Posted December 1, 2010
Robert Schlaberg, MD, FCAP
In November 2002, local physicians noted an outbreak of rapidly progressive respiratory disease in the Guangdong province of China. The disease presented as a febrile prodrome with headache, myalgias, and diarrhea followed by dry cough and dyspnea progressing to respiratory failure in approximately 20% of patients.1 In April, a novel coronavirus (SARS-CoV) was identified as the causative agent,2 and the epidemic started to wane in May of 2003. Diagnosis of the last naturally acquired case was made in China in December of 2003.3 More than 8,000 individuals in 29 countries contracted the disease, and more than 700 patients died.4 The case fatality ratio averaged ~10%4 but reached much higher levels in older individuals.5 At the time of this article’s writing, no cases had been diagnosed since 2004. The World Health Organization (WHO) publishes situation updates3 and areas of recent activity6.
Experts believe that Severe Acute Respiratory Syndrome (SARS) has a zoonotic origin with palm civets and horseshoe bats serving as the reservoir.7 Serological studies indicate that the outbreak of 2002/03 represented the first introduction of SARS-CoV into humans. Most infections occurred from person to person through the respiratory route.8 Nosocomial exposures were also common and health care workers were at particular risk. SARS-CoV is also excreted in feces for a prolonged time.9 The median incubation time is four to six days.8 Laboratory findings include lymphopenia and thrombocytopenia.1 Radiologic features most often consist of (multi)focal pulmonary opacities but can range from normal to an ARDS picture.10 At autopsy, lungs of affected individuals showed diffuse alveolar damage with varying acute exsudative changes.11, 12
Physicians should consult local or state health departments before performing diagnostic testing for SARS-CoV. Consider testing only in the absence of an alternative diagnosis 72 hours after start of diagnostic workup and for patients at high risk for SARS-CoV disease. In the absence of outbreaks, SARS-CoV disease should only be considered if:13
- Radiologically confirmed pneumonia requires hospitalization
- Epidemiologic history is consistent with SARS
- Within 10 days of disease onset, the patient
- Has travelled to China, Hong Kong, or Taiwan or has close contact with ill individuals with such travel history or
- Has occupational exposure risks or
- Is part of a cluster of atypical pneumonia without alternative diagnosis
Serologic (IgG EIA, IFA) and molecular (RT-PCR) assays developed by the Centers for Disease Control and Prevention (CDC) are the most commonly used diagnostic modalities. These assays will detect SARS-CoV in nasopharyngeal secretions (peak 10-14 days after onset of symptoms), in blood, and in stool. Seroconversion is delayed by 10-14 days and antibody testing considered negative only when specimens are obtained ? 28 days after onset of symptoms.14, 15 The CDC recommends the following diagnostic approach for suspected SARS:16
- Collect multiple specimens for RT-PCR (EDTA blood, respiratory, stool) and serology
- Test also for other respiratory pathogens (collected as soon as possible)
- If inconclusive and case definitions14, 17, 18 are met
- Repeat RT-PCR testing on blood, respiratory specimens, and stool 10-14 days after onset of symptoms
- Perform serology on convalescent serum collected = 28 days after onset of symptoms
Suitable specimens for RT-PCR include:16, 19
- Nasopharyngeal wash/aspirate, nasopharyngeal/oropharyngeal swabs (transport swabs in sterile container without transport medium)
- Bronchoalveolar lavage, tracheal aspirate, pleural fluid, sputum
- Serum, EDTA blood/plasma
- Fresh frozen tissue
The following test results, when confirmed, comprise a laboratory-confirmed infection:19
- Positive EIA on single specimen
- Four-fold increase in antibody titer from acute- to convalescent-phase serum
- Negative EIA on acute serum with positive EIA on convalescent serum
- Positive RT-PCR from specimens of two sources
- Positive RT-PCR from specimens of the same source collected on different days
Signed consent is recommended prior to testing.20 Guidelines for specimen handling and biosafety should always be followed.19 Report positive test results immediately to local and state public health laboratories. Contact your public health laboratory for detailed instructions and assistance with test interpretation.
Refer to the CDC and WHO SARS websites for the most current information:
- Centers for Disease Control and Prevention (CDC). Preliminary clinical description of severe acute respiratory syndrome. MMWR Morb Mortal Wkly Rep. 2003;52(12):255–256.
- Drosten C, Günther S, Preiser W, et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med. 2003;348(20):1967–1976.
- World Health Organization (WHO). Situation Updates - SARS. Geneva, Switzerland: World Health Organization. http://www.who.int/csr/sars/en/. Accessed May 25, 2010.
- CDC. Revised U.S. surveillance case definition for severe acute respiratory syndrome (SARS) and update on SARS cases--United States and worldwide, December 2003. MMWR Morb Mortal Wkly Rep. 2003;52(49):1202–1206.
- Donnelly CA, Leung GM, Hedley AJ, et al. Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. Lancet. 2003;361(9371):1761–1766.
- WHO. Areas with recent local transmission of SARS. Geneva, Switzerland: World Health Organization. http://www.who.int/csr/sars/areas/en/index.html. Accessed May 25, 2010.
- Wang LF, Shi Z, Zhang S, et al. Review of bats and SARS. Emerg Infect Dis. 2006;12(12):1834–1840.
- Donnelly CA, Fisher MC, Fraser C, et al. Epidemiological and genetic analysis of severe acute respiratory syndrome. Lancet Infect Dis. 2004;4(11):672–683.
- Liu W, Tang F, Fontanet A, et al. Long-term SARS coronavirus excretion from patient cohort, China. Emerg Infect Dis. 2004;10(10):1841–1843.
- Paul NS, Roberts H, Butany J, et al. Radiologic pattern of disease in patients with severe acute respiratory syndrome: the Toronto experience. Radiographics. 2004;24(2):553-563.
- Gu J, Korteweg C. Pathology and pathogenesis of severe acute respiratory syndrome. Am J Pathol. 2007;170(4):1136–1147.
- Guo Y, Korteweg C, McNutt MA, et al. Pathogenetic mechanisms of severe acute respiratory syndrome. Virus Res. 2008;133(1):4–12.
- CDC, Clinical Guidance on the Identification and Evaluation of Possible SARS-CoV Disease among Persons Presenting with Community-Acquired Illness. Atlanta, GA: Centers for Disease Control and Prevention, US Dept of Health and Human Services; 2005.
- Peiris JS, Chu CM, Cheng VC, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003;361(9371):1767–1772.
- Chen X, Zhou B, Li M, et al. Serology of severe acute respiratory syndrome: implications for surveillance and outcome. J Infect Dis. 2004;189(7):1158-1163.
- New York State Dept of Health. Laboratory Testing for SARS. 2004 Available from: http://www.nyhealth.gov/nysdoh/sars/sars_reporting/attachment_6_dear_doctor_lab.htm.
- WHO. Case Definitions for Surveillance of Severe Acute Respiratory Syndrome (SARS). Geneva, Switzerland: World Health Organization; 2003. http://www.who.int/csr/sars/casedefinition/en/. Accessed May 25, 2010.
- CDC. Updated Interim U.S. Case Definition for Severe Acute Respiratory Syndrome (SARS). Atlanta, GA: Centers for Disease Control and Prevention, US Dept of Health and Human Services; 2005. http://www.cdc.gov/ncidod/sars/casedefinition.htm. Accessed May 25, 2010.
- CDC. Public Health Guidance for Community-Level Preparedness and Response to Severe Acute Respiratory Syndrome (SARS) Version 2 - Supplement F: Laboratory Guidance. Atlanta, GA: Centers for Disease Control and Prevention, US Dept of Health and Human Services; 2005. http://www.cdc.gov/ncidod/sars/guidance/f/index.htm. Accessed May 25, 2010.
- CDC. Informed Consent for Laboratory Testing. Atlanta, GA: Centers for Disease Control and Prevention, US Dept of Health and Human Services; 2005. http://www.cdc.gov/ncidod/sars/lab/consent.htm. Accessed May 25, 2010.
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