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Medical Summary

This article primarily covers Middle East respiratory syndrome (MERS) and briefly discusses severe acute respiratory syndrome (SARS) but does not yet discuss other coronaviruses.

An outbreak of novel coronavirus pneumonia is occurring in China. For detailed information, see Coronavirus Disease 2019 Outbreak.

Introduction

Middle East respiratory syndrome (MERS) is an acute respiratory syndrome (caused by a coronavirus) that has resulted in more than 2,400 confirmed human cases since 2012, with a case-fatality rate (CFR) of 34%. Most cases have occurred in or originated from Saudi Arabia, with smaller numbers in neighboring countries. Widespread circulation of MERS coronavirus (MERS-CoV) has been reported in dromedary camels (single-humped and 94% of the world's camel population) throughout Africa and the Middle East; exposure to camels and to other cases in health care settings has been responsible for almost all human cases.

Severe acute respiratory syndrome (SARS) was a respiratory illness caused by a novel coronavirus at the time (now called SARS-associated coronavirus [SARS-CoV]), which first emerged in China in November 2002. Civet cats (eaten as delicacies in southern China) were probably the intermediate hosts and horseshoe bats may have been the original reservoir. The outbreak spread internationally and peaked in April 2003. By July 2003, all known SARS-CoV transmission had ended. A total of 8,096 cases were reported, with 774 deaths. Imported cases were observed in many countries, and limited local transmission occurred in Canada, Hong Kong, Singapore, and Vietnam. Up to 50% of cases were acquired in hospitals or health care settings before appropriate infection-control techniques were elucidated. Excretion of the virus by SARS patients was minimal in the first 5 days after symptom onset; this unusual feature made it difficult to develop a diagnostic test that would be useful early in the illness, but it led to interruption of human transmission by isolating cases in the preinfectious stage.

Epidemiology

According to WHO, more than 2,400 laboratory-confirmed human cases of MERS, including more than 850 deaths (34% of cases), have been reported globally as of November 2019. Approximately 9% of all cases have been reported since July 2018. Most cases (84%) have occurred in or originated from Saudi Arabia, and the incidence is sporadic throughout the year, with peaks of activity in late winter, spring, and early fall. The remaining cases have been acquired in United Arab Emirates, Jordan, Qatar, Oman, Kuwait, Yemen, Lebanon, Bahrain, and Iran. Approximately 32 cases have been exported since 2012 from the Arabian Peninsula and identified in Europe (Austria, France, Germany, Greece, Italy, Netherlands, Turkey, and U.K.), Africa (Algeria, Egypt, and Tunisia), Asia (China, Malaysia, Philippines, South Korea, and Thailand), and the Americas (U.S.). A single case imported into South Korea in 2015 resulted in almost 200 secondary local cases. No zoonotic transmission of MERS has been reported in eastern Africa, and the absence of known human MERS cases in the Horn of Africa may be due to a lack of research.

Ongoing low-level circulation of MERS-CoV in human populations may be occurring, but no evidence exists for community-based transmission of clinical cases or more than 1 generation of human-to-human transmission within the community. Nosocomial outbreaks have occurred in Saudi Arabia, South Korea, Jordan, United Arab Emirates, and Europe, but no community-based transmission has been reported from recent travel-associated cases.

Health care workers (HCWs) account for approximately 18% of cases overall; however, a much higher percentage has been reported in some large hospital-based outbreaks, which have been attributed to deficient infection-control practices. Secondary cases have occurred almost exclusively in health care settings (54% of cases occurring July 2018–June 2019, with 24% occurring in HCWs). Some cases have also occurred in close household contacts.

Mode of Transmission

In the community, camels are the initial reservoirs and the most likely source of MERS-CoV. The coronavirus is transmitted from infected camels to humans via inhalation of aerosolized respiratory secretions and ingestion of bodily fluids (including nasal and eye discharge); camels may not show any signs of infection. Camel-to-human transmission via direct contact is rare, even with prolonged contact. Some degree of virus persistence in the environment from animal products and excreta is now thought unlikely. Viral transmission via fomites has also been reported. No direct role has been identified for bats in recent outbreaks.

Lack of high-quality infection-control measures in health care settings has played a significant, if not causal, role in several generations of nosocomial transmission when it has occurred. Transmission has been reported in hospital settings via direct contact with surfaces, equipment, or samples contaminated with respiratory tract secretions, stool, urine, and serum from persons infected with MERS-CoV (even up to 1 month after infection). Tracheal secretions and bronchoalveolar lavage specimens have provided higher yield than nasopharyngeal swabs. Peak virus excretion occurs about 10 days after symptoms begin, but viable virus has been detected in respiratory secretions up to 25 days after recovery.

Aerosol-generating procedures (especially intubation and use of nebulizer treatments) increase risk of transmission. MERS-CoV remains stable during aerosolization at 20°C (68°F) and 40% relative humidity (RH) and is stable on surfaces in the environment from 8 hours at 30°C (86°F) and 80% RH to 48 hours at 20°C (68°F) and 40% RH. Also, viral RNA has been detected for up to 5 days on environmental surfaces after the last positive PCR from respiratory secretions. Although SARS was notable for large proportions of super-spreaders who infected more than 10 contacts each, such events have been limited to nosocomial MERS outbreaks in Saudi Arabia and South Korea.

Subclinical shedding has been reported, especially among young HCWs; however, its role in transmission cycles has not been studied. Seroconversion studies have identified asymptomatic infections.

Risk Factors

The following predisposing conditions, behaviors, or exposures increase the risk of infection:

  • Travel to areas where cases have been reported
  • Direct or indirect contact with camels (including carcasses, bodily fluids, secretions, urine, raw meat, droppings) or with persons engaging in animal-related activities (e.g., feeding, cleaning, slaughtering, birthing, milking)
  • Contact with people who have had contact with a camel, including those with subclinical infections acquired from camels
  • Consumption of unpasteurized camel milk, camel urine, or improperly cooked meat
  • Close contact with a person diagnosed with MERS (especially high risk)
  • Inpatient or outpatient visit to health care facilities in an endemic area
  • Underlying medical conditions (chronic diseases or immunosuppression)
  • Advanced age
  • Smoking
  • Pregnancy

Clinical Presentation

The disease course ranges from asymptomatic (uncommon) to severe acute respiratory failure. The median age is 52 years (range: < 1 year–94 years). Two-thirds of cases (especially in primary exposures) are male. Otherwise, healthy younger individuals and some secondary cases are more likely to have mild respiratory illness. The median incubation period of confirmed cases is 5 days, with a range of 2 to 13 days. The median time from symptom onset to hospitalization is 4 days, with a range of 0 to 16 days.

Symptoms of infection range from asymptomatic to mild (21% of cases) to severe, acute respiratory failure, with initial symptoms including fever, cough, and shortness of breath. Pneumonia occurs in 50% of cases; some cases progress rapidly to acute respiratory distress syndrome, septic shock, and multiorgan failure, and more than one-third of cases die. Gastrointestinal symptoms occur in about 30% of cases. About half of adult symptomatic patients require treatment in the intensive care unit, and up to 70% require mechanical intubation within 1 week. Renal injury requiring replacement occurs in 22% to 70% of severe infections.

The CFR is approximately 34% overall, with rates being much higher in older individuals (aged > 50 years) and in persons with an underlying health condition (e.g., diabetes, chronic lung disease, cardiovascular disease). Secondary cases acquired by hospital patients have a relatively high CFR, whereas cases in HCWs are generally mild with a low CFR. The incidence of secondary transmission to household members is very low.

No vaccine or preventive drugs are available for MERS-CoV infection.

Need for Medical Assistance

Any traveler with respiratory symptoms returning from the Arabian Peninsula or neighboring countries should observe respiratory hygiene (cough and sneeze etiquette), hand hygiene (frequent, thorough handwashing), and social distancing (maintaining a distance of 1 m [3 ft] from ill-appearing persons), wear a face mask, and seek immediate medical care. They should inform the provider of their travel history, including whether they visited a health care facility or had direct or indirect contact with camels.

MERS-CoV infection should be considered in any traveler presenting with fever or respiratory illness (or in immunocompromised travelers), with atypical signs and symptoms (such as vomiting or diarrhea) within 14 days of returning from Saudi Arabia and neighboring countries. Testing for MERS-CoV and other respiratory pathogens can be done simultaneously in persons who meet the above clinical and epidemiologic criteria. Testing for or positive results for another pathogen should not postpone or exclude MERS-CoV testing if indicated. Close contacts of confirmed cases must be monitored for symptoms for 14 days after last exposure. RT-PCR and serology testing should be performed at baseline and 21 days after baseline or later.

Diagnosis is confirmed by RT-PCR, and a laboratory-confirmed case requires positive real-time RT-PCR assay targeting at least 2 different genomic regions. Both upper- and lower-respiratory tract specimens should be collected. Viral load is higher in specimens from lower-respiratory tract sites (sputum, bronchoalveolar lavage, bronchial wash, or tracheal aspirate), but upper-respiratory tract sites (nasopharyngeal or oropharyngeal swab) may also provide positive yield, as would stool, urine, or serum samples. Multiple specimens collected at different times are recommended because a single negative test does not rule out MERS-CoV infection.

Prevention

Most infection-control guidelines advise standard contact, droplet, and airborne precautions until more information is available.

Travelers going to affected countries (especially older individuals and those with underlying health conditions) should:

  • Observe respiratory hygiene (cough and sneeze etiquette), hand hygiene (frequent, thorough handwashing), and social distancing (maintaining a distance of 1 m [3 ft] from ill-appearing persons)
  • Avoid physical contact with camels (even if not ill appearing)
  • Avoid consumption of camel products (e.g., unpasteurized milk, undercooked meat, and urine)
  • Be assessed for the advisability of travel to affected areas (especially Saudi Arabia during Hajj or Umra) if underlying chronic diseases are present
  • Be aware that the presence of infection-control standards sufficient to protect travelers presenting to hospitals with unrelated illnesses cannot be assumed

HCWs should:

  • Adhere closely to prescribed personal protective measures (wear a fitted N95 respirator, eye protection, gown, and gloves)
  • Be monitored for early symptoms of infection if they have had contact with a confirmed case

For cases under investigation, during initial assessment, patients should wear a face mask and be placed in the highest level airborne-infection isolation room available or isolated to the greatest extent possible pending transfer to a high-level isolation area. In health care facilities, use standard contact, droplet, and airborne precautions.

Entry point screening or travel restrictions are not currently recommended.