eMedicine Specialties > Infectious Diseases > Lower Respiratory Tract Infections

Severe Acute Respiratory Syndrome (SARS): Differential Diagnoses & Workup

Author: Richard L Oehler, MD, FACP, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases and Tropical Medicine, Univ of South Florida College of Medicine; Assistant Epidemiologist, Division of Infectious Diseases, Tampa VA Medical Center
Coauthor(s): Nicholas Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants; Asim A Jani, MD, MPH, FACP, Clinician-Educator and Epidemiologist, Consultant and Senior Physician, Florida Department of Health; Assistant Professor, University of Central Florida College of Medicine; Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Contributor Information and Disclosures

Updated: Oct 31, 2007

Differential Diagnoses

Adenoviruses
Mycobacterium Haemophilum
Arenaviruses
Mycobacterium Kansasii
Atelectasis
Mycobacterium Marinum
Bronchiectasis
Mycobacterium Xenopi
Bronchiolitis
Mycoplasma Infections
Bronchitis
Parainfluenza Virus
California Encephalitis
Pleural Effusion
Chronic Bronchitis
Pneumococcal Infections
Chronic Obstructive Pulmonary Disease
Pneumocystis Carinii Pneumonia
Coxsackieviruses
Pneumonia, Aspiration
Cytomegalovirus
Pneumonia, Bacterial
Dengue Fever
Pneumonia, Community-Acquired
Eastern Equine Encephalitis
Pneumonia, Fungal
Echoviruses
Pneumonia, Viral
Emphysema
Psittacosis
Foreign Body Aspiration
Q Fever
Influenza
Respiratory Failure
Japanese Encephalitis
Rhinitis, Allergic
Klebsiella Infections
Rhinoviruses
Lung Abscess
Rickettsialpox
Lung Cancer, Non-Small Cell
Sepsis, Bacterial
Lung Cancer, Oat Cell (Small Cell)
St. Louis Encephalitis
Lyme Disease
Upper Respiratory Infection
Meningitis
Venezuelan Encephalitis
Mycobacterium Avium-Intracellulare
West Nile Encephalitis
Mycobacterium Chelonae
Western Equine Encephalitis
Mycobacterium Fortuitum
Mycobacterium Gordonae

Workup

Laboratory 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

      Severe acute respiratory syndrome case definition...

      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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      Severe acute respiratory syndrome case definition...

      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.

  • 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 radiograph of a 52-year-old symptom...

    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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    Initial chest radiograph of a 52-year-old symptom...

    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.


    Chest radiograph of a 52-year-old symptomatic wom...

    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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    Chest radiograph of a 52-year-old symptomatic wom...

    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.


    Chest radiograph of a 52-year-old symptomatic wom...

    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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    Chest radiograph of a 52-year-old symptomatic wom...

    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.


    • 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.

Transmission electron micrograph of human coronav...

Transmission electron micrograph of human coronavirus OC43 (HCV-OC43). Courtesy of the US Centers for Disease Control and Prevention.

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Transmission electron micrograph of human coronav...

Transmission electron micrograph of human coronavirus OC43 (HCV-OC43). Courtesy of the US Centers for Disease Control and Prevention.


Electron microscopic view of a member of the Coro...

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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Electron microscopic view of a member of the Coro...

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.


Thin-section electron micrograph of the severe ac...

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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Thin-section electron micrograph of the severe ac...

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.


Electron micrograph of the severe acute respirato...

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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Electron micrograph of the severe acute respirato...

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.


Pathologic slide of pulmonary tissue infected wit...

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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Pathologic slide of pulmonary tissue infected wit...

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.


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

Schematic representation of the severe acute resp...

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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Schematic representation of the severe acute resp...

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.


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.

More on Severe Acute Respiratory Syndrome (SARS)

Overview: Severe Acute Respiratory Syndrome (SARS)
Differential Diagnoses & Workup: Severe Acute Respiratory Syndrome (SARS)
Treatment & Medication: Severe Acute Respiratory Syndrome (SARS)
Follow-up: Severe Acute Respiratory Syndrome (SARS)
Multimedia: Severe Acute Respiratory Syndrome (SARS)
References
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Further Reading

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Keywords

Coronaviridae, coronavirus, coronaviruses, SARS genome, SARS-associated coronavirus, SARS-CoV, human coronavirus 229E, HCV-229E, human coronavirus OC43, HCV-OC43, human metapneumovirus, HMP, respiratory syncytial virus, RSV, single-stranded RNA viruses, pneumonia, respiratory tract infection, respiratory failure, bronchiolitis obliterans-organizing pneumonia, BOOP, flulike syndrome, ribavirin, SARS virus, zoonotic virus transmission, zoonotic viral transmission, quarantinable disease, quarantinable communicable disease, communicable diseases

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Contributor Information and Disclosures

Author

Richard L Oehler, MD, FACP, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases and Tropical Medicine, Univ of South Florida College of Medicine; Assistant Epidemiologist, Division of Infectious Diseases, Tampa VA Medical Center
Richard L Oehler, MD, FACP is a member of the following medical societies: American College of Physicians, American Medical Association, Infectious Diseases Society of America, and Society for Healthcare Epidemiology of America
Disclosure: Nothing to disclose.

Coauthor(s)

Nicholas Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

Asim A Jani, MD, MPH, FACP, Clinician-Educator and Epidemiologist, Consultant and Senior Physician, Florida Department of Health; Assistant Professor, University of Central Florida College of Medicine
Asim A Jani, MD, MPH, FACP is a member of the following medical societies: American College of Physicians, American Medical Association, American Public Health Association, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital
Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, and World Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Charles V Sanders, MD, Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine at New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center
Charles V Sanders, MD is a member of the following medical societies: Alliance for the Prudent Use of Antibiotics, Alpha Omega Alpha, American Association for the Advancement of Science, American Association of University Professors, American Clinical and Climatological Association, American College of Physician Executives, American College of Physicians, American Federation for Medical Research, American Foundation for AIDS Research, American Geriatrics Society, American Lung Association, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Association for Professionals in Infection Control and Epidemiology, Association of American Medical Colleges, Association of American Physicians, Association of Professors of Medicine, Infectious Disease Society for Obstetrics and Gynecology, Infectious Diseases Society of America, Louisiana State Medical Society, Orleans Parish Medical Society, Royal Society of Medicine, Sigma Xi, Society of General Internal Medicine, Southeastern Clinical Club, Southern Medical Association, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Michael R Pinsky, MD, CM, FCCP, FCCM, Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease and Anesthesiology, Vice-Chair, Academic Affairs, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center
Michael R Pinsky, MD, CM, FCCP, FCCM is a member of the following medical societies: American College of Chest Physicians, American College of Critical Care Medicine, American Heart Association, American Thoracic Society, Association of University Anesthetists, Shock Society, and Society of Critical Care Medicine
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