AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

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

SARS initially manifests as a flulike syndrome that may progress to pneumonia, respiratory failure, and, in some cases, death. The mortality rate associated with SARS is significantly higher than that of influenza or other common respiratory tract infections.

The SARS coronavirus 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. In early 2004, several new cases of SARS were investigated in Beijing and in the Anhui province of China. All of these cases were epidemiologically linked to the National Institute of Virology in Beijing, where the outbreak is thought to have originated. The most recent outbreak was believed to have been successfully contained without spread into the general population. Despite concerns that new cases of SARS would emerge in the region, no new cases had been reported as of July 1, 2007. The world's attention has instead focused on the potential for a global avian influenza pandemic due to the H5N1 influenza strain. 

The World Health Organization (WHO) and the US Centers for Disease Control and Prevention (CDC) have posted guidelines and medical information (in both online and traditional forms) for health care professionals to help decrease the transmission of the SARS virus, to ensure appropriate isolation or quarantine of individuals suspected or confirmed to have SARS-CoV infection, and to guide the evaluation and treatment of the disease.^{1, 2}

For more information on this and other emerging infectious diseases, see Medscape's Emerging and Reemerging Infectious Diseases Resource Center.

Pathophysiology

Coronaviruses cause diseases in pigs, birds, and other animals. Preliminary research indicates that SARS-CoV may have originated in livestock (eg, chickens, ducks) or small mammals. Chinese horseshoe bats, which carry SARS-like viruses with genetic homology to SARS-CoV, may have also had a role. From its reservoir, the virus may have mutated, allowing transmission to and infection of humans, perhaps facilitated by the proximity in which humans and livestock live in rural southern China.

As shown in Image 19, the 3 existing coronaviruses include mammalian and avian viruses. These contribute to numerous veterinary diseases (eg, feline infectious peritonitis, avian infectious bronchitis). The coronaviruses can also cause both upper and, more commonly, lower respiratory tract illness in humans (group 1 [human coronavirus 229E] and group 2 [human coronavirus OC43]).

The 1997 avian flu epidemic in Hong Kong, which originated in poultry and spread to humans (resulting in the slaughter of 1.5 million chickens and ducks), is a prime example of this type of zoonotic transmission. Another theory holds that the SARS-CoV originated in small weasel-like animals called civet cats (see Image 18). Closely related to mongooses, these mammals were sold in Guangdong province wet markets as a delicacy. Close contact with the animals themselves, or with their saliva or feces, could have transmitted a mutated form of the virus to humans.

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.

SARS is thought to be primarily transmitted via close person-to-person contact. 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. SARS may also be spread when a person touches infectious secretions or a contaminated surface or object and then directly contacts his or her own eyes, nose, or mouth. 

The WHO reported that 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. However, an analysis by the WHO, entitled "Status of the outbreak and lessons for the immediate future," on the distribution of cases at this development has suggested that transmission may have occurred within the complex via airborne, virus-laden aerosols.³

In May 2003, the WHO reported that only 16 of the more than 7800 people infected with SARS-CoV had contracted the virus on airplanes. All of these cases had occurred before airlines began screening passengers for symptoms (including fever). The strict screening of passengers appeared to be effective in preventing transmission of SARS-CoV in the months following the original outbreak.

Frequency

United States

As of July 1, 2007, only 8 laboratory-confirmed cases of SARS had been reported in the United States—all related to the original outbreak. No SARS-related deaths have been reported in the United States. Current statistics can be reviewed at the Centers for Disease Control and Prevention Web site.²

International

Worldwide numbers of SARS cases from the original outbreak (November 2002 through July 31, 2003) included 8096 cases, 774 deaths, and 7295 recoveries. Individual country statistics are as follows:

• Mainland China - 5327 cases, 349 deaths
• Hong Kong - 1755 cases, 299 deaths
• Taiwan - 346 cases, 37 deaths
• Canada (primarily around Toronto, Ontario) - 251 cases, 43 deaths
• France - 7 cases, 1 death
• Malaysia - 5 cases, 2 deaths
• Philippines - 14 cases, 2 deaths
• Singapore - 238 cases, 14 deaths
• South Africa - 1 case, 1 death
• Thailand - 9 cases, 2 deaths
• Vietnam - 63 cases, 5 deaths

Current statistics can be accessed from the WHO Web site.¹ See Image 13 for a map showing the worldwide distribution of SARS cases during the 2002-2003 outbreak.

Mortality/Morbidity

SARS can result in significant illness and medical complications that require hospitalization, intensive care treatment, and mechanical ventilation.

• The mortality rate of SARS is higher than that of non-H5N1 influenza strains or other common respiratory tract infections.
• The overall mortality rate of SARS has been approximately 10%. According to the CDC and the WHO, the death rate among individuals older than 65 years exceeds 50%.
• The WHO has set the SARS containment period at 20 days. If no new cases of SARS are reported in a given area over a 20-day period, given the relatively short incubation period of the disease, the WHO considers SARS infections in that area to be contained.

Race

All races are equally affected.

Sex

Both sexes are equally affected.

Age

SARS-CoV infection has no predilection for any age group; however, as stated above, morbidity and mortality rates are greater in elderly patients.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

History

In addition to the clinical presentation outlined below, epidemiological statistics and exposure history are also critical to the diagnosis of severe acute respiratory syndrome (SARS). Although secondary SARS cases from the original outbreak occurred around the world, subsequent cases were confined to China. Note that the case definition for SARS is an essential tool from an epidemiological perspective that is continually updated by the CDC (see Updated Interim US Case Definition for Severe Acute Respiratory Syndrome).⁴

• Exposure history
• • Anyone who has close personal contact with a person with known or suspected SARS within 10 days of symptom onset (eg, health care workers, family members, caregivers) is at high risk of SARS-CoV infection.
  • Close contact is defined as caring for or living with a person known to have SARS or having a high likelihood of direct contact with respiratory secretions or body fluids from a patient known to have SARS. Examples of close contact include kissing, embracing, sharing eating or drinking utensils, conversing closely (<3 ft [1 m]), performing a physical examination, or sharing any other direct physical contact. Close contact does not include walking by a person or briefly sitting across a waiting room or office.
  • Research suggests that the major modes of SARS transmission are contact- and droplet-based. Fecal-oral transmission may also be possible via diarrhea. Evidence indicates that SARS may also be transmitted through airborne, virus-containing aerosols.
  • Traveling to an area where community transmission of SARS has been recently documented or suspected (including visiting an airport) within 10 days of symptom onset in that area is a risk factor.
• Clinical presentation
• • See Images 6-7 for the CDC's clinical and reporting criteria for SARS.
  • The exposure and incubation (asymptomatic) period is 2-7 days, although it may be as long as 10 days. An incubation period of up to 14 days has been reported.
  • Stage 1 is a flulike prodrome that begins 2-7 days after incubation and is characterized by fever (>100.4°F [38°C]), fatigue, headaches, chills, myalgias, malaise, anorexia, and, in some cases, diarrhea. This stage lasts 3-7 days.
  • Stage 2 is the lower respiratory tract phase and begins 3 or more days after incubation. Patients experience a dry cough, dyspnea, and, in many cases, progressive hypoxemia. Chest radiography findings may initially be normal, and 7 days or longer may elapse before findings become abnormal. Radiographs may show focal interstitial infiltrates that may progress to a more patchy, generalized distribution. Respiratory failure that requires mechanical ventilation may occur.
  • Documentation of a temperature of more than 100.4°F (38°C) is preferred for diagnosis, but clinical judgment is important in the absence of this finding. Extenuating circumstances for which this preference may be set aside include patients' subjective self-reports of fever, use of antipyretics, presence of conditions or therapies that induce a relative immunocompromised state, lack of access to health care, or inability to obtain a measured temperature.
  • Features consistent with respiratory illness, such as cough, wheezing, dyspnea, and other breathing difficulties, are noted.

Physical

Physical examination findings in patients with SARS are consistent with those of a combined mild-to-severe respiratory tract infection and influenzalike illness. However, from a respiratory standpoint, patients can deteriorate quickly and may require mechanical ventilation during hospitalization.

• Fever, typically higher than 100.4°F (38°C), is present.
• Moderate respiratory illness is indicated by fever (see Clinical presentation) and 1 or more clinical findings of respiratory illness (eg, hypoxia, cough, dyspnea, breathing difficulties).
• Severe respiratory illness is indicated by fever (see Clinical presentation), 1 or more clinical findings of respiratory illness (eg, hypoxia, cough, dyspnea, breathing difficulties), and radiographic evidence of pneumonia or respiratory distress syndrome or autopsy findings consistent with pneumonia or respiratory distress syndrome without an identifiable cause.
• Note that the cough associated with SARS can be mild to severe and tends to be dry and nonproductive.
• Less common findings in SARS include diarrhea, pharyngitis, chills, rigors, nausea, vomiting, and rhinorrhea.
• Chest auscultation results can be unremarkable. If abnormal, findings are more commonly upper respiratory tract in nature as opposed to lower respiratory tract.

Causes

The greatest number of SARS cases have occurred in China. Confirming exposure or possible exposure to SARS-CoV is critical in making an initial diagnosis. Morbidity and mortality rates among persons with SARS worsen with increasing age, especially in the elderly population (ie, >65 y). Coexisting chronic illnesses and immunosuppression are also likely to increase the probability of morbidity and mortality among persons with SARS.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• The laboratory tests discussed below can help confirm the diagnosis of severe acute respiratory syndrome (SARS) per CDC and WHO parameters. See Image 6 for the CDC's clinical criteria for SARS. SARS infection is clinically confirmed when any one of the following criteria is met:
• • Detection of antibodies to SARS-CoV in specimens obtained during acute illness or more than 28 days after illness onset
  • Detection of SARS-CoV RNA via reverse transcriptase-polymerase chain reaction (RT-PCR) and confirmed with a second PCR assay using a second aliquot of the specimen
  • Isolation of SARS-CoV in culture, with confirmation using a test validated by the CDC
• SARS-CoV infection is unconfirmed in the absence of antibodies to SARS-CoV in convalescent serum obtained 28 days or more after symptom onset.
• SARS-CoV infection is unconfirmed if laboratory testing is not performed or is incomplete.
• Data from the 2002-2003 outbreak indicate that SARS may be associated with the following laboratory findings:
• • Modest lymphopenia, leukopenia, and thrombocytopenia: Series have shown WBC counts of less than 3.5 X 10⁹/L and lymphopenia of less than approximately 1 X 10⁹/L.
  • Mild hyponatremia and hypokalemia
  • Elevated levels of lactate dehydrogenase, alanine aminotransferase, and hepatic transaminase
  • Elevated creatine kinase level
• Testing for SARS-CoV is as follows:
• • Coronavirus antibody testing methods: These include indirect fluorescent antibody or enzyme-linked immunosorbent assays, which are used to test for specific antibodies after infection. Although these antibodies are found in some patients during the acute phase (ie, within 14 d of onset), a negative test finding using a sample that has been obtained less than 28 days after symptom onset does not exclude the diagnosis of SARS.
  • RT-PCR: Results can be positive in some patients within the first 10 days of fever. RT-PCR can be used to detect SARS-CoV in serum, stool, and nasal secretions.
  • Viral culture: SARS-CoV can also be isolated in viral cultures.
  • A negative SARS-CoV antibody test finding less than 28 days after symptom onset, a negative PCR finding, and a negative viral culture finding do not exclude the diagnosis of SARS. Obtaining convalescent serum for a final antibody determination 28 days or more after symptom onset is critical to the diagnosis of SARS.
• Initial tests in patients suspected to have SARS include pulse oximetry, blood cultures, sputum Gram stain and culture, and viral respiratory pathogen tests, notably influenza A and B viruses and respiratory syncytial virus.
• • Legionella and pneumococcal urinary antigen testing should also be considered. Specimens should also be made available for antibody testing (as outlined above), PCR, and viral culture/isolation tests.
  • Acute and convalescent (>28 d after symptom onset) serum samples should be collected. Paired sera and other clinical specimens can be forwarded through state and local health departments for testing at the CDC.
  • Test results for human metapneumovirus, a virus genetically related to respiratory syncytial virus, have been positive in some patients with SARS. Although human metapneumovirus was once considered a potential etiology for SARS, the role of this finding is unclear. Investigators initially found paramyxoviruslike particles in patients with SARS in Hong Kong and Frankfurt; however, the relative importance of this finding is not clear and past studies elucidating SARS-CoV as the causative virus appear definitive.
• The following are the CDC's guidelines for the laboratory diagnosis of SARS-CoV infection as of January 8, 2004. Diagnosis is established based on detection of any of the following with a validated test, with confirmation in a reference laboratory:
• • Serum antibodies to SARS-CoV in a single serum specimen
  • A 4-fold or greater increase in SARS-CoV antibody titer between acute- and convalescent-phase serum specimens tested in parallel
  • Negative SARS-CoV antibody test result on acute-phase serum and positive SARS-CoV antibody test result on convalescent-phase serum tested in parallel
  • Isolation in cell culture of SARS-CoV from a clinical specimen, with confirmation using a test validated by the CDC
  • Detection of SARS-CoV RNA via RT-PCR validated by the CDC, with confirmation in a reference laboratory, from (1) 2 clinical specimens from different sources or (2) 2 clinical specimens collected from the same source on 2 different days

Imaging Studies

• SARS imaging protocols are still being formulated by the CDC, WHO, and various treating institutions around the world. See Radiological Appearances of Cases of Atypical Pneumonia in Hong Kong for images that show the atypical pneumonia associated with SARS.
• Clearly, the first images to obtain are high-quality posteroanterior and lateral chest radiographs. Serial chest radiography can be used to monitor and evaluate patient progress. Reviewing cases from the 2002-2003 outbreak can be helpful in identifying characteristic radiologic abnormalities found with SARS (see Images 8-10).
• • Initial chest radiography findings were found to be abnormal in approximately 60% of patients. Abnormalities on chest radiographs were observed in serial examinations in nearly all patients by 10-14 days after symptom onset.
  • Interstitial infiltrates can be observed early in the disease course.
  • In the early stage, a peripheral, pleural-based opacity (ranging from ground-glass opacification to frank consolidation) may be the only abnormality. High-resolution CT (HRCT) scanning of the chest during this time may reveal an infiltrate in the retrocardiac region.
  • As the disease progresses, widespread opacification affects large areas. These changes tend to affect the lower lung fields first. Calcification, cavitation, pleural effusion, and lymphadenopathy are not observed in SARS.
• HRCT scanning of the chest
• • The role of HRCT scanning in the evaluation of SARS is still controversial. Patients with abnormal chest radiographic findings do not need HRCT scanning. However, when SARS is a strong clinical possibility despite a normal chest radiographic finding, the clinician should consider HRCT scanning.
  • Findings consistent with SARS include ground-glass opacification, with or without thickening of the intralobular interstitium or interlobular interstitium, or frank consolidation.
  • A combination of ground-glass opacification (with or without thickening of the interstitium) and frank consolidation may be noted.

Histologic Findings

SARS-CoV is a member of the Coronavirus family. Coronaviruses, which are best known as the second most common cause of the common cold in humans, are enveloped viruses that replicate in the cytoplasm of the host cell. Coronaviruses were named for their crownlike appearance on electron microscopy images (see Images 1-2). Actual electron microscopic images of SARS-CoV can be viewed in Images 3-4. SARS-CoV infection causes significant damage to lung tissue, as is seen in Image 5.

SARS-CoV genetic material is a single-stranded, plus-sense RNA. The genome is approximately 30 kilobase in length. A schematic graph of the SARS viral genome is shown in Image 12. An entire article describing the SARS genome is contained in PDF format as Image 11 and is included in the bibliography.⁵

Single-stranded 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.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

Currently, no definitive medication protocol specific to severe acute respiratory syndrome (SARS) has been developed, although various treatment regimens have been tried without proven success. The CDC recommends that patients suspected or confirmed as having SARS receive the same treatment they would be administered if they had any serious community-acquired pneumonia.

Isolate patients confirmed or suspected to have SARS as outlined below, and provide aggressive treatment in a hospital setting. Mechanical ventilation and critical care treatment may be necessary during the illness. An infectious disease specialist, pulmonary specialist, and/or a critical care specialist should direct the medical care team. Communication with local and state health agencies, the CDC, and the WHO is critical.

• Antibiotics: Because SARS is a viral infection, antibiotics are not indicated. In some of the early cases, antibiotics were administered as part of the treatment regimen, but no positive effect was noted.
• Steroids: Various steroid regimens have been used around the world as part of the initial SARS treatment cocktail. In the initial Hong Kong cohort of patients, corticosteroids were first given (with ribavirin) because of the similarity of the clinical and radiographic findings of SARS to those of bronchiolitis obliterans-organizing pneumonia. Despite anecdotal reports of success, they have not subsequently been confirmed in a clinical trial. Future SARS cases in the United States may be managed with corticosteroids early in the treatment regimen, and dosages would likely reflect those used in patients with bronchiolitis obliterans-organizing pneumonia. The role of steroids in the treatment of SARS will probably not be fully defined until further clinical experience is obtained.
• Antiviral agents: Several antiviral medications have been tried as part of the SARS treatment regimen.
• • The most widely used of these to date is ribavirin (usually in conjunction with steroids). Despite early anecdotal reports of patients with SARS improving with a combination of ribavirin and steroids, ribavirin does not have proven activity against Coronaviridae members and should be strongly discouraged. Oseltamivir and lopinavir/ritonavir are other agents that have also been tried, but their efficacy has not been proven.
  • Thousands of other antiviral compounds have screened and tested for effect against SARS in the United States (eg, by the US Army) and internationally.
• Interferon: Preliminary testing at the US Army's biodefense laboratory has indicated that interferon may have an anti-SARS effect. Other studies have suggested that the combination of interferon alfacon-1 and corticosteroids resulted in more rapid improvement in radiographic abnormalities and oxygen saturation than when corticosteroids were used alone. Virus-infected macaques were also shown to have reduced virus excretion and lung damage after receiving pegylated interferon.⁶
• SARS-CoV vaccine
• • Chinese researchers began testing a SARS vaccine in humans in May 2004. The Chinese vaccine trial used an inactivated SARS virus vaccine developed through conventional vaccine technology.
  • The first US SARS vaccine trial began at the National Institutes of Health (NIH) in December 2004. The NIH vaccine is composed of a small circular piece of DNA that encodes the viral spike protein. The primary goal of the study is to determine if the experimental vaccine is safe in humans. A secondary goal is to assess how well the vaccine stimulates the immune system to produce antibodies and cellular immunity, in this case focusing on the SARS spike protein.
  • In June 2005, researchers reported on the development of an edible SARS-CoV vaccine created through genetically modified tomato and tobacco plants. The technology, still in the early stages of development, has the potential for producing an inexpensive and easily administered SARS vaccine.

Consultations

Patients suspected of having SARS should be properly identified by physicians and other health care professionals. They should be isolated as soon as possible and should receive aggressive medical care. Patients who possibly have SARS must be isolated in areas separate from those who probably have SARS, and their contacts over the past 10-14 days must be identified and evaluated.

The care team for patients who might have SARS includes an infectious disease specialist, a pulmonary specialist, and/or a critical care specialist. ICU treatment and mechanical ventilation may be necessary.

Diet

No specific dietary recommendations have been made for SARS. The SARS clinical presentation may include diarrhea, nausea, and vomiting in a minority (20%) of patients. Nutritional and fluid supplementation may be necessary. Observe isolation and infection precautions when caring for these patients because the SARS-CoV can survive for several days in human secretions.

Activity

The CDC has issued guidelines governing the activity and isolation of patients with SARS, their immediate contacts, and the health care professionals who treat them.

Patients with SARS pose a risk of transmission to close household contacts and health care personnel. The period before or after the onset of symptoms during which a patient with SARS is infectious is unknown. In household or residential settings, infection control measures, as described below, are recommended. These recommendations are based on preliminary experience and may be revised as more information becomes available.

• Patients with SARS should limit interactions outside the home and should not go to work, school, out-of-home child care facilities, or other public areas until 10 days after the fever resolves, provided respiratory symptoms are absent or improving. During this time, infection control precautions should be used to minimize the potential for transmission.
• • All members of a household with a patient with SARS should carefully follow recommendations for hand hygiene (eg, frequent hand washing, use of alcohol-based hand rubs), particularly after contact with body fluids (eg, respiratory secretions, urine, feces).
  • Disposable gloves should be used for any direct contact with the body fluids of a patient with SARS. However, gloves are not intended to replace proper hand hygiene. Immediately after activities involving contact with body fluids, gloves should be removed and discarded, and hands should be cleaned. Gloves must never be washed or reused.
• Each patient with SARS should be advised to cover his or her mouth and nose with a facial tissue when coughing or sneezing. If possible, patients with SARS should wear surgical masks during close contact with uninfected persons in order to prevent the spread of infectious droplets. If a patient with SARS cannot wear a surgical mask, his or her household members should wear surgical masks when in close contact.
• • Sharing of eating utensils, towels, and bedding between patients with SARS and others should be avoided, although such items can be used by others after routine cleaning (eg, washing with soap and hot water). Environmental surfaces soiled by body fluids should be cleaned with a household disinfectant according to manufacturer's instructions; gloves should be worn during this activity.
  • Household waste soiled with body fluids of patients with SARS, including facial tissues and surgical masks, may be discarded as normal waste.
• Household members and other close contacts of patients with SARS should be actively monitored by local health departments.
• • Household members or other close contacts of patients with SARS should be vigilant for the development of fever or respiratory symptoms and, if these develop, should seek a health care evaluation. Prior to the evaluation, health care providers should be informed when an individual is a close contact of a patient with SARS so necessary arrangements can be made to prevent transmission to others in the health care setting. Household members or other close contacts with symptoms of SARS should follow the precautions recommended for patients with SARS.
  • At this time, in the absence of fever or respiratory symptoms, the CDC recommends that household members or other close contacts of patients with SARS need not limit their activities outside the home.
• The following is an executive order regarding quarantinable communicable diseases issued by the President of the United States on April 4, 2003:⁷
  
  Executive Order 13295: Revised List of Quarantinable Communicable Diseases

By the authority vested in me as President by the Constitution and the laws of the United States of America, including section 361(b) of the Public Health Service Act (42 U.S.C. 264(b)), it is hereby ordered as follows:

Section 1. Based upon the recommendation of the Secretary of Health and Human Services (the "Secretary"), in consultation with the Surgeon General, and for the purpose of specifying certain communicable diseases for regulations providing for the apprehension, detention, or conditional release of individuals to prevent the introduction, transmission, or spread of suspected communicable diseases, the following communicable diseases are hereby specified pursuant to section 361(b) of the Public Health Service Act:

(a) Cholera; Diphtheria; infectious Tuberculosis; Plague; Smallpox; Yellow Fever; and Viral Hemorrhagic Fevers (Lassa, Marburg, Ebola, Crimean-Congo, South American, and others not yet isolated or named).

(b) Severe Acute Respiratory Syndrome (SARS), which is a disease associated with fever and signs and symptoms of pneumonia or other respiratory illness, is transmitted from person to person predominantly by the aerosolized or droplet route, and, if spread in the population, would have severe public health consequences.

Sec. 2. The Secretary, in the Secretary's discretion, shall determine whether a particular condition constitutes a communicable disease of the type specified in section 1 of this order.

Sec. 3. The functions of the President under sections 362 and 364(a) of the Public Health Service Act (42 U.S.C. 265 and 267(a)) are assigned to the Secretary.

Sec. 4. This order is not intended to, and does not, create any right or benefit enforceable at law or equity by any party against the United States, its departments, agencies, entities, officers, employees or agents, or any other person.

Sec. 5. Executive Order 12452 of December 22, 1983, is hereby revoked.
GEORGE W. BUSH
THE WHITE HOUSE
April 4, 2003

FOLLOW-UP

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• Severe acute respiratory syndrome (SARS) is a severe viral illness that requires prompt medical attention and hospitalization.
• • Isolation protocols described in this article must be followed.
  • Local, state, and federal health agencies must be notified.
  • Every attempt must be made to identify individuals who were in contact with a patient with possible or confirmed SARS within the 2 weeks before symptom onset.
  • Patients with SARS may require mechanical ventilation and ICU care.

Further Outpatient Care

• Once the patient is discharged, confirm that the post–28-day convalescent serum has been collected (or is scheduled to be collected) for diagnostic confirmation.
• • Schedule follow-up care with the patient's primary care physician.
  • Confirm that all the patient's pre-illness contacts have been identified and evaluated.
  • Confirm that all the necessary patient samples have been collected per local, state, and federal health agency regulations.

In/Out Patient Meds

• No medication protocols are currently approved for patients with SARS. All patients with SARS should be treated on a case-by-case basis in cooperation with an infectious disease specialist. Input from pulmonary specialists and critical care specialists may also be required.

Deterrence/Prevention

• See Activity and Multimedia for material pertaining to CDC-recommended SARS isolation and infection-prevention procedures. Travel restrictions and recommendations issued by the WHO should also be reviewed.⁸
• Airport screening measures include the following:
• • Airport screening for potentially sick and/or febrile passengers is being conducted in SARS-affected regions in Asia.
  • Infrared scanners designed for use by the military for night operations have been adapted for airport screening use in various locales (eg, Singapore). These scanners are used to identify potentially febrile passengers by measuring their body heat.
  • Individuals with positive screening results on these infrared scanners are then temporarily isolated and brought to a special cubicle, where temperatures are confirmed with an oral thermometer.
  • Any person with a skin temperature of 99.5°F (37.5°C) or greater glows bright red on the scanner. The software is color-coded in temperature ranges; as skin temperature increases, the colors on the scanner change (eg, black to green to yellow and, finally, to red).
  • Many other noninfectious causes can increase skin temperature, including sunburn, ingestion of alcoholic beverages, recent cigarette smoking, or brisk exercise. Thus, false-positive results are common with these scanners.

Complications

• As with most viral illnesses, SARS encompasses a spectrum of disease severity.
• • Mortality statistics have shown a significant increase with advancing age. Mortality rates are approximately 4-5% in the third decade of life or younger and are approximately 50% in patients older than 65 years. The overall mortality rate is approximately 10%.
  • Recovery may be prolonged, including care in an ICU setting and mechanical ventilation. Complications related to a prolonged illness (eg, deep venous thrombosis, myocardial infarction, stroke) can occur.

Prognosis

• See Mortality/Morbidity. Note that the evaluation criteria for this illness are largely based on data obtained during the original 2002-2003 outbreak.
• Some data have suggested that certain risk factors—including older age, chronic hepatitis B infection, and laboratory features such as marked lymphopenia and elevated polymorphonuclear lymphocyte count, lactate dehydrogenase level, and alanine aminotransferase level—are associated with more progressive disease.

Patient Education

• Check the World Health Organization and Centers for Disease Control and Prevention Web sites and see Multimedia for further education on SARS.
• For excellent patient education resources, visit eMedicine's Pneumonia Center, Public Health Center, and Bacterial and Viral Infections Center. Also, see eMedicine's patient education articles Viral Pneumonia, Flu in Adults, Foreign Travel, and Severe Acute Respiratory Syndrome (SARS).

MISCELLANEOUS

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• No specific medicolegal pitfalls are associated with severe acute respiratory syndrome (SARS).

Special Concerns

• Visit the CDC's SARS Information for Travelers Web page for the latest travel alerts and advisories. Details regarding CDC travel alerts versus travel advisories are as follows:
• • Definitions
  • • Travel alert: These alerts notify the public that an outbreak of a disease is occurring in a geographic area. The purpose of an alert is to provide accurate information to travelers and resident expatriates about the status of the outbreak, how they can reduce their risk of infection, and what to do if they should become ill while in the area. The risk for the individual traveler is felt to be definable and limited; transmission has occurred in defined settings or is associated with specific risk factors (eg, transmission in a health care or hospital setting where ill patients are being treated). Nonessential travel to the area is not discouraged.
    • Travel advisory: These advisories notify the public that a disease is occurring in a geographic area. The purpose of an advisory is to provide accurate information to travelers and resident expatriates about the status of the outbreak and how they can reduce their risk of infection. They also serve to reduce the volume of traffic to the affected areas, which, in turn, can reduce the risk of translocating the disease to previously unaffected sites. Nonessential travel to the area is discouraged because the risk for the traveler is considered to be much higher than for a simple travel alert notice. For example, the risk is increased because of evidence of community transmission and/or inadequate containment.
  • Criteria for instituting alerts and advisories
  • • Disease transmission: The magnitude and scope of the outbreak in the area will affect the decision to issue an advisory or an alert. Criteria that can be used include the presence or absence of community transmission and evidence that cases have been exported from the area.
    • Containment measures: The presence or absence of acceptable outbreak control measures in the affected area can influence the decision to issue a travel advisory or alert. Areas where the disease is occurring and that are considered to have poor or no containment measures in place may have the potential for a higher risk of transmission to exposed persons and translocation to other sites. (Note that isolation refers to the implementation of infection-control measures to isolate individuals who are sick, whereas quarantine refers to the restriction of individuals who are relatively well.)
    • Quality of surveillance: Criteria include whether health authorities in the area have the ability to accurately detect and report cases and to conduct appropriate contact tracing of exposed persons. Areas where the disease is occurring and that are considered to have poor surveillance systems may have the potential for a higher risk of transmission.
    • Quality and accessibility of medical care: Areas where the disease is occurring and that are considered to have suboptimal medical services or infection control procedures in place and remote locations without access to medical evacuation may be considered to present a higher level of risk for the traveler.
  • To downgrade a travel advisory to a travel alert, the following criteria should be met:
  • • Adequate surveillance data from the area
    • No evidence of ongoing community transmission for 2 maximal incubation periods after the date of onset of symptoms for the last case (For SARS, this period would be 20 days.)
  • To remove a travel alert, the following criteria should be met:
  • • Adequate surveillance data from the area: For example, with SARS, the area would be reporting both probable and suspected cases.
    • No evidence of new cases for 3 maximal incubation periods after the date of onset of symptoms for the last case: For SARS, this period would be 30 days.
    • Limited or no recent instances of unintentional exported cases from the area: This excludes intentional or planned evacuations.
• WHO travel recommendations
• • Visit the WHO's Travel Web page for the most recent travel recommendations.
  • The most important message for international travelers concerning SARS is to be aware of the main symptoms of SARS: high fever (ie, 100.4°F [38°C]), dry cough, shortness of breath, or breathing difficulties. Persons who experience these symptoms and who have been in an area where recent local transmission of SARS has occurred in the last 10 days are advised to contact a doctor.
  • In the absence of effective drugs or a SARS vaccine, control of this disease relies on the rapid identification of patients and appropriate treatment, including the isolation of suspected and probable cases and the treatment of close contacts. In the great majority of countries, these measures have prevented imported cases from spreading the disease.
  • • To further reduce the risk that travelers may carry the SARS virus to new areas, international travelers departing from areas with local transmission in the B or C categories should be screened for possible SARS at the point of departure.
    • Such screening involves answering 2-3 questions and may include a temperature check. Travelers with 1 or more symptoms of SARS who have a history of exposure, who have a fever, or who appear acutely ill should be assessed by a health care worker and may be advised to postpone their trip until they have recovered.
  • The WHO does not presently conclude that goods, products, or animals arriving from areas with SARS outbreaks pose a risk to public health. No restrictions in this regard are recommended.
  • • The WHO further recommends that persons arriving from areas with recent local transmission should be aware of the main symptoms of SARS described above and should seek medical advice, initially by telephone, if they develop symptoms in the 10 days after they have left the outbreak area. Healthy persons who are not contacts of probable cases require no special measures and should be free to carry out normal activities.
    • Contacts of probable cases should not travel until 10 days after the last contact, assuming they themselves remain well. If, despite the advice above, a contact of a probable case travels to another country, the person should be placed in voluntary isolation and kept under active surveillance by the health authorities in the country of arrival.
  • Travelers are advised to contact their doctors or national health authorities for supplementary information because individual countries may adapt WHO recommendations to take into account national considerations. Many national health authorities have established Web sites with excellent information.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Transmission electron micrograph of human coronavirus OC43 (HCV-OC43). Courtesy of the US Centers for Disease Control and Prevention.
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Media file 2:  Electron microscopic view of a member of the Coronavirus family. These viruses have a crownlike (corona) appearance when viewed in this fashion. Courtesy of the US Centers for Disease Control and Prevention.
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Media file 3:  Thin-section electron micrograph of the severe acute respiratory syndrome–associated coronavirus isolated in FRhK-4 cells. Courtesy of the Government Virus Unit, Department of Health, Hong Kong SAR, China.
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Media file 4:  Electron micrograph of the severe acute respiratory syndrome–associated coronavirus. Note the negatively staining virus particles. Courtesy of the Government Virus Unit, Department of Health, Hong Kong SAR, China.
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Media file 5:  Pathologic slide of pulmonary tissue infected with severe acute respiratory syndrome–associated 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.
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Media file 6:  Severe acute respiratory syndrome case definition put forth by the US Centers for Disease Control and Prevention (CDC) on April 29, 2003. Courtesy of the CDC.
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Media file 7:  Clinical and laboratory criteria for severe acute respiratory syndrome cases and infection per the US Centers for Disease Control and Prevention (CDC) on April 29, 2003. Courtesy of the CDC.
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Media file 8:  Initial chest radiograph of a 52-year-old symptomatic woman with severe acute respiratory syndrome (March 15, 2003). Ground-glass, bilateral, and peripheral changes are noted in the lower lung fields. Courtesy of Michael E. Katz, MD.
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Media file 9:  Chest radiograph of a 52-year-old symptomatic woman with severe acute respiratory syndrome (March 19, 2003) taken 4 days after presentation. Moderately severe ground-glass and consolidative bilateral changes are noted in the lower lung fields and are somewhat worse on the left side. Courtesy of Michael E. Katz, MD.
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Media file 10:  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 ground-glass and consolidative bilateral changes are noted in the lung fields and are somewhat worse on the left side. Courtesy of Michael E. Katz, MD.
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Media file 11:  Downloadable PDF file of the article "The Genome Sequence of the SARS-Associated Coronavirus." Courtesy of the Sciencexpress.
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Media file 12:  Schematic representation of the severe acute respiratory syndrome–associated coronavirus genome from the article "The Genome Sequence of the SARS-Associated Coronavirus." Courtesy of the Sciencexpress.
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Media file 13:  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.
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Media file 14:  PDF file of the US Centers for Disease Control and Prevention (CDC) fact sheet titled "Information For Close Contacts of SARS Patients." Courtesy of the CDC.
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Media file 15:  Empty jewelry showcases from the Hong Kong and Singapore Zurich Trade Fair. The effect of severe acute respiratory syndrome (SARS) on the economies of affected Asian countries and Canada is thought to run into the billions of dollars. This photograph was published by the US Centers for Disease Control and Prevention as part of a PowerPoint presentation in the Web cast "Public Health Community Preparedness for SARS."
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Media file 16:  Yellow health alert card given to international travelers arriving in the United States from Canada. Courtesy of the US Centers for Disease Control and Prevention.
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Media file 17:  Hospital infection control strategies have been essential to containing severe acute respiratory syndrome (SARS) outbreaks in affected countries. Health care workers are advised to follow strict contact and airborne precautions when caring for a patient suspected of having SARS. This photo was published by the US Centers for Disease Control and Prevention as part of a Powerpoint presentation in the Web cast "Public Health Community Preparedness for SARS."
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Media file 18:  One theory holds that the severe acute respiratory syndrome–associated coronavirus originated in small weasel-like animals called civet cats. Closely related to mongooses, these mammals were sold in a Guangdong (China) marketplace as a delicacy. Close contact with the animals themselves, or with their saliva or feces, could have transmitted a mutated form of the virus to humans.
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Media file 19:  Coronaviruses. Image adapted from the University of Leicester Microbiology & Immunology Web site.
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REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

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3. Centers for Disease Control and Prevention. Executive order 13295: Revised list of quarantinable communicable diseases. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/ncidod/sars/executiveorder040403.htm. Accessed October 2007.
4. World Health Organization. Severe acute respiratory syndrome (SARS): Status of the outbreak and lessons for the immediate future. World Health Organization. Available at http://www.who.int/csr/media/sars_wha.pdf. Accessed October 2007.
5. Marra MA, Jones SJ, Astell CR, et al. The Genome sequence of the SARS-associated coronavirus. Science. May 30 2003;300(5624):1399-404. [Medline].
6. Liang WN, Liu M, Chen Q, et al. Assessment of impacts of public health interventions on the SARS epidemic in Beijing in terms of the intervals between its symptom onset, hospital admission, and notification. Biomed Environ Sci. Jun 2005;18(3):153-8. [Medline].
7. Zakhartchouk AN, Viswanathan S, Moshynskyy I, Petric M, Babiuk LA. Optimization of a DNA Vaccine Against SARS. DNA Cell Biol. Jul 31 2007;[Medline].
8. World Health Organization. WHO recommended measures for persons undertaking international travel from areas affected by severe acute respiratory syndrome (SARS). Wkly Epidemiol Rec. Apr 4 2003;78(14):97-9. [Medline].
9. Anand K, Ziebuhr J, Wadhwani P, et al. Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs. Science. Jun 13 2003;300(5626):1763-7. [Medline].
10. Armed Forces Institute of Pathology. Severe Acute Respiratory Syndrome (SARS). Armed Forces Institute of Pathology. Available at http://www.afip.org/Departments/Pulmonary/SARS/. Accessed 2003.
11. Bartlam M, Xu Y, Rao Z. Structural proteomics of the SARS coronavirus: a model response to emerging infectious diseases. J Struct Funct Genomics. Aug 7 2007;[Medline].
12. Bloom BR. Lessons from SARS. Science. May 2 2003;300(5620):701. [Medline].
13. Booth CM, Matukas LM, Tomlinson GA, et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA. Jun 4 2003;289(21):2801-9. [Medline].
14. Centers for Disease Control and Prevention. Clinical Guidance on the Identification and Evaluation of Possible SARS-CoV Disease among Persons Presenting with Community-Acquired Illness, Version 2. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/ncidod/sars/clinicalguidance.htm.
15. Centers for Disease Control and Prevention. Frequently Asked Questions about SARS. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/ncidod/sars/faq.htm.
16. Centers for Disease Control and Prevention. Guidelines for Laboratory Diagnosis of SARS-CoV Infection. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/ncidod/sars/clinicalguidance.htm.
17. Centers for Disease Control and Prevention. In the Absence of SARS-CoV Transmission Worldwide: Guidance for Surveillance, Clinical and Laboratory Evaluation, and Reporting, Version 2. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/ncidod/sars/clinicalguidance.htm.