Middle East respiratory syndrome (MERS) is a serious lung infection caused by the MERS coronavirus (MERS-CoV). It was first discovered in Saudi Arabia in 2012 and mainly occurs in countries in or connected to the Arabian Peninsula (such as Saudi Arabia, the United Arab Emirates, Qatar, and Oman). The disease is considered dangerous because it has a high death rate of about 35%, which is much higher than most other respiratory viruses.
MERS is a zoonotic disease, meaning it spreads from animals to humans. Dromedary camels (a common camel species in the Middle East) are believed to be the main source of the virus. The infection can also spread from person to person, mostly through close, unprotected contact, especially in hospitals or clinics where patients and healthcare workers are in close contact. Large outbreaks have mostly happened in healthcare settings rather than in the general community.
Symptoms usually appear 2 to 14 days after infection and include fever, cough, and difficulty breathing. In severe cases, it can lead to pneumonia (infection of the lungs) and acute respiratory distress syndrome (ARDS), a life-threatening condition where the lungs cannot supply enough oxygen to the body. People with serious health conditions such as diabetes, kidney disease, cancer, or weakened immune systems are at higher risk of severe illness and complications like kidney failure or shock.
Although most cases occur in Saudi Arabia and nearby countries, infections have been reported in other parts of the world through international travel. One major example was the 2015 South Korea outbreak, which began when a traveler brought the virus from the Middle East and spread it to others inside hospitals.
There is no approved vaccine or specific antiviral treatment for MERS. Care mainly focuses on supporting breathing and treating complications.
History and Emergence
Middle East respiratory syndrome (MERS) was first detected in Saudi Arabia in 2012 after doctors observed several patients with a severe form of pneumonia that did not match any known virus at the time. Laboratory testing later confirmed that this illness was caused by a new type of coronavirus, now known as MERS-CoV. It is genetically different from other human coronaviruses, including SARS (2003) and the later SARS-CoV-2 (the virus responsible for COVID-19).
Further research traced the virus to dromedary camels, which serve as a reservoir, an animal population in which the virus naturally lives and can spread to humans. Evidence suggests that the virus had likely been circulating in camels for decades before it was identified in humans. Since its discovery, human outbreaks have occurred sporadically, mostly in the Arabian Peninsula, often linked to either direct contact with infected camels or healthcare-associated transmission.
Global Epidemiology
Since 2012, MERS cases have been reported in over 27 countries, though the large majority have occurred in Saudi Arabia and neighboring Gulf states. From 2012 to 2025, the World Health Organization (WHO) documented approximately 2,600 laboratory-confirmed cases and about 900 deaths, resulting in a case fatality rate of around 35%. This makes MERS one of the most lethal respiratory viruses known to infect humans.
Cases outside the Middle East have mainly resulted from international travel, where an infected traveler introduces the virus to another country. One of the most notable travel-related outbreaks occurred in South Korea in 2015, causing 186 cases and 38 deaths. Transmission in this outbreak happened almost entirely within hospitals, highlighting the importance of rapid detection and strong infection control measures.
Despite these exported cases, MERS has not shown sustained human-to-human spread in the general community, which is one reason it has not become a pandemic.
Causes and Transmission
Middle East respiratory syndrome (MERS) is caused by a virus known as MERS-CoV. The transmission primarily involves specific routes and animal sources that contribute to human infections.
Origin of the MERS-CoV Virus
Extensive genetic sequencing has shown that bats are the likely original hosts of MERS-CoV or its ancestral form. Bats carry a wide range of coronaviruses that typically do not make them sick but can spill over into other species. While bats harbor related viruses, there is no evidence that they infect humans directly in the case of MERS. Instead, the virus appears to have established long-term circulation in dromedary camels, likely decades before it was first detected in humans. Studies of archived camel samples from the 1980s and 1990s reveal antibodies to MERS-CoV, suggesting silent circulation well before the first recognized human infections.
A key factor enabling MERS-CoV to infect humans is its ability to bind to the DPP4 (dipeptidyl peptidase-4) receptor, a protein found on the surface of human cells. This receptor is especially abundant in the lower respiratory tract, which helps explain why MERS tends to cause deep lung infections rather than mild upper respiratory illness. The virus can also infect kidney and intestinal cells, which aligns with clinical findings of kidney failure and occasional gastrointestinal symptoms in severe cases.
Primary Transmission Routes
Human transmission of MERS-CoV generally requires close and prolonged contact, which is why large outbreaks are more common in healthcare environments than in community settings. Four major transmission routes are known:
1. Respiratory Droplets
Virus-containing droplets are expelled when an infected person coughs, sneezes, or talks at close range. Transmission usually occurs when another person breathes in these droplets or they land on the mucous membranes of the nose, mouth, or eyes.
2. Healthcare Settings (Nosocomial Transmission)
Hospitals and clinics have played a major role in spreading MERS, particularly when infection control practices are inadequate. In situations where patients are not promptly diagnosed or properly isolated, healthcare workers, patients, and visitors can become infected. The 2015 South Korean outbreak highlighted how hospital environments can amplify spread even in countries where camels are not present.
3. Direct Contact with Infected Individuals
Family members or caregivers providing close, unprotected care can become infected. This usually occurs in households or during transport of a sick patient.
4. Contaminated Surfaces (Fomites)
The virus can survive on surfaces for short periods under certain conditions. Infection can occur if a person touches a contaminated surface and then touches their mouth, nose, or eyes. However, this is considered a less efficient mode of transmission.
Unlike SARS-CoV-2, MERS-CoV does not spread efficiently through casual, short-term contact, nor has it shown sustained airborne transmission across long distances. This is one of the reasons the virus has not caused a global pandemic.
Animal Sources and Reservoirs
Dromedary camels are the primary animal host and ongoing source of human MERS infections. Surveillance studies have detected:
- High antibody levels in camels across the Middle East and parts of Africa, indicating widespread past infection.
- Active virus (viral RNA) in camel nasal secretions, which increases the risk of transmission during close contact.
- Viral strains in camels that are nearly genetically identical to those found in infected humans.
Human infection most often arises from direct or indirect contact with camels, including:
- Handling camels during farming, breeding, or transport,
- Exposure to respiratory fluids (such as nasal discharge),
- Slaughterhouse and butchering activities,
- Drinking raw (unpasteurized) camel milk,
- Consuming undercooked camel meat.
While bats are considered the evolutionary origin of the virus, there is no evidence that they currently play an active role in human transmission. Other livestock species such as cows, goats, or sheep have been studied but have not been identified as meaningful sources of infection.
Clinical Presentation
The incubation period, the time between exposure to the virus and the onset of symptoms is typically 5 to 6 days, but can range from 2 to 14 days. The length of this period has important implications for quarantine policies, monitoring of exposed individuals, and the timing of diagnostic testing.
MERS usually begins with nonspecific early symptoms, similar to other viral respiratory illnesses. These commonly include:
- High fever
- Cough (usually dry, but can become productive later)
- Shortness of breath or difficulty breathing
- Sore throat
- Chills and body aches (myalgia)
- Headache
- Fatigue or malaise
Gastrointestinal symptoms such as diarrhea, nausea, abdominal pain, or vomiting can also occur, particularly in severe infections. In some patients, digestive symptoms may appear before respiratory symptoms, which can delay suspicion of MERS and complicate early diagnosis.
As the illness progresses, patients frequently develop lower respiratory tract involvement, leading to pneumonia. Chest imaging (X-ray or CT scan) commonly shows bilateral lung infiltrates, indicating widespread inflammation. Respiratory distress tends to worsen over time, often requiring supplemental oxygen and, in severe cases, mechanical ventilation or intensive care support.
Severity and Complications
The severity of MERS varies widely:
- Mild cases may present as a flu-like illness without pneumonia and may resolve without hospitalization.
- Moderate cases involve noticeable respiratory symptoms and require medical evaluation and oxygen support.
- Severe cases rapidly progress to acute respiratory distress syndrome (ARDS), respiratory failure, or multi-organ involvement.
Severe disease is more common in individuals with pre-existing conditions such as:
- Diabetes
- Chronic kidney disease
- Chronic heart or lung disease
- Cancer
- Immune suppression (including transplant recipients)
- Older age (particularly over 60 years)
Children appear to be less commonly infected, and when infected, they often display milder symptoms, although severe pediatric cases have been reported in infants and children with underlying medical problems.
In the most severe cases, MERS can lead to:
- ARDS (Acute Respiratory Distress Syndrome) – a life-threatening lung failure requiring intensive care
- Septic shock – a dangerous drop in blood pressure caused by systemic infection
- Acute kidney injury – sometimes requiring dialysis
- Multi-organ failure – including involvement of the liver, heart, and circulatory system
- Disseminated intravascular coagulation (DIC) – a severe disorder affecting blood clotting in advanced illness
Complications usually develop within 7 to 10 days after symptoms begin, which is typically the point at which hospitalization and intensive care become necessary for high-risk patients.
Not all individuals experience obvious symptoms. Some infections, particularly among healthy adults or healthcare workers, may be asymptomatic or mildly symptomatic, leading to detection only through screening during outbreak investigations. In others, especially the elderly, symptoms may appear atypical, such as confusion or generalized weakness, without pronounced respiratory signs at first.
Diagnosis and Detection
Because the disease often presents with non-specific respiratory symptoms similar to influenza, COVID-19, and other viral pneumonias, laboratory confirmation plays a central role in distinguishing MERS-CoV infection from other respiratory pathogens.
Laboratory Testing Methods
1. Real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR)
RT-PCR remains the gold standard for MERS detection. The test identifies viral RNA directly from patient samples. It typically targets multiple viral gene regions such as the upstream E protein (upE) gene for screening and open reading frame 1a (ORF1a) or nucleocapsid (N) gene for confirmatory testing. Using multiple genetic targets reduces the risk of false negatives due to viral mutation or low viral load.
Preferred Samples
MERS-CoV replicates in the lower respiratory tract; therefore, lower respiratory samples yield much higher viral loads than upper airway swabs. The most reliable specimen types include:
- Bronchoalveolar lavage (BAL)
- Tracheal aspirate
- Sputum (if spontaneously produced)
Upper respiratory samples such as nasopharyngeal and oropharyngeal swabs may still be used in patients unable to produce sputum, but a negative upper airway result does not rule out infection unless a lower respiratory sample also tests negative.
2. Serological Testing
Serology is mainly used for epidemiological investigations and identifying past exposure. It detects MERS-CoV–specific IgM and IgG antibodies in blood. Antibodies typically appear between 10–14 days after symptom onset. Therefore, serology is:
- Not reliable for early diagnosis
- Useful for retrospective outbreak mapping
- Valuable in mild or asymptomatic infections that might otherwise go undetected
3. Viral Culture and Genomic Sequencing
Virus isolation in cell culture is technically feasible but performed primarily in research or reference laboratories. Culturing infectious viruses carries a significant biosafety risk and must be conducted in BSL-3 facilities. Whole genome sequencing, when performed, helps track viral evolution and identify transmission clusters, especially during large outbreaks.
Sample Handling and Biosafety Considerations
Because MERS-CoV causes a high case fatality rate and spreads through droplets and potentially aerosols during medical procedures, strict sample handling protocols are essential. Healthcare workers must use:
- Appropriate PPE (N95 or higher, gloves, gown, face shield)
- Sealed triple-layer packaging during transport
- Rapid refrigeration or freezing to preserve viral RNA integrity
Failure to follow proper biosafety protocol may increase risk of laboratory-acquired infection and compromise test sensitivity.
Clinical Criteria for Diagnosis
Laboratory findings alone are not sufficient without pairing them with clinical context. Diagnosis is guided by a syndromic and risk-based approach.
1. Symptom Evaluation
Clinically, most patients present with:
- Fever
- Cough
- Shortness of breath
- Radiological evidence of pneumonia or ARDS
Some patients, especially immunocompromised individuals may initially present with atypical symptoms, including gastrointestinal manifestations such as diarrhea and abdominal pain. This variability necessitates a high index of suspicion in endemic areas or among exposed individuals.
2. Epidemiological Linkage
A patient is flagged as a suspected case when respiratory symptoms coincide with any of the following risk factors:
- Travel to or residence in the Arabian Peninsula, where MERS-CoV is endemic
- Direct or indirect contact with dromedary camels, the primary animal reservoir
- Exposure to a laboratory-confirmed MERS case
- Occupational risk, especially healthcare workers involved in patient care
This epidemiological link is important in early triage, especially when laboratory resources are limited or test results are delayed.
Case Classification
| Classification | Clinical Indicators | Laboratory Findings | Epidemiological Link |
| Suspected case | Compatible symptoms (fever, cough, dyspnea ± pneumonia) | Test not yet performed | Recent travel/exposure risk |
| Probable case | Compatible symptoms + radiologic evidence | Inconclusive or indeterminate RT-PCR | Strong epidemiologic link |
| Confirmed case | Compatible symptoms | Positive RT-PCR from ≥1 appropriate specimen | Epidemiologic link not required after confirmation |
Probable cases are managed as confirmed infections until laboratory results clarify status because delayed isolation significantly increases the risk of hospital outbreaks.
Diagnostic Challenges
MERS diagnosis can be complicated by:
- Late presentation after peak viral shedding has passed
- Inadequate or poorly collected respiratory samples
- Immunocompromised patients with delayed or muted antibody response
- Co-infections with bacterial pneumonia or other viruses masking presentation
Because of these challenges, repeat RT-PCR testing is often recommended if initial tests are negative but the patient meets strong epidemiological and clinical criteria.
Treatment and Management
Supportive care is the cornerstone of treatment, as most patients require respiratory assistance to manage hypoxemia and prevent deterioration. The intensity of care provided depends on the severity of respiratory compromise and systemic involvement.
Respiratory Support
Patients with mild to moderate disease may require low-flow or high-flow oxygen therapy. In advanced cases with rapidly progressive respiratory distress or acute respiratory distress syndrome (ARDS), mechanical ventilation becomes necessary. Some patients fail conventional ventilation and may require extracorporeal membrane oxygenation (ECMO), especially in contexts where lung injury is profound and refractory to standard care.
Fluid and Hemodynamic Management
Intravenous fluids are administered cautiously. In contrast to conditions such as severe viral gastroenteritis, fluid overload in a MERS patient can precipitate worsening pulmonary edema. In critically ill individuals, hemodynamic monitoring is crucial to balance organ perfusion against the risk of fluid-induced respiratory compromise. Vasopressor support may be introduced in cases of septic shock.
Monitoring and Complication Prevention
Close monitoring includes:
- Serial blood gases to evaluate oxygenation and ventilation
- Renal function assessment due to high rates of acute kidney injury (AKI) in severe MERS
- Surveillance for secondary bacterial or fungal infections, which are common in ICU settings
- Inflammatory markers (e.g., CRP, ferritin, IL-6) to track disease progression
Management strategies also include thromboprophylaxis, as prolonged immobilization and systemic inflammation increase the risk of venous thromboembolism.
Antiviral and Experimental Therapies
There is no definitively proven antiviral therapy for MERS-CoV. Multiple drug combinations have been tested during outbreaks, especially in Saudi Arabia and South Korea, but clinical evidence remains inconsistent and often limited to small observational studies.
Ribavirin and Interferons
The most widely used experimental regimen involves ribavirin in combination with interferon-alpha or interferon-beta, based on evidence from in vitro studies and animal models. However, the effectiveness appears to depend on timing: benefits are greater when therapy is initiated early, before irreversible lung injury develops. In late-stage disease, when immune-mediated tissue damage becomes dominant, antiviral benefit is limited.
Protease Inhibitors and Repurposed Antivirals
Drugs such as lopinavir/ritonavir, originally used for HIV treatment have been trialed based on their success in related coronaviruses, particularly SARS-CoV-1. Some countries have deployed these agents under compassionate-use protocols, but large clinical trials have not demonstrated statistically robust survival improvement.
Monoclonal Antibodies and Novel Agents
More recent research has shifted toward:
- Neutralizing monoclonal antibodies targeting the viral spike protein
- Fusion inhibitors designed to block viral entry into host cells
- Broad-spectrum coronavirus antivirals
Experimental antibody therapies have shown promise in animal models and early-phase trials, but large-scale human data remain limited.
Critical Care and ICU Management
Patients progressing to respiratory failure frequently require ICU admission. Severe MERS is often complicated by:
- ARDS
- Septic shock
- Multi-organ dysfunction
- Renal failure (sometimes requiring dialysis)
Early institution of lung-protective ventilation strategies reduces ventilator-associated lung injury. ECMO is reserved for selected patients with potentially reversible respiratory failure who do not respond to maximal ventilatory support.
Case Fatality Rates and Outcomes
MERS has a case fatality rate (CFR) of approximately 35%, significantly higher than seasonal influenza and even SARS-CoV-2 in most contexts. However, CFR varies widely based on age, comorbidities, and clinical stage at presentation.
| Risk Factor | Effect on Outcome |
| Older age (>60 years) | Markedly higher mortality |
| Diabetes mellitus | Poor immune response, worse prognosis |
| Chronic kidney disease | Increased risk of ICU admission and death |
| Immunosuppression | Higher viral load and prolonged infection |
| Delayed hospitalization | More complications and organ failure |
Among critically ill patients requiring ICU-level care, mortality may exceed 50–60%, especially in those with ARDS. Conversely, patients diagnosed early and managed promptly with supportive therapy have substantially better recovery rates.
Prevention and Control Measures
For Healthcare Workers
- Wear a fit-tested N95 or FFP2/FFP3 respirator when caring for suspected or confirmed MERS patients.
- Wear eye protection (goggles or face shield) during all patient interactions involving respiratory secretions.
- Use a long-sleeved fluid-resistant gown and medical gloves before entering the patient’s room.
- Perform hand hygiene immediately before and after PPE use and after touching patient surroundings.
- Place patients in negative-pressure airborne isolation rooms whenever available.
- Keep the patient’s movement restricted to medically essential transfers only.
- Use dedicated medical equipment (stethoscope, BP cuff, pulse oximeter) for each patient.
- Dispose of PPE safely and immediately after room exit to avoid cross-contamination.
- Keep non-essential personnel out of patient rooms to minimize exposure risk.
For Aerosol-Generating Procedures (High-Risk Settings)
(Intubation, bronchoscopy, suctioning, CPR, nebulization)
- Use a fit-tested particulate respirator (N95/FFP2/FFP3) with proper seal check before procedure.
- Wear a face shield or integral eye protection to prevent droplet splash.
- Use a long-sleeved, impermeable gown and sterile gloves if applicable.
- Perform procedures in a room with ≥6–12 air changes per hour (mechanical ventilation) or ≥60 L/s/patient air flow (natural ventilation).
- Limit the number of healthcare workers present to essential personnel only.
- Avoid nebulizers when possible and prefer MDIs (metered-dose inhalers) to reduce aerosol formation.
- Perform hand hygiene immediately after PPE removal and before touching any surface.
Environmental & Facility Infection Control
- Disinfect high-touch surfaces (bed rails, doorknobs, bedside tables, monitors) frequently with coronavirus-effective disinfectants.
- Use dedicated waste disposal bins for infected patient materials.
- Handle linen as infectious material and avoid shaking or dispersing droplets.
- Maintain adequate room ventilation at all times.
- Train staff routinely on PPE donning/doffing, isolation procedures, and outbreak readiness.
Household & Community-Level Prevention
- Avoid direct contact with camels, especially in farms, markets, and slaughterhouses in endemic regions.
- Do not consume raw camel milk, camel urine, or undercooked camel meat.
- Wear gloves and a mask when caring for a symptomatic relative at home.
- Isolate the sick person in a separate, well-ventilated room and minimize shared spaces.
- Clean frequently touched household objects (phones, faucets, doorknobs) daily.
- Practice respiratory hygiene: cover coughs/sneezes and dispose of used tissues safely.
- Use alcohol-based hand sanitizers ≥60% ethanol or isopropanol after any contact.
- Seek medical evaluation immediately if respiratory symptoms develop after travel to affected regions or animal contact.
Maintain isolation for at least 24 hours after complete resolution of symptoms, as currently recommended in absence of definitive infectivity data.
Outbreaks and Case Studies
MERS outbreaks have occurred sporadically since its identification in 2012. These events provide insight into transmission patterns and healthcare challenges. Responses to outbreaks reveal critical gaps in infection control and public health readiness.
Notable Outbreaks
The 2015 South Korea outbreak is the largest outside the Middle East, with 186 confirmed cases and 38 deaths. It was traced to a single traveler returning from the Arabian Peninsula. Hospital settings amplified the spread due to close contact and delayed diagnosis.
Saudi Arabia remains the epicenter, reporting the majority of cases since 2012. Clusters often emerge in healthcare environments or through camel-to-human transmission. Sporadic cases continue despite improved surveillance and public awareness.
Lessons Learned from Responses
Rapid identification and strict isolation protocols are vital to limit MERS transmission. South Korea’s experience demonstrated the need for better hospital infection control and quicker diagnostic testing. Public communication helped curb panic and misinformation.
Cross-sector coordination between health authorities and hospitals proved crucial. Surveillance of camel populations and awareness campaigns reduced animal-associated transmission. Strengthening healthcare infrastructure remains a priority in affected countries.