctive genetic, structural, and functional properties make them promising candidates for the development of effective and therapeutic interventions against MERS-CoV, as strongly advocated by global health authorities.

Abstract

Wild dromedary camels in the Arabian Peninsula and Africa have harbored antibodies against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) for decades, predating zoonotic spillover to humans. However, the potency, specificity, and structural characteristics of these antibodies remain poorly understood. Here, we characterize the antibody responses of naturally infected wild dromedary camels in Tunisia, a MERS-CoV-endemic region. Plasma antibodies from nine camels exhibited variable neutralizing activity, generally increasing with age, and were largely autologous, with minimal cross-reactivity to SARS-CoV-1 or SARS-CoV-2. From a VHH antibody library derived from the peripheral blood mononuclear cells (PBMCs) of a single camel (D17), we identified 34 unique sequences with previously unreported germline origins and unusually long complementarity-determining region 3 (CDR3) sequences. Eight representative VHHs, expressed as human Fc fusions, displayed high-affinity binding to the MERS-CoV receptor-binding domain (RBD) and broad neutralization to RBD mutants (IC50: 1.05 to 9.55 ng/mL). Crystal structural analysis revealed distinct neutralization mechanisms: VHH-227 fully blocked DPP4 binding, achieving complete neutralization, while VHH-T71, with partial neutralization (~80%), targeted the RBD core subdomain. This study provides comprehensive characterization of wild dromedary antibody responses, identifying novel nanobodies (Nbs) with broad and potent neutralization to naturally occurring RBD mutants. These findings offer insights into camel immunity and highlight promising candidates for MERS-CoV prophylactic and therapeutic development.

Source: 

Link: https://www.pnas.org/doi/10.1073/pnas.2513716123

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#Epidemiology and #genomic features of #MERS #coronavirus in #Africa: a systematic and meta-analysis review

 

Highlights

• 74% pooled MERS-CoV seroprevalence in African dromedaries

• Highest MERS-CoV RNA incidence (15.3%) observed in juvenile dromedaries

• 2.4% pooled MERS-CoV seroprevalence in camel-exposed humans

• African MERS-CoV clade C exhibits unique polymorphisms

• Clade-specific features might explain low MERS-CoV infection rates in Africa

Abstract

Objective

We explored factors contributing to the low human MERS-CoV prevalence in Africa by assessing MERS-CoV epidemiological and genomic features.

Methods

We followed the PRISMA guidelines. We searched for articles on epidemiological and virological MERS-CoV characteristics in humans and camels in Africa until August 2025. We used a generalised linear mixed-effects model to calculate pooled proportions. We identified relevant polymorphisms in African MERS-CoV lineages compared with the prototypic EMC/2012 and contemporary Arabian MERS-CoV (clade B5).

Results

We included 53 articles, with 31 used in the meta-analysis. Kenya, Egypt, and Ethiopia contributed to 66.03% of all included studies. Pooled MERS-CoV RNA positivity in African dromedaries was 6.09%, with juveniles (15.29%) having a higher incidence than adults (4.51%). The pooled MERS-CoV seroprevalence was 73.67%, with adults (80.96%) higher than juveniles (36.02%). In human-focused studies, only nine PCR-confirmed MERS cases were reported, six travel-associated and three autochthonous cases, despite a pooled seroprevalence of 2.4%. Genomic analyses identified MERS-CoV clade C-specific polymorphisms in the Spike and accessory genes with putative phenotypic impact.

Conclusion

We found the highest MERS-CoV RNA positivity in young dromedaries. Elevated MERS-CoV seroprevalence in mainly asymptomatic camel-exposed humans suggests an underestimation of MERS-CoV infections in Africa. The ongoing MERS-CoV evolution emphasises the need for active genomic surveillance to monitor signatures of human adaptation.

Source: 

Link: https://www.ijidonline.com/article/S1201-9712(26)00091-3/fulltext

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A stabilized #MERS-CoV #spike ferritin #nanoparticle #vaccine elicits robust and protective neutralizing #antibody responses

 

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as a human pathogen in 2012 and causes ongoing sporadic infections and outbreak clusters. Despite case fatality rates (CFRs) of over 30% and considerable pandemic potential, a safe and efficacious vaccine has not been developed. Here we report the design, characterization, and preclinical evaluation of MERS-CoV antigens. Our lead candidate comprises a stabilized spike displayed on a self-assembling ferritin nanoparticle that can be produced from a high-expressing, stable cell pool. This vaccine elicits robust MERS-CoV pseudovirus and authentic virus neutralizing antibody titers in BALB/c mice. Immunization of male non-human primates (NHPs) with one dose of Alhydrogel-adjuvanted vaccine elicited a > 103 geometric mean titer of pseudovirus neutralizing antibodies that was boosted with a second dose. Sera from these NHPs exhibited cross-reactivity against spike-pseudotyped lentiviruses from MERS-CoV clades A, B, and C as well as a distant pangolin merbecovirus. In human DPP4 transgenic mice, immunization provided dose-dependent protection against MERS-CoV lethal challenge, and in an established alpaca challenge model using female alpacas, immunization fully protected against MERS-CoV infection. This MERS-CoV nanoparticle vaccine is a promising candidate for clinical advancement to protect at-risk individuals and for future use in a potential outbreak setting.

Source: 

Link: https://www.nature.com/articles/s41467-026-68458-5

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The #impact of clade B #lineage 5 #MERS #coronaviruses #spike #mutations from 2015 to 2023 on virus entry and replication competence

 

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging coronavirus that can cause zoonotic disease in humans with lethal severe viral pneumonia. Dromedary camels are the source of zoonotic infection. As of November 2025, MERS-CoV has resulted in a total of 2630 reported cases, 37% of these being fatal. The number of reported human cases has been on a decreasing trend since 2016 and reached a nadir during the COVID-19 pandemic. The reason for the reduction of cases is unclear and may be multifactorial. We hypothesized that mutations accumulating in the virus spike protein may have reduced zoonotic potential. Here, we investigate the impact of recently emerged virus spike-protein mutations on virus replication competence using pseudoviruses and replication-competent recombinant viruses. We found that virus spike variants detected in 2019 and some from 2023 show a reduced cell entry, lower viral replication and reduced fitness in human primary alveolar epithelial cells and multiple cell lines. All the MERS-CoV spikes tested showed a cell-entry pathway preference via the cell-surface TMPRSS2 route. Mechanistically, we showed the V530A mutation in the 2019 spike sequence had a reduced human DPP4 binding phenotype. Our data highlighted MERS-CoV spike mutations can modulate viral fitness in human cells and provide new insights to understand recent MERS epidemiology.

Source: 

Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013336

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Structural basis for #human #DPP4 #receptor recognition by #MERS-like #coronaviruses 2014-422 and GX2012

 

Abstract

Since its emergence in 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has posed a significant threat to human health. Recently, novel MERS-like coronaviruses with the potential for cross-species transmission have been identified. In this study, we focused on two newly isolated bat strains with putative health concern: BatCoV/Ii/GD/2014-422 (2014-422) and BtTp-BetaCoV/GX2012 (GX2012). We determined the cryo-EM structures of the spike glycoprotein trimer in the closed state for these two viruses. These structures display a more compact conformation compared to MERS-CoV spike. Biochemical characterization demonstrates that the spike receptor-binding domains (RBDs) of 2014-422 and GX2012 can bind to human dipeptidyl peptidase 4 (hDPP4). To investigate the structural determinants of pseudovirus infection, we solved the cryo-EM structures of 2014-422 RBD-hDPP4 and GX2012 RBD-hDPP4 complexes. The binding mode of the complex is conserved, but the angle of the RBD binding undergoes significant tilting. Detailed structural analysis reveals that an additional residue at position 514 interacts with the N321 glycan in hDPP4, altering the binding angle and thus influencing receptor recognition. These findings offer valuable insights into the receptor utilization of Merbecovirus and provide a structural basis for future surveillance efforts.

Author summary

Two MERS-like coronaviruses, BatCoV/Ii/GD/2014-422 (2014-422) and BtTp-BetaCoV/GX2012 (GX2012), have recently emerged as potential zoonotic threats. In this study, we provide a detailed structural analysis of these two viruses, focusing on their spike proteins and interactions with human Dipeptidyl Peptidase 4 (hDPP4), the receptor used by MERS-CoV. Using cryo-electron microscopy (cryo-EM), we determined high-resolution structures of 2014-422 and GX2012 spike glycoproteins in their closed conformations. Our results show that GX2012 mediates efficient pseudovirus entry into human cells, whereas 2014-422 shows markedly reduced entry efficiency. This difference is linked to structural variations, including a unique residue at position 514 in both viruses that affects the RBD binding angle and receptor recognition. Together, these findings provide key insights into the structural basis of receptor usage by MERS-like coronaviruses and suggest that HKU4r-CoVs may acquire the ability to infect human cells through two evolutionary routes: within bats and through pangolins as intermediate hosts.

Source: 

Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013792

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Phylogenetic Characteristics and High Prevalence of a #Merbecovirus in #Hedgehogs from Greenspace of a Metropolis, #China

 

Abstract

SARS-CoV, MERS-CoV, and SARS-CoV-2 have posed tremendous threats to human health, highlighting the necessity of monitoring cross-species transmission of animal coronaviruses to humans. Hedgehogs infected with coronaviruses have been reported in several countries across Europe and Asia, raising concerns about the potential transmission of coronaviruses from hedgehogs to humans. In this study, we investigated coronavirus infections in hedgehogs inhabiting greenspaces in metropolitan Beijing and identified a Merbecovirus subgenus coronavirus with a prevalence rate of 30% (95% CI: 25–35%) among 317 hedgehogs. Phylogenetic analysis of 23 complete viral genome sequences revealed a monophyletic origin, showing close relatedness to Erinaceus hedgehog coronavirus HKU31 (Ea-HedCoV HKU31) with genome-wide nucleotide identities of 93.24–96.42%, and evidence of recombination with Tylonycteris bat coronavirus HKU4. These findings suggest that the increase in wildlife populations associated with urban greenspace development may pose a potential threat to human health that should not be overlooked.

Source: 

Link: https://www.mdpi.com/2076-2607/14/1/83

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#MERS #Coronavirus - Global #update (#WHO D.O.N., Dec. 24 '25)

 

Situation at a glance

Since the beginning of 2025 and as of 21 December 2025, a total of 19 cases of Middle East respiratory syndrome coronavirus (MERS- CoV), including four deaths have been reported to WHO globally. 

Of the 19 cases, 17 were reported by the Kingdom of Saudi Arabia (KSA), and two were reported from France. 

Between 4 June and 21 December 2025, the Ministry of Health (MoH) of KSA reported a total of seven cases of MERS-CoV infection, including two deaths. 

In addition, at the beginning of December 2025, the National IHR Focal Point (IHR NFP) for France also reported two MERS-CoV travel – associated cases; involving individuals with recent travel to countries in the Arabian Peninsula. 

The notification of these latest cases does not change the overall risk assessment, which remains moderate at both the global and regional levels. 

These cases show that the virus continues to pose a threat in countries where it is circulating in dromedary camels, with regular spillover into the human population. 

WHO recommends implementation of targeted infection, prevention and control (IPC) measures to prevent the spread of health care-associated infections of MERS-CoV and onward human transmission.

Description of the situation

Since the first report of MERS-CoV in the KSA and Jordan in 2012, a total 2635 laboratory-confirmed cases of MERS-CoV infection, with 964 associated deaths (Case Fatality Ratio (CFR) of 37%), have been reported to WHO from 27 countries, across all six WHO regions (...). 

The majority of cases (84%; n=2224), have been reported from the KSA (...). 

Since the beginning of 2025 and as of 21 December, a total of 19 cases have been reported to WHO. 

Overall, 17 cases were reported in the KSA from five regions named: Riyadh (n=10), Taif (n=3), Najran (n=2), Hail (n=1), and Hafr Al-Batin City (n=1) (...). 

In addition, two travel associated cases of MERS-CoV infection have been reported in France, with likely exposure occurring during recent travel in the Arabian Peninsula (...). 

This disease outbreak news report focuses on the recent nine cases of MERS-CoV infection reported between 4 June - 21 December 2025: seven cases from the KSA and the two imported cases to France. 

The details of cases reported earlier in 2025 can be referred to in the previously published disease outbreak news on 13 March 2025 and 12 May 2025.

Between 4 June and 21 December 2025, the MoH of the KSA reported a total of seven cases of MERS CoV infection. 

The cases were reported from three regions: Najran (2), Riyadh (3), and Taif (2). 

No epidemiological links were identified between the seven cases. 

In addition, between 2 and 3 of December 2025, the IHR NFP for France reported two cases of MERS – CoV with recent travel to the Arabian Peninsula during the month of November.

Follow-up has been completed for all contacts and no secondary infections have been identified or reported. 

From September 2012, France has recorded a total of four laboratory-confirmed cases of MERS-CoV infection, including one death: two cases were reported in 2013, and the latest two cases in December 2025. 

All cases had been travelers exposed in the Arabian Peninsula and returning back to France.

(...)

Epidemiology

Middle East respiratory syndrome (MERS) is a respiratory illness caused by a coronavirus (MERS-CoV). The case fatality ratio (CFR) among confirmed cases is around 37%. The CFR is calculated based solely on laboratory-confirmed infections and may overestimate the actual mortality rate since milder cases often go undetected or unreported.

Humans can contract MERS-CoV through multiple transmission pathways; the primary route being through direct or indirect contact with dromedary camels, which serve as the virus’s natural host and primary zoonotic reservoir. 

Additionally, human-to-human transmission can occur via infectious respiratory particles primarily in close-contact situations and can also occur through direct or indirect contact; this is especially prominent in health-care settings. 

Human-to-human transmission of the virus has occurred in health care facilities in several countries, including transmission from patients to health care providers and transmission between patients before MERS-CoV was diagnosed. 

It is not always possible to identify patients with MERS‐CoV early or without testing because symptoms and other clinical features may be non‐specific. 

Outside these environments, there has been limited documented human-to-human transmission. 

MERS can present with no symptoms (asymptomatic), mild symptoms (including mild respiratory issues), or severe illness leading to acute respiratory distress and death. 

Common symptoms include: 

- fever, 

- cough, and 

- breathing difficulties, 

- with pneumonia frequently observed, though not always present. 

Some patients also experience gastrointestinal symptoms such as diarrhoea. 

Severe cases may require intensive care, including mechanical ventilation. 

Those at higher risk of severe outcomes include older adults, individuals with weakened immune systems, and those with chronic conditions like diabetes, kidney disease, cancer, or lung disorders.

The number of MERS-CoV infections reported to WHO substantially declined since the beginning of the COVID-19 pandemic. 

Initially, this was likely the result of epidemiological surveillance for SARS-CoV-2 being prioritized. 

Similar clinical pictures of both diseases may have resulted in reduced testing and detection of MERS-CoV infections. 

However, the MoH of the KSA has been working to improve testing capacities for better detection of MERS-CoV since the easing of the COVID-19 pandemic, with MERS-CoV included into sentinel surveillance testing algorithms since the second quarter of 2023, for samples that test negative for both influenza and SARS-CoV-2. 

In addition, recommended IPC measures (e.g., mask-wearing, hand hygiene, physical distancing, improving ventilation) and public health and social measures in the community to reduce SARS-CoV-2 transmission, (stay-at-home orders, reduced mobility) also likely reduced onward human-to-human transmission of respiratory infections including MERS-CoV. 

Potential cross-protection conferred from infection with or vaccination against SARS-CoV-2 and any reduction in MERS-CoV infection or disease severity and vice versa has been hypothesized but requires further investigation. [1,2]  

Public health response

WHO is supporting Member States in strengthening preparedness and response.

Activities in the Kingdom of Saudi Arabia include:

-- Strengthened surveillance with immediate notification of all suspected and confirmed cases.

-- Strict implementation of infection prevention and control transmission-based precautions (Contact and Droplet precautions) in healthcare facilities for suspect or confirmed patients, and airborne precautions for patients undergoing aerosol-generating procedures.

-- Identification of health and care worker contacts and perform risk assessment of their exposure, considering the timely identification of symptomatic patients, implementation of IPC measures, and correct utilization of PPE while treating patients,

-- Exposed health and care workers are followed up for 14 days to monitor symptoms. If they develop symptoms, they are to be removed from working with patients until tested and symptoms are fully resolved.

-- Patients exposed to MERS-CoV in the healthcare setting must be tested to determine their ability to continue working with patients without further transmission, which could potentially lead to outbreaks in the healthcare facility. 

-- Identification of all potential community contacts and active follow-up to monitor symptoms for 14 days.

-- All community acquired cases are investigated for having direct or indirect contact with camels or their products.

-- Cases linked to camel exposures are notified to the National Center for Prevention and Control of Plants, Pests, and Animal Diseases (Weqaa) to investigate potential camel sources.

-- Camels identified as a presumed source are quarantined and tested for MERS-CoV, and if live virus is detected, the quarantine period will be extended until live virus is no longer detected in camel.

Activities in France include:

-- On 4 December 2025, MoH France published information regarding the two imported cases of MERS-CoV in the country.

-- Genomic sequencing was conducted from the first case and reported as being the same lineage that is circulating in the Arabian Peninsula. Further laboratory analyses are ongoing.

-- Contact tracing was initiated as soon as the first case was detected for the monitoring and surveillance of fellow travellers and co-exposed individuals, high-risk contacts, and hospital contacts. It was completed in week 51 and no additional cases among the travellers have been reported, nor any secondary cases as of 19 December 2025. 

-- Asymptomatic co-exposed individuals and at-risk contacts located in France were offered a full testing protocol (nasopharyngeal swab, sputum, rectal swab and serology) on a voluntary basis up to 29 days after their last exposure, even if they did not exhibit any symptoms.

WHO risk assessment

As of 21 December 2025, a total of 2635 laboratory-confirmed cases of MERS-CoV infection have been reported globally to WHO, with 964 associated deaths. 

The majority of these cases have occurred in countries on the Arabian Peninsula, including 2224 cases with 868 related deaths (CFR 39%) reported from the KSA.

A notable outbreak outside the Middle East occurred in the Republic of Korea, in May 2015, during which 186 laboratory-confirmed cases (185 in the Republic of Korea and 1 in China) and 38 deaths were reported. However, the index case in that outbreak had a history of travel to the Middle East.

Three limited healthcare-related clusters have recently been reported from the KSA, two in 2024 comprised of three and two cases each, and one in 2025 comprised of 7 cases; the previous cluster before that had been observed in May 2020, also in the KSA. 

Extensive contact tracing was applied in the 2025 cluster, which lead to detection of four asymptomatic and two mild cases, who fully recovered. 

Despite these recent clusters, zoonotic spillover remains an important mode of human infection, leading to isolated cases and limited onwards transmission between humans.

Global total cases reflect laboratory-confirmed cases reported to WHO under IHR (2005) or directly by Ministries of Health from Member States. These figures may underestimate the true number of cases if some were not reported to WHO, as they may be missed by current surveillance systems and not be tested for MERS-CoV – either due to similar clinical presentation as other circulating respiratory diseases or because infected individuals remained asymptomatic or had only mild disease. The total number of deaths includes those officially reported to WHO through follow-up with affected Member States. 

The notification of these new cases does not change the overall risk assessment. 

WHO expects that additional cases of MERS-CoV infection will be reported from the Middle East and/or other countries where MERS CoV is circulating in dromedaries, and that cases will continue to be exported to other countries by individuals who were exposed to the virus through contact with dromedaries or their products (for example, consumption of raw camel milk,  camel urine, or eating meat that has not been properly cooked), or in a healthcare setting. 

Due to the similarity of symptoms with other respiratory diseases that are widely circulating, like influenza or COVID-19, detection and diagnosis of MERS cases may be delayed, especially in unaffected countries, and provide an opportunity for onward human-to-human transmission to go undetected. 

WHO continues to monitor the epidemiological situation and conducts risk assessments based on the latest available information.  

No vaccine or specific treatment is currently available, although several MERS-CoV-specific vaccines and therapeutics are in development. 

Treatment remains supportive, focusing on managing symptoms based on the severity of the illness.

WHO advice

-- Surveillance:

- Based on the current situation and available information, WHO re-emphasizes the importance of strong surveillance by all Member States for acute respiratory infections, with the inclusion of MERS-CoV into the testing algorithm where warranted, and to carefully review any unusual patterns.  

-- Clinical Management:

- The incubation period is typically 2-15 days (median 5 days), although prolonged incubation periods have been reported in the immunocompromised. 

- Although mild disease does occur, clinicians should be aware that symptoms may frequently progress rapidly non-specific signs of upper respiratory tract infection, cough and breathlessness, to respiratory failure and cardiovascular collapse.[3]

- MERS-CoV infection should be managed supportively with respiratory support titrated to the needs of the patient; there is a wide spectrum of severity, with many patients requiring mechanical ventilation.

- The largest clinical trial in MERS compared a combination of lopinavir–ritonavir and interferon β-1b with placebo (95 patients).[4] 

- Active treatment caused lower 90-day mortality in hospitalized patients with laboratory-confirmed MERS (90-day mortality of 48% and 29% respectively). 

- Further analysis suggested a positive effect only in patients treated within 7 days of symptom onset. 

- Although there is increasing use of corticosteroids for some respiratory conditions (specifically in COVID-19 and some other forms of pneumonia), their use in MERS-CoV is of uncertain benefit, and harms relating to their immunomodulatory effects may be significant; more data are needed. 

- The use of convalescent plasma has not been proven, although has been used in a limited number of patients in a non-trial setting. 

- While antibiotics have been used in severe disease to presumptively treat concurrent bacterial infection, there are no controlled data on efficacy. 

- A retrospective analysis of 349 MERS patients examined macrolide antibiotic therapy. No difference in 90-day mortality was found in the 136 patients receiving macrolides compated with those who did not.[5]

-- Infection prevention and control:

- Human-to-human transmission of MERS-CoV in healthcare settings has been associated with delays in recognizing the early symptoms of MERS-CoV infection, slow triage of suspected cases and delays in implementing timely IPC measures. 

- IPC measures are therefore critical to prevent the spread of MERS-CoV in healthcare facilities and onwards in the community. 

- Healthcare workers should always apply standard precautions consistently with all patients and perform risk assessments at every interaction in healthcare settings to determine the necessary protection measures. 

- For patients with suspected MERS-CoV infection that require hospitalization, place patient in an adequately ventilated single room away from other patient care areas. 

- In addition to standard precautions. Droplet and contact precautions should be implemented when providing care to patients with symptoms of acute respiratory infection who are suspects of any respiratory disease, including probable or confirmed cases of MERS-CoV infection.[6,7]

- Droplet and contact precautions should be maintained until the patient is no longer symptomatic (for at least 24 hours) and has two upper respiratory (URT) swabs (taken 24hrs apart) test negative in RT-PCR or according to local guidance. 

- Additionally, airborne precautions should be applied when performing aerosol generating procedures or in settings where aerosol generating procedures are conducted. 

- Early identification, case management and prompt isolation of suspected respiratory infected patients and cases, quarantine of contacts, together with appropriate IPC measures in health care settings, including improving ventilation in enclosed spaces and public health awareness can prevent the spread of human-to-human transmission of MERS-CoV. 

-- Public health and social measures:

- MERS-CoV appears to cause more severe disease in people with underlying chronic medical conditions such as diabetes, renal failure, chronic lung disease, and immunosuppression. 

- Therefore, people with these underlying medical conditions should avoid close contact with animals, particularly dromedaries, when visiting farms, markets, or barn areas where the virus may be circulating.

- General hygiene measures, such as regular hand hygiene before and after touching animals or animal products and avoiding contact with sick animals, should be adhered to. 

- In addition, hygiene practices should be observed including the five keys to safer food should be followed when dealing with food items of camels; people should avoid drinking raw camel milk or camel urine or eating meat that has not been properly cooked. 

- WHO does not advise special screening at points of entry with regard to this event, nor does it currently recommend the application of any travel or trade restrictions. 

Further information

-- Infection prevention and control during health care for probable or confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection:interim guidance: updated October 2019.   [Internet]. [cited 2025 Dec 10]. Available from: https://iris.who.int/handle/10665/174652

-- Transmission-based precautions for the prevention and control of infections: aide-memoire [Internet]. [cited 2025 Dec 10]. Available from: https://iris.who.int/handle/10665/356853.

-- Standard precautions for the prevention and control of infections: aide-memoire.[cited 2025 Dec 10] Available from https://iris.who.int/handle/10665/356855

-- MERS fact sheet, updated 11 December 2025. Available from: https://www.who.int/news-room/fact-sheets/detail/middle-east-respiratory-syndrome-coronavirus-(mers-cov)

-- 2015 MERS outbreak in Republic of Korea [Internet]. [cited 2025 Dec 10]. Available from: https://www.who.int/westernpacific/emergencies/2015-mers-outbreak

-- WHO MERS-CoV dashboard. [cited 2025 Dec 10]. Available from: https://data.who.int/dashboards/mers

-- Disease Outbreak News [Internet]. [cited 2025 Dec 10]. Available from: https://www.who.int/emergencies/disease-outbreak-news

-- EPI-WIN webinar: MERS-CoV, a circulating coronavirus with epidemic and pandemic potential - Pandemic preparedness, prevention and response with a One Health approach [Internet]. [cited 2025 Dec 10]. Available from: https://www.who.int/news-room/events/detail/2023/05/24/default-calendar/epi-win-webinar-mers-cov-a-circulating-coronavirus-with-epidemic-and-pandemic-potential-pandemic-preparedness-prevention-and-response-with-a-one-health-approach

-- MERS Outbreak Toolbox [Internet]. [cited 2025 Dec 10]. Available from: https://www.who.int/emergencies/outbreak-toolkit/disease-outbreak-toolboxes/mers-outbreak-toolbox

-- Middle East Respiratory Syndrome (MERS) | Policy&Services : KDCA [Internet]. [cited 2025 Dec 10]. Available from: https://www.kdca.go.kr/contents.es?mid=a30329000000

-- Middle East respiratory syndrome: global summary and assessment of risk - 16 November 2022 [Internet]. [cited 2025 Dec 10]. Available from: https://www.who.int/publications/i/item/WHO-MERS-RA-2022.1

-- OpenWHO.org - Middle East respiratory syndrome [Internet]. [cited 2025 Dec 10]. Available from: https://openwho.org/channel/Middle+East+respiratory+syndrome/574814

-- Practical manual to design, set up and manage severe acute respiratory infections facilities [Internet]. [cited 2025 Dec 10]. Available from: https://iris.who.int/items/eb2cb9aa-ef45-4952-8307-a00cbeee70a6

-- Strategic plan for coronavirus disease threat management: advancing integration, sustainability, and equity, 2025–2030 [Internet]. [cited 2025 Dec 10]. Available from: https://www.who.int/publications/i/item/9789240117662

-- Update 88: MERS-CoV, a circulating coronavirus with epidemic and pandemic potential - Pandemic preparedness, prevention and response with a One Health approach [Internet]. [cited 2025 Dec 10]. Available from: https://www.who.int/publications/m/item/update-88-mers-cov-a-circulating-coronavirus-with-epidemic-and-pandemic-potential-pandemic-preparedness--prevention-and-response-with-a-one-health-approach

-- WHO EMRO - MERS outbreaks [Internet]. [cited 2025 Dec 10]. Available from: https://www.emro.who.int/health-topics/mers-cov/mers-outbreaks.html?format=html 

References:

[1] AlKhalifah, J. M., Seddiq, W., Alshehri, M. A., Alhetheel, A., Albarrag, A., Meo, S. A., Al-Tawfiq, J. A., & Barry, M. (2023). Impact of MERS-CoV and SARS-CoV-2 Viral Infection on Immunoglobulin-IgG Cross-Reactivity. Vaccines, 11(3), 552. https://doi.org/10.3390/vaccines11030552

[2] Zedan, H. T., Smatti, M. K., Thomas, S., Nasrallah, G. K., Afifi, N. M., Hssain, A. A., Abu Raddad, L. J., Coyle, P. V., Grivel, J. C., Almaslamani, M. A., Althani, A. A., & Yassine, H. M. (2023). Assessment of Broadly Reactive Responses in Patients With MERS-CoV Infection and SARS-CoV-2 Vaccination. JAMA network open, 6(6), e2319222. https://doi.org/10.1001/jamanetworkopen.2023.19222

[3] Middle East respiratory syndrome, Memish, Ziad A et al. The Lancet, Volume 395, Issue 10229, 1063 – 1077

[4] Arabi, Y. M., Asiri, A. Y., Assiri, A. M., Balkhy, H. H., Al Bshabshe, A., Al Jeraisy, M., Mandourah, Y., Azzam, M. H. A., Bin Eshaq, A. M., Al Johani, S., Al Harbi, S., Jokhdar, H. A. A., Deeb, A. M., Memish, Z. A., Jose, J., Ghazal, S., Al Faraj, S., Al Mekhlafi, G. A., Sherbeeni, N. M., Elzein, F. E., … Saudi Critical Care Trials Group (2020). Interferon Beta-1b and Lopinavir-Ritonavir for Middle East Respiratory Syndrome. The New England journal of medicine, 383(17), 1645–1656. https://doi.org/10.1056/NEJMoa2015294

[5] Macrolides in critically ill patients with Middle East Respiratory Syndrome, Arabi, Yaseen M. et al., International Journal of Infectious Diseases, Volume 81, 184 - 190

[6] Infection prevention and control during health care for probable or confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Available at https://www.who.int/publications/i/item/10665-174652

[7] Transmission-based precautions for the prevention and control of infections: aide-memoire. Available at: https://www.who.int/publications/i/item/WHO-UHL-IHS-IPC-2022.2

Citable reference: https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON591

Source: 

Link: https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON591

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#MERS-COV in the Middle East, a #OneHealth #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.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S2352771425003180?via%3Dihub

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