Middle East Respiratory Syndrome (MERS): A Comprehensive Report (2025)
1) Overview
What is MERS?
Middle East Respiratory Syndrome (MERS) is a zoonotic viral illness caused by Middle East respiratory syndrome coronavirus (MERS-CoV), a betacoronavirus first recognized in 2012. It primarily causes acute respiratory disease, ranging from mild upper-respiratory symptoms to severe pneumonia and respiratory failure.
Concise definition
A severe, often nosocomial (hospital-amplified) respiratory infection by MERS-CoV with a typical incubation of ~5 days (range 2–14), limited human-to-human transmission, frequent severe disease in people with comorbidities, and a historically high case-fatality among lab-confirmed cases.
Affected organs
Lungs (pneumonia/ARDS) are most affected; extrapulmonary involvement includes acute kidney injury (AKI), shock, and multiorgan failure. Kidney involvement is biologically plausible because the virus uses DPP4 (CD26)—highly expressed in lung and kidney—as the entry receptor.
Prevalence & significance
Since 2012, cases have occurred mainly on the Arabian Peninsula, with travel-related clusters elsewhere (notably the Republic of Korea in 2015). As of 13 March 2025, WHO reports 2,618 laboratory-confirmed cases and 945 deathsacross 27 countries; the high crude CFR (~36%) reflects counting mainly severe, confirmed cases.
2) History & Discoveries
Identification (2012): A novel coronavirus was isolated from a patient in Jeddah by Dr. Ali Mohamed Zaki; sequencing and characterization were led with collaborators at Erasmus MC (Netherlands). Retrospective investigation tied an earlier cluster to April 2012 in Jordan.
Major breakthroughs:
Receptor discovery: MERS-CoV uses DPP4/CD26 for cell entry (2013), with structural details of spike-receptor interaction resolved by X-ray crystallography.
Animal reservoir: Strong molecular, serologic, and epidemiologic evidence identifies dromedary camels as the principal animal reservoir and source of primary human infections.
Nosocomial amplification: Large hospital outbreaks clarified the importance of airborne-precaution-level controls during aerosol-generating procedures.
Evolving understanding: Early concern for sustained community transmission gave way to a model of repeated camel-to-human spillover with limited human spread, punctuated by superspreading in healthcare settings (e.g., Korea 2015: 186 cases, 38 deaths).
3) Symptoms
Early: fever, chills/rigors, myalgia, headache, sore throat, non-productive cough; sometimes GI upset (nausea/diarrhea).
Progression: dyspnea with hypoxemia and radiographic pneumonia, often worsening around week 1; some progress to ARDS, shock, and multiorgan failure.
Common vs. rare: common—fever, cough, dyspnea, pneumonia; less common—GI symptoms; rare—neurologic complications. AKI is relatively frequent in severe disease.
Timeline: incubation 2–14 days (median ~5); hospitalization median ~4 days after onset; ICU ~5 days; death median ~12 days in fatal cases.
4) Causes
Biological: Infection by MERS-CoV via binding of viral spike to DPP4/CD26 on host cells; robust replication in lower respiratory tract.
Environmental/zoonotic: Primary human infections are linked to exposure to dromedary camels (direct contact, raw camel milk/meat/urine, contaminated environments).
Genetic/hereditary factors: No single inherited determinant is established for susceptibility; disease severity is more strongly associated with age and comorbidities. (Exploratory data suggest host immune status—e.g., cytokine profiles—modulates response to therapy.)
Triggers/exposures: Camel markets, abattoirs, farms; healthcare settings during aerosol-generating procedures; no clear seasonality.
5) Risk Factors
Most at risk:
Older adults and those with diabetes, chronic kidney disease, chronic lung/cardiac disease, or immunosuppression have higher risk of severe disease/death.
Occupational: camel herders, abattoir workers, and others with routine camel contact show higher seroprevalence.
Male predominance is consistently observed (partly reflecting occupational exposure patterns).
6) Complications
Severe pneumonia/ARDS, acute kidney injury, septic shock, cardiac injury, and multiorgan failure. AKI is common among critically ill patients and may relate to high renal DPP4 expression.
Long-term impact: Survivors of critical illness may experience persistent pulmonary deficits and post-ICU syndromes; high acute mortality among confirmed cases (~36%), with risk concentrated in those with underlying conditions.
7) Diagnosis & Testing
Clinical suspicion: compatible illness + epidemiologic risk (residence/travel in Arabian Peninsula, camel exposure, or healthcare exposure to a case).
Laboratory tests (preferred): RT-PCR on respiratory specimens—lower respiratory samples (sputum, tracheal aspirate, BAL) yield higher sensitivity. WHO and CDC recommend upE gene RT-PCR for screening with confirmatory targets (e.g., ORF1a/1b or N). Rapid isothermal (RT-LAMP) formats exist but are adjunctive.
Serology: Used for confirmation of past infection and outbreak investigations.
Imaging: CXR/CT often show bilateral ground-glass opacities or consolidation in pneumonia.
Early detection effectiveness: Molecular tests detect infection during acute illness; sensitivity improves with appropriate specimen type and timing.
8) Treatment Options
Standard of care: Supportive therapy (oxygen, prone ventilation for ARDS, vasopressors, renal replacement/ECMO as needed) with strict infection-prevention measures. No universally approved MERS-specific antiviral exists.
Antiviral/immune therapies (evidence to date):
Interferon-β1b + lopinavir/ritonavir (MIRACLE RCT): In hospitalized adults (KSA), the combination reduced 90-day mortality vs placebo (28% vs 44% deaths; one-sided P=0.024), with the strongest effect when started ≤7 days from symptom onset.
Human polyclonal anti-MERS antibodies (SAB-301): Phase 1 in healthy volunteers showed acceptable safety and predictable PK; therapeutic efficacy data in patients are still limited.
Remdesivir & others: Animal models suggested activity; definitive patient data for MERS remain limited. (Clinical use has focused on COVID-19.)
Surgery/other therapies: No surgical role; corticosteroids are not routinely recommended outside specific indications. (Critical-care practices align with ARDS management.)
Emerging/clinical-trial landscape:
Vaccines: The ChAdOx1 MERS vaccine showed safety and immunogenicity in phase 1 (UK) and phase 1b(Saudi Arabia) trials, supporting advancement to phase 2 evaluation. Other candidates include MVA-MERS-Svectors under dose-finding studies. No licensed MERS vaccine yet.
9) Prevention & Precautionary Measures
Personal/Community:
Avoid direct contact with camels and do not consume raw camel milk, urine, or undercooked camel meat, especially if older or with chronic disease. Hand hygiene and avoiding touching the face after animal contact are key.
During outbreaks, follow public-health guidance for exposure monitoring and testing.
Healthcare:
Prompt triage/isolation; contact and droplet precautions, and airborne precautions for aerosol-generating procedures; strict environmental cleaning and PPE training.
Vaccines/screening: No licensed human vaccine; targeted vaccination of high-risk workers or camels remains a research priority. Entry screening relies on risk-based assessment rather than population-wide testing.
10) Global & Regional Statistics (as of 2025)
Worldwide totals: 2,618 confirmed cases and 945 deaths reported to WHO since 2012 (updated 13 Mar 2025). Most cases occurred in Saudi Arabia; travel-related outbreaks occurred elsewhere (notably Republic of Korea 2015).
Mortality: Crude CFR among lab-confirmed cases ≈ 36% (overestimates true infection fatality because mild/asymptomatic infections are under-detected).
Country highlights:
Saudi Arabia: Majority of primary cases and clusters; many linked to camel exposure and healthcare settings.
Republic of Korea (2015): 186 cases, 38 deaths—illustrative of nosocomial amplification and superspreading.
United States (2014): Two imported cases in healthcare workers returning from KSA; no sustained spread.
11) Recent Research & Future Prospects
Therapeutics: MIRACLE RCT results support early interferon-β1b + lopinavir/ritonavir as potentially beneficial; precision-medicine analyses suggest cytokine profile and timing influence effect size—pointing toward biomarker-guided therapy in future trials.
Vaccines: Progress with ChAdOx1 MERS and MVA-MERS-S platforms; one-health strategies include exploring camel vaccination to reduce zoonotic spillover.
Epidemiology & modeling: Ongoing work examines camel-human interface, sero-epidemiology in Africa/Middle East camels, and drivers of healthcare transmission—key to keeping R₀ < 1 outside hospitals.
Surveillance: Enhanced molecular surveillance and rapid diagnostics (including portable RT-PCR/RT-LAMP) facilitate faster case finding and containment.
12) Interesting Facts & Lesser-Known Insights
Why kidneys so often? MERS-CoV’s receptor DPP4 is abundant in renal tissue; AKI is common among ICU patients and MERS RNA has been detected in urine in some cases.
Not just the Middle East: While most human cases are on the Arabian Peninsula, MERS-CoV is widespread in camels across Africa—yet human disease there is rare, likely reflecting exposure patterns, under-detection, or viral ecology.
Myths vs facts:
Myth: “MERS spreads like seasonal flu.”
Fact: Sustained community transmission has not been observed; spread is usually limited to close contacts and healthcare settings.
Myth: “There’s a licensed MERS vaccine for people.”
Fact: No licensed human vaccine yet; the most advanced candidates are in early-phase trials.
Practical Takeaways
Risk hinges on exposure (camels or healthcare) and host factors (age/comorbidities).
Think early testing with lower-respiratory specimens when clinically suspected.
Infection control saves lives—airborne precautions for aerosol procedures and rigorous hospital IPC are non-negotiable.
References
WHO Disease Outbreak News: MERS—Kingdom of Saudi Arabia, cumulative totals (13 Mar 2025).
Arabi YM, et al. Middle East Respiratory Syndrome. N Engl J Med. 2017;376:584–594.
Lu G, et al. Molecular basis of MERS-CoV binding to CD26/DPP4. Nature 2013.
Azhar EI, et al. Camel-to-human transmission evidence. N Engl J Med. 2014.
CDC Clinical Overview of MERS (updated Dec 2024).
WHO Laboratory testing for MERS-CoV (guidance; upE + confirmatory targets).
Arabi YM, et al. Interferon-β1b + lopinavir/ritonavir RCT (MIRACLE). N Engl J Med. 2020.
Bosaeed M, et al. ChAdOx1 MERS phase 1b—safety/immunogenicity in Middle Eastern adults. Lancet Microbe2022.
Al-Tawfiq JA & Memish ZA. Lack of seasonal variation. Travel Med Infect Dis. 2019.