Middle East respiratory syndrome coronavirus: Treatment and prevention

Author:: Kenneth McIntosh, MD
Section Editor:: Martin S Hirsch, MD
Deputy Editor:: Allyson Bloom, MD

Literature review current through: Jan 2024.

This topic last updated: Jan 17, 2023.

INTRODUCTION — In September 2012, a case of novel coronavirus infection was reported involving a man in Saudi Arabia who was admitted to a hospital with pneumonia and acute kidney injury in June 2012 [1]. Only a few days later, a separate report appeared of an almost identical virus detected in a second patient with acute respiratory syndrome and acute kidney injury [2,3]. The second patient initially developed symptoms in Qatar but had traveled to Saudi Arabia before he became ill and then sought care in the United Kingdom [4]. Many subsequent cases and clusters of infections have been reported.

This novel coronavirus, initially termed human coronavirus-EMC (for Erasmus Medical Center), has been named Middle East respiratory syndrome coronavirus (MERS-CoV) [5].

Updated information about MERS-CoV can be found on the World Health Organization's website and the United States Centers for Disease Control and Prevention's website.

The treatment and prevention of MERS-CoV are discussed here. The virology, epidemiology, clinical manifestations, and diagnosis of MERS-CoV are discussed separately. Community-acquired coronaviruses and severe acute respiratory syndrome coronavirus are reviewed separately. (See "Middle East respiratory syndrome coronavirus: Virology, pathogenesis, and epidemiology" and "Middle East respiratory syndrome coronavirus: Clinical manifestations and diagnosis" and "Coronaviruses" and "Severe acute respiratory syndrome (SARS)".)

TREATMENT — The World Health Organization (WHO) has issued recommendations for the management of severe respiratory infections suspected to be caused by MERS-CoV [6]. No antiviral agents are specifically recommended for the treatment of MERS-CoV infection [7].

Several antiviral and immunomodulating therapies are being evaluated.

Emerging data suggest that the combination of lopinavir/ritonavir plus subcutaneous interferon (IFN)-beta-1b is clinically effective, although further studies are warranted to confirm this finding before the combination can be routinely recommended. In a double-blind trial of 95 patients with laboratory-confirmed MERS-CoV infection in Saudi Arabia, all-cause 90-day mortality was lower among those randomly assigned to lopinavir/ritonavir plus IFN-beta-1b for up to 14 days compared with placebo (28 versus 44 percent), and there were no excess adverse events with the intervention [8]. There was also a trend toward lower 28-day mortality with the combination regimen, although this was not statistically significant. Subgroup analysis suggested that treatment was only associated with reduced mortality when given within seven days of symptom onset. However, the trial was stopped early because of the apparent benefit, and this could have overestimated the treatment effect.

Other regimens of interest include IFN plus ribavirin. In a retrospective cohort study in patients with severe MERS-CoV infection, combination therapy with ribavirin and IFN-alpha-2a, started a median of three days after diagnosis (in 20 patients), was associated with significantly improved survival at 14 days, compared with 24 patients who received only supportive care (70 versus 29 percent survival), but not at 28 days (30 versus 17 percent survival, a nonsignificant difference) [9]. There were greater declines in hemoglobin in the ribavirin-IFN group than in the controls (4.32 versus 2.14 g/L). However, in a retrospective cohort study of 349 critically ill patients with laboratory-confirmed MERS infection from 14 hospitals in Saudi Arabia, crude 90-day mortality was higher in patients who received ribavirin and/or IFN-alpha-2a, IFN-alpha-2b, or IFN-beta-1a than in those who did not receive antiviral therapy [10]. After adjusting for confounders, antiviral therapy was not associated with a change in 90-day mortality (adjusted hazard ratio [aHR] 1.03, 95% CI 0.73-1.44) or with more rapid MERS-CoV RNA clearance (aHR 0.65, 95% CI 0.30-1.44). Ribavirin plus IFN-alpha-2b had appeared promising in vitro and in animal studies [11,12].

In an analysis of 309 adults with MERS, 151 of whom received glucocorticoids, glucocorticoid treatment was not associated with a difference in mortality but was associated with a delay in clearance of virus [13]. Their use is not recommended for MERS-CoV infections.

Other experimental therapies being investigated include convalescent plasma, neutralizing monoclonal antibodies [14-20], a polyclonal hyperimmune antibody produced from transchromosomic cattle [21], an inhibitor of the main viral protease, entry/fusion inhibitors targeting the MERS-CoV spike protein, remdesivir, and a prodrug of a nucleotide analog [14,22-36].

Although the immunosuppressive agent mycophenolate mofetil has in vitro activity against MERS-CoV, in a study of severe infection in common marmosets, it was not effective [37]. Cyclophilin inhibitors, such as cyclosporin and alisporivir, have shown promise in a mouse model of MERS pneumonia, probably through their ability to stimulate production of interferon gamma [38].

PREVENTION

Infection control — The World Health Organization (WHO) and the United States Centers for Disease Control and Prevention (CDC) have issued recommendations for the prevention and control of MERS-CoV infections in healthcare settings [39-42]. An increased level of infection control precautions is recommended when caring for patients with probable or confirmed MERS-CoV infection compared with that used for patients with community-acquired coronaviruses or other community-acquired respiratory viruses.

The WHO recommends that standard and droplet precautions be used when caring for patients with acute respiratory tract infections [39]. Contact precautions and eye protection should be added when caring for probable or confirmed cases of MERS-CoV infection. Airborne precautions should be used when performing aerosol-generating procedures.

The CDC recommends the use of standard, contact, and airborne precautions for the management of hospitalized patients with known or suspected MERS-CoV infection [42-44].

Because respiratory secretions from MERS-CoV–infected patients have been shown to contain viral RNA for at least three weeks after symptom onset and because viable virus has been isolated from hospital room air samples and surfaces two and three weeks after first diagnosis [45], infection control precautions should be applied until lower respiratory tract samples (sputum or tracheal aspirates) become RNA negative or until discharge, whichever occurs first [46].

The efficacy of these recommended measures has not been formally tested. However, a large 2015 hospital-based outbreak in Riyadh, Saudi Arabia, ended after an aggressive prevention program was instituted by a Ministry of Health Rapid Response Team [47]. Although several hospital functions had to be closed down in the process, it seems likely that infection control measures played a role in ending the epidemic.

Additional information can be found on the WHO's website and the CDC's website.

Interim home care and isolation — The CDC recommends that ill individuals who are being evaluated for MERS-CoV infection and do not require hospitalization may be cared for and isolated in their home [48]. Healthcare providers should contact their state or local health department to determine whether home isolation or additional measures are indicated because recommendations might be modified as more data become available. Isolation is defined as the separation or restriction of activities of an ill person with a contagious disease from those who are well. Additional information on home care and isolation guidance is available on the CDC's website.

Avoiding camels — The WHO recommends that individuals at high risk of severe disease, such as immunocompromised hosts and those with diabetes, chronic lung disease, or preexisting renal failure, take precautions when visiting farms, barn areas, camel pens, or market environments where camels are present [49]. These measures include avoiding contact with camels, practicing good hand hygiene, avoiding drinking raw camel milk or camel urine, avoiding eating meat that has not been cooked thoroughly, and avoiding eating food that may be contaminated with animal secretions or products unless they are properly washed, peeled, or cooked.

The WHO recommends that when visiting a farm or barn, members of the general public adhere to general hygiene measures, including regular hand washing before and after touching animals, avoiding contact with sick animals, and following food hygiene practices [50]. Unless wearing a face mask and protective clothing, individuals should avoid contact with any camel that has tested positive for MERS-CoV until subsequent tests have confirmed that the animal is free of virus [49].

Specific recommendations for camel farm and slaughterhouse workers can be found on the WHO's website.

Travel recommendations — The WHO does not recommend either special screening for MERS-CoV at points of entry or the application of any travel or trade restrictions. However, the WHO recommends that countries outside the affected region maintain a high level of vigilance, especially countries with large numbers of travelers or guest workers returning from the Middle East [39].

There has been both active and passive screening of symptomatic and asymptomatic travelers returning from the Hajj and, to a lesser extent, Umrah, and, although many respiratory viruses have been detected, no cases of MERS-CoV infection have been reported among Hajj pilgrims from countries outside Saudi Arabia [51,52]. Eight cases of MERS were reported among foreign pilgrims attending Umrah between 2012 and 2014 [53]. Several of these cases had high-risk exposures, such as exposure to known MERS cases. Despite the low risk associated with Hajj and Umrah pilgrimages, it is nevertheless recommended that MERS surveillance in these settings continue [54].

In May 2014, the CDC's travel notice was upgraded to a Level 2 Alert, which includes enhanced precautions for travelers to countries in or near the Arabian Peninsula who plan to work in healthcare settings [48]. Such individuals should review the CDC's recommendations for infection control for confirmed or suspected MERS patients before they depart, practice these precautions while in the area, and monitor their health closely during and after their travel.

The CDC recommends that all United States travelers to countries in or near the Arabian Peninsula protect themselves from respiratory diseases, including MERS-CoV, by washing their hands often and avoiding contact with persons who are ill [48]. If travelers to the region have onset of fever with cough or shortness of breath during their trip or within 14 days of returning to the United States, they should seek medical care. They should call ahead to their healthcare provider and mention their recent travel so that appropriate isolation measures can be taken in the healthcare setting. More detailed travel recommendations related to MERS are available on the CDC's website.

Vaccine development — There is no licensed MERS-CoV vaccine for use in humans, although several experimental candidate MERS-CoV vaccines are being developed [55,56]. Examples include a vaccine based on the major surface spike protein using recombinant nanoparticle technology, a recombinant modified vaccine Ankara (MVA) vaccine expressing full-length MERS-CoV spike protein, a vesicular stomatitis virus (VSV)-based vaccine in which the full-length S protein has been substituted for the VSV G protein, DNA vaccines, and vaccines encoding the full-length MERS-CoV S protein and the S1 extracellular domain of S protein using adenovirus vectors [57-64]. The MVA-based and one of the adenovirus-based vaccines have undergone successful phase I human trials [65-67]. In addition, early vaccine trials in camels have shown partial protection from symptoms of infectious challenge [68].

Animal models have been used to evaluate candidate vaccines that could eventually be used in humans. In one study, immunogens based on full-length S DNA and S1 subunit protein administered in a prime-boost regimen elicited robust serum neutralizing activity against several MERS-CoV strains in mice and rhesus macaques [69]. Immunization of rhesus macaques reduced the severity of MERS-CoV–induced pneumonia, as assessed by computed tomography. In another study, a DNA vaccine encoding the MERS spike protein induced potent cellular immunity and neutralizing antibodies in mice, macaques, and camels [70]. Following a challenge with MERS-CoV, vaccinated macaques were protected from MERS-CoV infection and showed no signs of clinical or radiographic signs of pneumonia.

Another candidate vaccine is based on self-amplifying RNA replicons that are propagation deficient because the envelope gene and several accessory open reading frames had been removed [71]. These replicons induced sterilizing immunity in mice, appear to be safe, and are candidates for immunizing either camels or humans.

An alternative approach to vaccinating humans involves immunizing camels against MERS-CoV, since camels are hosts for MERS-CoV and are likely to be an important source of MERS-CoV. In one study, an MVA vaccine expressing the MERS-CoV spike protein conferred mucosal immunity in dromedary camels [72]. Significant reductions of excreted infectious virus and viral RNA transcripts were observed in vaccinated animals following MERS-CoV challenge compared with controls. Protection correlated with the presence of serum neutralizing antibodies against MERS-CoV.

Monoclonal antibodies — Monoclonal antibodies are being investigated for both prophylaxis and treatment of MERS. None are licensed for use. Monoclonal antibodies are discussed in greater detail above. (See 'Treatment' above.)

PROGNOSIS

●Mortality – Based on the number of laboratory-confirmed MERS-CoV infections reported to the World Health Organization, the estimated crude case fatality rate is 35 percent [73]. Because individuals with mild symptoms are less likely to be evaluated than patients with severe disease, those with MERS-CoV and mild disease might be underrepresented in published reports and reports from the World Health Organization (WHO) [74]. The reported case-fatality rate might therefore be an overestimate. This hypothesis is supported by an analysis pointing out that 14 of 19 (74 percent) patients with infection detected through routine surveillance died compared with 5 of 24 (21 percent) of secondary cases [75].

Increasing age is associated with higher mortality rates [75-82]. As an example, in one study of 835 patients in Saudi Arabia from 2012 to 2015, overall mortality was 43 percent [81]. Mortality rates increased from 26 percent in those younger than 55 years of age, to 54 percent in those age 55 to 65 years, to 79 percent in those older than 65 years. In a subsequent analysis of 1408 cases, the overall mortality rate was 32 percent, and only 19 percent in those younger than 32 years [82].

Medical comorbidities, such as underlying cardiac disease or cancer, and acquisition as a hospitalized patient are also risk factors for death [78,79,83]. In a small series of nine adults with cancer (seven of whom had a hematologic malignancy), the case fatality rate of MERS-CoV was 100 percent [84].

Mortality may also differ by population, likely related to differing age range and prevalence of comorbidities. In a WHO analysis of 2223 cases reported between 2013 and 2018, most from Saudi Arabia, mortality rates were lower among the 415 health care workers with infection (of whom 338 had confirmed “secondary” or hospital-acquired infections) compared with 642 non-health care workers (5 versus 36 percent) [85]. Health care workers were also younger (mean age 40 versus 52 years) and were less likely to have comorbidities (9 versus 34 percent).

●Other outcomes – Chronic fatigue and psychiatric illnesses have been reported among survivors of MERS-CoV.

As an example, in a long-term study of 63 individuals who had MERS-CoV infection during the outbreak in Korea, nearly half (29 of 63) had a diagnosis of chronic fatigue syndrome at 12 months [86]. Suicidality was reported in 22 to 10 percent at follow-up visits over two years and was seven to eight times more likely among those who had chronic fatigue syndrome.

In another study of all survivors of the outbreak in Korea, 43 percent reported post-traumatic stress disorder (PTSD) at 12 months [87]. Greater anxiety during the outbreak and greater awareness of the stigma attached to the disease were both predictors of PTSD.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Middle East respiratory syndrome coronavirus".)

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Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Middle East respiratory syndrome coronavirus (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Supportive care – There is currently no treatment recommended for MERS-CoV infection except for supportive care as needed. (See 'Treatment' above.)

●Infection control – The United States Centers for Disease Control and Prevention (CDC) recommends the use of standard, contact, and airborne precautions for the management of hospitalized patients with known or suspected MERS-CoV infection. (See 'Infection control' above.)

●Travel recommendations – The World Health Organization (WHO) does not recommend either special screening for MERS-CoV at points of entry or the application of any travel or trade restrictions. (See 'Travel recommendations' above.)

●No available vaccine – There is no licensed vaccine for MERS-CoV. (See 'Vaccine development' above.)

●WHO and CDC links – Additional information about MERS-CoV can be found on the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) websites.

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Topic 106550 Version 40.0

خرید پکیج

Middle East respiratory syndrome coronavirus: Treatment and prevention

References