Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

From Transmission to Novel Treatments

Author: Miguel Nonaka

Abstract:

The Middle East respiratory syndrome coronavirus is one of the recently discovered respiratory illnesses, in human beings. This disease was first identified in Saudi Arabia, in 2012⁸. It has since spread to several other countries, such the Republic of Korea, causing a widespread panic. However, with the rise of modern treatments and preventions, new novel techniques will be developed and will lead to fewer outbreaks in the future.

MERS-CoV

MERS-CoV, also called the Middle East Respiratory Syndrome Coronavirus, is a novel coronavirus that originated from Saudi Arabia in 2012⁸. It is known as a coronavirus, because of its crown-like projections on its surface. MERS-CoV comes from a large family of coronaviruses, six of which are known to infect humans and can cause disease ranging from the common cold to SARS (Severe Acute Respiratory Syndrome)¹⁰. Once infected with MERS-CoV, the individual will display signs of fever, cough, shortness of breath, pneumonia, gastrointestinal symptoms, and including diarrhea. However, the fatality rate is as high as 40% to 60% in areas found near Saudi-Arabia and its neighboring countries⁹. There have also been many reports of outbreaks outside the Arabian Peninsula, such in the United-States since travelers or healthcare workers were traveling in infected areas of the country. However, the largest known outbreak to occur outside this peninsula happened in the Republic of Korea in 2015 where 36 people died from this disease¹⁴.

Introduction:

Outbreaks of MERS-CoV were first documented from Jordan in 2012. Since then, several outbreaks, in Jordan, the Arabian Peninsula and abroad, including the Republic of Korea, have caused organizations and government, for instance, the World Health Organization, to implant preventions methods to contain the widespread contamination of this disease. Nevertheless, even though four years passed since the discovery of this disease, the path to treating this illness has remained elusive to scientists. The only research treatments available for this disease, such the Interferon-Alfa, and Ribavirin⁵, were tested in animals, for instance, monkeys, have all given the public some understanding of MERS-CoV. Moreover, human experimentation with these novel treatments has still not gotten under way or aren’t yet finished.¹²

Transmission:

Just like many other types of coronary viruses, MERS-CoV is said to be transmitted from a person’s respiratory secretions, such as when one is coughing. However, through background research on known infected victims, led by the World Health Organization (WHO)¹⁵, it was concluded that the Middle East respiratory syndrome coronavirus (MERS-CoV) was transmitted through close contacts with other people in the infected environment, such as in hospitals or any others healthcare setting. Furthermore, it has been indicated that the dromedary camels, who are the animal hosts of MERS-CoV, are part of the direct or indirect transmission of the virus to human beings. Nevertheless, the exact way the virus spread remains unknown and not well understood by scientists.⁷

Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) Test:

 RT-PCR, also called Reverse Transcriptase-Polymerase Chain Reaction test, is a novel detection technique that has been widely used in the field, because of its high efficiency and sensibility to detect the presence of viral pathogens (ex: HIV) and pathogenic bacteria (ex: E. coli). It works by combining two different methods; the synthesis of cDNA (complementary DNA) from RNA by reverse transcription (RT) and the amplification of a specific cDNA by the polymerase chain reaction (PCR)¹. This technique has been an essential tool for identifying MERS-CoV in patients that have had the signs and symptoms of the disease and appropriate risks factors, such as working with infected individuals or in a contaminated environment, during the outbreak of 2013. Once they have detected the infected individuals, researchers must get the lung secretions and blood of these people and send it to a qualified MERS-CoV laboratory for analyzing. Although this technique is fast sensitive and safe, contamination can still occur in laboratories, due to the method’s high sensitivity and it can also cause the data to be inconsistent.¹

ELISA (Enzyme-Linked Immunosorbent Assay):                                                             

Another widely used detection technique is ELISA, also called Enzyme-Linked Immunosorbent Assay, that has been used, because of its high accuracy and sensibility, when compared to other immunoassay methods. However, it is used more widely in a laboratory setting rather than patient care. It is a screening test used to detect the presence and concentration of antibodies to bind to a viral protein, such as that of MERS-CoV. Within a few hours, ELISA determines if the sample is antibody-positive. If it is antibody-positive, then organizations, such the CDC (Center for Disease Control), will then use IFA (Immunofluorescence Assay) to confirm the results they got by ELISA⁶. Although this technique is highly accurate, safe and sensible, they are not cheap, very specific to an antigen (won’t recognized any other antigen), and plasma constituents can affect this test.³

Interferon-Alfa (IFN-?) and Ribavirin:

This novel treatment is the most recent known treatment to have been successfully seen as a primary and preventive treatment for the MERS-CoV infections. Research on this treatment, led by Heinz Feldmann, was shown through clinical trials on two different group of rhesus macaques, a type of monkey; the untreated infected and the treated infected. It was demonstrated through collected data that the ones that received interferon-alfa (IFN-?) and ribavirin did not acquire breathing abnormalities, showed low levels of serum and lung proinflammatory conditions. Also, they also showed no or very mild radiographic indication of pneumonia. Following the pattern in the data, it was proven that the treatment had improved the outcome of reducing the virus replication of MERS-CoV in the rhesus macaque⁵. Moreover, a human clinical trial of this treatment is underway in a patient and prophylaxis with his wife¹³. This combination of treatment and prevention is the first one of its kind.

GLS-5300

This novel treatment (vaccine) is one of the first to be tested in human beings. The study’s recently started in January of 2016 and will end May of 2017. Its purpose is to see if the vaccine is safe for people. This vaccine will be tested on civilians and military personnel alike, in a one year period by WRAIR (Walter Reed Army Institute of Research)¹². GLS-5300 is a DNA plasmid vaccine, whose use is to stimulate humoral and cellular immune responses to protein antigens efficiently (https://clinicaltrials.gov/ct2/show/results/NCT02670187). 

Future Outlook:

ELISA and RT-PCR tests will continue to play a significant role in the development of diagnostic tests of MERS-CoV. Even though each of them has their weaknesses and strengths, they are the best tools out there for the detection of this kind of virus. Advantages of these devices range from high sensibility and accuracy, while disadvantages range from high sensitivity, costly, very specific to an antigen and inconsistencies in data. Therefore, there need to be newer techniques that will not be as highly sensible and expensive as the ones that are now in use. Furthermore, the only success in treatment (vaccine) development was the use of interferon-alfa (IFN-?) and ribavirin in rhesus macaques⁵, which resulted in reducing the replication of MERS-CoV. Moreover, there also been new clinical trials underway on genetically modified cattle, who have been designed to produce a significant amount of human polyclonal antibodies, when vaccinated with an antigen, such as MERS-CoV. Even though some human clinical trials are going on for a new vaccine called CLS-5300¹², in the treatment of MERS-CoV, there is not much information known about it. However, since there is no available vaccine, only supportive care, such as medical attention to help relieve symptoms, exists for human patients. Therefore, there needs to be more vaccine research and development, in order, to make a safe vaccine specifically for people.

Work Cited:

1. Definition of RT-PCR – MedicineNet. (n.d.). Retrieved from http://www.medicinenet.com/script/main/art.asp?articlekey=22766
2. Sandra Gonzalez Gompf, F. (2016). MERS (Middle East Respiratory Syndrome) Symptoms, Treatment, Causes – How do health-care professionals diagnose an MERS-CoV infection? – MedicineNet. Retrieved 26 December 2016, from http://www.medicinenet.com/mers_middle_east_respiratory_syndrome/page5.htm
3. MERS-CoV | Laboratory Testing for MERS-CoV | CDC. (2016). gov. Retrieved 26 December 2016, from https://www.cdc.gov/coronavirus/mers/lab/lab-testing.html
4. Future treatment strategies for novel Middle East respiratory syndrome coronavirus infection, Future Medicinal Chemistry, Future Science. (2016). Future-science.com. Retrieved 26 December 2016, from http://www.future-science.com/doi/full/10.4155/fmc.13.183
5. Falzarano, D., de Wit, E., Rasmussen, A., Feldmann, F., Okumura, A., & Scott, D. et al. (2016). Treatment with interferon-?2b and ribavirin improves outcome in MERS-CoV–infected rhesus macaques. Retrieved 26 December 2016, from http://www.nature.com/nm/journal/v19/n10/abs/nm.3362.html#contrib-auth
6. ELISA Advantages. (2016). Elisa-antibody.com. Retrieved 26 December 2016, from http://www.elisa-antibody.com/ELISA-Introduction/elisa-advantages
7. MERS-CoV | Prevention and Treatment of MERS | Coronavirus | CDC. (2016). gov. Retrieved 26 December 2016, from https://www.cdc.gov/coronavirus/mers/about/prevention.html
8. MERS-CoV | Home | Middle East Respiratory Syndrome | Coronavirus | CDC. (2016). gov. Retrieved 26 December 2016, from https://www.cdc.gov/coronavirus/mers/
9. WHO | Middle East respiratory syndrome coronavirus (MERS-CoV) summary and literature update – as of 13 August 2013, (2016). int. Retrieved 26 December 2016, from http://www.who.int/csr/disease/coronavirus_infections/update_20130813/en/

• Coronavirus | Home | CDC. (2016). gov. Retrieved 26 December 2016, from https://www.cdc.gov/coronavirus/

11. Coronavirus Infections: MedlinePlus. (2016). gov. Retrieved 26 December 2016, from https://medlineplus.gov/coronavirusinfections.html
12. First-in-Human Phase 1 Clinical Trial of MERS Vaccine Begins. (2016). MHRP | Military HIV Research Program. Retrieved 27 December 2016, from http://www.hivresearch.org/news/first-human-phase-1-clinical-trial-mers-vaccine-begins
13. Khalid M, e. (2016). Ribavirin and interferon-?2b as primary and preventive treatment for Middle East respiratory syndrome coronavirus: a preliminary report of two cases. – PubMed – NCBI. nlm.nih.gov. Retrieved 27 December 2016, from https://www.ncbi.nlm.nih.gov/pubmed/24831606
14. Middle East respiratory syndrome coronavirus (MERS-CoV) – Republic of Korea. (2016). World Health Organization. Retrieved 27 December 2016, from http://www.who.int/csr/don/25-october-2015-mers-korea/en/
15. MERS-CoV | Transmission of MERS | Coronavirus | CDC. (2016). gov. Retrieved 27 December 2016, from https://www.cdc.gov/coronavirus/mers/about/transmission.html