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==Overview==
==Overview==
[[MERS|Middle East Respiratory Syndrome]] ([[MERS]]) is a viral respiratory illness. MERS is caused by a [[coronavirus]] called “Middle East Respiratory Syndrome Coronavirus” (MERS-CoV). MERS-CoV is a beta coronavirus. It was first reported in 2012 in Saudi Arabia. MERS-CoV used to be called “novel coronavirus,” or “nCoV”. It is different from other coronaviruses that have been found in people before.
MERS-CoV is a viral respiratory illness caused by a lineage C betacoronavirus, an enveloped, spherical (120 nm in diameter), single-stranded, positive-strand [[RNA virus]] that belongs to the family ''[[Coronaviridae]]''. Its clinical significance was initially described following an outbreak in 2012 in Jeddah, Saudi Arabia. To date, little is known about MERS-CoV virus. The natural reservoir of MERS-CoV is unknown, but either bats or camels are thought to be the most likely natural reservoir with unconfirmed potential for sustained human-to-human transmission. MERS-CoV has been associated with residence in 9 countries in the Middle East and in South Korea. Approximately, 1,300 cases have been reported with a case-fatality rate reaching 30-40%. Following exposure, patients with MERS-CoV often remain asymptomatic during the viral [[incubation period]] for 5 to 14 days. Patients typically develop non-specific flu-like symptoms, such as high-grade [[fever]], [[myalgia]], [[sore throat]], and [[cough]]. Many patients experience spontaneous self-resolution of symptoms a few days following the onset of symptoms. Individuals with systemic chronic comorbidities and [[immunosuppression]] are at high risk of developing worsening clinical features, such as [[acute respiratory distress syndrome]] (ARDS), [[acute kidney injury]] (AKI), [[pericarditis]], [[disseminated intravascular coagulopathy]] (DIC), [[septic shock]], and death. According to the Centers of Disease Control and Prevention (CDC), laboratory confirmation of MERS-CoV infection requires either a positive [[PCR]] test of ≥ 2 specific genomic targets or a single positive target followed by successful sequencing of a second. [[Serology|Serologic testing]] is recommended in patients when PCR is not available. Additional lab testing is not diagnostic buy may be useful to monitor for the development of complications. Antiviral therapy against MERS-CoV is not yet recommended. Supportive care is the mainstay of management of MERS-CoV, but monitoring for and early management of MERS-CoV-associated complications are equally important. While there is no vaccine available for MERS-CoV, at-risk individuals are advised to implement infection control measures to prevent the spread of the infection in hospitals and in the communities.


==Historical Perspective==
==Historical Perspective==
The Middle East respiratory syndrome coronavirus (MERS-CoV) was first reported to cause human infection in September 2012. In July 2013, the [[World Health Organization]] (WHO) International Health Regulations Emergency Committee determined that [[MERS-CoV]] did not meet criteria for a "public health emergency of international concern," but was nevertheless of "serious and great concern".
The index case of MERS-CoV infection was reported in Saudi Arabia in September, 2012. Dr. Ali Mohamed Zaki, an Egyptian virologist, was the first to attribute MERS-CoV to coronavirus.


==Pathophysiology==
==Pathophysiology==
Potential animal reservoirs and mechanism(s) of transmission of MERS-CoV to humans remain unclear.  A zoonotic origin for MERS-CoV was initially suggested by high genetic similarity to bat [[coronavirus]]es , and some recent reports have described serologic data from camels and the identification of related [[virus]]es in bats. However, more epidemiologic data linking cases to infected animals are needed to determine if a particular species is a host, a source of human infection, or both.
[[MERS-CoV]] has a strong [[tropism]] for the [[cilium|non-ciliated]] [[bronchial]] [[epithelium]]. The [[virus]] has the capacity to evade the [[innate immune system]] and inhibit [[interferon]] production. It uses the DPP4 (or CD26) receptor to bind to the host cell and to release [[viral]] [[nucleocapsid]] into the [[cellular]] [[cytoplasm]]. Once inside the cell, viral replication follows and proteins are expressed. The viral genes encode 4 structural proteins and 5 accessory proteins.


==Causes==
==Causes==
Ten years after the [[outbreak]] of [[SARS-CoV]], the [[MERS-CoV]] is identified as the agent of a [[lethal]] [[pneumonia]] in patients who have recently been related to the Arabian Peninsula. The [[Middle east respiratory syndrome]] [[coronavirus]] ([[MERS-CoV]]), also termed '''EMC/2012''' (HCoV-EMC/2012), is positive-sense, single-stranded [[RNA]] novel [[species]] of the genus ''Betacoronavirus''.<ref name=deGroot>{{cite journal
MERS-CoV is caused by a lineage C betacoronavirus, an enveloped, spherical (120 nm in diameter), single-stranded, positive-strand RNA virus that belongs to the family ''[[Coronaviridae]]'' of the order ''[[Nidovirales]]''. The natural reservoir of MERS-CoV is unknown, but bats are thought to be the most likely natural reservoir. MERS-CoV is thought to have a zoonotic activity, whereby transmission occurs from animals to humans. Limited data is available to confirm or rule out human-to-human transmission.
|author=De Groot RJ |title=Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Announcement of the Coronavirus Study Group |journal=Journal of Virology |date=15 May 2013
|doi=10.1128/JVI.01244-13 |pmid=23678167 |pmc=3700179 |volume=87 |issue=14 |pages=7790–2|author-separator= |author2=and others |displayauthors=1 }}</ref><ref name="Perlman2013">{{cite journal|last1=Perlman|first1=S.|title=The Middle East Respiratory Syndrome--How Worried Should We Be?|journal=mBio|volume=4|issue=4|year=2013|pages=e00531-13–e00531-13|issn=2150-7511|doi=10.1128/mBio.00531-13}}</ref> First called ''novel coronavirus 2012'' or simply ''novel coronavirus'', it was first reported in 2012 after [[genome]] sequencing of the [[virus]], isolated from [[sputum]] samples of patients, affected by a 2012 outbreak of a "new [[flu]]". Until May 2013, [[MERS-CoV]] was being described as a ''[[SARS]]-like virus'' or colloquially as "Saudi [[SARS]]. Since then it is known to be distinct, not only from [[SARS-CoV]], but also from other known [[endemic]] [[coronaviruses]], such as betacoronavirus HCoV-OC43 and HCoV-HKU1, as well as from the [[common cold virus|common cold coronavirus]].<ref name=sciencenews27feb2013>{{cite news |first=Tina Hesman |last=Saey|title=Scientists race to understand deadly new virus: SARS-like infection causes severe illness, but may not spread quickly |journal=[[Science News]] |volume=183 |number=6 |date=27 February 2013| url=http://www.sciencenews.org/view/generic/id/348643/description/Scientists_race_to_understand_deadly_new_virus|page=5}}</ref> As of May 2014, several [[MERS-CoV]] cases have been reported in different countries, including Saudi Arabia, Malaysia, Jordan, Qatar, Egypt, the United Arab Emirates, Tunisia, Kuwait, Oman, Algeria, Bangladesh, the United Kingdom and the United States.<ref>{{cite web|url=http://rt.com/usa/158852-mers-florida-health-virus/|title=Patient with deadly MERS virus waited hours in Florida ER|date=2014-05-14|accessdate=2014-05-14}}</ref>


==Differentiating Middle East Respiratory Syndrome Coronavirus Infection from Other Diseases==
==Differentiating Middle East Respiratory Syndrome Coronavirus Infection from Other Diseases==
The differential diagnosis of the [[middle east respiratory syndrome coronavirus]] infection include other respiratory tract infection, such as [[influenza]].
MERS-CoV must be differentiated from other respiratory tract infections that cause flu-like symptoms, such as [[influenza]] virus, [[respiratory syncytial virus]] ([[RSV]]), and other coronaravirus infections.


==Epidemiology and Demographics==
==Epidemiology and Demographics==
As of September 20, 2013, a total of 130 cases from eight countries have been reported to WHO; 58 (45%) of these cases have been fatal. All cases have been directly or indirectly linked through travel to or residence in four countries: Saudi Arabia, Qatar, Jordan, and the United Arab Emirates (UAE).  Most reported cases involved severe respiratory illness requiring hospitalization.
MERS-CoV has been associated with residence in 9 countries in the Middle East and in South Korea. However, cases with a history of recent travel had been reported in several countries worldwide. As of June 2015, 1289 laboratory-confirmed cases of MERS-CoV infection have been reported. The case fatality rate of MERS-CoV ranges between 30% to 40%. The median age at infection is 47 years with no age preponderance to MERS-CoV infection (range: 9 months to 94 years). Approximately 2/3 of infected patients are males.
 
As of May 28, 2014, globally, 636 laboratory-confirmed cases of infection with MERS-CoV have officially been reported to WHO, including 193 deaths. This global total includes all of the cases reported in this update, plus 17 laboratory confirmed cases officially reported to WHO by Saudi Arabia between 16 and 18 May, 2014.


==Risk Factors==
==Risk Factors==
Some individuals have higher risk of being [[infected]] with [[MERS-CoV]]. Those who have either close contact with an [[infected]] traveler from [[endemic]] areas or who travel to [[endemic]] areas such as Arabian Peninsula, are at increased risk of contracting [[MERS|''Middle East'' respiratory syndrome (MERS)]]. [[Healthcare]] personnel who have close contact with ''probable or confirmed cases'' without using recommended [[infection control]] precautions, are also more likely to be [[infected]] with [[MERS-CoV]]. However, according to the available data, individuals with underlying clinical conditions are more likely to contract the [[infection]]. The [[Comorbidity|preexisting medical conditions]] that may increase the risk of [[infection]] by [[MERS-CoV]], include: [[diabetes]], [[cancer]], [[immunodeficiencies]] and [[CKD|chronic kidney]], [[lung disease|lung]] and [[heart disease]].<ref name=CDC1>{{cite web | title = Symptoms & Complications | url = http://www.cdc.gov/coronavirus/MERS/about/symptoms.html }}</ref>
Risk factors in the development of either MERS-CoV infection or MERS-CoV-associated complications include recent travel to the Arabian Peninsula, exposure to patients with suspected or confirmed MERS-CoV infection, immunocompromised status, and history of prior systemic comorbidities, such as diabetes mellitus, hypertension, active malignancy, chronic kidney disease, respiratory disease, liver disease, and chronic cardiac disease.


==Natural History, Complications and Prognosis==
==Natural History, Complications and Prognosis==
[[MERS|Middle East Respiratory Syndrome]] ([[MERS]]) is a [[viral]] [[respiratory disease|respiratory illness]]. It is caused by an emerging [[coronavirus]], specifically a ''betacoronavirus'' called [[Middle East respiratory syndrome coronavirus|MERS-CoV]] ([[Middle East respiratory syndrome coronavirus|Middle East Respiratory Syndrome Coronavirus]]), first discovered in 2012. Being a relatively novel [[virus]], there is no [[virus]]-specific [[prevention]] or treatment options for [[MERS]] patients. Attending to the fact that a [[vaccine]] hasn't been developed yet, enhancing [[infection]] prevention and control measures is critical to prevent the possible spread of [[MERS-CoV]] in hospitals and communities. To date, the [[mortality rate]] of [[MERS-CoV]] is approximately 30%. Cases have been reported where critically ill patients have developed [[complications]] such as: [[acute renal failure]], [[pericarditis]] and [[disseminated intravascular coagulation]].<ref name="pmid23782859">{{cite journal| author=Drosten C, Seilmaier M, Corman VM, Hartmann W, Scheible G, Sack S et al.| title=Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection. | journal=Lancet Infect Dis | year= 2013 | volume= 13 | issue= 9 | pages= 745-51 | pmid=23782859 | doi=10.1016/S1473-3099(13)70154-3 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23782859  }} </ref><ref name="pmid24841273">{{cite journal| author=Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J et al.| title=Repurposing of clinically developed drugs for treatment of Middle East Respiratory Coronavirus Infection. | journal=Antimicrob Agents Chemother | year= 2014 | volume=  | issue=  | pages=  | pmid=24841273 | doi=10.1128/AAC.03036-14 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24841273  }} </ref><ref name=WHO>{{cite web | title = Clinical management of severe acute respiratory infections when novel coronavirus is suspected: What to do and what not to do | url = http://www.who.int/csr/disease/coronavirus_infections/InterimGuidance_ClinicalManagement_NovelCoronavirus_11Feb13u.pdf }}</ref><ref name=CDC>{{cite web | title = MERS Prevention and Treatment | url = http://www.cdc.gov/coronavirus/MERS/about/prevention.html }}</ref>
Following exposure, patients with MERS-CoV remain asymptomatic during the incubation period for 5 to 14 days. If left untreated, patients typically develop non-specific flu-like symptoms, such as high-grade [[fever]], [[myalgia]], [[sore throat]], and [[cough]]. Many patients experience spontaneous self-resolution of symptoms a few days following the onset of symptoms. Patients with systemic chronic comorbidities and immunosuppression are at high risk of developing worsening clinical features, such as [[acute respiratory distress syndrome]] (ARDS), [[acute kidney injury]] (AKI), [[pericarditis]], [[disseminated intravascular coagulopathy]] (DIC), and [[septic shock]]. Approximately 30-40% of patients die following MERS-CoV infection.


==History and Symptoms==
==Diagnosis==
The symptoms of the middle east respiratory syndrome coronavirus infection include [[fever]], [[cough]], [[shortness of breath]] and gatsrointestinal symptoms.
===History and Symptoms===
Symptoms of MERS-CoV typically include high-grade [[fever]], [[cough]], [[headache]], [[dyspnea]], and [[myalgia]]. Gastrointestinal symptoms such as [[diarrhea]], [[vomiting]], and [[abdominal pain]] may also be present.


==Physical Examination==
===Physical Examination===
A patient [[infected]] with [[MERS-CoV]], during [[physical examination]], might present with [[fever]] or [[hypothermia]], [[tachypnea]], [[hypotension]], [[tachycardia]], and/or low [[oxygen saturation]]. Additionally, patients may present with [[dyspnea]], [[confusion]] and [[cyanosis]], in which case will require immediate attention.<ref name="pmid24841273">{{cite journal| author=Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J et al.| title=Repurposing of clinically developed drugs for treatment of Middle East Respiratory Coronavirus Infection. | journal=Antimicrob Agents Chemother | year= 2014 | volume=  | issue=  | pages=  | pmid=24841273 | doi=10.1128/AAC.03036-14 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24841273  }} </ref><ref name=WHO>{{cite web | title = Clinical management of severe acute respiratory infections when novel coronavirus is suspected: What to do and what not to do | url = http://www.who.int/csr/disease/coronavirus_infections/InterimGuidance_ClinicalManagement_NovelCoronavirus_11Feb13u.pdf }}</ref><ref name=CDC>{{cite web | title = MERS Prevention and Treatment | url = http://www.cdc.gov/coronavirus/MERS/about/prevention.html }}</ref>
Patients with MERS-CoV infection typically present with vital signs derangement, such as high-grade fever, tachycardia, tachypnea, and decreased oxygen saturation. Signs on physical examination may include decreased breath sounds, crackles, dullness on percussion, and increased tactile fremitus on pulmonary auscultation. Signs of complications may also be present, such as profound hypotension (suggestive of shock) or pericardial rub (suggestive of pericarditis).


==Laboratory Findings==
===Laboratory Findings===
Laboratory findings for [[MERS]] on admission may include [[leukopenia]], [[lymphopenia]], [[thrombocytopenia]], and elevated [[lactate dehydrogenase]] ([[LDH]]) levels. [[MERS-CoV]] can be detected with higher [[viral load]] and longer duration in the [[lower respiratory tract]], compared to the [[upper respiratory tract]], and has been detected in [[feces]], [[serum]], and [[urine]].<ref name=CDC>{{cite web | title = MERS Clinical Features| url = http://www.cdc.gov/coronavirus/mers/clinical-features.html }}</ref>
Laboratory findings of MERS-CoV may include [[leukopenia]], [[lymphopenia]], [[thrombocytopenia]], elevated inflammatory markers, and elevated [[lactate dehydrogenase]] ([[LDH]]) levels.<ref name=CDC>{{cite web | title = MERS Clinical Features| url = http://www.cdc.gov/coronavirus/mers/clinical-features.html }}</ref> Lab findings are not diagnostic of MERS-CoV but are useful to monitor for the development of MERS-CoV infection.


==CT==
===Chest x ray===
Despite the increasing number of publications on [[MERS]] [[infection]], the description of [[chest]] [[CT|CT image]] findings is scarce. According to a study in which patients with laboratory-confirmed [[MERS]] [[infection]] underwent [[chest]] [[CT scanning]], the most prevalent findings were bilateral airspace abnormalities, predominantly located at the [[Base of lung|
[[Radiographic]] findings [[MERS-CoV]] [[infection]] include unilateral or bilateral patchy densities or opacities, interstitial infiltrates, consolidation] and [[pleural effusions]] on chest x-ray.
bases of the lungs]] essentially [[pleura|subpleural]] and characteristically consistent with ground-glass opacities, suggesting a pattern of organizing [[pneumonia]]. Attending to the broad range of [[symptoms]] and the different stages evolution of [[infection]], understanding early patterns of [[CT|CT images]], particularly in patients related to [[endemic|endemic areas]], might help in the early [[diagnosis]] of the condition.<ref name="AjlanAhyad2014">{{cite journal|last1=Ajlan|first1=Amr M.|last2=Ahyad|first2=Rayan A.|last3=Jamjoom|first3=Lamia Ghazi|last4=Alharthy|first4=Ahmed|last5=Madani|first5=Tariq A.|title=Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: Chest CT Findings|journal=American Journal of Roentgenology|year=2014|pages=1–6|issn=0361-803X|doi=10.2214/AJR.14.13021}}</ref>


==Medical Therapy==
===CT===
[[MERS|Middle East Respiratory Syndrome]] ([[MERS]]) is a [[viral]] [[respiratory disease|respiratory illness]]. It is caused by an emerging [[coronavirus]], specifically a ''betacoronavirus'' called [[Middle east respiratory syndrome coronavirus|MERS-CoV]] ([[Middle east respiratory syndrome coronavirus|Middle East Respiratory Syndrome Coronavirus]]), first discovered in 2012. Being a relatively novel [[virus]], there is no [[virus]]-specific [[prevention]] or treatment options for [[MERS]] patients. Attending to the fact that a [[vaccine]] hasn't been developed yet, enhancing [[infection]] prevention and control measures is critical to prevent the possible spread of [[MERS-CoV]] in hospitals and communities. Health‐care facilities that provide care for patients suspected or confirmed to be [[infected]] with [[MERS-CoV]], should take appropriate measures to decrease the risk of [[transmission]] of the [[virus]] from an infected patient to others. It is not always possible to identify patients with [[MERS-CoV]] early in time due to the fact that some have mild or unusual [[symptoms]]. For this reason, it is mandatory that health‐care providers apply precaution measures consistently with all patients, regardless of their [[diagnosis]], in all work practices.<ref name="pmid24841273">{{cite journal| author=Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J et al.| title=Repurposing of clinically developed drugs for treatment of Middle East Respiratory Coronavirus Infection. | journal=Antimicrob Agents Chemother | year= 2014 | volume= | issue= | pages= | pmid=24841273 | doi=10.1128/AAC.03036-14 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24841273  }} </ref><ref name=WHO>{{cite web | title = Clinical management of severe acute respiratory infections when novel coronavirus is suspected: What to do and what not to do | url = http://www.who.int/csr/disease/coronavirus_infections/InterimGuidance_ClinicalManagement_NovelCoronavirus_11Feb13u.pdf }}</ref><ref name=CDC>{{cite web | title = MERS Prevention and Treatment | url = http://www.cdc.gov/coronavirus/MERS/about/prevention.html }}</ref>
On chest CT-scan, patients with MERS-CoV may demonstrate changes similar to patients with [[ARDS]]. CT scan may demonstrate bilateral airspace abnormalities with ground glass opacities, predominantly located at the bases of the lungs, suggestive of organizing [[pneumonia]].<ref name="AjlanAhyad2014">{{cite journal|last1=Ajlan|first1=Amr M.|last2=Ahyad|first2=Rayan A.|last3=Jamjoom|first3=Lamia Ghazi|last4=Alharthy|first4=Ahmed|last5=Madani|first5=Tariq A.|title=Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: Chest CT Findings|journal=American Journal of Roentgenology|year=2014|pages=1–6|issn=0361-803X|doi=10.2214/AJR.14.13021}}</ref>


==Contact and Airborne Precautions==
===Other Diagnostic Studies===
Standard, contact, and airborne precautions are recommended for management of hospitalized patients with known or suspected [[MERS-CoV]] infection. In addition, ill people who are being evaluated for MERS-CoV infection and do not require hospitalization for medical reasons may be cared for and isolated in their home. Isolation  at home is defined as the separation or restriction of activities of an ill person with a contagious disease from those who are well.
Laboratory confirmation of [[MERS-CoV]] infection requires either a positive [[PCR]] test of ≥2 specific genomic targets or a single positive target followed by successful sequencing of a second.<ref name=CDC>{{cite web | title = MERS Clinical Features| url = http://www.cdc.gov/coronavirus/mers/clinical-features.html }}</ref> If a patient has a positive [[serologic]] test, but no [[PCR]] or [[sequencing]] test, the individual is considered a ''probable case''.
==Treatment==
===Medical Therapy===
Antiviral therapy against MERS-CoV is not yet recommended. Supportive care is the mainstay of management of MERS-CoV. Monitoring for and early management of MERS-CoV-associated complications is also important.


==Primary Prevention==
===Contact and Airborne Precautions===
Enhancing infection prevention and control awareness and measures is critical to prevent the possible spread of MERS‐CoV in health care facilities. Health‐care facilities that provide care for patients suspected or confirmed to be infected with MERS‐CoV infection should take appropriate measures to decrease the risk of transmission of the [[virus]] from an infected patient to other patients, health‐care workers and visitors. It is not always possible to identify patients with MERS‐CoV early because some have mild or unusual symptoms. For this reason, it is important that health‐care workers apply standard precautions consistently with all patients – regardless of their diagnosis – in all work practices all the time.
Implementation of [[infection]] prevention and control measures is critical to prevent the possible spread of [[MERS-CoV]] in hospitals and communities. Hospitalized patients should be admitted to airborne infection isolation rooms. All healthcare personall should also wear personal protective equipment, including gloves, gowns, and eye and respiratory protection, when exposed to patients with MERS-CoV. Patients evaluated for [[MERS-CoV]] [[infection]] who do not require [[hospitalization]] may be treated and isolated at home to prevent the nosocomial spread of infection. ''Isolation at home'' is defined as the separation or restriction of activities of an ill person with a [[contagious]] disease from those who are well.<ref name=CDC>{{cite web | title = MERS Prevention and Treatment | url = http://www.cdc.gov/coronavirus/MERS/about/prevention.html }}</ref>
 
===Primary Prevention===
There is no [[vaccine]] available for the prevention of [[MERS]] [[infection]]. All individuals should implement precaution measures including washing hands with soap, avoiding personal physical contact or sharing utensils with sick individuals, and avoiding drinking raw food that may be contaminated with animal products.


==References==
==References==
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.

Overview

MERS-CoV is a viral respiratory illness caused by a lineage C betacoronavirus, an enveloped, spherical (120 nm in diameter), single-stranded, positive-strand RNA virus that belongs to the family Coronaviridae. Its clinical significance was initially described following an outbreak in 2012 in Jeddah, Saudi Arabia. To date, little is known about MERS-CoV virus. The natural reservoir of MERS-CoV is unknown, but either bats or camels are thought to be the most likely natural reservoir with unconfirmed potential for sustained human-to-human transmission. MERS-CoV has been associated with residence in 9 countries in the Middle East and in South Korea. Approximately, 1,300 cases have been reported with a case-fatality rate reaching 30-40%. Following exposure, patients with MERS-CoV often remain asymptomatic during the viral incubation period for 5 to 14 days. Patients typically develop non-specific flu-like symptoms, such as high-grade fever, myalgia, sore throat, and cough. Many patients experience spontaneous self-resolution of symptoms a few days following the onset of symptoms. Individuals with systemic chronic comorbidities and immunosuppression are at high risk of developing worsening clinical features, such as acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), pericarditis, disseminated intravascular coagulopathy (DIC), septic shock, and death. According to the Centers of Disease Control and Prevention (CDC), laboratory confirmation of MERS-CoV infection requires either a positive PCR test of ≥ 2 specific genomic targets or a single positive target followed by successful sequencing of a second. Serologic testing is recommended in patients when PCR is not available. Additional lab testing is not diagnostic buy may be useful to monitor for the development of complications. Antiviral therapy against MERS-CoV is not yet recommended. Supportive care is the mainstay of management of MERS-CoV, but monitoring for and early management of MERS-CoV-associated complications are equally important. While there is no vaccine available for MERS-CoV, at-risk individuals are advised to implement infection control measures to prevent the spread of the infection in hospitals and in the communities.

Historical Perspective

The index case of MERS-CoV infection was reported in Saudi Arabia in September, 2012. Dr. Ali Mohamed Zaki, an Egyptian virologist, was the first to attribute MERS-CoV to coronavirus.

Pathophysiology

MERS-CoV has a strong tropism for the non-ciliated bronchial epithelium. The virus has the capacity to evade the innate immune system and inhibit interferon production. It uses the DPP4 (or CD26) receptor to bind to the host cell and to release viral nucleocapsid into the cellular cytoplasm. Once inside the cell, viral replication follows and proteins are expressed. The viral genes encode 4 structural proteins and 5 accessory proteins.

Causes

MERS-CoV is caused by a lineage C betacoronavirus, an enveloped, spherical (120 nm in diameter), single-stranded, positive-strand RNA virus that belongs to the family Coronaviridae of the order Nidovirales. The natural reservoir of MERS-CoV is unknown, but bats are thought to be the most likely natural reservoir. MERS-CoV is thought to have a zoonotic activity, whereby transmission occurs from animals to humans. Limited data is available to confirm or rule out human-to-human transmission.

Differentiating Middle East Respiratory Syndrome Coronavirus Infection from Other Diseases

MERS-CoV must be differentiated from other respiratory tract infections that cause flu-like symptoms, such as influenza virus, respiratory syncytial virus (RSV), and other coronaravirus infections.

Epidemiology and Demographics

MERS-CoV has been associated with residence in 9 countries in the Middle East and in South Korea. However, cases with a history of recent travel had been reported in several countries worldwide. As of June 2015, 1289 laboratory-confirmed cases of MERS-CoV infection have been reported. The case fatality rate of MERS-CoV ranges between 30% to 40%. The median age at infection is 47 years with no age preponderance to MERS-CoV infection (range: 9 months to 94 years). Approximately 2/3 of infected patients are males.

Risk Factors

Risk factors in the development of either MERS-CoV infection or MERS-CoV-associated complications include recent travel to the Arabian Peninsula, exposure to patients with suspected or confirmed MERS-CoV infection, immunocompromised status, and history of prior systemic comorbidities, such as diabetes mellitus, hypertension, active malignancy, chronic kidney disease, respiratory disease, liver disease, and chronic cardiac disease.

Natural History, Complications and Prognosis

Following exposure, patients with MERS-CoV remain asymptomatic during the incubation period for 5 to 14 days. If left untreated, patients typically develop non-specific flu-like symptoms, such as high-grade fever, myalgia, sore throat, and cough. Many patients experience spontaneous self-resolution of symptoms a few days following the onset of symptoms. Patients with systemic chronic comorbidities and immunosuppression are at high risk of developing worsening clinical features, such as acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), pericarditis, disseminated intravascular coagulopathy (DIC), and septic shock. Approximately 30-40% of patients die following MERS-CoV infection.

Diagnosis

History and Symptoms

Symptoms of MERS-CoV typically include high-grade fever, cough, headache, dyspnea, and myalgia. Gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain may also be present.

Physical Examination

Patients with MERS-CoV infection typically present with vital signs derangement, such as high-grade fever, tachycardia, tachypnea, and decreased oxygen saturation. Signs on physical examination may include decreased breath sounds, crackles, dullness on percussion, and increased tactile fremitus on pulmonary auscultation. Signs of complications may also be present, such as profound hypotension (suggestive of shock) or pericardial rub (suggestive of pericarditis).

Laboratory Findings

Laboratory findings of MERS-CoV may include leukopenia, lymphopenia, thrombocytopenia, elevated inflammatory markers, and elevated lactate dehydrogenase (LDH) levels.[1] Lab findings are not diagnostic of MERS-CoV but are useful to monitor for the development of MERS-CoV infection.

Chest x ray

Radiographic findings MERS-CoV infection include unilateral or bilateral patchy densities or opacities, interstitial infiltrates, consolidation] and pleural effusions on chest x-ray.

CT

On chest CT-scan, patients with MERS-CoV may demonstrate changes similar to patients with ARDS. CT scan may demonstrate bilateral airspace abnormalities with ground glass opacities, predominantly located at the bases of the lungs, suggestive of organizing pneumonia.[2]

Other Diagnostic Studies

Laboratory confirmation of MERS-CoV infection requires either a positive PCR test of ≥2 specific genomic targets or a single positive target followed by successful sequencing of a second.[1] If a patient has a positive serologic test, but no PCR or sequencing test, the individual is considered a probable case.

Treatment

Medical Therapy

Antiviral therapy against MERS-CoV is not yet recommended. Supportive care is the mainstay of management of MERS-CoV. Monitoring for and early management of MERS-CoV-associated complications is also important.

Contact and Airborne Precautions

Implementation of infection prevention and control measures is critical to prevent the possible spread of MERS-CoV in hospitals and communities. Hospitalized patients should be admitted to airborne infection isolation rooms. All healthcare personall should also wear personal protective equipment, including gloves, gowns, and eye and respiratory protection, when exposed to patients with MERS-CoV. Patients evaluated for MERS-CoV infection who do not require hospitalization may be treated and isolated at home to prevent the nosocomial spread of infection. Isolation at home is defined as the separation or restriction of activities of an ill person with a contagious disease from those who are well.[1]

Primary Prevention

There is no vaccine available for the prevention of MERS infection. All individuals should implement precaution measures including washing hands with soap, avoiding personal physical contact or sharing utensils with sick individuals, and avoiding drinking raw food that may be contaminated with animal products.

References

  1. 1.0 1.1 1.2 "MERS Clinical Features".
  2. Ajlan, Amr M.; Ahyad, Rayan A.; Jamjoom, Lamia Ghazi; Alharthy, Ahmed; Madani, Tariq A. (2014). "Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: Chest CT Findings". American Journal of Roentgenology: 1–6. doi:10.2214/AJR.14.13021. ISSN 0361-803X.