Signs and Symptoms
MERS-CoV infection presents as a nonspecific acute respiratory illness. Patients typically have fever, cough and shortness of breath. Gastrointestinal symptoms can include nausea, vomiting and diarrhea. Severely ill patients may develop pneumonia, ARDS and renal failure. Mortality is reported to be about 30–40% and occurs more commonly in people with underlying medical conditions. Some patients may be infected and fully recover, having either no symptoms or a mild respiratory illness without progression to severe disease. This cohort, however, is less likely to present to the ED.
The incubation period for MERS ranges from 2–14 days, typically about 5–6 days. This is the reason for screening for risk factors within 14 days prior to symptom onset. Comorbidities, such as diabetes, cancer, and chronic heart, lung, and kidney disease, portend a greater risk of contracting MERS and of progressing to more severe illness.
While it is unclear exactly how MERS is contracted, it is likely to spread via an infected person’s respiratory secretions like other coronaviruses. To date, there has not been widespread sustained community human-to-human transmission. It appears that close contact with an infected person is necessary for disease transmission. Close contact is defined as encountering a patient without appropriate protective gear within six feet or being in a care room for prolonged periods or having direct exposure to infected secretions. Healthcare facilities have reported spread from person-to-person much more so than in communities, possibly when suboptimal infection control was practiced for patients with higher viral loads than those not hospitalized.7
Reported cases have been linked to countries in and near the Arabian Peninsula either for persons who live in, have traveled to, or have had contact with an infected person who had been in the region. MERS is a zoonotic virus that is transmitted from animals to humans. It is believed to have originated in bats and then to have been transmitted to camels sometime in the distant past. According to epidemiologic and surveillance data, there is a strong likelihood that dromedary (one-hump) camels (Figure 2) serve as a reservoir for zoonotic transmission of the virus to humans.8 This has resulted in warnings to avoid close contact with camels and not drink raw camel milk or urine, or ingest raw camel meat.
People Who May Be at Increased Risk for MERS
In addition to persons who have had close contact with infected dromedary camels within 14 days before symptom onset, the following groups are at risk for contracting MERS:
Elderly and immunocompromised patients are at higher risk of becoming infected with MERS than healthy hosts if they are exposed to the conditions described above.
MERS can be confirmed at a state or CDC laboratory via polymerase chain reaction (PCR) assays performed on respiratory samples. In addition, serum antibody titers can be measured for both acute infection as well as evidence of prior exposure and immunity. Serologic testing includes (1) enzyme-linked immunosorbent assay (ELISA) as a screening test, (2) immunofluorescent assay (IFA) for confirmation, and (3) neutralizing antibody assay as a definitive confirmatory test that takes longer to process.
As MERS presents initially with a non-specific influenza like illness, the differential diagnosis can include many other respiratory and gastrointestinal infections. The key action is to identify a potential exposure within 14 days prior to symptom onset at initial patient presentation so that MERS can be considered.
Treatment for MERS is primarily supportive care. Hydration and antipyretics, such as in other viral illnesses, are the mainstays of therapy. If a secondary bacterial infection such as pneumonia develops, appropriate antibiotics are indicated. While drugs for treatment of severe acute respiratory syndrome such as beta interferons and protease inhibitors are reported to be under investigation,9 there are currently no approved specific treatments or vaccines for MERS.
Prevention of MERS-CoV transmission involves avoiding exposure. Travelers to regions where MERS has been detected should avoid close contact with potentially infected persons or dromedary camels. Healthcare personnel must practice strict standard, contact, and airborne precautions while caring for patients under investigation (including symptomatic close contacts) as well as patients with probable or confirmed MERS infections. Laboratory workers and others collecting and handling specimens for potential MERS patients should adhere to the same guidelines. Adequate respiratory protection is particularly important when performing aerosolizing procedures.
Admission criteria for patients who are at risk for MERS are similar to those for any other patient. If patients do not meet medical criteria for hospitalization, they may be isolated at home during the evaluation period. Emergency physicians must notify local public health authorities so that appropriate monitoring and community protective measures can be instituted. Return precautions should include attention to any signs or symptoms of pneumonia, ARDS or renal failure.
The Identify-Isolate-Inform tool initially developed for Ebola virus disease and subsequently adapted for measles can be modified for the ED evaluation and management of patients under investigation (PUI) for MERS (Figure 3). A PUI is a person who has both clinical features of MERS and an epidemiologic risk factor. The MERS tool could be accessed real-time on a triage nurse’s computer screen or printed as a poster for display in the triage area. The first step is to identify patients with a possible MERS-CoV exposure within 14 days before symptom onset. CDC and the World Health Organization (WHO) provide case definitions that are comprehensive,10,11 but do not lend themselves to use by frontline emergency personnel who must make rapid risk assessments. Therefore, the 3I tool provides a concise and simplified version of exposure types coupled with symptoms for both severe and milder illness.
If a patient is not identified as having an exposure risk coupled with symptoms, triage may proceed as usual. A caveat is that the Vital Sign Zero12 concept must be applied to all patients before direct patient contact is made to measure traditional vital signs. Vital Sign Zero refers to a mindset of first determining whether the patient may be a risk to expose or contaminate healthcare personnel prior to them having contact with the patient in order to measure traditional vital signs. By first assessing whether the patient is contaminated or contagious, the healthcare provider can don risk-appropriate personal protective equipment before continuing with a full evaluation.
For patients who have positive exposure plus symptom findings, the second step in the algorithm is to immediately “isolate.” A surgical mask should be placed on such patients and they should be directed to an airborne infection isolation room. (If airborne isolation is not available, the patient should be placed in a private room until transfer to an appropriate facility can be arranged.) Staff entering the room should adhere to standard, contact and airborne precautions. They should don appropriate PPE to include a fit-tested N95 respirator or equivalent, eye protection, gown and gloves. Isolated patients should have samples obtained urgently and sent to the local public health department laboratory for disease confirmation.
The final action of the tool is to “inform.” In addition to notifying the hospital infection prevention and control team, emergency physicians should promptly report suspected MERS patients to the local public health department at all times of the day or night. Additional stakeholders, including hospital leadership, occupational health, and the laboratory would need notification through established communications processes at the facility.
Patients who do not meet medical criteria for admission can be isolated at home during the evaluation phase. However, as MERS is a serious contagious disease, an assessment of the home environment must first be performed. The patient needs to be reliable and compliant with home isolation. The home environment needs to have adequate support to offer proper care, including the means for a rapid return for reevaluation if the patient’s condition deteriorates. Health department officials can assist with providing such patients with appropriate public health monitoring and measures to prevent infection transmission.
Areas of Ambiguity
While the WHO uses the terminology MERS-CoV, they specifically suggest that the name should be avoided, stating that such nomenclature may have “unintended negative impacts by stigmatizing certain communities or economic sectors.”13 In addition, as has been the case for other emerging infection diseases such as the 2009 H1N1 pandemic, even purely science-based guidance from authoritative bodies is sometimes conflicting. For example, WHO recommends droplet precautions (surgical mask) unless an aerosolizing procedure is being performed, whereas the U.S. CDC endorses airborne precautions (N95 respirators or equivalent) for all circumstances. Even though there is no good evidence that the virus is transmitted by airborne routes (in the absence of aerosolizing procedures), some would argue that, to avoid transmission, it is better to be more conservative. However, this approach is not without downsides as, if the virus becomes more widespread, it could result in shortages of N95 respirators. Such shortages occurred during the 2009 H1N1 pandemic leading to concerns that respirators might be unavailable for patients with clear indications, such as those with tuberculosis. There is also a substantial cost both for purchasing and stockpiling and for training and fit testing for each new brand of N95 respirator if this approach is used.
Another challenging area is that of lack of standardization in case definitions. WHO and CDC information overlap but is not entirely the same. For example, CDC makes no mention of close contact with dromedary camels in the 14 days prior to symptom onset as a MERS risk factor.
As with all contagious infectious diseases, the question of when to use the public health tools of quarantine and isolation is critical.14,15 While it is clear that ill patients should be immediately isolated, the efficacy of the use of quarantine is more ambiguous. In general quarantine of asymptomatic patients is only beneficial in cases where the infected person is contagious prior to the onset of symptoms. For example, in the case of Ebola, other public health monitoring tools would make more scientific sense than quarantine as the disease becomes contagious only after symptom onset.4,14,15 As with other respiratory viruses, MERS may be contagious prior to symptom onset, but it does not seem to be easily transmissible from person to person. Furthermore, if it can be transmitted prior to symptom onset, it is unclear how many days prior. Given the current state of knowledge, avoidance of exposure, and, if exposed, implementation of public health monitoring measures other than quarantine are probably appropriate.
MERS is an emerging infectious disease that is not yet fully understood in terms of mode of transmission and potential for widespread dissemination. As with any novel infection, it is important not only to identify and treat individual patients, but also to protect healthcare providers and the public health. The Identify-Isolate-Inform tool can be used real-time on the front lines to rapidly detect and manage patients at risk for MERS presenting to the ED. As with the similar 3I tools for Ebola and measles, it can be applied in any acute care setting such as clinics and prehospital environments. Use of the 3I tool will aid emergency physicians and other emergency personnel in performing rapid and appropriate screening for MERS.