Chapter II REVIEW OF RELATED LITERATURE This chapter discusses the review of related literature and studies written by authorities and researcher in the fields of medicine and other allied fields which are available and closely related to the study

Chapter II
REVIEW OF RELATED LITERATURE
This chapter discusses the review of related literature and studies written by authorities and researcher in the fields of medicine and other allied fields which are available and closely related to the study. The study dealt on the Knowledge on Middle East Respiratory Corona Virus (MERS CoV) of Nurses in Central Security Hospital in Saudi Arabia.

Discovery of MERS CoV
In the midst of June 2012, in Jeddah, Saudi Arabia, a mysterious Corona Virus (CoV) was found from the sputum of a patient who is diagnosed with pneumonia and renal failure. This was temporarily named as Human Corona Virus Erasmus Medical Center. By, September 2012, the same type of virus was named Human Corona Virus England 1; which was taken from a patient with a serious respiratory illness, who has been transferred from Gulf region of the Middle East to the London United Kingdom. However, the new disease was traced at an earlier time. Last April 2012, numerous pneumonia cases in health care workers happen in the Intensive care unit in Zarqa, Jordan. Two staff died, both who were rooted with the infectious with novelcorona virus through a demonstrative or retrospective analysis of stored samples. These findings cause high considerable concern and alarmed the government. With the available laboratory – confirmed cases is limited (34 of 12 as of May 2013), the morbidity and mortality of infection is disturbing and alarming as it has a strange resemblance and clinical features of the Severe Acute Respiratory Syndrome (SARS). Although in some cases the patient developed a mild disease, most of the patients showed a severe acute respiratory condition that requires hospitalization; and the death rate during this time is around 60%.
The emerging infection appears to be linked to the geographical profile of persons being affected – the Middle East. With the cases originating from Jordan, Saudi Arabia, Qatar and the United Arab Emirates. Out of the three patients who suffered from the disease outside Arab Countries, two of the infected in the United Kingdom through contact exposure to an index patient, after his visit from Pakistan to Saudi Arabia. While in France, a tourist from the United Arab Emirates become sick and transfers the infection to another patient who was with him in the same hospital room. The full-length genome sequences were recognized for three independent virus isolates from Saudi Arabia, Jordan and United Kingdom, with more than 90% sequence identity ( -100 nucleotide variation in a 30.1-kb genome), these signify that these viruses diverged from the same ancestors.
MERS-CoV- The New Corona Virus
From the initial discovery, the virus has been described in the scientific literature, databases and other media in various names ((e.g., human betacoronavirus 2c EMC, human betacoronavirus 2c England-Qatar, human betacoronavirus 2C Jordan-N3, betacoronavirus England 1) with Novel Corama Virus as one of the most commonly used. With the lack of uniformity in naming the virus this complicates the communication in research fields and healthcare authorities, governments and the general public, the Coronavirus Study Group (CSG) of the International Committee on Taxonomy and Viruses took a lead to deal with this issue.
After a thorough discussion and wide array of consultation, the CSG has decided to make the new coronavirus “Middle East Respiratory Syndrome-Corona Virus (MERS Cov). The name is approved by the discoverers of the virus and other researchers that pioneered the study of the disease, by the World Health Organization and the Saudi Ministry of Health. The name was highly recommended for the scientific and other forms of communication.
Coronavirus in Saudi Arabia and the Middle East
June 13, 2012, in Jeddah, Saudi Arabia, the first reported case of MERS-CoV 1 was documented. That had resulted in an outbreak of infection, common among health care workers who were in direct patient care, indicating that the virus can be transmitted from human to human via air droplets. This encouraged strict compliance to infection control precautions, such as isolation and the use of personal protective equipment, i.e., gloves, N 95-type masks, and gowns.

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In Saudi Arabia, many cases of MERS-CoV were reported in various provinces, such as Riyadh Jeddah, Makka, Al-Hassa, and Qassim being the most commonly affected cities. Additionally, outbreaks were commonly reported in hospitals, causing the affected hospitals to close down and not to accept any infected patients.
Many patients who died has compromised immune system, having underlying such as chronic renal failure, congestive heart failure, and diabetes or having recently received organ transplants (e.g., kidney transplants). After its initial outbreak in the Kingdom, MERS-CoV was reported and seen in several neighboring countries like Tunisia, Jordan, Kuwait, Bahrain, and Qatar.

MERS CoV Statistics:
Report form the Minister of Health in Saudi Arabia, from June 13, 2012 until February 23, 2018, a total of 1800 cases of MERS-CoV have been reported, with 1062 recovered, 8 still under treatment, and 732 died due to MERS-CoV-related symptoms. The Minister of Health, Particularly healthcare facilities, and public health officials immediately sought to educate the population in Saudi Arabia through internet, lectures, and brochures and continued to carefully record each new case in order to improve knowledge and therapeutic strategies for this virus.

190501231900The latest report from the WHO on June 2018 showed that MERS-COV has been identified in 27 countries, with 2291 confirmed cases and 791 deaths globally. Notably, the highest numbers of both reported cases and deaths have been in the Saudi Arabia
MERS CoV Affected Countries
From its discovery in 2012, the infectious MERS CoV has been reported in 27 different countries including Philippines, Algeria, Austria, Bahrain, Egypt, France, Germany, China, Greece, Islamic Republic of Iran, Jordan, Malaysia, Italy, Lebanon, Oman, Qatar, Peoples Republic of Korea, Kuwait, the Kingdom of Saudi Arabia, the Netherlands, Thailand, Tunisia, Turkey, United Arab Emirates, United Kingdom, Yemen, and United States. The Kingdom of Saudi Arabia reported about 80% of human cases. Cases that are identified beyond the Gulf region are people who were infected in the Middle East and traveled to areas outside these countries. Rare occasions, only small outbreaks have developed outside the Middle East.

Diseases Process
From the WHO – The evolution of MERS-CoV and the reservoirs and hosts of human infection are on ongoing studies, but, there are many indications that it is a zoonosis. The MERS virus is transmitted primarily from animals to people, but transmission from people to people is also possible.

MERS-CoV and bats
Coronavirus was a zoonotic virus or known to be on animal origin; however, this MERS-CoV is a novel virus, although zoonotic transmission occurs is well identified. Different international studies taken out from the year 2012 to 2014 in European countries (i.e., Germany, Ukraine, the Netherlands, and Romania), Mexico, South Africa, and Ghana have tested and examined if bats may be carriers of MERS-CoV. The studies have tested bats using blood, fecal, and oral samples mainly for the 329-bp fragment of RdRp. Several species of bats that were tested in these studies are  Neoromiciazuluensis,. nathusii, P. pygmaeus, Nycteris, and Pipistrelluspipistrellus, P. with 5.3–24.9% positive for MERS-CoV, the most positive results (> 70%) being seen in fecal samples with high viral loads . Thus, it may conclude the possibility for transmission to occur through bats; however, in the Kingdom of Saudi Arabia, the species of bats that patients may have come in contact with are different from those tested, including Taphozousperforatus, P. kuhlii, Eptesicusbottae, Rhinopomahardwickii, Rhinopomamicrophyllum, Rosettusaegyptiacus Eidolon helvum, and Eidolon helvum. With the positive association between bats and corona virus infection, there was no association between MERS-CoV and bats. Therefore, it can be concluded with this data that MERS CoV is not transmitted through bats.

MERS-CoV and camels.
Researchers have also tested and examined camels whether they may be associated with the epidemic infection of this MERS-CoV in Saudi Arabia. This have been carried out in different Gulf countries, including United Arab Emirates, Saudi Arabia, Qatar, Oman, and Egypt, with the use of samples from the lung,the nose, and rectal swabs. Positive for MERS-CoV through RT-PCR for the RdRp was found in 1.6–61.5% of samples, majority form lung and nasal swabs. Using anti-MERS-CoV analysis, antibodies revealed that 98–100% of camels are highly positive for MERS-CoV; with such consistency, the rate of MERS-CoV in humans is 23 times higher in workers in the slaughterhouse than in the general population. And 15 times higher in shepherds of camel. With these data it can be claimed that the most important route of transmission of coronavirus from camels is through the respiratory system.
The Pathogen
The Virus Distinctiveness
MERS-CoV is an envelope, single-stranded, positive-sense RNA of virus. The genome weight about 30.1kb long and has at least 10 predicted open reading frames (ORF), that are expressed from seven subgenomic mRNAs. These ORFs mainly include ORF 1a/1ab, which encode for large polyproteins like containing conserved functional domains and several non-structural (NS) proteins of CoV, the small-envelope (E) protein, the spike-surface glycoprotein (S), the nucleocapsid (N) protein the matrix (M) protein, and protein the matrix (M) protein.

MERS-CoV belongs to lineage C within the Coronavirinae subfamily which is the Betacoronavirus genus, together with several viruses found in bats in China, Africa and Europe. MERS-CoV is the foremost Betacoronavirus lineage C member isolated from humans, and it is much different from SARS and distinct from the common-cold coronavirus and common human betacoronaviruses HCoV-229E and HCoV-NL63, HCoV-HKU1, and HCoV-OC43.

MERS-CoV genomes are phylogenetically classified into two clades: the clades A and clades B. The first viral genomes detected cases in humans (clade A cluster; EMC/2012 and Jordan-N3/2012) are genetically different from the others (i.e. clade B). Many other distinct MERS-CoV genotypes are present, possibly each from a separate zoonotic event. However, all sequences from human and camel samples connected to the epidemic in the Middle East are closely related, and mostly are identical.

Distribution of pathogen
In Humans
From March 2012, autochthonous MERS cases have been found only in the Middle East (Jordan, Saudi Arabia, United Arab Emirates, Iran, Oman, Kuwait, Lebanon Yemen, and Iran Qatar). MERS cases have also been detected in some geographic areas with primary cases having history of travel connections to the Arabian Peninsula: in Europe (France, United Kingdom, Germany, Italy, the Netherlands and Greece), in Africa (Algeria and Tunisia), in Asia (Malaysia and the Philippines) and in the United State of America (USA).

Animal hosts
Dromedary camels: The increasing serological and molecular data that the dromedary camel (Camelus dromedarius) is an identified host species for the MERS-CoV and that transmission of MERS-CoV or MERS-like CoV in dromedaries in Africa and the Arabian Peninsula were occurring well prior to the year 2012. The availability of MERS-CoV-neutralizing antibodies in dromedaries has been reported in Saudi Arabia, Islands of Spain in Jordan, United Arab Emirates, Oman, Nigeria, Tunisia Egypt, Qatar , and Ethiopia .

Bats: With the study of the Taphozous perforates bats, only small fragments of the conserved viral polymerase region identical to MERS-CoV has been seen but these findings might not be sufficient and are not reliable and still needs to be confirmed.

Other animals: Other countries of the Arabian Peninsula cattle, goats, swine, sheep, water buffalo, chicken and other wild birds have been tested for antibodies to MERS-CoV, no positive results has been detected.

Viability of the virus
From Europe’s journal on Infectious Disease Surveillance, Epidemiology, Prevention and Control (Volume 18, Issue 38, 19/Sep/2013) , MERS-CoV remains alive upto 48 hours at 20 °C and 40% relative humidity, in comparison to an indoor environment such as on metal and plastic surfaces. The viruses are sensitive and susceptible to heat, non ionic detergents, lipid solvents, ultraviolet light and oxidizing agent. In an experiment using aerosol, MERS-CoV retains most of its viability at 20 °C and 40% relative humidity. The lifespan of virus decreases at higher temperatures or higher levels of relative humidity. And from the CDC, unpasteurized camel milk, MERS-CoV remains contagious beyond three days after and infectious viruses could not be found after pasteurization.
MERS CoV and SARS (Severe Acute Respiratory Syndrome)
Middle East Respiratory Syndrome (MERS-CoV) is a viral respiratory illness that was first reported in Saudi Arabia in 2012 and has since spread to several other countries. Most people infected with MERS-CoV developed severe acute respiratory illness, including fever, cough, and shortness of breath; many of them died. Severe acute respiratory syndrome (SARS-CoV), also a severe viral respiratory illness, was first reported in Asia in February 2003 and spread to dozens of countries before being contained. Since 2004, there have been no known SARS cases. Both MERS and SARS belong to a family of viruses called coronaviruses.( National Institute for Allergy and Infectious Disease (NIAID)
Two coronaviruses, MERS-CoV and SARS-CoV, cause much more severe respiratory infections in humans than other coronaviruses. In 2012, the coronavirus MERS-CoV was identified as the cause of Middle East respiratory syndrome (MERS). In late 2002, SARS-CoV was identified as the cause of an outbreak of severe acute respiratory syndrome (SARS).

It has long been known that viruses can cross species barriers and adapt from animals to humans to sometimes evolve human to human transmission, as was seen for small pox, measles and influenza. The latter, also called the Spanish flu, caused a pandemic back in 1918-19, killing approximately 50 million people. More recent examples of viruses crossing species barriers are H5N1 and H7N9 influenza, which crossed-over from poultry to humans with cases reported in Asia, even though no efficient human to human transmission was reported for both viruses thus far. A virus which did evolve human to human transmission was SARS-CoV, which crossed over from bats via intermediate hosts to humans in China. SARS-CoV was the first coronavirus causing a pandemic back in 2002/2003, after which a search began for novel coronaviruses with human to human transmission like SARS-CoV. In September 2012 the 6th coronavirus was discovered with human to human transmission, but it was the second coronavirus, after SARS-CoV, which caused severe symptoms of the lower respiratory tract, and therefore deserved extra attention in fear of the next coronavirus causing a global epidemic. The new coronavirus, formerly known as human coronavirus-Erasmus Medical Center (EMC/2012),is now officially named Middle East Respiratory Syndrome Coronavirus (MERS-CoV), because all index patients appear to originate from the Middle-East, in contrast to the Asian origin of SARS-CoV.

Like SARS-CoV, MERS-CoV seems to be originating from coronaviruses circulating in bats. In the case of SARS-CoV, intermediate hosts were identified, namely Himalayan palm civets (Paguma larvata) and raccoon dogs (Nyctereutes procyonoides) present on the Chinese wet markets, establishing a reservoir for the virus from which it could adapt to humans. For MERS-CoV such a zoonotic reservoir has not yet been clearly established, despite the recent isolation of the first MERS-CoV from a camel on a Qatari farm, with fragment analysis showing sequence alignment to two confirmed MERS cases who had reported contact with the camels on that farm. Also the presence of neutralizing antibodies in dromedary camels from Qatar, Oman and Egypt support the idea that camels are the intermediate reservoir of MERS-CoV. Despite the similar clinical symptoms and similar phylogenetic background, the viruses use different human receptors to enter the cells. SARS-CoV uses the angiotensin-converting enzyme 2 (ACE2) as a receptor, while MERS-CoV uses dipeptidyl peptidase 4 (DPP4), also known as CD26, as a receptor to enter the cells.The difference in the receptor usage establishes a small difference in human cellular tropism. MERS-CoV has a preference of infecting unciliated bronchial epithelial cells, while SARS-CoV primarily infects ciliated bronchial epithelial cells.
Thus far, only limited human to human transmission has been documented for MERS-CoV in contrast to SARS-CoV back in 2003. The case fatality rate of MERS-CoV, however, seems to exceed the one of SARS-CoV fourfold (40% compared to 10%), which might be an overestimation with presumable undetected cases. If MERS-CoV were to adapt more efficiently to humans, as SARS-CoV appears to have done, an epidemic with a mortality rate exceeding that of SARS could be expected when no proper precautions will be taken.

MERS and SARS are the same syndrome in that both are caused by coronavirus, and are associated with fever, respiratory symptoms, and a relevant travel history. In other words, the severity, acuteness, and respiratory syndrome in MERS is no less severe than SARS. There is no need to create a new name and abbreviation each time a coronavirus emerges.

Clinical Manifestation
According to CDC (2016), the clinical manifestation of MERS cov is similar to typical pulmonary infections such as fever, body weakness, cough, purulent sputum, shortness of breath and severe respiratory illness. Based on the information we have to date, the incubation period for MERS (time between when a person is exposed to MERS-CoV and when they start to have symptoms) is usually about 5 or 6 days, but can range from 2 to 14 days.
However, some people had gastrointestinal manifestation such as diarrhea, nausea, and vomiting. MERS has a signs and symptoms flu-like illness with the manifestation of pneumonia. Early reports of its signs and symptoms described as similar to SARS. Some people also had gastrointestinal symptoms including diarrhea and nausea/vomiting. For many people with MERS, more severe complications followed, such as pneumonia and kidney failure. About 3 to 4 out of every 10 people reported with MERS have died. Most of the people who died had an underlying medical condition. Some infected people had mild symptoms (such as cold-like symptoms) or no symptoms at all; they recovered.
Based on what researchers know so far, people with pre-existing medical conditions (also called co-morbidities) may be more likely to become infected with MERS-CoV, or have a severe case. Pre-existing conditions from reported cases for which we have information have included diabetes; cancer; and chronic lung, heart, and kidney disease. Individuals that are immune compromised or with weakened immune systems are also at higher risk for getting MERS or having a severe case.

Many individuals with MERS may elicit a mild respiratory illness with or no symptoms.

Some will have severe respiratory distress that needs mechanical ventilation and has spend a long time in the hospital.
Case Definition of MERS Cov
After consultation with the World Health Organization the Ministry of Health (MOH) ‘s medical experts come up with protocols and recommendations which are being executed by the WHO and CDC in formulating suspected case definitions, detecting, identifying, and management of MERS Cov which include the following:
SUSPECTED CASE
CLINICAL PRESENTATION EPIDEMIOLOGIC LINK
Severe pneumonia (severity score ?3 points) (Appendix A) or ARDS (based on clinical or radiological evidence) Not required
Unexplained deterioration** of a chronic condition of patients with congestive heart failure or chronic kidney disease on hemodialysis Not required
Acute febrile illness (T ?380 C) with/without respiratory symptoms OR Within 14 days before symptom onset: 1. Exposure*** to a confirmed case of MERS-CoV infection OR 2. Visit to a healthcare facility where MERS-CoV patients(s) has recently (within 2 weeks) been identified/treated OR 3. Contact with dromedary camels**** or consumption of camel products (e.g. raw meat, unpasteurized milk, urine)
Gastrointestinal symptoms (diarrhea or vomiting), AND leukopenia (WBC?3.5×109 /L) or thrombocytopenia (platelets < 150×109/L) After consultation with the World Health Organization the Ministry of Health (MOH) ‘s medical experts come up with protocols and recommendations which are being executed by the WHO and CDC in formulating suspected case definitions, detecting, identifying, and management of MERS Cov which include the following:
* All suspected cases should have samples collected for MERS-CoV testing (nasopharyngeal swabs or sputum, and when intubated, lower respiratory secretions)
** Chronic renal failure and congestive heart failure patients may exhibit fever and presence of fluid overload may mask the radiological features of pneumonia
*** Exposure is defined as a contact within 1.5 meters with a confirmed MERS-CoV patient.

**** Exposure to camels include:
Direct physical contact with camels or their surroundings (milking and handling excreta are especially risky), drinking raw camel milk or other unpasteurized products derived from camel milk, and handling raw camel meat.
Indirect contact include casual contact with camel places like visiting camel market or farms without direct physical contact with camels, living with a household member who had direct contact with camels.

Severity Scores for Community-Acquired Pneumonia (CURB 65)
CLINICAL FACTORS POINTS
Confusion 1
Blood urea nitrogen ; 19 mg per dL 1
Respiratory rate ? 30 breaths per minute 1
Systolic blood pressure ; 90 mm Hg OR Diastolic blood pressure ? 60 mm Hg 1
Age ? 65 years 1
TOTAL POINTS CONFIRMED CASE
A Confirmed case is defined as a suspected case with laboratory confirmation of MERS-CoV infection.

Laboratory Testing for Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
CDC works closely with state and local public health departments, travel industry partners, and others to identify and test people who may be infected with MERS-CoV. CDC conducts several different laboratory tests to detect MERS-CoV infection.

In general, these lab tests fall into two categories the (1) Molecular tests, which look for evidence of active infection; and (2) Serology tests, which look for previous infection by detecting antibodies to MERS-CoV. Serology tests are for surveillance or investigational purposes and not for diagnostic purposes.

Molecular Tests
Molecular tests are used to diagnose active infection (presence of MERS-CoV) in people who are thought to be infected with MERS-CoV based on their clinical symptoms and having links to places where MERS has been reported.

The Real-time reverse-transcription polymerase chain reaction (rRT-PCR) assays are molecular tests that can be used to detect viral RNA in clinical samples. CDC’s current case definition for laboratory confirmation of MERS-CoV infection requires either a positive rRT-PCR result for at least two specific genomic targets, or a single positive target with sequencing of a second target.

Most state laboratories in the United States are approved to test for MERS-CoV by using an rRT-PCR assay developed by CDC. This test is done under authority of an Emergency Use Authorization because there are no FDA-cleared/approved tests available for this purpose in the United States.

The success of rRT-PCR testing depends on several factors, including the experience and expertise of laboratory personnel, laboratory environment (e.g., avoidance of contamination), and the type and condition of specimens being tested. For this rRT-PCR assay, CDC recommends collecting multiple specimens, including lower (bronchalveolar lavage, sputum and tracheal aspirates) and upper (e.g., nasopharyngeal and oropharyngeal swabs) respiratory samples, serum, and stool specimens.

CDC considers a patient under investigation to be negative for active MERS-CoV infection following one negative rRT-PCR test on the recommended specimens. Since a single negative result does not completely rule out MERS-CoV infection, in some circumstances additional specimens may be tested.CDC also considers a known MERS patient to be negative for active MERS-CoV infection following two consecutive negative rRT-PCR tests on all specimens.

Serology Tests
Serology testing is used to detect previous infection (antibodies to MERS-CoV) in people who may have been exposed to the virus. Antibodies are proteins produced by the body’s immune system to attack and kill viruses, bacteria, and other microbes during infection. The presence of antibodies to MERS-CoV indicates that a person had been previously infected with the virus and developed an immune response.

Evidence to date suggests there may be a broader range of MERS disease than was initially thought. For example, public health investigators have identified individuals who are PCR-positive but have no MERS symptoms; we do not know if MERS-CoV can be spread by these people. For this reason, public health scientists are working to learn more about how the virus is transmitted. One way to do this is through voluntary testing of blood samples from people who had close contact with people known to have MERS.

CDC has a two-phase approach for serology testing, using two screening tests and one confirmatory test to detect antibodies to MERS-CoV. The ELISA, or enzyme-linked immunosorbent assay, is a screening test used to detect the presence and concentration of specific antibodies that bind to a viral protein. CDC tests by ELISAS for antibodies against two different MERS-CoV proteins, the nucleocapsid (N) and spike (S).If a clinical sample is determined to be antibody-positive by either ELISA, CDC then uses the microneutralization test to confirm the positive result.

The microneutralization assay is a highly specific confirmatory test used to measure neutralizing antibodies, or antibodies that can neutralize virus. This method is considered a gold standard for detection of specific antibodies in serum samples. However, compared with the ELISA, the microneutralization assay is labor-intensive and time-consuming, requiring at least 5 days before results are available.

If a clinical sample is positive by either ELISA, and positive by microneutralization, the specimen is determined to be confirmed positive.

If a clinical sample is positive by both ELISAs,  and negative by microneutralization, the sample is determined to be indeterminate.

If a clinical sample is positive by only one ELISA, and negative by microneutralization, the sample is determined to be negative.

If a clinical sample is negative by both ELISAS, the sample is determined negative.

In the end, a final determination of a confirmed positive serology result requires a positive ELISA test and confirmation by microneutralization assay. MERS-CoV serology tests are for surveillance or investigational purposes and not for diagnostic purposes – they are tools developed in response to the MERS-CoV outbreak.

MERS Cov Transmission
According to the WHO (2017), there is no enthralling confirmation of airborne transmission of MERS Cov for instance stable and not critically ill patient, droplet and contact precautions are advised. For unstable and critically ill with signs and symptoms of respiratory syndrome, contact and airborne precautions are recommended due to anticipation of high aerosol generating procedures
Human transmission of MERS-CoV can occur by airborne inhalation from infected camel and patient. In health care settings, it may be associated with considerable sickness. Surveillance and infection control measures are critical to a global public health response (New England Journal of Medicine, 2015). As cited in the policy code number PP-BCH-IC-017-APP-E of the Buraidah Central Hospital as adopted from WHO guidelines, a duration and infectivity of MERS Cov infection in the present is still unknown.
Management of MERS Cov
According to the published guidelines of the WHO as adopted by the MOH of Saudi Arabia, the following are the recommended management and prevention of the MERS Cov. First, quarantine and isolating those suspected and confirmed case patients with negative pressure room. Second, strict infection control by utilizing the principles of chain of infection, breaking the mode of transmission and applying personal protective equipment (PPE) strictly in handling MERS Cov suspected and confirmed case. Third, enhancing the immunity by proper rest, drinking of adequate fluids and eating a highly nutritious foods. Fourth, supportive management to preserve vital organ functions. Fifth, administration of antiviral and antibiotic drugs. Lastly, hand washing is the most important and most basic technique in preventing and controlling infections and preventing transmission of the pathogens.

For those patients with suspected, probable, or confirmed case of MERS-Cov infection who are stable and not critically ill, standard, contact, and droplet precautions are recommended for management. For those patients who are critically ill presenting signs and symptoms of pneumonia with respiratory distress and hypoxemia, standard, contact, and airborne precautions are highly recommended due to the high likelihood of requiring aerosol-generating procedures as cited in the policy code numbers PP-BCH-IC-004(2)-APP-E or known as ” Guidelines of Handling Suspected/Confirmed MERS Cov patient in the triage area”. The standard, contact, and airborne precautions should be used all the times for critically ill patients when anticipating or performing aerosol- generating intervention which may be associated with an increased risk of transmission including both elective procedures such as bronchoscopy, sputum induction, elective intubation and extubation, and emergency procedures such as cardiopulmonary resuscitation (CPR), emergency intubation, open suctioning of airways, manual ventilation via umbo bagging through a mask before intubation as cited in the policy code number PP-BCH-017-APP-E or known as ” Isolation Precaution for MERS Cov infection”.

However, cited in the policy code number PP-BCH-IC-003-APP-E or known as “Management of Patients with Suspected/Confirmed MERS Cov”, standard precaution is a cornerstone for delivering safe health care practices and reducing the risk of further infection it includes hand hygiene, use of PPEs, respiratory hygiene and cough etiquette. To support this statement derived from the cited policy, a code policy number PP-BCH-IC-017-APP-E otherwise known as ” Isolation Precaution for MERS Cov infection” states that standard precaution should continue to be applied always in addition to isolation precaution and must be used during the entire duration of infectivity until 48 hours after resolution of symptoms. For the patient with difficulty of breathing, rescue drugs like administration bronchodilators can ease the symptoms and oxygen may be given during assessment in emergency area (Hitner ; Nagle, 2006).

Furthermore, the main focus of respiratory primary prevention is to keep vaccination records well updated and ensuring annual flu vaccine updated in the yearly basis and once every five years of anti-pneumonia vaccine (Lemone et al, 2007). However, after a series of clinical trials for MERS Cov vaccine at the present, there is no effective vaccine yet in preventing it (CDC, 2016).
This protocol and guidelines recommendation has been implemented to government hospitals in Buraidah, Al Qassim Saudi Arabia specifically the Buraidah Central Hospital and this guidelines became the policy and procedure of the said institution.

Buraidah Central Hospital implements policy to avoid the spread of the infection between patients and health care workers. The policy includes hand hygiene, proper observation of respiratory and coughs etiquette and use of isolation room or private single room. The area must be visibly isolated from other patient care areas. If transport is required, patient is compulsory to wear a face mask to contain secretions. On the other hand, medical workers who had contacts with confirmed MERS-CoV infection should use PPE to avoid direct contract with patient’s blood or body fluids, secretions and wear clean, non-sterile, long sleeved disposable gown; eye protection, a fit tested and seal checked N95 mask; do hand hygiene, before and after touching the patient and after removal of PPE; abstain from touching their eyes, nose or mouth with potentially contaminated gloved or ungloved hands; clean and disinfect patient- contact surfaces.
The patients suspected of MERS-CoV and medical workers including physician, nurses and paramedics who had protected exposure to a confirmed case of MERS-CoV infection are encouraged to adhere to the cited policies. Most importantly they are encouraged to conduct or attend a training to further enhance their knowledge and skills in taking care of hospitalized patients. Thus, infection control and prevention measures are very crucial to prevent the possible spread of MERS Cov in the hospital setting. It is very difficult to identify patients with MERS Cov in an initial stage of infection hence the primary symptoms of it are non- specific in nature. Finally, the WHO encourages all countries to endure their surveillance for any acute respiratory infections and to carefully review any significant health deviations. Therefore, all health care professionals including nurses should always apply conscientiously a standard precaution with consistently in all health care setting regardless of diagnosis.

MERS CoV INFECTION CONTROL PRACTICES
ADMINISTRATIVE INTERVENTION
Guidelines published in 2018 of the Ministry of Health Saudi Arabia, to prevent the transmission of respiratory infections in the healthcare settings, including MERS-CoV and influenza, the following infection control administrative measures should be incorporated into infection control practices and implemented:
A. Triaging patients with Acute Respiratory Illness (ARI):
That visual triage must be utilized for early identification of all patients with Acute Respiratory Infection (ARI) in the Emergency Department and dialysis units and should be placed at the entrance of all healthcare facility such as in emergency room entrance, and in the dialysis unit entrance or other selected areas and attended by a fully trained nurse or nurse assistant.
Patients who are attending hemodialysis care and all emergency room attendees (with the exception of those with immediate life-threatening conditions) must be sorted out at the entrance using predefined scoring as follows.
Appendix B
Visual Triage Checklist
Points
(adult) Points
(Children) Score
A. Clinical symptom/sign Fever 2 1 Cough (New or worsening) 2 1 Shortness of breath (New or worsening) 2 1 Nausea, Vomiting, diarrhea 1 _ throat and/or runny nose 1 _ Chronic renal failure, CAD/heart failure 1 _ B. Risk of exposure to MERS
Exposure to a confirmed MERS case in the last two weeks 3 3 Exposure to camel or products (Direct or indirect*) in the last two weeks 2 2 Visit to a healthcare facility that had MERS case in the last two weeks 1 1 TOTAL SCORE * Patient or household A SCORE ? 4, PLACE PATIENT IN AN ISOLATION ROOM AND INFORM MD FOR ASSESSMENT MERS COV TESTING SHOULD BE DONE ONLY ACCORDING TO CASE DEFINITION
An identified ARI patient should be asked to perform hand hygiene and offer to wear a surgical mask. They must be isolated and immediately evaluated in an area separate from other patients, ideally an isolation room.
A dedicate a waiting area for the ARI patients with spatial separation of at least 1.2 meter between each ARI patient, Minimum of 1.2 meters in General words, Hemodialysis units and Emergency units and Minimum of 2.4 meters in Critical care units.

Post visual alerts (in appropriate languages) at the entrance of healthcare facilities (e.g., emergency rooms and clinics). Messages in the visual alerts include the following: Covering mouth and nose with a tissue when coughing or sneezing, Dispose of the tissue in the nearest waste receptacle immediately after use, Perform hand hygiene (e.g., hand washing with non-antimicrobial soap and water, alcohol-based hand sanitizer, or antiseptic hand wash) after having contact with respiratory secretions and contaminated objects or materials and prevent overcrowding in clinical areas to reduce the risk of transmission between patients and to staff.
2. TRANMISSION PRECAUTION
MERS-CoV is believed to spread among humans mainly through contact and respiratory droplets. However, transmission through small particle droplet nuclei (aerosols) may occur. Environmental contamination during outbreaks in healthcare facilities can be extensive and might contribute to amplifying outbreaks if adequate disinfection procedures are not followed.
For patients with confirmed, or suspected MERS-CoV infection who are NOT CRITICALLY ILL, Standard, Contact, and Droplet precautions are recommended and for patients who are CRITICALLY ILL, Airborne, Contact, and Standard, precautions are recommended due to the high likelihood of requiring aerosol-generating procedures.

3. PATIENT PLACEMENT
Every healthcare facility should have the capacity to care for patients with transmissible infections including airborne infections. However, the availability of single rooms and negative pressure rooms are a challenge in most facilities. The infection control teams should take the lead in managing isolation rooms.
Patients with suspected or confirmed MERS-CoV infection who are not critically ill should be placed in single patient rooms in an area that is clearly segregated from other patient-care areas. The HEPA filter is a type of air filter being used for isolation and respiratory infectious areas for MERS Cov facility. HEPA filters constitute a mat of randomly arrange threads. This fibers or threads are composed of fiber glass with a diameter between 0.5 and 0.2 micrometers.
According to Ryback (2016), HEPA filters are purely intended to trap as much as smaller microbes and particles. These microbes will stick to the HEPA filter’s fiber by the following mechanism: First is interception, where a microbes of a following line of flow in the air come within one side of the fiber and any smallest particles will stick to it. Second, impaction, it will increase the effects of diminishing fiber separation and higher air velocity. Lastly, diffusion, wherein the effect causes gas collision into small particles.HEPA filter used to remove for at least 99.9% airborne particles and it has a minimal resistance to airflow. For this reason, HEPA filter is used for MERS cov patient to prevent airborne transmission. As cited in the policy code PP-BCH-IC-003-APP-E or known as “Management of Patients with Suspected or Confirmed MERS Cov”, a portable HEPA filter must be place in the patient’s bed side to minimize airborne transmission and also reduce the circulating air infections.
Critically ill patients with suspected or confirmed MERS-CoV infection should be placed in Airborne Infection Isolation Rooms (Negative Pressure Rooms), if available. When negative pressure rooms are not available, the patients should be placed in adequately ventilated private rooms with a portable HEPA filter and is placed according to the manufacturer recommendations. When single rooms are not available, suspected or confirmed MERS-CoV other patients should be placed with other patients of the same diagnosis (cohorting). If this is not possible, place patient beds at least 1.2 meters apart.
The negative room pressure is a quarantine procedure used in different hospitals and medical centers to avoid cross-contaminations. It includes a ventilation system that generates negative pressure to allow air to flow into the isolation room but not escape from the room. Negative pressure is produced by a ventilation system that uses to eliminate more exhaust air from the room than air is allowed in to the room. The negative pressure room should be sealed as possible, not allowing air in passing through cracks and gaps, such as those around windows, light fixtures and electrical outlets. Leakage from these sources can eliminate room negative pressure. For proper room placement for MERS Cov patient as cited in the policy code PP-BCH-IC-003-APP-E or known as “Management of Patients with Suspected or Confirmed MERS Cov”, placing a patient to Airborne Infection Isolation Room (AIIR) or negative pressure, but it is not available for some circumstances place patient into ventilated single room provided with HEPA filter being place in the patient’s bed side.
4. Guidelines for MERS-CoV Sample Collection, Packaging and Shipping
Appropriate collection, transportation and storage of sample for MERS CoV Testing according to the international standards play a major role in the accuracy of the results.
a. General Considerations: Sample collection:
Before collecting and handling specimens for Middle East Respiratory Syndrome Coronavirus (MERS-CoV), determine whether the person meets the current case definitions for Suspect, Probable or Confirmed cases.
Appropriate PPE should be worn by all laboratory staff handling these specimens.

Proper biosafety policies and procedures should be maintained when collecting specimens
Use approved collection methods and equipment when collecting specimens.
Handle, store, and ship specimens following appropriate protocols.

It is very important to include patient national, Iqama or passport number in the request form to help trace records for patients that do doctor shopping. For illegal residents please put a note in the request which demonstrates that no Iqama is available due to illegal residency.

2. Specimen type and priority:
Best upper respiratory tract (URT) specimen is nasopharyngeal (NP) swab or combined nasopharyngeal and oropharyngeal (NP/OP) swab specimens in.

To increase the likelihood of detecting infection, lower respiratory Tract (LRT) specimens (Sputum, tracheal aspirate (TA), Endotracheal secretions, or Broncheoalveolar lavage(BAL)) are preferred. Based on the current data, they are the most likely to provide positive results. However, this should not exclude another specimen from the URT to enhance viral detection in challenging samples.

Additional specimens such as blood and serum can be collected on presentation and in convalescence period.
. Respiratory specimens should be collected as soon as possible after symptoms start, ideally within 7 days and before antiviral medications are administered.
However, if more than a week has passed since onset of illness and the patient is still symptomatic, lower respiratory samples are the preferred samples.
Samples should not be stored in hospitals for more than 4 hours (at 4 – 8oC) before delivering by the courier. Delivery of MERS-CoV specimens allowed ONLY by the courier. Specimens pick up SHOULD be requested at the following number (800 6149999).
Label each specimen container with the unique MERS-CoV number; patient hospital ID number, specimen type, the date and the time of sample collection include patient national, Iqama or passport number.

Specimen Collection:
Use powder-less clean (Non-surgical) gloves when collecting specimens for MERS-CoV for PCR testing since, trace amount of powder in the sample could inhibit PCR testing producing false negative result.
All specimens should be regarded as potentially infectious, and HCWs, courier, laboratory personnel who collect, transport, or handle the clinical specimens should adhere rigorously to standard precautions to minimize the possibility of exposure to pathogens.
Ensure that HCWs who collect specimens should be properly trained on the technique and wear PPE appropriate for aerosol generating procedures.
Health caring facilities will assign and train personnel to perform nasopharyngeal swabbing.
Respiratory Specimens:
Lower respiratory tract
Broncheo-alveolar lavage (BAL), tracheal aspirate (TA) and/or pleural fluid should be collected whenever clinically appropriate: Collect 2-3 ml into a sterile, leak-proof, screw-cap sputum collection cup or sterile dry container. Refrigerate specimen at 2- 8°C up to 48 hours; if exceeding 48 hours, freeze at -70°C and ship on dry ice.
Sputum: (induced or spontaneous) ask the patient to rinse the mouth with water then expectorate deep cough sputum directly into a sterile, leak-proof, screw-cap sputum collection cup or sterile dry container. Refrigerate specimen at 2-8°C up to 48 hours; if exceeding 48 hours, freeze at -70°C and ship on dry ice.
Mucoid specimens such as BAL, TA and sputum can be placed in VTM after collection to liquefy the specimens and preserve the trapped virus.
Upper respiratory tract
Nasopharyngeal and Oropharyngeal swabs (NP/OP swabs) MUST BE TAKEN TOGETHER. Use only synthetic fiber swabs with plastic shafts. Do not use calcium alginate swabs or swabs with wooden shafts, as they may contain substances that inactivate some viruses and inhibit PCR testing. Place swabs immediately into sterile tubes containing 2-3 ml of viral transport media. NP/OP specimens MUST BE combined, placing both swabs in the same vial. Refrigerate specimen at 2-8°C up to 48 hours; if exceeding 48 hours, freeze at – 70°C and ship on dry ice.
Nasopharyngeal swabs: Insert a swab into the nostril parallel to the hard palate. Leave the swab in place for a few seconds to absorb secretions. Swab both nasopharyngeal areas.

Oropharyngeal swabs: Swab the posterior pharynx, avoiding the tongue.
Nasopharyngeal wash/aspirate or nasal aspirates: Collect 2-3 ml into a sterile, leak-proof, screw-cap sputum collection cup or sterile dry container (If highly mucoid, better collect in VTM container). Refrigerate specimen at 2-8°C up to 48 hours; if exceeding 48 hours, freeze at -70°C and ship on dry ice.

Blood Components
Serum (for Serological testing)
For serum antibody testing: Serum specimens should be collected during the acute stage of the disease, preferably during the first week after onset of illness, and again during convalescence ? 3 weeks after the acute sample was collected. However, a single serum sample collected 14 or more days after symptom onset may be beneficial. Serological testing is for research/surveillance purposes and not yet for diagnostic purposes. Currently it is NOT available at the MOH regional laboratories but will be implemented soon.

Serum / Plasma (for rRT-PCR testing) (Not recommended for routine testing):
For rRT-PCR testing (i.e., detection of the virus and not antibodies), a single serum or plasma specimen collected optimally during the first week after symptom onset, preferably within 3-4 days may be also beneficial but is not recommended for routine testing.

Children and adults. Collect 1 tube (5-10 ml) of whole blood in a serum separator tube. Allow the blood to clot, centrifuge briefly, and separate sera into sterile tube container. The minimum amount of serum required for testing is 500 µl. Refrigerate the specimen at 2-8°C and ship on ice- pack; freezing and shipment on dry ice is permissible..
Infants. A minimum of 1 ml of whole blood is needed for testing of pediatric patients. If only 1 ml can be obtained, use a serum separator tube to achieve a minimum of 400 µl serum sample.
EDTA blood (plasma): Collect 1 tube (10 ml) of EDTA (purple-top) blood. Avoid using heparinized (green-top) blood as this will interfere with the test and inhibit PCR. Refrigerate specimen at 2-8°C and ship on ice pack; do not freeze.

5. PATIENT TRANSPORT
Avoid the movement and transport of patients out of the isolation room or area unless medically necessary. The use of designated portable X-ray, ultrasound, echocardiogram and other important diagnostic machines is recommended when possible. If transport is unavoidable, ape per the MOH MERS CoV Guidelines for Healthcare professionals; Patients should wear a surgical mask during movement to contain secretions. Use routes of transport that minimize exposures of staff, other patients, and visitors, notify the receiving area of the patient’s diagnosis and necessary precautions as soon as possible before the patient’s arrival is of general considerations and lastly, ensure that healthcare workers (HCWs) who are transporting patients wear appropriate PPE and perform hand hygiene is necessary. With these measures it can be ascertained that the spread of microorganism can be prevented during the transportation of the patient.
5. PERSONAL PROTECTIVE EQUIPMENT (PPE) FOR HEALTHCARE WORKERS (HCWS)
According to Ruiz (2015), PPE is a special medical and protective equipment designed to protect a person from infection. It reduces the chance of being exposed to secretions, touching, inhaling directly to the main source of infection. It also prevents medical health workers from cross contamination. In management of MERS cov, wearing important PPEs include the following: gloves, eye protection gloves, gown and N95 respirator as cited in the policy number PP-BCH-IC-003-APP-E.

The CDC imposed the proper pattern or sequence of removing PPE after patient contact are as follows: remove the gloves first, then eye protection goggles, and lastly the mask or N95 respirator. Afterwards, perform proper hand washing. The following PPE should be worn by HCWs upon entry into patient rooms or care areas in the respected order:
Gowns (clean, non-sterile, long-sleeved disposable gown).
Surgical mask (or N95 when airborne precautions are applied)
Eye protection (goggles or face shield).
Gloves.
For patients on airborne precautions, any person entering the patient’s room should wear a fit-tested N95 mask instead of a surgical mask. The protection offered by a disposable particulate respirator (e.g.N95) depends on its tight fitting to the user’s face. Standardized respirator fit testing helps identify the correct respirator size and shape. Healthcare workers are required to have a respirator fit test at least once every 2 years and if weight fluctuates or facial/dental alterations occur.A fit test only qualifies the specific brand/make/model of a respirator with which an acceptable fit testing result was achieved and therefore users should only wear the specific brand, model, and size he or she wore during a successful fit test. Each time a respirator is donned, a seal check must be performed using the procedures recommended by the manufacturer of the respirator
For those who failed the fit testing of N95 masks (e.g. those with beards), an alternative respirator, such as a powered air-purifying respirator (PAPR), should be used. Upon exit from the patient room or care area, PPEs should be removed and discarded. Except for N95 masks, remove PPE at the doorway or in the anteroom. Remove N95 mask after leaving the patient room and closing the door. Remove PPEs in the following sequence: 1. Gloves, 2. Goggles or face shield, 3. Gown and 4. Mask or respirator.
6. ENVIRONMENTAL CLEANING AND DISINFECTION
The environment in healthcare facilities used for MERS-CoV patients is widely contaminated. Systematic environmental disinfection and cleaning are critical. The Infection Control team must designate specific, well-trained housekeeping personnel not only in cleaning but more importantly disinfecting of MERS-CoV patient rooms/units. Housekeeping personnel should wear PPE as described above. Housekeeping staff should be trained well about MERS-CoV, the proper procedures for the use of PPE and its removal, and emphasize thee importance of hand hygiene. Always keeping cleaning materials and equipment outside the patient room (specifically at the anteroom or storage area). The use of MOH-approved disinfectants. Always follow manufacturer’s recommendations for use-dilution, duration of contact, and care in handling. This will make sure that acquiring the disease will likely happen.

After an aerosol-generating procedure like intubation, make sure to clean and disinfect all surfaces around the patient. Be sure to clean and disinfect immediately after each procedure. For blood and body fluids spills, recommendations for spill management outlined in the GCC Infection Prevention and Control Manual, 3rd edition must be followed.
7. MEDICAL WASTE DISPOSAL
Proper waste disposal is a major factor to protect and preserve the environment and to prevent cross-contamination to other patients. Each health care worker must be knowledgeable about the proper segregation of waste according to the nature of it. The policy code CSH-IC-12-016 also known as “Central Security Hospital Infection Control Policy for Waste Disposal” and policy code CSH-IC-12-85 also known as “Central Security Hospital Policy for Safe Handling of Hazardous Waste” state that all infectious waste including tissue soaked with body discharge, blood, gloves, face mask or N95 used or anything that is potentially infectious and causing contamination must be in the “yellow bin”. On the other hand, all non-potentially for contamination for instance, facial tissue, used paper must be in the “blue bin”.For this reason, all possible contaminations of the patient’s environment will be reduced or prevented if the above discussion will be strictly implemented in caring for MERS CoV patient.

8. INFECTION PREVENTION AND CONTROL PRECAUTIONS FOR AEROSOL-GENERATING PROCEDURES
An aerosol-generating procedure (AGP) is defined as any medical procedure that can induce the production of aerosols of various sizes, including small (; 5 microns) particles. AGPs includes, bronchoscopy, sputum induction, intubation and extubation, cardiopulmonary resuscitation, open suctioning of airways, Ambu bagging, nebulization therapy, high frequency oscillation ventilation and Bilevel Positive Airway Pressure ventilation- BiPAP (BiPAP is not recommended in MERS-CoV infected patients because of the high risk of generating infectious aerosols and lack of evidence for efficacy).
As per the 2018 MOH MERS CoV guidelines additional precautions should be observed when performing aerosol-generating procedures, which may be associated with an increased risk of infection transmission: The procedure must be done in a negative pressure room, limit the number of persons present in the room to the absolute minimum required for the patient’s care and support, wearing the proper PPE is recommended and the performance hand hygiene before and after contact with the patient and his or her surroundings and after PPE removal must always be practices
MANAGEMENT OF HEALTH CARE WORKERS EXPOSED TO MERS CoV
1. Healthcare workers exposed to a MERS-CoV case
As per the guidelines for the MERS CoV management of 2018, Healthcare facilities should identify and trace all healthcare workers who had protected (proper use of PPE) or unprotected (without wearing PPE or PPE used improperly) exposure to patients with suspected, or confirmed MERS-CoV infection. The decision to permit a healthcare worker to resume his/her duress after an exposure to MERS-CoV should be individualized. Infection control team will be ultimately responsible for taking that decision.
For asymptomatic healthcare workers WITH protected exposure OR unprotected low-risk exposure (more than 1.5 meters of the patient) Testing healthcare workers for MERS-CoV is not recommended and can continue their duties. However, they shall be assessed daily for 14 days post exposure for the development of symptoms and are advised to delay travel until cleared by infection control team.

Healthcare workers who had unprotected high-risk exposure (within 1.5 meters of the patient) or have suggestive symptoms regardless of exposure type are advised to stop performing their duties immediately andTesting (Nasopharyngeal swabs) for MERS-CoV is required (preferably 24hr or more after the exposure). They shall not resume their duties until cleared by infection control team and cannot travel until cleared.
Healthcare workers who test positive for MERS-CoV (regardless of the exposure type); healthcare workers who develop MERS-CoV suggestive symptoms (regardless of the exposure type) and healthcare workers who had unprotected high-risk exposure are considered CLEAR if they are asymptomatic for at least 48 hrs, the observation period is over (14 days post exposure) and had at least one negative RT-PCR for MERS-CoV. This is strictly implemented in all hospitals in the kingdom.
2. Patients exposed to a MERS-CoV case
Patients can be exposed to MERS-CoV patients prior to diagnosis or due to the failure of implementing recommended isolation precautions. The following are general guidelines but management will depend on the infection control team risk assessment.
Patients sharing the same room (any setting e.g. ward with shared beds, open ICU, open emergency unit…etc) with a confirmed case of MERS-CoV for at least 30 minutes. Testing (Nasopharyngeal swabs or deep respiratory sample if intubated) for MERS-CoV is required (preferably 24hr or more after the exposure). Patients should be followed daily for symptoms for 14 days after exposure. If negative on initial testing exposed patients should be retested with RT-PCR if they develop symptoms suggestive of MERS-CoV within the follow-up period. Patients discharged during the follow-up period must be reported to the public health department to continue monitoring for symptoms.

3. PATIENT TRANSPORTATION AND PREHOSPITAL EMERGENCY MEDICAL
SERVICES
The MERS CoV Guidelines for Healthcare Workers for 2018 also recommends that Patients who may have MERS-CoV infection may be safely transported in an emergency vehicle with the proper precautions. Training EMS staff, including drivers, on basic infection control skills with emphasis on respiratory protection and use of PPE’s. Like other healthcare workers, respirator fit testing is also required. The use a vehicle equipped with a HEPA filter incorporated into the ventilation unit especially for transporting patients on mechanical ventilation. If this unit is not available, set the regular vehicle’s ventilation system to the non-circulating mode.
Coordination with the receiving facility to receive the patient at the ambulance door is also mandatory to limit the need for personnel to enter the emergency department. Lastly Clean and disinfect the vehicle and reusable patient-care equipment using a MOH-approved hospital disinfectant and the personnel performing the cleaning should wear a disposable gown and gloves (a respirator is generally not needed). And more important ensure appropriate follow-up and care of EMS personnel who transport MERS-CoV patients as recommended for HCWs. This measure helps in the spread of the infection.
4. ISOLATION PRECAUTIONS FOR MERS-COV INFECTION
According to Herwaldt and M. D. Decker.Thorofare (1998) Isolation practices are designed to minimize the transmission of infection in the hospital, using the current understanding of the way infections can transmit. Isolation should be done in a user-friendly, well-accepted, inexpensive way that interferes as little as possible with patient care, minimizes patient discomfort, and avoids unnecessary use.

The infectivity period for MERS-CoV may last as long as the virus is being shed. Out of protocol testing in confirmed MERS-CoV patients is discouraged. For all patients, re-testing can be done at the end of the first week of confirmation. In order to discontinue isolation precautions, two negative lower respiratory samples 24 hours apart are required for ventilated patients and one negative respiratory sample in other patients including home isolated individuals.
Prevention
At present, there is no vaccine available to prevent MERS-CoV infection. The United State. National Institutes of Health is on ongoing study for the likelihood of developing such. CDC continuously advises that people help keep themselves from respiratory illnesses by taking preventive measures such as :
Always wash your hands with soap and water for 40 to 60 seconds, and teach children to do perform hand washing. The use of alcohol-based hand sanitizer is also encouraged if soap and water are unavailable.

Always practice coughing and sneezing etiquettes by covering nose and mouth with a tissue when you coughing or sneezing, then throw the tissue in yellow bins or trash.

Keep away from touching eyes, nose and mouth with dirty hands.

Avoid personal contact, sharing utensils, with sick people.

Make sure that frequently touched surfaces and objects, such as doorknobs are cleaned and disinfected.

Treatment
As per the CDC, up to date, no specific antiviral treatment recommended for MERS-CoV infection. Persons infected with MERS usually receive medical care to help relieve symptoms. In patients with severe cases, treatment includes care to support vital organ functions.

Form the Infection and Chemotherapy Journal (IC journal) (2015); also states that there are no antiviral drugs with a clear proof that clinical effect in the treatment of MERS-CoV infection. Antiviral studies reported have commonly been laboratory studies, and so the concrete clinical data for the use of antivirals are inadequate. Some data with the use of animal experiments and a small amount of clinical data for type 1 interferon, ribavirin, and lopinavir/ritonavir. Type 1 interferons consist of interferon-?2a, -?2b, and -?1a. In this animal experiment in rhesus macaques, a combination regimen of interferon-?2b and ribavirin showed clinical improvements with reduced severity. There are also clinical case reports of patients who improved after combining the therapy with interferon-?2b and ribavirin. However, this still on discussion due to the insufficient clinical studies on combination therapy using type 1 interferon and ribavirin. 
In data on 108 patients during the South Korean epidemic, more than 50 years and difficulty of breathing were significant risk factors, while on analysis, underlying diseases and bilateral pneumonia were also linked with death (unpublished data). In a presentation study by Omrani et al., antiviral treatment considerably improved 14-day survival in patients with severe MERS that requires mechanical ventilation. Therefore, to patients with risk factors for death or development to severe MERS, active antiviral treatment is suggested. Mycophenolic acid, chloroquine, chlorpromazine, and loperamide are some drugs to have an antiviral effect against MERS-CoV in laboratory tests.
Complications
From the CDC, many people with MERS, more severe complications arise, such as pneumonia and kidney failure. On an average of 3 to 4 out of every 10 people reported with MERS have died. The majority of the people who died had an underlying medical condition. Some of the infected people had mild symptoms (such as flu-like symptoms) or asymptomatic at all; they recovered.

Based on what researchers know so far, people with pre-existing medical conditions or co morbidities may be more likely to become infected with MERS-CoV, or may end up to a severe case. Pre-existing conditions from reported cases for which we data were available includes diabetes; cancer; and chronic lung, heart, and kidney disease. Persons with weak immune systems are of higher risk for getting MERS.

A study from The Korean Academy of Medical Sciences (2015) some cases of Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) infection with renal function impairment after the first MERS-CoV patient died of progressive respiratory and renal failure. Thus, MERS-CoV may cause kidney tropism. However, reports about the natural courses of MERS-CoV infection in terms of renal complications are limited. Half of the patients in the study showed proteinuria, and more than one-fourth of the patients developed Acute Kidney Injury (AKI). The incidence of AKI was uncommon, and AKI can be affected by multiple factors including the virus itself, associated systemic inflammation, and hypotension. Detailed evaluation and management of kidney damage like quantitative assessment of proteinuria and frequent monitoring of eGFR is seriously needed.

From the Journal of Neurology (July 2017) a study was conducted and evaluated to four patients with confirmed laboratory for MERS coronavirus (CoV) infections who presented with neurological complications during MERS treatment. These 4 patients were from a group of 23 patients who were treated at a designated hospital during the outbreak in the Republic of Korea last 2015. The clinical presentations, laboratory findings, and prognoses are described; four of the 23 admitted MERS patients with reports of neurological symptoms during or after MERS-CoV management and treatment. The possible diagnoses in these four cases included Bickerstaff’s encephalitis overlapping with Guillain-Barré syndrome, intensive-care-unit-acquired weakness, and or other toxic or infectious neuropathies. Neurological complications did not appear along with with respiratory symptoms, this was delayed by 2–3 weeks. The neuromuscular complications are not rare during MERS management and treatment, and they may have been under diagnosed. Understanding the neurological signs and symptoms is important in an infectious disease such as MERS, because these manifestations are not commonly evaluated thoroughly during treatment, and they may interfere with the prognosis or this can require treatment adjustment.
From Open Forum Infectious Diseases, (October 2017) reports that there are few data about long-term respiratory complications following Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection. A total of 73 patients with MERS-CoV infection during the 2015 MERS outbreak in South Korea participated in this prospective multicenter study. Test such as Pulmonary function tests and 6-minute walking were performed a year after infection. Radiologic result was defined as fibrosis or atelectasis on chest computer tomography and severe pneumonia was defined as that requiring oxygen therapy. Multivariate linear regression tests were used to measure and evaluate the effect of infection severity on their respiratory functions. The patients with more severe pneumonia by MERS-CoV had more impaired respiratory function after a year of follow-up, which was compatible with radiologic follow-up.