Severe Acute Respiratory Syndrome is a respiratory disease in humans which is caused by the SARS coronavirus (SARS-CoV). Between November 2002 and July 2003 an outbreak of SARS in Hong Kong nearly became a pandemic, with 8,422 cases and 916 deaths worldwide (10.9% fatality) according to the WHO. Within weeks SARS spread from Hong Kong to infect individuals in 37 countries in early 2003.
As of today, the spread of SARS has been fully contained, with the last infected human case seen in June 2003 (disregarding a laboratory induced infection case in 2004). However, SARS is not claimed to have been eradicated (unlike smallpox), as it may still be present in its natural host reservoirs (animal populations) and may potentially return into the human population in the future.
The fatality of SARS is less than 1% for people aged 24 or younger, 6% for those 25 to 44, 15% for those 45 to 64, and more than 50% for those over 65. For comparison, the fatality of influenza is usually around 0.6% (primarily among the elderly) but can rise as high as 33% in severe epidemics of new strains.
nitial symptoms are flu-like and may include: fever, myalgia, lethargy symptoms, cough, sore throat and other nonspecific symptoms. The only symptom common to all patients appears to be a fever above 38 °C (100.4 °F). Shortness of breathmay occur later. The patient has symptoms as with a cold in the first stage, but later on they resemble influenza.
||The following text needs to be harmonized with text in SARS coronavirus.
Coronaviruses are positive-strand, enveloped RNA viruses that are important pathogens of mammals and birds. This group of viruses cause enteric or respiratory tract infections in a variety of animals, including humans, livestock and pets.
Initial electron microscopic examination in Hong Kong and Germany found viral particles with structures suggesting paramyxovirus in respiratory secretions of SARS patients. Subsequently, in Canada, electron microscopic examination found viral particles with structures suggestive of metapneumovirus (a subtype of paramyxovirus) in respiratory secretions. Chinese researchers also reported a Chlamydophila-like disease may be behind SARS. The Pasteur Institute in Paris identified coronavirus in samples taken from six patients, as did the laboratory of Malik Peiris at the University of Hong Kong, which in fact was the first to announce (on 21 March 2003) the discovery of a new coronavirus as the possible cause of SARS, after successfully cultivating it from tissue samples and was also amongst the first to develop a test for the presence of the virus. The CDC noted viral particles in affected tissue (finding a virus in tissue rather than secretions suggests it is actually pathogenic rather than an incidental finding). Upon electron microscopy, these tissue viral inclusions resembled coronaviruses, and comparison of viral genetic material obtained by PCR with existing genetic libraries suggested the virus was a previously unrecognized coronavirus. Sequencing of the virus genome — which computers at the British Columbia Cancer Agency in Vancouver completed at 4 a.m. Saturday, 12 April 2003 — was the first step toward developing a diagnostic test for the virus, and possibly a vaccine. A test was developed for antibodies to the virus, and it was found that patients did indeed develop such antibodies over the course of the disease, which is highly suggestive of a causative role.
On 16 April 2003, the WHO issued a press release stating a coronavirus identified by a number of laboratories was the official cause of SARS. Scientists at Erasmus University in Rotterdam, the Netherlands demonstrated that the SARS coronavirus fulfilled Koch's postulates thereby confirming it as the causative agent. In the experiments, macaques infected with the virus developed the same symptoms as human SARS victims.
An article published in The Lancet identifies a coronavirus as the probable causative agent.
In late May 2003, studies from samples of wild animals sold as food in the local market in Guangdong, China found the SARS coronavirus could be isolated from palm civets (Paguma sp.), but the animals did not always show clinical signs. The preliminary conclusion was the SARS virus crossed the xenographic barrier from palm civet to humans, and more than 10,000 masked palm civets were destroyed in Guangdong Province. Virus was also later found in raccoon dogs (Nyctereuteus sp.), ferret badgers (Melogale spp.) and domestic cats. In 2005, two studies identified a number of SARS-like coronaviruses in Chinese bats. Phylogenetic analysis of these viruses indicated a high probability that SARS coronavirus originated in bats and spread to humans either directly, or through animals held in Chinese markets. The bats did not show any visible signs of disease, but are the likely natural reservoirs of SARS-like coronaviruses. In late 2006, scientists from the Chinese Centre for Disease Control and Prevention of Hong Kong University and the Guangzhou Centre for Disease Control and Prevention established a genetic link between the SARS coronavirus appearing in civet cats and humans, bearing out claims that the disease had jumped across species.
Coronavirus (CoV) genome replication takes place in the cytoplasm in a membrane-protected microenvironment and starts with the translation of the genome to produce the viral replicase. CoV transcription involves a discontinuous RNA synthesis during the extension of a negative copy of the subgenomic mRNAs. The requirement for base pairing during transcription has been formally demonstrated in arteriviruses and CoVs. The CoV N protein is required for coronavirus RNA synthesis and has RNA chaperon activity that may be involved in template switch. Both viral and cellular proteins are required for replication and transcription. CoVs initiate translation by cap-dependent and cap-independent mechanisms. Cell macromolecular synthesis may be controlled after CoV infection by locating some virus proteins in the host cell nucleus. Infection by different coronaviruses cause in the host alteration in the transcription and translation patterns, in the cell cycle, the cytoskeleton, apoptosis and coagulation pathways, inflammation and stress responses. The balance between genes up- and down-regulated could explain the pathogenesis caused by these viruses. Coronavirus expression systems based on single genome constructed by targeted recombination, or by using infectious cDNAs, have been developed. The possibility of expressing different genes under the control of transcription regulating sequences (TRSs) with programmable strength and engineering tissue and species tropism indicates that CoV vectors are flexible. CoV based vectors have emerged with high potential vaccine development and possibly for gene therapy.
SARS may be suspected in a patient who has:
- Any of the symptoms, including a fever of 38 °C (100.4 °F) or higher, and
- Either a history of:
- Contact (sexual or casual, including tattoos) with someone with a diagnosis of SARS within the last 10 days OR
- Travel to any of the regions identified by the WHO as areas with recent local transmission of SARS (affected regions as of 10 May 2003 were parts of China, Hong Kong, Singapore and the province of Ontario, Canada).
With the advent of diagnostic tests for the coronavirus probably responsible for SARS, the WHO has added the category of "laboratory confirmed SARS" for patients who would otherwise fit the above "probable" category who do not (yet) have the chest X-ray changes, but do have positive laboratory diagnosis of SARS based on one of the approved tests (ELISA, immunofluorescence or PCR).
The chest X-ray (CXR) appearance of SARS is variable. There is no pathognomonic appearance of SARS, but is commonly felt to be abnormal with patchy infiltrates in any part of the lungs. The initial CXR may be clear.
White blood cell and platelet counts are often low. Early reports indicated a tendency to relative neutrophilia and a relative lymphopenia — relative because the total number of white blood cells tends to be low. Other laboratory tests suggest raised lactate dehydrogenase and slightly raised creatine kinase and C-reactive protein levels.
With the identification and sequencing of the RNA of the coronavirus responsible for SARS on 12 April 2003, several diagnostic test kits have been produced and are now being tested for their suitability for use.
Three possible diagnostic tests have emerged, each with drawbacks. The first, an enzyme-linked immunosorbent assay (ELISA) test detects antibodies to SARS reliably, but only 21 days after the onset of symptoms. The second, an immunofluorescence assay, can detect antibodies 10 days after the onset of the disease, but is a labour- and time-intensive test, requiring an immunofluorescence microscope and an experienced operator. The last test is a polymerase chain reaction (PCR) test that can detect genetic material of the SARS virus in specimens from blood, sputum, tissue samples and stools. The PCR tests so far have proven to be very specific, but not very sensitive. This means while a positive PCR test result is strongly indicative the patient is infected with SARS, a negative test result does not mean the patient does not have SARS.