Middle East respiratory syndrome

5 Interesting Facts of Middle East respiratory syndrome

  1. Middle East respiratory syndrome is a potentially severe viral infection that is currently rare and connected to the Arabian Peninsula, but it is an emerging disease that may change course
  2. Consider diagnosis in residents of or travelers to the Arabian Peninsula and nearby countries, or countries with secondary outbreaks, who present with fever and respiratory complaints
  3. Diagnostic testing can be obtained through public health channels
  4. Only available treatment is supportive and mortality is high, especially in older patients and those with underlying disease
  5. Preventive measures are confined to avoidance of exposure; follow standard infection control procedures for known or suspected patients in medical care or home care settings

Middle East respiratory syndrome is an acute infection by a coronavirus originating in the Arabian Peninsula; it is characterized by potentially severe respiratory involvement and may be associated with clinical signs of sepsis, including multiorgan failure

Clinical Presentation

Symptoms of Middle East respiratory syndrome

  • Incubation period of Middle East respiratory syndrome is 2 to 14 days 
  • Infection is mild or asymptomatic in some cases
    • Mild cases may manifest with rhinorrhea, sore throat, dry cough, and myalgia 
  • Fever (67%-89%), nonproductive cough (83%-89%), and dyspnea (48%-92%) are the most common presenting complaints 
    • Other reported symptoms include myalgias, malaise, sore throat, vomiting, and diarrhea 
    • Chest pain occurs in more than 40% of patients 
  • May progress over the course of 2 to 4 days to severe pneumonitis; respiratory failure, septic shock, and multiorgan failure may develop

To date, patients with Middle East respiratory syndrome had either lived in the endemic area (Arabian Peninsula and neighboring countries), traveled to the endemic area, or been exposed to an infected person who had acquired the infection while traveling in the endemic area 

  • Countries in the Arabian Peninsula and those neighboring include Bahrain, Iraq, Iran, Israel, the West Bank, and Gaza, Jordan, Kuwait, Lebanon, Oman, Qatar, Saudi Arabia, Syria, the United Arab Emirates, and Yemen 
  • Outside these areas of known outbreaks, consider diagnosis in patients presenting with a compatible illness and the following: 
    • Travel to countries in or near the Arabian Peninsula within 14 days of symptom onset
    • Close contact with a symptomatic traveler who developed fever and acute respiratory illness within 14 days after traveling from countries in or near the Arabian Peninsula
    • Close contact with a confirmed case while that person was unwell
    • History of being in a health care facility within the 14 days before symptom onset in a country in or near the Arabian Peninsula in which recent health care–associated cases have been identified
    • Part of a cluster of patients with severe acute respiratory illness of unknown etiology in which MERS-CoV (Middle East respiratory syndrome coronavirus) is being evaluated, in consultation with state and local health departments
  • Close contact is defined as either of the following: 
    • Being within approximately 6 feet or within the same room or care area, as a confirmed case for a prolonged period of time while not wearing recommended personal protective equipment (eg, gowns, gloves, disposable N95 respirator, eye protection)
      • Examples include caring for, living with, or visiting a patient with confirmed disease, or sharing a health care waiting area or hospital room with a patient with confirmed disease
    • Direct contact with infectious secretions of a confirmed case while not wearing recommended personal protective equipment

Physical examination

  • Case series and individual case reports have not detailed specific physical findings, except to note that fever is often high and persistent 

Causes of Middle East respiratory syndrome

  • Middle East respiratory syndrome coronavirus (MERS-CoV)
    • Zoonotic betacoronavirus belonging to C subclass, found in humans and camels; similar to several bat coronaviruses 
    • Camels are considered the primary host and source of human infection; bats may also be a reservoir of infection 
    • Human to human transmission can occur; particularly in the setting of prolonged close contact 

Risk factors and/or associations

Age
  • More common in persons aged 45 years or older 
Sex
  • More common in men (about 60%) than women (about 40%) 
Other risk factors/associations
  • Residence or travel in the Middle East (particularly the Arabian Peninsula)
    • Travel to areas outside the Arabian Peninsula may also put travelers at risk, given the 2015 outbreak in South Korea
  • Contact with camels and camel products (eg, milk, waste) 
  • Close contact with an infected person
    • Transmission to household members has been documented
    • Transmission within hospitals has created large outbreaks in Saudi Arabia, Jordan, United Arab Emirates, and South Korea; patients ill enough to require hospital admission appear to be highly infectious (superspreaders) 

How is Middle East respiratory syndrome diagnosed

Primary diagnostic tools

  • Diagnosis is suggested by epidemiologic risk factor, symptoms, and characteristic radiographic, hematologic, and biochemical abnormalities
  • Diagnosis is confirmed by identifying the virus in blood or respiratory secretions by molecular techniques, or by demonstration of serum antibodies
  • CDC criteria for testing: 
    • Fever and either pneumonia or acute respiratory distress syndrome, combined with 1 or more of the following:
      • Travel from the Arabian Peninsula or nearby countries within 14 days of symptom onset
      • Recent (within 14 days) close contact with a traveler from the Arabian Peninsula who developed fever and respiratory symptoms within 14 days of travel
      • Member of a cluster of persons with unexplained acute respiratory illness being investigated by public health authorities in which MERS-CoV is being considered
    • Fever and symptoms of respiratory illness (not necessarily pneumonia) with a history of being in a health care facility (as patient, visitor, or health care worker) in or near the Arabian Peninsula in which health care–associated cases have occurred recently
    • Fever or respiratory symptoms that follow close contact with a confirmed case during that person’s illness

Laboratory

  • Real-time reverse transcriptase polymerase chain reaction tests 
    • Detect viral RNA in respiratory secretions and serum
    • Lower respiratory tract secretions contain higher viral loads for longer periods than upper respiratory tract secretions 
    • Submission of multiple specimens from different sites enhances likelihood of detection; CDC recommends submitting a combination of specimens from the lower respiratory tract (eg, bronchoalveolar lavage, sputum, or tracheal aspirate), upper respiratory tract (eg, nasopharyngeal and oropharyngeal swabs), and serum 
    • Testing is available through CDC, WHO, and some state or regional public health agencies
  • MERS-CoV serology
    • Recommended if symptom onset was more than 14 days before testing 
  • Other laboratory abnormalities recorded in hospitalized cases include:
    • Leukocytosis or leukopenia (approximately 15% and 10%, respectively); lymphopenia is often noted 
    • Thrombocytosis or thrombocytopenia (approximately 5% and 20%, respectively) 
    • Elevated serum creatinine (approximately 40%) 
    • Elevated transaminases (approximately 20%) 
    • Elevated serum lactate
    • Hypoxemia (approximately 30%) 

Imaging

  • Chest radiograph
    • Most published cases demonstrate abnormal findings 
    • May include unilateral or bilateral patchy densities or opacities, interstitial infiltrates, consolidation, and pleural effusions 
  • Chest CT
    • Commonly demonstrates bilateral ground-glass opacities 

Procedures

Bronchoalveolar lavage
General explanation
  • Fiberoptic bronchoscopy with infusion and aspiration of saline
Indication
  • Obtaining specimens of deep respiratory secretions for laboratory testing
Contraindications
  • Inability to support ventilation during procedure
Interpretation of results
  • Positive molecular testing confirms diagnosis of Middle East respiratory syndrome

Differential Diagnosis

Most common

  1. Influenza
  2. Bacterial pneumonia

in adults Presentation of Bacterial pneumonia includes fever, cough, and dyspnea; pleuritic pain occurs in some cases Physical examination may reveal signs of consolidation (ie, dullness to percussion, auscultatory rales, tubular breath sounds)

Chest radiography usually reveals lobar consolidation or localized patchy infiltrate

Sputum examination may reveal abundant polymorphonuclear leukocytes and a predominant bacterial organism

Pneumococcal or legionella antigens may be detectable in urine

Other viral pneumonias (Related: )Community-acquired pneumonia in adults Presentations include fever, dry cough, and dyspnea

Physical examination may reveal scattered rales

Chest radiography usually reveals diffuse patchy infiltrates

Diagnosis is usually clinical; testing for specific viral etiologies may be done (eg, respiratory syncytial virus, adenovirus) 

Severe acute respiratory syndrome is a viral infection with clinical similarities to Middle East respiratory syndrome, but no cases have been reported since 2004

How is Middle East respiratory syndrome treated?

Treatment Goals

  • Prevent or mitigate the most severe manifestations of disease (eg, multiorgan failure)

Admission criteria

Admit most patients in whom Middle East respiratory syndrome is suspected on the basis of fever, respiratory symptoms, abnormal chest radiography findings, and an epidemiologic risk factor

Presence of comorbidities such as diabetes, hypertension, renal insufficiency, or cardiovascular disease may worsen prognosis and should be considered in decision to admit

Criteria for ICU admission
  • Severe respiratory compromise
  • Hypotension refractory to fluid resuscitation and requiring pressor support

Recommendations for specialist referral

  • Pulmonologist to perform bronchoalveolar lavage, obtain deep specimens for diagnosis (if necessary), and optimize oxygenation
  • Infectious disease specialist to evaluate for other possible infectious etiologies and coordinate special diagnostic testing with public health authorities
  • Nephrologist to optimize renal function or provide renal replacement therapy if needed
  • Public health officials to provide access to diagnostic testing for Middle East respiratory syndrome coronavirus

Treatment Options

Treatment consists of supportive care; no effective antiviral therapy has been identified 

  • Use of corticosteroids to mitigate inflammatory effects is not recommended 
  • Experimental therapies, including ritonavir-lopinavir, ribavirin and interferon, macrolide antibiotics, and convalescent plasma have been studied but are not associated with significantly improved outcomes 
  • A 2020 randomized controlled trial reported that a combination of recombinant interferon β-1b and lopinavir-ritonavir led to lower mortality than placebo among patients hospitalized with laboratory-confirmed Middle East respiratory syndrome; the effect was greatest when treatment was started within 7 days after symptom onset 

Provide fluid resuscitation, ventilatory support, and vasopressor support as needed during acute phase of disease 

Nondrug and supportive care 

Fluid resuscitation in accordance with standard sepsis management

Oxygen supplementation

Noninvasive positive pressure ventilation

Mechanical ventilation

Procedures
Renal replacement therapy

General explanation

  • Hemodialysis, peritoneal dialysis, or ultrafiltration

Indication

  • Acute renal failure

Contraindications

  • Hemodialysis is not feasible in severe hypotension

Comorbidities

  • Comorbidities have been present in most reported patients (up to 75%), including:
    • Diabetes
    • Hypertension
    • Preexisting renal insufficiency
    • Cardiac disease
    • Lung disease
  • Several of the published case series in which comorbidities are listed were reports of nosocomial outbreaks 

Special populations

  • Older adult patients and those with chronic underlying conditions are at risk for more severe disease than younger, healthier patients
  • Infection reported in a pregnant patient who survived, but the pregnancy ended in stillbirth 

Complications

  • Renal failure
  • Multiorgan failure
  • Pulmonary fibrosis 
  • Death

Prognosis of Middle East respiratory syndrome

  • Reported mortality rate exceeds 35% overall; in a small series primarily affecting health care workers, the mortality rate was 22% 
  • The following factors are associated with more severe disease and poorer outcomes: 
    • Advanced age
    • Male sex
    • Comorbid conditions (eg, diabetes, obesity, heart disease, immunocompromise)
    • Hypoalbuminemia
    • Concomitant infections

Screening and Prevention

How is Middle East respiratory syndrome prevented

  • Travelers to the Arabian Peninsula and nearby countries are advised to take general measures such as avoiding contact with people who are unwell, avoiding contact with sick animals, and washing hands frequently; in addition, it is recommended that travelers avoid drinking raw (unpasteurized) camel milk and eating undercooked meat (particularly camel meat). High-risk travelers (eg, people who are immunocompromised, are diabetic, or have kidney disease) should avoid contact with camels 
    • There are currently no restrictions on travel or specific screening of travelers to affected regions
  • Hospital settings 
    • Health care facilities need to develop procedures (eg, screening questions regarding travel and exposure to travelers) to ensure prompt identification and triage of patients at risk for Middle East respiratory syndrome
    • Place patient in a single room with negative pressure, if available; otherwise, place a face mask on the patient
    • Use standard, contact, and airborne precautions
      • Gowns, gloves, eye protection, and N95 respirator
        • Don in order: gown, respirator, eye protection, gloves
        • Doff in order: gloves, eye protection, gown, respirator
  • Household settings 
    • Restrict contact to minimum number of caregivers
    • Use disposable face masks, gowns, and gloves
    • Wash hands after all contact
    • Do not share personal items such as towels, dishes, or utensils before proper cleaning
    • Wash laundry and “high-touch” surfaces frequently

Sources

Azhar EI et al: The Middle East respiratory syndrome (MERS). Infect Dis Clin North Am. 33(4):891-905, 2019 Reference

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