Thursday, 3 January 2013

The Return of SARS?

Sophia Ho

The presence of a new coronavirus was confirmed by the World Health Organisation (WHO) on September 22nd 2012, following tests on a hospitalized 49 year old Qatari man who first presented symptoms of acute respiratory infection on September 3rd. After being admitted into intensive care in Doha, Qatar a few days later, he was then moved to a hospital in London by air-ambulance on September 11th. The novel virus contracted by the man was found in only one other case, that of a 60-year old Saudi Arabian. In addition, it has been reported in late September that five other individuals in Denmark have been placed in isolation as a result of carrying symptoms of the same viral illness and are to be tested. They included an individual who had travelled to Qatar and four members of a family whose father had recently gone to Saudi Arabia. At the time of writing, 3 of the 5 cases from Saudi Arabia and both cases from Qatar have resulted in fatality. 
Coronaviruses are a group of viruses that have a halo, or
 crown-like (corona) appearance when viewed under an
electron microscope

What makes these cases appear alarming is the understanding that the coronaviruses are a genus of viruses that includes the SARS coronavirus, or SARS-CoV, which causes the well-known and potentially fatal Severe Acute Respiratory Syndrome. SARS is characterized by symptoms of fever, muscle pain and headache, followed by coughing, dyspnea (shortness of breath) and pneumonia. It can also lead to a decrease in circulating lymphocytes (a type of white blood cell). During the outbreak in 2003, which originated in Guangdong province in Southern China, over 8000 cases were reported worldwide in addition to approximately 800 deaths, leading to a mortality rate of around 10%. However, this was considerably higher for victims over 50 years of age, reaching up to 50%.

SARS-CoV itself is an enveloped, single-stranded RNA virus (as opposed to double-stranded DNA, as found in most other living organisms) with a genome size of 29.7kb, among the largest within RNA viruses. Its life cycle begins with host cell entry, requiring the uncoating of the virus particle and insertion of its RNA genome into the host cell cytoplasm. Once internalized, all viruses utilize their host’s cellular machinery (proteins, cytoskeleton etc) for their own replication requirements. Different coronavirus infections can have various effects on the host cell’s transcription and translation processes, resulting in effects on the cell cycle, cell survival/death, the cytoskeleton and, on a bigger scale, inflammation and immune or stress responses.

Schematic representation of a coronavirus
Other coronaviruses are known to be among the major causes of the common cold, and some are able to infect the gastrointestinal tract. The virus is spread via droplets produced during coughs and sneezes. The illnesses observed in the recent cases described above show similarities to SARS, in that they also produce severe respiratory conditions and have the potential to cause fatality. The WHO therefore proceeded to “further characterize the novel coronavirus", and the UK’s Health Protection Agency are also working to sequence the virus using samples derived from the Qatari case.

Since then, virologists in Holland have been able to sequence the entire genome of the new virus (temporarily named ‘Novel coronavirus 2012’, ‘London1_novel CoV 2012’, and ‘Saudi SARS’) and have claimed that it appears more closely related to coronaviruses that infect bats than human SARS-CoV. Bats are a natural carrier of many types of coronaviruses, making them a likely reservoir. It is also probable that, rather than contracting the virus directly from bats, transference to humans may have occurred via an additional host(s), such as the civet cat. Indeed, very recently released research findings suggest that the novel virus uses host receptor molecules that are present in primates, pigs and bats, leading to the possibility of cross-species spread. Alternatively, it has been speculated that it may be a mutation of a previously existing virus.

Despite this new data, information about the novel coronavirus is still considered too limited to draw solid conclusions. It is not yet clear whether the pathogenesis exhibited by the small numbers of cases so far represent the normal effects of the new virus on humans, or merely very rare incidences of severe disease caused by the virus. Health officials and virology experts have not so far raised much alarm concerning safety of the public for a number of reasons.

1. The number of cases where the new virus has been detected have so far been very few. In addition, none of the 60 people who recently came into contact with one of the victims were shown to have any indication of being infected with the virus, after being tracked. It is therefore not believed to be as contagious as SARS.

2. No increase in the numbers of new cases of respiratory illness has been observed in countries where the patients originated from. This strongly suggests that, as of now, the virus may not be able to spread between humans but instead acquired from an animal source.

3. Coronaviruses are easily destroyed using normal cleaning agents and detergents and are only able to live for one day outside of the human body, making them easy to manage.

As a result, the WHO have not yet proposed any travel or trade restrictions, but plans have been made to continue closely monitoring the situation and to review new findings. Dutch virologist Dr. Ron Fouchier and his group, who were responsible for sequencing the novel coronavirus genome, have issued a diagnostic test for the virus, enabling suspected cases to be verified worldwide, and are working to find proof that the virus is the main cause of the disease (as opposed to, for example, compromising the immune system and enabling another agent to cause the fatal respiratory illnesses observed), using macaques and ferrets. Fouchier also stated that vaccine design can now begin for the virus, using alterations to existing knowledge based on experimental vaccines for SARS. Due to the nature of viral reproduction, which usually involves a high mutation rate during replication, there is still some chance that the Novel coronavirus 2012 may at some point modify to become a more dangerous, transmissible pathogen. However, given that there is no evidence of human-to-human transmission as of now, there appears to be little need to panic for the time being.