The Agents

Corona Virus (320x240)
credit: CDC - Dr. Fred MurphyImage of a coronavirus showing the crown-like (corona) appearance.

SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) are infectious respiratory diseases that are caused by members of a class of viruses known as coronaviruses. The name coronavirus comes from appearance of the virus under the microscope – it has a spiky or crown-like (corona) appearance. Both diseases can be fatal to humans.

SARS is caused by SARS-associated coronavirus (SARS-CoV), while MERS is caused by Middle East respiratory syndrome coronavirus (MERS-CoV).

SARS-CoV emerged over a decade ago in China and spread rapidly to other countries, but was quickly contained and no new cases have been reported since the initial outbreak. MERS-CoV emerged in 2012 in Saudi Arabia and continues to circulate throughout the Middle East. It has been carried by travelers to other parts of the world including the United States, Europe, Africa, and Asia, and has recently caused the largest outbreak, outside the Middle East, in South Korea.  

SARS

SARS was first recognized in Guangdong Province, China in November of 2002. It then spread extremely rapidly to other regions within China, Hong Kong, Vietnam, Singapore, Taiwan, and Toronto, Canada in the early half of 2003.

SARS is characterized by severe, pneumonia-like symptoms which can be fatal. SARS-CoV was transmitted from person to person mainly through respiratory droplets produced when a person sneezes or coughs and through direct contact with a surface contaminated with infected respiratory droplets.

Altogether, more than 8,000 people were documented to have been infected with SARS-CoV and over 800 died.

The global scientific response to SARS was unprecedented. Within weeks after the respiratory disease was first reported, the agent that causes the disease was identified, diagnostic tests were developed, and the entire genome of the virus was sequenced. 

Epidemiologists gathered evidence that the first people infected had had contact with wild game in the markets of Guangdong Province in China. It is likely that these individuals were infected through direct contact with infected animals, particularly palm civets, which harbored very closely related coronaviruses. The virus then is thought to have mutated to adapt to its human host, and consequently human-to-human transmission became more efficient, setting off the SARS epidemic.

Fortunately, the SARS outbreak was short-lived, and public health containment procedures and coordinated responses proved effective in preventing further spread of the disease.

Until recently, SARS-CoV was the only member of the coronavirus family known to cause death or severe respiratory disease in humans. The other previously known viruses in this group cause mild upper-respiratory infections in humans and are associated with respiratory, gastrointestinal, and neurologic diseases in animals.

One reason that SARS-CoV might have been more lethal than other coronaviruses is that it appears to interfere with an enzyme system in humans that is critical for regulating body fluid balance. Therefore, the virus could disrupt normal functioning of the lungs by blocking this enzyme system and allowing fluid to leak into the air sacs of the lungs, resulting in severe respiratory illness.

MERS

MERS
credit: NIAIDTransmission electron micrograph of Middle East Respiratory Syndrome Coronavirus

A new member of the coronavirus family, MERS-CoV, emerged in the fall of 2012 in the Arabian Peninsula. Although MERS-CoV is distinct from SARS-CoV, the disease caused by MERS is similar to SARS, in that it is characterized by a severe respiratory illness that can be fatal in humans. The mortality rate is estimated to be between 30 and 40 percent. People with certain conditions, such as diabetes, renal failure, chronic lung disease, and immunocompromised persons, as well as the elderly, are considered to be at high risk of severe disease from MERS-CoV infection.

Like SARS, MERS is thought to have originated in bats, but MERS-CoV has been passed to camels, which serve as the primary source of human MERS-CoV infection. Precautions are recommended for persons who have contact with camels or their products, especially those at high risk of contracting severe disease. Once a person becomes infected with MERS-CoV, it can be spread to close contacts such as family members and healthcare workers.

The first and vast majority of cases of MERS have occurred in Saudi Arabia, although infections have been reported in other countries in the region including Iran, Jordan, Kuwait, Lebanon, Oman, Qatar, United Arab Emirates, and Yemen. Travel-associated cases have been reported in countries in Europe, Asia, Africa, and North America. Two unrelated MERS-CoV infections were confirmed in the United States in May of 2014 in healthcare providers who had worked in Saudi Arabia.

In May of 2015, the first reported case of transmission of MERS-CoV outside the Middle East was reported. A man who had traveled through several countries in the Middle East returned to South Korea and transmitted the virus to an unusually large number of people through contact with healthcare workers, other patients, or family members in several hospitals. These individuals further passed the virus to other close contacts. One of the infected individuals traveled to China. By early July, 185 cases and 36 deaths were in reported in South Korea, but there have been no new infections documented since that time. 

The outbreak in South Korea is the largest outside of the Middle East, as the spread of the virus in South Korea proceeded more rapidly than it had previously in other countries. A more rapid spread can cause concern that a virus has mutated to become more transmissible, but genetic sequencing of the MERS-CoV that circulated in South Korea indicated that it had not mutated. Rather, the delayed recognition of MERS-CoV in the original patient coupled with poor infection control appears to have allowed it to spread quickly.

Altogether, approximately 1370 cases of MERS-CoV infection have been documented globally, including at least 480 deaths. More than 1000 of these cases occurred in Saudi Arabia. The country with the next highest case number is South Korea, followed by the United Arab Emirates.

The Problem

MERS (320x240)
credit: NIAIDColorized scanning electron micrograph of Middle Eastern Respiratory Syndrome virus particles (yellow) attached to the surface of an infected cell (blue)

Although there are currently no known human cases of SARS, it is still possible that another outbreak of SARS could occur. It is probable that SARS-CoV still lurks in an animal host in the wild, and human contact with this animal(s) could again spark a SARS epidemic. Scientists have reported that the Chinese horseshoe bat is likely to be the animal that is the hiding place of the SARS virus. Genetic analysis of the virus in bats showed that it is closely related to the human SARS virus, although it is still not clear how the SARS virus was transmitted from bats to humans. 

Despite the large amount of knowledge that has been gained about SARS-CoV following the outbreak, there are still no vaccines or antivirals approved for preventing or treating SARS-CoV infections.

Currently, the much greater concern is the potential for MERS-CoV to continue to spread. MERS is a severe disease in most infected people. It has been documented in more than 25 countries, both within and near the Arabian Peninsula and in many other countries, including the United States and countries in Europe, Africa, and Asia due to travel-associated cases.

MERS remains centered in Saudi Arabia. A sharp uptick in cases occurred in the spring of 2014, tripling the number of cases and deaths since the end of 2013. Some of this increase has been attributed to insufficient infection control measures in Saudi hospitals. The rate of new infections has since dropped. MERS circulates in camels which are common in the Middle East, and MERS-CoV seems to jump more readily from infected animals to humans than SARS-CoV does. A worry is that the millions of Islamic pilgrims who travel to Saudi Arabic during the annual hajj could carry MERS back to their country of origin, resulting in a MERS epidemic or even pandemic.

In late May of 2015, MERS emerged in South Korea as a result of a single traveler arriving from the Middle East. His infection was not initially recognized as MERS, and the patient had multiple contacts in different health care settings before he and his contacts were isolated. This allowed the virus to spread quickly through hospital settings. In a little over a month after the virus arrived in South Korea, there were over 180 infections, including more than 30 deaths, making this the largest outbreak outside the Arabian Peninsula. The outbreak appears to have been contained by July. Nevertheless, MERS exacted an economic and political toll within South Korea, as schools and businesses were shuttered, and people were fearful of visiting public places.

The emergence of MERS-CoV in South Korea highlights the ease in which diseases can spread around the world and the difficulty in identifying "new" diseases when they appear in a location where they have not been seen before. It also illustrates the importance of remaining vigilant in order to quickly identify the agent of infection and enact immediate infection control measures, such as restricting contact with infected individuals.

At this time, there is no vaccine or specific treatment for MERS.

The Research

SARS Virus (320x240)
credit: CDC - James GathanyResearcher processing SARS specimens in a biocontainment facility

Following the SARS outbreak of 2003, investigators in the Department of Molecular Virology and Microbiology at Baylor College of Medicine were awarded funds for development of a SARS-CoV research program (as an expansion of the existing Virus Respiratory Pathogens Research Unit in a contract arrangement between BCM and the National Institutes of Health). The program focused on the pathogenesis of SARS-CoV infection and disease, development of a virus-like particle vaccine for SARS, and clinical trials of a SARS vaccine.

Results of an evaluation of candidate vaccines against the SARS virus were published by Drs. Robert Atmar and Robert Couch, along with colleagues at The University of Texas Medical Branch in Galveston, Texas. A whole virus inactivated vaccine was tested in ferrets and nonhuman primates and a virus-like particle vaccine was tested in mice. The vaccines provided protection against infection. However, the vaccines caused damage to the lungs of mice infected with the virus, so it is unlikely that these vaccine candidates would be developed for use in humans.

In another approach, Drs. Peter Hotez and Maria Elena Bottazzi of the Departments of Pediatrics – Tropical Medicine and Molecular Virology and Microbiology and the National School of Tropical Medicine at BCM received funding from the National Institute of Allergy and Infectious Diseases of the NIH to develop a recombinant protein-based SARS vaccine.

Drs. Hotez and Bottazzi and their collaborators based their vaccine development on a segment of the SARS-CoV spike protein (a protein found on the outside of the virus that interacts with the host cell) known as the receptor binding domain (RBD). The idea is that the vaccine would stimulate neutralizing antibodies which would block the attachment of the virus to its receptor on the host cell, thus preventing infection by SARS-CoV. The researchers have shown that the RBD vaccine candidate does elicit a strong neutralizing antibody response and protects vaccinated animals against a challenge SARS-CoV infection.

In order to optimize this potential vaccine, they have made modifications to the RBD protein and tested the various candidates in mice. They have found an RBD variant that induced significantly stronger RBD-specific antibody responses and a higher level of neutralizing antibodies in immunized mice than the original version. This optimized SARS vaccine candidate can be used as the basis for the further development of a SARS vaccine. A vaccine would be beneficial to help avert a potential newly emergent outbreak of SARS, as well as for biodefense preparedness in the event of the deliberate release of SARS as an agent of bioterrorism.

The scientists have advocated for prioritized funding for a MERS vaccine and hope to apply the knowledge gained during their investigations of SARS vaccine candidates to the development of a vaccine against MERS.