Six months into its history, scientists are beginning to unravel the microbiology, clinical manifestations, and containment of severe acute respiratory syndrome. No specific treatment recommendations can yet be made.

Severe acute respiratory syndrome (SARS)—a new clinical entity that has received worldwide media attention—is an acute respiratory syndrome of unknown etiology. To date, more than 4,400 suspected SARS cases have been reported to the World Health Organization (WHO), primarily from locations in Asia, North America, and Europe.1,2 As of this writing, the vast majority of cases have occurred in China (2,422), Hong Kong (1,488), and Singapore (192).2 There have been 140 cases in Canada and 37 in the United States.2 Clusters of SARS-infected people have been identified, suggesting that SARS is highly contagious. A fatality rate of 3% to 4% has been observed in patients with SARS.1

Investigators have isolated a previously unknown coronavirus from patients with SARS.3-5 Urbani SARS-associated coronavirus has been proposed as a name for the virus.5

Respiratory illness of unknown etiology with onset since February 1, 2003, and the following:

measured temperature —>38.°C;

one or more clinical findings of respiratory illness (cough, shortness of breath, difficulty breathing, hypoxia, or radiographic findings of either pneumonia or adult respiratory distress syndrome; and travel within 10 days of onset of symptoms with either a person with a respiratory illness who has traveled to a SARS area or a person under investigation for (or suspected of having) SARS—or—close contact within 10 days of onset of symptoms with either a person with a respiratory illness who has traveled to a SARS area or a person under investigation for (or suspected of having) SARS. Close contact is defined as having cared for, having lived with, or having had direct contact with respiratory secretions and/or body fluids of a patient suspected of having SARS.
Table 1. Updated interim definition for severe acute respiratory syndrome. Adapted from MMWR Morb Mortal Wkly Rep.1

Microbiology
Members of the family Coronaviridae are large, enveloped, plus-stranded RNA viruses that cause disease in humans and domestic animals. They were given their name because of the unusual petal-shaped projections that emanate from their envelopes, thereby giving the virus the appearance of a solar corona. The virus is roughly spherical, with long, helical nucleocapsids, and can range in size from 60 nm to 220 nm.3 Coronaviruses have the largest genome of all RNA viruses and display a unique replication strategy, genome organization, and messenger-RNA structure that produce a high frequency of genetic recombination.6 The frequency with which genetic recombination between the genomes of different but related coronaviruses produces a virus with new biological properties can be as high as 25%.6 Viral progeny are produced in the cytoplasm and are released by exocytosis, eventually killing the infected cell.

Different members of the family Coronaviridae display specificity for the respiratory tract, gastrointestinal organs, liver, or brain. Until now, no evidence had been obtained to link human coronaviruses with any human disease other than the common cold.

Transmission and Incubation
The primary mode of spread of SARS is through respiratory secretions. Close person-to-person contact is usually needed. Most cases of SARS have involved people who cared for or lived with a person infected by this virus, or had direct contact with infectious material. Touching the skin of other people or objects contaminated by the virus and then touching the eyes, nose, or mouth may spread SARS. This can happen when people who have SARS sneeze, cough, or talk, distributing respiratory droplets onto themselves, other people, or nearby surfaces. The SARS virus is also present in fecal matter, and fecal transmission has been proposed to explain some case clusters.

Most SARS patients have been adults 25 to 70 years old who were previously healthy.7 The incubation period for SARS is typically 2 to 7 days; however, some reports have suggested an incubation period as long as 10 days.7 Whether an infected person can transmit SARS before or after the period during which symptoms are evident is unknown.8

SARS has occurred in health care workers who had previously cared for SARS patients. This may be of particular concern to RTs. According to the Centers for Disease Control and Prevention (CDC), the agency has received “anecdotal reports that aerosol-generating procedures may have facilitated transmission of the etiologic agent of SARS in some cases. Procedures that induce coughing can increase the likelihood of droplet nuclei being expelled into the air. These potentially aerosol-generating procedures include aerosolized medication treatments, diagnostic sputum induction, bronchoscopy, airway suctioning, and endotracheal intubation.”8 The CDC recommends evaluating patients for SARS before they undergo aerosol-generating procedures and following the infection-control measures currently recommended to prevent the transmission of Mycobacterium tuberculosis.8

Clinical Manifestations
The WHO has provided an updated clinical definition of SARS (Table 1). SARS typically begins with a prodrome of high fever that may be accompanied by chills, rigors, headache, malaise, and myalgia. Some patients experience mild respiratory distress at the onset of illness. Rash and gastrointestinal findings are normally absent. The severity of SARS ranges from mild illness to death.

Approximately 3 to 7 days after the onset of symptoms, a lower-respiratory phase begins. This is characterized by a dry, nonproductive cough or dyspnea, which may progress to hypoxemia. In 10% to 20% of cases, SARS is severe enough for the patient to require intubation and mechanical ventilation.2

Chest radiographs may be normal during the prodrome phase and throughout the course of illness. In many patients, however, the lower-respiratory phase is characterized by early focal interstitial infiltrates that can progress to more generalized patchy interstitial infiltrates. In the late stages of SARS, chest radiographs may show areas of consolidation. Laboratory findings of patients with SARS are summarized in Table 2.

  • Decreased absolute lymphocyte count early in the course of disease
  • Normal or slightly decreased overall white–blood-cell count early in the course of disease; leukopenia in 50% of patients at the peak of the lower-respiratory phase
  • Normal or slightly decreased platelet count early in the course of disease;       thrombocytopenia or low-normal platelet count (50,000 to 150,000/mL) at the peak of the lower-respiratory phase
  • Elevated serum creatine phosphoki nase levels (as high as 3,000 IU/L) and serum hepatic transaminases (two to six times the upper limit of normal) at the peak of the lower-respiratory phase
  • Normal renal function
Table 2. Typical laboratory findings in patients with severe acute respiratory syndrome. Adapted from MMWR Morb Mortal Wkly Rep.7

Treatment and Reporting
No specific treatment recommendations can be made at this time. Empiric therapy should include coverage of organisms associated with any community-acquired pneumonia of unclear etiology, and should include agents with activity against both typical and atypical respiratory pathogens.9 Treatment choices may be influenced by the severity of the illness. Infectious disease consultation is recommended.

The CDC requests that health care personnel who suspect cases of SARS report the cases to their state health departments. State health departments, international airlines, cruise ships, and cargo carriers are asked to report cases directly to the SARS Investigative Team at the CDC Emergency Operations Center by calling (770) 488-7100.

Additional and updated information about SARS—including infection-control guidance and detailed procedures for reporting suspected cases—is available at www.cdc.gov/ncidod/sars.  Updated worldwide case counts are available at www.who.int. 

John D. Zoidis, MD, is a contributing writer for RT. Phyllis C. Braun, PhD, is professor, Department of Biology, Fairfield University, Fairfield, Conn.

References
1. CDC. Update: outbreak of severe acute respiratory syndrome—worldwide, 2003. MMWR Morb Mortal Wkly Rep. 2003;52:241-248.
2. WHO. SARS: cumulative number of reported probable cases. Available at: http://www. who.int/csr/sars/map2003_04_24.gif. Accessed May 2, 2003.
3. Peiris J, Lai S, Poon L, et al. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet. 2003;361:1319-1325.
4. Drosten C, Gunther S, Preiser W, et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med. Available at: http://content.nejm.org/ early_release/sars.dtl. Accessed May 8, 2003.
5. Ksiazek TG, Erdman D, Goldsmith CS, et al. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003;348:1947-1958.
6. Lai MM. Genetic recombination in RNA viruses. Curr Top Microbiol Immunol. 1992;176:21-32.
7. CDC. Preliminary clinical description of severe acute respiratory syndrome. MMWR Morb Mortal Wkly Rep. 2003;52:255-256.
8. CDC. Infection control precautions for aerosol-generating procedures on patients who have suspected severe acute respiratory syndrome (SARS). Available at: http://www. cdc.gov/ncidod/ sars/aerosolinfectioncontrol.htm. Accessed May 8, 2003.
9. CDC. Severe acute respiratory syndrome (SARS): treatment. Available at: http:// www.cdc.gov/ncidod/sars/treatment.htm. Accessed May 2, 2003.