Severe Acute Respiratory Syndrome (SARS)

Severe acute respiratory syndrome (SARS) is a viral respiratory illness caused by a coronavirus, called SARS-associated coronavirus (SARS-CoV). SARS was first reported in Asia in February 2003. Over the next few months, the illness spread to more than two dozen countries in North America, South America, Europe, and Asia before the SARS global outbreak of 2003 was contained. Background: This atypical pneumonia has been named Severe Acute Respiratory Syndrome (SARS) by World Health Organization (WHO). SARS is an infectious disease of the respiratory system characterized by atypical

inflammation of the lungs (pneumonia). Scientists at CDC and other laboratories have detected a previously unrecognized coronavirus in patients with SARS. This new coronavirus is the leading hypothesis for the cause of SARS. SARS appears to be primarily spread from person-to-person through droplet transmission when in direct close contact with a person with SARS. Potential ways in which SARS can be spread include touching the skin of other people or objects that are contaminated with infectious droplets and then touching your eye(s), nose, or mouth. SARS is an emerging disease. Knowledge about its clinical behavior, response to treatment, and modes and risks of transmission are continually evolving. Early symptoms in patients with SARS have included fever (>100F), muscle aches, dry cough, shortness of breath, or difficulty breathing. The illness usually begins with a fever (measured temperature greater than 100.4F [>38.0C]) which is sometimes associated with chills or other symptoms, including headache, general feeling of discomfort and body aches. Some people also experience mild respiratory symptoms at the outset. After 2 to 7 days, SARS patients may develop a dry, nonproductive cough that might be accompanied by or progress to the point where insufficient oxygen is getting to the blood. Ten percent of 20 percent of SARS cases may progress to requiring the use of a respirator. No specific treatment recommendations can be made at this time, however, medical personnel is instructed to treat general clinical signs. CDC currently recommends that patients with SARS receive the same treatment that would be used for any patient with serious community-acquired atypical pneumonia. The virus suspected to be

the cause of SARS (coronavirus) is being tested against various antiviral drugs to see if an effective treatment can be found. Epidemiologic Criteria: 1. Travel (including transit in an airport) within ten days of onset of symptoms to an area with current or previously documented or suspected community transmission of SARS. 2. Close contact within ten days of onset of symptoms with a person known or suspected to have SARS. Mode of Transmission: 1. The primary mode of transmission appears to be direct mucous membrane (eye, nose, and mouth) 2. Contact with infectious respiratory droplets and/or through exposure to fomites. 3. Transmission through casual and social contacts has occasionally occurred as a result of intense exposure to a case of SARS (in work place, in vehicles) or in high risk transmission settings, such as health care settings, and in household settings. 4. Contamination of inanimate materials or objects by infectious respiratory secretions or body fluids (saliva, tears, urine, and stool) which have been found to contain the virus. For how long will the SARS virus exist on surfaces? 1. The virus is stable in urine and feces at room temperature for at least one to two days, in stool from patients with diarrhea for up to four days. 2. It survives on paper, on a plastered wall after 36 hours, on plastic surface and stainless steel after 72 hours, on a glass slide after 96 hours.

3. Hospital environmental samples from a number of sites, including walls and the ventilation system, tested positive for SARS virus. 4. Virus loses infectivity after exposure to different commonly used disinfectants and fixatives. Heat at 56C rapidly kills the virus. 5. Other risk factors: a. Household contact with a probable case of SARS b. Increasing age c. Male sex d. Presence of co-morbidities What are the signs and symptoms of SARS? 1. Sudden onset of high grade fever, usually greater than 38C 2. Headache and overall feeling of discomfort and body aches 3. Mild respiratory symptoms at the start and after two days, the patient develops dry cough and have respiratory difficulty. Treatment: No specific treatment recommendations can be made at this time. Empiric therapy should include coverage for organisms associated with any community-acquired pneumonia of unclear etiology, including agents with activity against both typical and atypical respiratory pathogens. Treatment choices may be influenced by severity of the illness. Consultation is recommended. Clinical Course and Management of SARS: 1. It is difficult to decide on the appropriate time to discharge a SARS patient. 2. SARS appears to have lingering after effects once the acute phase of the disease ends. 3. Psychosocial aspects of this illness should not be underestimated. Preventive Measures:

1. Consult a doctor promptly if there are respiratory symptoms such as fever, malaise, chills, headache, joint pain, dizziness, rigors, cough, sore throat and runny nose. Early treatment is the KEY. 2. Build up good body immunity. This means taking proper diet, having regular exercise and adequate rest, reducing stress, and avoiding smoking. 3. Maintain good personal hygiene. Cover nose and mouth when sneezing or coughing. 4. Wear mask if you develop runny nose, sore throat and cough. 5. Wear protective mask in public areas, classrooms, computer rooms, public transports, and communal areas in hostels. 6. Wash hands properly and keep them clean. Use liquid soap for hand washing and disposable towels for drying hands. Resources: Handbook of Common Communicable and Infectious Diseases 2006 Ed American Red Cross Centers for Disease Control and Prevention (CDC)
http://nursingcrib.com/communicable-diseases/severe-acute-respiratory-syndrome-sars/

Background

Severe acute respiratory syndrome (SARS) is a serious, potentially life-threatening viral infection caused by a previously unrecognized virus from the Coronaviridae family.[1] This virus has been named the SARS-associated coronavirus (SARS-CoV). Previously, Coronaviridae was best known as the second-mostfrequent cause of the common cold. (See the images below.)

Thin-section electron micrograph of the severe acute respiratory syndromeassociated coronavirus isolated in FRhK-4 cells. Courtesy of the Government Virus Unit, Department of Health, Hong Kong

SAR, China. Chest radiograph of a 52-year-old symptomatic woman with severe acute respiratory syndrome (March 20, 2003) taken 5 days after presentation. Moderately severe-to-severe groundglass and consolidative bilateral changes are noted in the lung fields and are somewhat worse on the left side. Courtesy of Michael E. Katz, MD.

The SARS-CoV strain is believed to have originated in Guangdong province in southern China prior to its spread to Hong Kong, neighboring countries in Asia, and Canada and the United States during the 2002-2003 outbreak.[2, 3, 4, 5, 6] In early 2004, several new cases of SARS were investigated in Beijing and in the Anhui province of China. The most recent outbreak was believed to have been successfully contained without spread into the general population. There have subsequently been three instances of laboratory-acquired infection, and one reintroduction from animals in Guangdong Province, China. (See Epidemiology.)[7, 8]

Despite concerns that new cases of SARS would emerge in the region, no new human-to-human transmission has been reported. The reasons for this maybe (1) a very high prevalence of serious illness, making identification of cases and transmission easier and (2) a low risk of transmission before the development of severe illness. The World Health Organizations (WHOs) timely updates on where SARS cases were occurring, the clinical and epidemiologic features of infection, laboratory methods, strategies to control the diseases spread, and the intensive collaborative global response to SARS were also responsible for the effective prevention of a global pandemic. (See Epidemiology, Workup, and Treatment.)[9,
10]

Global efforts to acknowledge and research the CoV have virtually eradicated SARS as a threat. Although much has already been learned about the virus, ongoing efforts are being made to better understand it in hopes of developing medications and vaccinations to maintain its suppression. Global organizations, including WHO, the Centers for Disease Control and Prevention (CDC), and the National Institutes of Health (NIH) are still facilitating research on the virus and its family. (See Etiology, Workup and Treatment.)
Pathophysiology
The lungs and gastrointestinal tract have been demonstrated to be the only major organ systems that support SARS-CoV replication.[11, 12] After establishment of infection, SARS-CoV causes tissue damage by (1) direct lytic effects on host cells and (2) indirect consequences resulting from the host immune response. Autopsies demonstrated changes that were confined mostly to pulmonary tissue, where diffuse alveolar damage was the most prominent feature. (See the image below.)

Pathologic slide of pulmonary tissue infected with severe acute respiratory syndromeassociated coronavirus. Diffuse alveolar damage is seen along with a multinucleated giant cell with no conspicuous viral inclusions. Courtesy of the US Centers for Disease Control and Prevention.

Multinucleated syncytial giant cells were thought to be characteristic of SARS but were rarely seen. Angiotensin-converting enzyme-2 (ACE-2), being a negative regulator of the local renninangiotensin system, was thought to be a major contributor to the development of this damage.[13] The other mechanism was thought to be the induction of apoptosis. The SARS-CoV3a and 7a proteins have been demonstrated to be inducers of apoptosis in various cell lines.[14] Immunologically, SARS is characterized by a phase of cytokine storm, with various chemokines and cytokines being elevated.[12, 15]

tiology
Sources
Coronaviruses (CoVs) are found in a wide range of animal species, including in cats, dogs, pigs, rabbits, cattle, mice, rats, chickens, pheasants, turkeys, and whales, as well as in humans.[16] They cause numerous veterinary diseases (eg, feline infectious peritonitis, avian infectious bronchitis); they can also cause upper and, more commonly, lower respiratory tract illness in humans (group 1 [human CoV 229E] and group 2 [human CoV OC43]). The near absence of SARS-CoV antibodies in persons who did not have SARS demonstrated that SARS-CoV had not circulated to any significant extent in humans before 2003 and was introduced into humans from animals.[17] markets. A wide range of other coronaviruses in bats has been found,[18, 19] suggesting that bats are the most likely animal reservoir for the SARS outbreak. SARS infection in animals before arrival in the markets was uncommon, and these animals were probably not the original reservoir of the outbreak, although they may have acted as amplifying hosts. The proximity in which humans and livestock live in rural southern China may have led to the transmission of the virus to humans.[18] like viruses were not found in animals prior to arrival in the

Cellular binding
Single-stranded ribonucleic acid (RNA) viruses such as the SARS-CoV have no inherent proofreading mechanism during replication. Accordingly, mutations in the RNA sequence replication of coronaviruses are relatively common. Such mutations can cause the resulting new virus to be either less or more virulent.[20]

The surface envelop S protein of SARS-CoV is thought to be a major determinant in establishing infection and cell and tissue tropism.[21] This protein, after binding to its receptorwhich is thought to be angiotensin-converting enzyme 2 (ACE-2) and is expressed in a variety of tissues, including pulmonary, intestinal, and renalundergoes conformational change and cathepsin L mediated proteolysis within the endosome.[22, 23] The binding of SARS-CoV to DC-SIGN (dendritic cellspecific intercellular adhesion molecule grabbing nonintegrin), which recognizes a variety of microorganisms, does not lead to entry of the virus into dendritic cells. It instead facilitates the transfer and dissemination within the infected host.[24]

Immune response
The type I interferon (IFN-alfa/beta) system represents a powerful part of the innate immune system and has potent antiviral activity. However, SARS-CoV discourages attack by the IFN system. Replication of the virus occurs in cytoplasmic compartments surrounded by a double membrane layer. Such concealment within cells probably causes a spatial separation of the viral pathogen-associated molecular patterns (PAMPs) and the cellular cytoplasmic pattern recognition receptors (PRRs).[25, 26, 27, 28] In addition, the activation of IFN regulatory factor3 (IRF-3) is actively inhibited by SARSCoV, with IRF-3 being targeted by 5 known SARS-CoV proteins in order to prevent IFN-system activation. IFN induction can also be affected by unspecific degradation of host messenger RNA (mRNA).[28] These defensive measures prevent tissue cells from mounting an antiviral IFN attack following SARS-CoV infection. Ultimately, however, an IFN immune response can occur. Plasmacytoid dendritic cells (pDCs) use Toll-like receptors (TLRs) to recognize pathogen structures and use IRF-7 to induce IFN transcription. Large amounts of IFN are thus produced by the pDCs following infection with SARS-CoV.[29, 28] In a study that examined 40 clinically well-defined human SARS cases, high levels of IFN were , x , IFN [28, 30] correlated with a beneficial outcome for the infected individuals.

Nuclear factor
SARS-CoV membrane protein, most likely by interacting directly with IkappaB kinase (IKK), also suppresses nuclear factor-kappaB (NF-kappaB) activity and reduces cyclooxygenase-2 (COX-2) expression. These disturbances may aid SARS pathogenesis.[20, 31]
Previous

pidemiology
In November 2002, an unusual epidemic of severe pneumonia of unknown origin in Guangdong Province in southern China was noted. There was a high rate of transmission to health care workers (HCWs).[2, 3] Some of these patients were positive for SARS-CoV in the nasopharyngeal aspirates(NPA), whereas 87% patients had positive antibodies to SARS-CoV in their convalescent sera. Genetic analysis showed that the SARS-CoV isolates from Guangzhou had

the same origin as those in other countries, with a phylogenetic pathway that matched the spread of SARS to other parts of the world. The 2002-2003 SARS outbreak predominantly affected mainland China, Hong Kong, Singapore, and Taiwan. In Canada, a significant outbreak occurred in the area around Toronto, Ontario. In the United States, 8 individuals contracted laboratory-confirmed SARS. All patients had traveled to areas where active SARS-CoV transmission had been documented.[2, 3, 4, 10] SARS is thought to be transmitted primarily via close person-to-person contact, through droplet transmission.[32] Most cases have involved persons who lived with or cared for a person with SARS or who had exposure to contaminated secretions from a patient with SARS. Some affected patients may have acquired SARS-CoV infection after their skin, respiratory system, or mucous membranes came into contact with infectious droplets propelled into the air by a coughing or sneezing patient with SARS. Leaky, backed-up sewage pipes; fans; and a faulty ventilation system were likely responsible for a severe outbreak of SARS in the Amoy Gardens residential complex in Hong Kong. Transmission may have occurred within the complex via airborne, virus-laden aerosols.[33] The worldwide number of SARS cases from the original outbreak (November 2002 through July 31, 2003) reached more than 8000 persons, including 1706 healthcare workers. Of those cases, 774 resulted in death, with a case fatality ratio of 9.6% deaths, and 7295 recoveries. The majority of these cases occurred in mainland China (5327 cases, 349 deaths), Hong Kong (1755 cases, 299 deaths), with Taiwan (346 cases, 37 deaths), and Singapore (238 cases, 33 deaths). In North America, there were 251 cases, with 43 resulting in death (all in Canada).[9] The map below shows the worldwide distribution of SARS cases during the 2002-03 outbreak.

World map of severe acute respiratory syndrome (SARS) distribution from the 2002-2003 outbreak infection. The greatest number of past and new cases of SARS are in mainland China, Hong Kong, Taiwan, and Singapore (red). Canada, more specifically Toronto, Ontario (yellow), is the fifth-ranked area, although community transmission of SARS now appears to be contained, according to the US Centers for Disease Control and Prevention. Green represents the other countries reporting SARS cases.

rognosis
WHO data indicate that mortality from SARS is highly variable. The mortality rate has been found to range from less than 1% in patients below age 24 years to more than 50% in patients aged 65 and older. Certain risk factors, including the following, have been associated with a poorer prognosis[34, 35] :

Older age Chronic hepatitis B infection Laboratory features - Including marked lymphopenia and leukocytosis, elevated lactate dehydrogenase level, hepatitis, high SARS-CoV viral load, and comorbidities such as diabetes mellitus

Elevated levels of interferon-inducible protein 10 (IP-10), monokine induced by IFN-gamma (MIG), and interleukin 8 (IL-8) during the first week, as well as an increase of MIG during the second week, have also been associated with a poor prognosis.[36] A study of SARS survivors found that most of these had significant improvement clinically, radiographically, and in their pulmonary function studies. However, 27.8% of patients still exhibited abnormal radiographs at 12 months. Significant reductions in the diffusing capacity of carbon monoxide and in exercise ability (6-min walking distance) were also documented at 12 months.[37] Polyneuropathy and myopathy associated with critical illness, avascular necrosis (possibly steroid induced), steroid toxicity, and psychosis were some of the other long-term sequel observed in the SARS survivors.[38]

Morbidity and mortality

SARS can result in significant illness and medical complications that require hospitalization, intensive care treatment, and mechanical ventilation.[39] Morbidity and mortality rates were observed to be greater in elderly patients. The overall mortality rate of SARS has been approximately 10%. According to the CDC and WHO, the death rate among individuals older than age 65 years exceeds 50%.