Introduction
Severe acute respiratory syndrome (SARS) is a highly infectious disease caused by the coronavirus, SARS-coronavirus (SARS-CoV), that can cause severe illness and death. [1][2] Coronaviruses are a group of “positive sense, single-stranded RNA viruses that infect humans and animals.” [3] The corona viruses cause enteric and respiratory diseases. SARS-CoV has the largest viral RNA genome currently known, including 29,727 nucleotides containing 14 functional open reading frames. Two big 5’-terminal functional open reading frames, known as 1a and 1b, make up the “replicase gene encoding the proteins complex” that is needed for viral RNA transcription and replication to take place. The other 12 functional open reading frames encode four main structural proteins of SARS-CoV: the spike protein, nucleocapsid protein, membrane protein, and the small envelope protein. [4]
SARS-CoV is a zoonotic virus (diseases transmissible from animals to humans), which is a virus that lives in natural-reservoir hosts, such as bats, but is also able to infect intermediate hosts (usually small animals like palm civets) before it is transmitted to humans. SARS-CoV is mainly transmitted by respiratory secretions and close contact. The “infectious viral particles” found in patients who have SARS can also be excreted in stool, urine and sweat. This virus causes damage to lung tissue resulting in atypical pneumonia that quickly leads to the deterioration and failure of the respiratory system. Once the virus enters the body it adheres to primary target cells in the respiratory system, enters these cells and then replicates itself. These “matured virions” are subsequently released to infect more target cells. SARS-CoV is also able to infect the mucosal cells in the intestines, tubular epithelial cells in the kidneys, “epithelial cells of renal tubules, cerebral neurons, and immune cells. [1] The average incubation period on humans is 4 days, but ranges from 2 to 10 days. [5] The SARS-CoV can last on surfaces for more than a day and up to 4 days in the feces of infected individuals. [2] Early in the epidemic, there were a small number of patients who were extremely infectious and termed “super spreaders.” It is thought that these individuals may have been so infectious because of the lack of early infection-control efforts, a higher “SARS-CoV load,” and a higher volume of respiratory secretions. [6]
The first known case of SARS was in November of 2002 in Guangdong province in China. The virus remained in China from November 2002 until February 21, 2003 when a doctor infected with SARS-CoV traveled from Guangdong province to Hong Kong. While staying at a hotel, the doctor infected at least 16 other hotel guests. Those SARS-infected people subsequently spread the virus to various parts of the world, including an American businessman traveling to Hanoi, Vietnam; three women from Singapore; two Canadians; and a Hong Kong resident. The American businessman became ill while in Hanoi and infected 20 health-care workers at a local hospital. Of those infected health-care workers, Carlo Urbani, an Italian epidemiologist working for the World Health Organization (WHO) in Hanoi, was the first to formally identify SARS as a “unique disease” on February 28, 2003. [7] The Hong Kong resident infected by the Chinese doctor while staying at the hotel became ill and was admitted to a Hong Kong hospital for what seemed to be severe pneumonia. Subsequently, 138 people became ill with pneumonia: 34 nurses, 20 doctors, 16 medical students, and 15 additional health-care workers. One of the Canadian travelers who was originally infected in the Hong Kong hotel, returned to Toronto and died in the hospital on March 5, 2003. The health-care workers in the Toronto hospital were unaware of the problems in China and within 6 weeks more than 130 SARS cases and 15 deaths were reported by the Canadian government. [5]
On March 21, 2003 a SARS epidemic began in a large, private Hong Kong apartment complex called Amoy Gardens. The virus spread rapidly, infecting 321 people and causing 42 deaths by April 15, 2003. Most individuals began to experience symptoms within 3 days (between March 24th and 26th). The SARS cases at the Amoy Gardens apartment complex made up 18% of the total reported cases in Hong Kong. Studies conducted on this particular outbreak of SARS determined that environmental factors played a significant role in the spread of the virus. Researchers found that this outbreak of SARS was largely spread through the air, specifically through the building plumbing and then from building to building by wind, which is unlike typical virus outbreaks that are spread from person to person. The Amoy Gardens epidemic was characterized by “extensive and rapid” virus transmission. Typical virus transmission takes place within a short distance, not more than 3 feet. Researchers concluded that transmission of the SARS virus at the Amoy Gardens occurred across hundreds of feet. The results of the studies on the Amoy Gardens SARS outbreak have public health implications for the control and prevention of environmental transmissions of other highly infectious diseases. [2]
Other flu viruses have originated in the Guangdong province because of the cultural cuisine practices that bring together live animals, animal parts, and humans in wild-game animal markets called “wet markets.” In these environments, it is easier for pathogens to genetically mutate and move from animal hosts to humans. A large number of those individuals who were originally infected with SARS-CoV in November and December of 2002 worked in the wild-game trade and had direct contact with the animals in the wet markets. A SARS-CoV-like virus with over “99% nucleotide homology to the human SARS-CoV” was found in samples taken from animals in the wet markets of Guangdong province. Many of the wet-market workers who handled the animals had antibodies to the SARS-CoV-like animal virus, but they had no symptoms associated with the SARS virus. Given the flu-virus history of Guangdong province and the links that the SARS outbreak had to the area, it is thought that the wet markets in this region provided the crossing point needed for human transmission of the virus. [7]
The World Health Organization issued a travel warning on March 15, 2003 for travelers heading to Southeast Asia, calling SARS a “worldwide health threat.” This formal warning by the WHO was not a common occurrence and was a result of the growing evidence of the global spread of the virus. [5] SARS cases in the United States, United Kingdom, Spain, Slovenia, and Germany were reported to the WHO within days of this travel warning. Initially, the alerts and isolation procedures seemed to be working as evidenced by the lack of infected health-care workers in countries reporting small numbers of cases. However, in countries where transmission occurred prior to the WHO warnings, SARS was spreading outside of the isolated patients. The World Health Organization responded to the increased threat by making recommendations for mandatory screenings and potential quarantines of individuals who had been traveling in SARS-affected areas of Southeast Asia, including China and Hong Kong. At the request of infectious disease specialists in April of 2003, the WHO recommended that all non-essential travel to Hong Kong and the Guangdong province of China be stopped.
An unprecedented international collaboration coordinated by the World Health Organization led to the identification of this new coronavirus, SARS-CoV, in April of 2003, just months after the initial outbreak. [1] Scientists at the British Columbia Cancer Agency in Vancouver, Canada sequenced the genome of SARS-CoV. Just days later, scientists at the US Centers for Disease Control and Prevention in Atlanta, Georgia confirmed 99% of the Canadian scientists’ findings. [5] On July 5, 2003 the World Health Organization reported that the “global outbreak” had ended. [6][7] The last reported cases of SARS were caused by laboratory contamination and occurred in Beijing and Anhui, China in April of 2004. [1] Although the SARS outbreak has ended, sources of the virus, such as animal carriers including Himalayan palm civets, raccoon dogs, and bats have been identified. There is also the possibility of another laboratory contamination or escape of the virus. Due to the virus not being eliminated, the potential for more human infections still exists. A SARS vaccine is needed to prevent or control outbreaks in the future. [8]
Statistic
- For the general population, the mortality rate of SARS is 9.6%, but it affects more than 50% of patients aged 65 years and older.
- By September 23, 2003 there were a total of 8098 SARS cases and 774 deaths.
- SARS spread to five continents and 29 countries around the globe.
- One fifth of those infected with SARS-CoV were health-care workers.
- Acute respiratory distress syndrome (ARDS) occurred in 16% of all reported SARS patients; of those patients who suffered from ARDS, the mortality rate was 50%.
- The geographical impact of SARS included 5327 cases and 349 deaths in Mainland China; 1756 cases and 299 deaths in Hong Kong and Macau; 346 cases and 37 deaths in Taiwan; 238 cases and 33 deaths in Singapore; 30 cases and 6 deaths in the Philippines, Thailand, Malaysia, and Indonesia; 33 cases and 1 death in Europe; 63 cases and 5 deaths in Vietnam; 251 cases and 43 deaths in Canada; 27 cases and no deaths in the United States; 1 case and 1 death in South Africa; 3 cases and no deaths in India; 1 case and no deaths in Kuwait; 10 cases and no deaths in Russia and Mongolia; 3 cases and no deaths in Korea; 7 cases and no deaths in Australia and New Zealand. [1][6][7][8][9]
Signs and Symptoms
The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.
The symptoms associated with SARS are similar to flu including a high fever (>38°C), headache, malaise, dry cough and shortness of breath. Most patients who have SARS develop pneumonia. Approximately 20% of patients need mechanical ventilation. [2] Other symptoms that may associate with SARS are muscular stiffness, sore throat, loss of appetite, confusion, diarrhea, nausea and skin irritation. [5][10] SARS patients have showed a slight decrease in platelet counts. Chest radiography of SARS patients shows changes that are compatible with viral pneumonitis. More than a third of SARS patients have a CD4+ T-cell count of less than 200 cells/ mm3 indicating that there is increased vulnerability to secondary infections. [7]
Treatment Options
Conventional
There are no licensed vaccines or treatments currently recommended or available for SARS. However, there have been several vaccines constructed and tested since the outbreak in 2002. [1][6][8] For example, patients infected with SARS-CoV have shown improvement when treated with serum from formerly infected patients, suggesting that “passive immunotherapy” could potentially be developed for treatment of SARS and other infectious diseases. [3] Isolation and quarantine are the methods of control until a vaccine is developed. Supportive therapies are also used in the treatment of SARS, such as oxygen and ventilation. Antiviral and anti-inflammatory drug therapies are also used in SARS treatment.6 Prior to the identification of SARS-CoV, researchers screened already existing antiviral medications that were used for other diseases. Clinically available antivirals, such as ribavirin, oseltamivir, and interferons, were used to treat patients. When interferons were combined with ribavirin, “improved antiviral effects” occurred. Total death and intubation rates were reduced in SARS patients who were given lopinavir with ritonavir, which is an antiretroviral combination drug treatment used for HIV and AIDS. Once SARS-CoV was sequenced, research was conducted that has provided drug candidates which “effectively inhibit the SARS-CoV replication.” [11]
Nutritional Supplementation
There are no nutritional treatments for SARS. However, there may be a case to be made for improved nutritional status and the relative immune status of those who may be at risk of being infected. [12]
Herbal Supplementation
Since the first case of SARS was identified in 2002, there has been little time for the research community to respond with evaluation of botanicals that may be useful in prevention and/or treatment. However, there have been studies of various Chinese herbal formulas that have been used. In 2004, the World Health Organization published a series of reports of Traditional Chinese Medicine used in combination with Western therapies in treating SARS. [13] These reports reviewed two TCM formulas and their use in combination with anti-viral medications.
At this time, however, there is not enough clinical data available to fully validate any type of botanical treatment for SARS.
Clinical Notes
Initial tests to diagnose the presence of SARS-CoV include blood cultures; Gram stain; chest radiograph; and those for other respiratory viruses, such as influenza A and B. If SARS is suspected, further diagnostic tests are conducted. [5] There are three main methods for the diagnosis of SARS: (1) viral RNA detection by reverse transcription polymerase chain reaction; (2) virus-induced antibodies by immunofluorescence assay; or (3) by enzyme-linked immunosorbent assay (ELISA) of nucleocapsid protein. [3]
References
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- K.R. McKinney, Y.Y. Gong, T.G. Lewis. Environmental transmission of SARS at Amoy Gardens. Journal of Environmental Health. 2006;68(9):26-30.
- M.R. Suresh, P.K. Bhatnagar, D. Das. Molecular targets for diagnostics and therapeutics of severe acute respiratory syndrome (SARS-CoV). J Pharm Pharmaceut Sci. 2008;11(2):1s-13s.
- S. Chen, H. Luo, J. Chen. An overall picture of SARS coronavirus (SARS-CoV) genome-encoded major proteins: structures, functions and drug development. Current Pharmaceutical Design. 2006;12:4539-4553.
- B. Wilmoth Lerner, K.L. Lerner. Severe acute respiratory syndrome. In: Longe JL, editor. Gale encyclopedia of medicine. Vol. 4, 3rd edition. Detroit (MI): Gale; 2006. p. 3355-3358.
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- J.S.M. Peiris, Y. Guan, K.Y. Yuen. Severe acute respiratory syndrome. Nature Medicine. 2004;10(12): S88-97.
- S.U. Kapadia, I.D. Simon, J.K. Rose. SARS vaccine based on a replication-defective recombinant vesicular stomatitis virus is more potent than one based on a replication-competent vector. Virology. 2008; 376: 165-172.
- L.J. Stockman, R. Bellamy, P. Garner. SARS: systematic review of treatment affects. PLoS Med. 2006; 3(9): 1525-1531.
- World Health Organization. Frequently asked questions on severe acute respiratory syndrome (SARS). Available from: http://www.who.int/csr/sars/sarsfaq/en/print.html. [Accessed on 23 October 2009].
- Y.S. Wu, W.H. Lin, J.T. Hsu. Antiviral drug discovery against SARS-CoV. Current Medicinal Chemistry. 2006; 13: 2003-2020.
- M.A. Beck, J. Handy, O.A. Levander. Host nutritional status: the neglected virulence factor. Trends Microbiol. Sep2004;12(9):417-423.
- World Health Organization: SARS: Clinical Trials on Treatment Using Traditional Chinese Medicine and Western Medicine. Available from http://apps.who.int/medicinedocs/en/d/Js6170e/14.html . [Accessed on 8 December 2009].
