SARS - what do we know about it?
Prof Don Hendry
As of June 6th, a cumulative total of 8404 probable cases with 779 deaths has
been reported from Severe Acute Respiratory Syndrome (SARS) in 29 countries.
Since February this year when the world was alerted to this mysterious new
illness, health practitioners and scientists have risen to the immense challenge
to identify and control SARS. Just under four months down the line, what do we
know about this disease?
What is SARS?
SARS is an infectious respiratory disease which has mainly affected adults
aged between twenty five and seventy 25 - 70 years. It starts with a fever,
chills, headache, body aches and within two to seven days, a dry cough. One of
its distinguishing features is the onset of breathing difficulty. Scientists
have pegged the case-fatality rate at between three and ten percent.
In addition to the symptoms, radiography can provide corroborative evidence
of SARS by diagnosing pneumonia in severe cases. In addition, SARS is suspected
if autopsy shows no other recognizable cause of death!
What causes SARS? Meet the virus
 SARS
is a previously unrecognized coronavirus (CoV). Coronaviruses are the cause of
mild to moderate upper-respiratory diseases and accounts for approximately 30%
of all colds in humans. In animals, this virus causes gastro-intestinal, liver
and neurological diseases in addition to respiratory diseases.
The virus itself is a spherical enveloped virion, between 80 and 160 nm
diameter, and has single stranded (ss)RNA of about 30 kilobases, the largest
genome of all ssRNA viruses. As the electron micrograph image above shows,
glycoproteins on the virus' surface gives the virions a halo or crown-like
appearance, hence the name coronavirus.
There are several known coronaviruses which affect birds, mice, cattle,
turkeys, pigs, dogs, cats and also rabbits.
All coronaviruses have a similar gene arrangement and replication strategy.
They all contain five major genes that collectively code for the enzymes
(polymerases and proteases) required for virus replication and for the
structural proteins that will form the virus shell. A fascinating feature of
this virus family is that the structural protein genes are each expressed via a
smaller (subgenomic) copy of the original gene. These subgenomic RNAs,
irrespective of their size, all have identical starting and ending sequences,
indicating that the virus synthesizes them by a copying mechanism unique in
molecular biology.
The coronaviruses have a very high frequency of mutations due to an
inefficient mechanism for checking the code during replication of the viral RNA
to make more copies. In addition, deletions and point mutations incurred during subgenomic
RNA synthesis frequently give rise to mutant viruses with altered virulence.
This occurs particularly in the large surface protein (the "petal" in
the corona) which, together with the high mutation rate, produces within a virus
population many variant viruses with differing pathogenicities.
So is it a new type of coronavirus?
From throat swabs specimens from SARS patients, scientists have been able to
grow the virus in African green monkey kidney cells. It is usually very
difficult to grow the human coronaviruses in cells, so scientists were surprised
at the relative ease with which this virus grew during cell
culture experiments. Electron microscopy showed that the SARS virus was a
typical coronavirus and moreover reacted with polyclonal coronavirus antibodies.
RT-PCR of a polymerase gene fragment using consensus primers indicated that it
was indeed a distantly-related coronavirus. Identical sequences were obtained
from 12 SARS patients, confirming that the same virus was involved in each case.
Considering that the SARS virus first came to global attention in late
February and was recognized as a coronavirus by early April, scientists managed
in record time to sequence the entire SARS-Coronavirus (SARS- CoV) genome by
end-April! . Their work revealed that the SARS-CoV genome consists of 29751
nucleotides making a total of 11 (the five major plus six smaller) genes. The
genome organization is in fact similar to other coronaviruses, but sequence
comparisons definitely showed that the SARS-CoV is unrelated to any
well-characterised coronaviruses of human or animal origin! The fact that there
is surprisingly little variation in all the SARS-CoV genomes sequenced to date
(~8 sequenced , mutations at only ~30 nucleotides) suggests the virus entered
the human population recently from a point source.
How does one get SARS?
SARS is spread by close person-to-person contact. A typical scenario for
example would be an infected person coughing or sneezing droplets onto
themselves, other people or objects. An uninfected person would be susceptible
to the virus by touching skin or objects contaminated with infectious droplets,
then touching mouth, nose or eyes. The SARS- CoV is stable on surfaces such as
door handles for days.
Criteria for identification as SARS
If a case of SARS is suspected, identifying whether it is in fact this
disease depends on laboratory evidence as well as where or with whom the person
has been in contact. Questions a healthcare practitioner will ask are whether
the person has travelled or been in transit travel within 10 days of the onset
of symptoms to an area such as China, Hong Kong or Taiwan currently affected by
SARS, or whether the person has had close contact within 10 days of the onset of
symptoms with a known/suspected SARS patient.
In the laboratory, scientists are now able to provide definitive proof of
SARS through detection of antibody to SARS-CoV, the detection of SARS-CoV RNA by
RT-PCR and the isolation of SARS-CoV in the patients blood.
Treatment of SARS
While much research has been conducted, it is still early days for a
recommended treatment. Doctors have thus used a combination of treatment regimes
common to that for treating respiratory illnesses and pneumonia. Antiviral drugs
such as ribavirin have been administered but their efficacy remains uncertain.
Some have also provided oral or intravenous steroids to sufferers, while the
Center for Disease Control, USA, recommends the same treatment as for any
serious community-acquired atypical pneumonia.
Origin of SARS
But the million dollar (or billion yen!) question is: where did the SARS
virus come from. Many have speculated that it resulted from a recombination
event between two existing CoV strains, but there is no evidence for this from
sequencing data obtained. Some have even suggested that the virus arrived from
space! One possibility is that SARS is the result of a mutation of an existing
coronavirus causing it to become pathogenic for humans. There is some evidence
for this. The SARS-CoV appears to be similar to a civet CoV. Civet cats are
eaten in parts of China and it is not that far-fetched that the virus could have
jumped the species barrier from these animals to humans, perhaps during routine
handling of this animal.
More information:
World Health Organization www.who.int
Relevant scientific papers:
A Novel Coronavirus Associated with Severe Acute Respiratory Syndrome,
T.Ksiazek et al. Published at www.nejm.org
The Genome Sequence of the SARS-Associated Coronavirus, Marco A. Marra et al.
Published at www.nejm.org
Characterization of a Novel Coronavirus Associated with Severe Acute
Respiratory Syndrome, Paul A. Rota et al. Published at www.nejm.org
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