MERS-CoV is a zoonotic betacoronavirus first identified in Saudi Arabia in September 2012, with a case fatality rate of ~35% and over 2,500 confirmed cases reported globally. [1-2] It remains a WHO priority pathogen due to its high mortality, epidemic potential, and lack of approved specific therapies. [3] Global cases declined during the COVID-19 pandemic and remain lower than pre-pandemic levels, though whether this reflects true decline or underascertainment is unclear. [4]
1. History
- Key HPI questions: Onset and progression of fever, cough, dyspnea; GI symptoms (diarrhea, vomiting, abdominal pain); timeline of symptom evolution
- Epidemiologic link is essential: Travel to or residence in the Arabian Peninsula within 14 days; direct/indirect contact with dromedary camels (nasal secretions, raw milk, urine, meat); contact with a confirmed MERS case; visit to a healthcare facility in an endemic area [1-2]
- Incubation period: 2–14 days [1]
- Symptom characterization: Fever, chills, rigors, headache, non-productive cough, sore throat, myalgia, arthralgia → progressing to dyspnea. GI symptoms (nausea, vomiting, diarrhea, abdominal pain) may precede respiratory illness [2]
- Important negatives: 25–50% of infections are asymptomatic or mild; atypical presentations include afebrile respiratory illness or isolated GI illness preceding pneumonia [2]
2. Alarm Features
- Rapidly progressive dyspnea, hypoxemia (SpO₂ <94%)
- Median time from hospitalization to ICU admission: 2 days [1]
- Septic shock, multiorgan failure
- Acute kidney injury (up to 50% of critically ill patients) [1]
- Altered mental status or neurologic findings suggestive of encephalitis [1]
- Radiographic progression from unilateral to bilateral opacification within 48 hours [5]
- Predictors of pneumonia progression: age >56, high fever, thrombocytopenia, lymphopenia, CRP ≥2 mg/dL, high viral load (Ct <28.5) [2]
3. Medications
- No approved specific antiviral therapy exists for MERS-CoV [1-2]
- Supportive care is the mainstay: antipyretics, analgesics, IV fluids, organ support [2]
- Empirical antibiotics should be administered per community-acquired or hospital-acquired pneumonia protocols while MERS-CoV testing is pending; co-infections are common [1]
- Investigational agents studied:
- Interferon beta-1b + lopinavir-ritonavir: The MIRACLE trial showed a mortality benefit when initiated within 7 days of symptom onset [6]
- Ribavirin + interferon alfa-2a: Associated with 14-day survival benefit in one retrospective cohort, but no 28-day benefit; a larger observational study found no association with reduced 90-day mortality [7-8]
- Remdesivir: Showed efficacy in animal models (rhesus macaque) but has not been tested in human MERS trials [9-10]
- Convalescent plasma, corticosteroids: Used empirically without robust evidence [2]
- Avoid: Aerosol-generating nebulizers in uncontrolled settings (infection control risk) [2]
4. Diet
- Avoid unpasteurized camel milk, raw/undercooked camel meat — potential transmission route [2-3]
- Adequate hydration is critical, especially in patients with fever, diarrhea, and vomiting
- No specific dietary interventions for acute management beyond standard supportive care
5. Review of Systems
- Respiratory: Cough (productive or non-productive), dyspnea, sore throat, coryza
- GI: Diarrhea, nausea, vomiting, abdominal pain (up to one-third of critically ill patients) [1]
- Neurologic: Hypersomnolence, weakness, tingling/paresthesias (Guillain-Barré-like), altered mental status [2]
- Constitutional: Fever, chills, rigors, myalgia, arthralgia, headache, dizziness
- Renal: Hematuria, decreased urine output (AKI common in severe cases) [2]
6. Collateral History and Family History
- Collateral contacts: Identify all close contacts (household, healthcare workers, visitors) for contact tracing and quarantine [2]
- Occupational exposure: Camel herders, slaughterhouse workers, veterinarians at increased risk [2]
- Healthcare exposure: Approximately half of all reported MERS cases result from human-to-human transmission in healthcare facilities [2]
- Family clusters have been documented with variable severity among household members [5][11]
- No known hereditary susceptibility, but comorbidities (diabetes, CKD, chronic lung disease) dramatically increase severity [12]
7. Risk Factors
- Age >60 years (mortality ~45% vs ~20% in younger patients) [2]
- Male sex (male:female case ratio ~3.3:1) [11]
- Comorbidities: Diabetes mellitus, chronic kidney disease, chronic lung disease (COPD), heart disease, obesity, cancer, immunosuppression [2][12]
- Smoking: DPP-4 receptors are upregulated in smokers' lungs [2][12]
- Healthcare workers caring for MERS patients without adequate PPE [2][12]
- Direct/indirect contact with dromedary camels in endemic regions [2]
- Low serum albumin, high pneumonia severity index at admission [2][12]
8. Differential Diagnosis
- Influenza A/B — seasonal pattern, rapid antigen testing available
- COVID-19 (SARS-CoV-2) — similar presentation; distinguish by PCR and epidemiologic context
- SARS-CoV-1 — historically relevant; no current circulation
- Community-acquired pneumonia (bacterial: Streptococcus pneumoniae, Legionella, Mycoplasma)
- Other viral pneumonias: RSV, parainfluenza, adenovirus, hMPV
- Avian influenza (H5N1, H7N9) — poultry exposure history
- Tuberculosis — in endemic populations with chronic cough
- Sepsis from other sources — especially if multiorgan failure predominates
- Co-infection with other respiratory pathogens is common and should not deter MERS-CoV testing when suspicion is high [1]
9. Past Medical History
- 96% of patients in one early Saudi cohort had underlying comorbid conditions [11]
- Key comorbidities to document: diabetes, CKD (especially dialysis patients — outbreaks in dialysis units), COPD, heart failure, malignancy, immunosuppression
- Prior episodes of respiratory illness, smoking history
- Surgical history (particularly transplant recipients)
10. Physical Exam
- Vital signs: Fever ≥38°C (may be absent in atypical presentations), tachypnea, tachycardia, hypoxemia
- Respiratory: Crackles, decreased breath sounds, signs of respiratory distress (accessory muscle use, nasal flaring)
- General: Ill-appearing, diaphoretic in severe cases
- Neurologic: Altered mental status, weakness, sensory deficits (rare but reported) [2]
- Abdominal: May have tenderness if GI symptoms predominate
- Concerning findings: Hypotension (septic shock in ~80% of ICU patients requiring vasopressors), oliguria [13-14]
11. Lab Studies
- CBC: Leukopenia, lymphopenia (hallmark), thrombocytopenia, anemia [1]
- CMP: Elevated creatinine (AKI), elevated aminotransferases (mild-moderate), low albumin (prognostic) [1-2]
- Inflammatory markers: Elevated CRP (≥2 mg/dL associated with pneumonia progression), elevated LDH, ferritin [2]
- Coagulation studies: DIC workup in severe cases
- ABG: Hypoxemia; PaO₂/FiO₂ ratio often severely depressed (median ~106 in MERS ICU patients vs ~176 in non-MERS SARI) [13]
- Blood cultures: To rule out bacterial co-infection/sepsis
- Urinalysis: Hematuria and proteinuria in AKI [2]
12. Imaging
- First-line: Chest X-ray
- Ground-glass opacity is the most common finding (66%), followed by consolidation (18%) [15]
- Lower lobes affected more than upper lobes early in disease [2]
- Bilateral involvement common; rapid progression to diffuse opacification possible within 48 hours [5]
- Pleural effusions associated with poor prognosis [15-16]
- Normal imaging in mild illness [1]
- CT chest (HRCT):
- Ground-glass opacities with peripheral and basilar predominance [17]
- Subpleural and peribronchovascular distribution suggestive of organizing pneumonia pattern [17]
- Progressive findings: crazy-paving pattern, tree-in-bud, centrilobular nodules, cavitation [2]
- Higher CT lung score correlates with mortality [16]
- Imaging unnecessary in asymptomatic or very mild cases
The following figure illustrates the rapid radiographic progression characteristic of severe MERS pneumonia, showing bilateral opacification evolving over just 48 hours in a previously healthy patient:
13. Special Tests
- Real-time RT-PCR is the diagnostic mainstay [1]
- Lower respiratory tract specimens (sputum, BAL, tracheal aspirate) have the best sensitivity, especially within 7 days of symptom onset [1]
- Upper respiratory specimens (NP swab) may be used but have lower sensitivity
- Serum RT-PCR also recommended in hospitalized patients [1]
- Repeat testing over several days increases diagnostic yield [1]
- Serology: For patients presenting ≥14 days after symptom onset; requires staged confirmation (ELISA → immunofluorescence → plaque-reduction neutralization) [1][18]
- Pneumonia severity index (PSI) and APACHE II/SOFA scores for ICU prognostication [2][14]
- CDC persons under investigation (PUI) criteria updated in 2024 — combine clinical features with epidemiologic risk to guide testing decisions [4]
14. ECG
- No MERS-specific ECG findings
- ECG indicated for patients with hemodynamic instability, septic shock, or pre-existing cardiac disease
- Monitor for arrhythmias in critically ill patients, particularly those on vasopressors or with electrolyte derangements
- QTc monitoring if empirical medications with QT-prolonging potential are used
15. Assessment
- Severity spectrum: Asymptomatic/mild (25–50%) → pneumonia → ARDS → multiorgan failure → death [1-2]
- Case fatality rate: ~35% overall; ~74% in ICU cohorts; ~20% in the 2015 Korean outbreak [1-2][14]
- Rapid progression is characteristic — median 2 days from hospitalization to ICU [1]
- Complications: ARDS, AKI (up to 50%), septic shock, DIC, secondary bacterial infections, neuromuscular complications [1-2]
- Atypical presentations (afebrile, GI-predominant) can delay diagnosis — maintain high index of suspicion with appropriate epidemiologic link [2]
16. Treatment Plan
- Immediate infection control: Airborne isolation (negative pressure room preferred); contact and droplet precautions; N95 respirator for all aerosol-generating procedures [12][19]
- Supportive care:
- Supplemental oxygen targeting SpO₂ ≥92–95%
- IV fluid resuscitation (judicious in ARDS)
- Antipyretics (acetaminophen)
- Empirical antibiotics for community-acquired pneumonia pending cultures [1]
- Severe/critical disease:
- Lung-protective mechanical ventilation (low tidal volume, 6 mL/kg IBW)
- Prone positioning for refractory hypoxemia
- ECMO for refractory respiratory failure (~6% of ICU patients) [13]
- Vasopressors for septic shock
- Renal replacement therapy for AKI (~49% of ICU patients) [13]
- Investigational antivirals: If available through clinical trial or compassionate use, interferon beta-1b + lopinavir-ritonavir may be considered, ideally within 7 days of symptom onset [6]
- Notify public health authorities immediately (local health department, CDC) [19]
17. Disposition
- Admission criteria:
- Hypoxemia (SpO₂ <94% on room air)
- Radiographic pneumonia
- Significant comorbidities with any respiratory symptoms
- Hemodynamic instability
- Inability to maintain oral intake
- ICU admission: Respiratory failure, need for mechanical ventilation, vasopressor requirement, multiorgan dysfunction (89% of patients in one early cohort required ICU; 87% required mechanical ventilation) [11]
- Discharge criteria: Clinical improvement, stable oxygenation on room air, ability to tolerate oral intake, negative or declining viral load on repeat RT-PCR, adequate home isolation plan
- Mild cases may be managed at home with strict isolation if no risk factors for progression [2]
- Specialist consultation: Infectious disease (mandatory), pulmonary/critical care, nephrology (if AKI), neurology (if neurologic manifestations)
18. Follow Up / Return Precautions
- Follow-up: Close monitoring within 48–72 hours for patients discharged with mild illness; repeat RT-PCR to document viral clearance
- Contact tracing: All close contacts should be monitored for 14 days from last exposure [19]
- Return immediately for: Worsening dyspnea, persistent high fever, inability to maintain hydration, confusion, chest pain, decreased urine output
- Expected course: Mild cases typically resolve within 1–2 weeks; severe cases have prolonged ICU stays (median mechanical ventilation ~13 days in non-survivors) [16]
- Patient counseling: Strict respiratory and hand hygiene; avoid contact with others during isolation period; no specific post-recovery immunity data to guide re-exposure risk
- Healthcare worker exposure: Unprotected exposure requires quarantine and serial testing [12]
References
1. Middle East Respiratory Syndrome. — Arabi YM, Balkhy HH, Hayden FG, et al. The New England Journal of Medicine. 2017.
2. Middle East Respiratory Syndrome. — Memish ZA, Perlman S, Van Kerkhove MD, Zumla A. Lancet. 2020.
3. Middle East Respiratory Syndrome Coronavirus. — Al-Tawfiq JA, Azhar EI, Memish ZA, Zumla A. Seminars in Respiratory and Critical Care Medicine. 2021.
4. Update on the Epidemiology of Middle East Respiratory Syndrome Coronavirus - Worldwide, 2017-2023. — Lambrou AS, South E, Midgley CM, et al. MMWR. Morbidity and Mortality Weekly Report. 2025.
5. Family Cluster of Middle East Respiratory Syndrome Coronavirus Infections. — Memish ZA, Zumla AI, Al-Hakeem RF, Al-Rabeeah AA, Stephens GM. The New England Journal of Medicine. 2013.
6. Interferon Beta-1b and Lopinavir–Ritonavir for Middle East Respiratory Syndrome. — Arabi YM, Asiri AY, Assiri AM, et al. The New England Journal of Medicine. 2020.
7. Ribavirin and Interferon Alfa-2a for Severe Middle East Respiratory Syndrome Coronavirus Infection: A Retrospective Cohort Study. — Omrani AS, Saad MM, Baig K, et al. The Lancet. Infectious Diseases. 2014.
8. Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study. — Arabi YM, Shalhoub S, Mandourah Y, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2020.
9. Comparative Therapeutic Efficacy of Remdesivir and Combination Lopinavir, Ritonavir, and Interferon Beta Against MERS-CoV. — Sheahan TP, Sims AC, Leist SR, et al. Nature Communications. 2020.
10. Prophylactic and Therapeutic Remdesivir (GS-5734) Treatment in the Rhesus Macaque Model of MERS-CoV Infection. — de Wit E, Feldmann F, Cronin J, et al. Proceedings of the National Academy of Sciences of the United States of America. 2020.
11. Epidemiological, Demographic, and Clinical Characteristics of 47 Cases of Middle East Respiratory Syndrome Coronavirus Disease From Saudi Arabia: A Descriptive Study. — Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, et al. The Lancet. Infectious Diseases. 2013.
12. Middle East Respiratory Syndrome Coronavirus: Risk Factors and Determinants of Primary, Household, and Nosocomial Transmission. — Hui DS, Azhar EI, Kim YJ, et al. The Lancet. Infectious Diseases. 2018.
13. Critically Ill Patients With the Middle East Respiratory Syndrome: A Multicenter Retrospective Cohort Study. — Arabi YM, Al-Omari A, Mandourah Y, et al. Critical Care Medicine. 2017.
14. Presentation and Outcome of Middle East Respiratory Syndrome in Saudi Intensive Care Unit Patients. — Almekhlafi GA, Albarrak MM, Mandourah Y, et al. Critical Care. 2016.
15. Acute Middle East Respiratory Syndrome Coronavirus: Temporal Lung Changes Observed on the Chest Radiographs of 55 Patients. — Das KM, Lee EY, Al Jawder SE, et al. AJR. American Journal of Roentgenology. 2015.
16. CT Correlation With Outcomes in 15 Patients With Acute Middle East Respiratory Syndrome Coronavirus. — Das KM, Lee EY, Enani MA, et al. AJR. American Journal of Roentgenology. 2015.
17. Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: Chest CT Findings. — Ajlan AM, Ahyad RA, Jamjoom LG, Alharthy A, Madani TA. AJR. American Journal of Roentgenology. 2014.
18. Transmission of MERS-Coronavirus in Household Contacts. — Drosten C, Meyer B, Müller MA, et al. The New England Journal of Medicine. 2014.
19. Identify-Isolate-Inform: A Modified Tool for Initial Detection and Management of Middle East Respiratory Syndrome Patients in the Emergency Department. — Koenig KL. The Western Journal of Emergency Medicine. 2015.