Severe Acute Respiratory Syndrome (SARS) Workup
- Author: Manish N Trivedi, MD; Chief Editor: Michael R Pinsky, MD, CM, FCCP, FCCM more...
Approach Considerations
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, polymerase chain reaction (PCR) assay, 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.
Histologic findings
Autopsies demonstrated changes mostly confined to pulmonary tissue, with diffuse alveolar damage being the most prominent feature. Multinucleated syncytial giant cells were thought to be characteristic but were rarely seen.[11] SARS-CoV infection causes significant damage to lung tissue, as shown below.
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. Airport identification
Infrared scanners designed for use by the military for night operations were adapted for airport screening use in various locales (eg, Singapore). These scanners were used to identify potentially febrile passengers by measuring their body heat. False-positive results were common with these scanners. Individuals with positive scanner results were temporarily isolated and brought to a special cubicle, where temperatures were confirmed with an oral thermometer.[41]
Laboratory Findings and Techniques
Data from the 2002-2003 outbreak indicate that SARS may be associated with the following laboratory findings[2, 3, 4, 43] :
- Modest lymphopenia, leukopenia, and thrombocytopenia - Series have shown white blood cell (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
Coronavirus antibody testing methods 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.[44, 45]
Reverse-transcriptase PCR (RT-PCR) assay results can be positive in some patients within the first 10 days of fever. RT-PCR assay can be used to detect SARS-CoV in serum, stool, and nasal secretions. 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 assay 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 disease’s diagnosis.
Below are the CDC's guidelines for the laboratory diagnosis of SARS-CoV infection.[41] Diagnosis is established based on the 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 assay validated by the CDC, with confirmation in a reference laboratory, from (1) two clinical specimens from different sources or (2) two clinical specimens collected from the same source on 2 different days[46]
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.
Imaging Studies
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.[47, 48]
Interstitial infiltrates can be observed early in the disease course, although in the early stage, a peripheral, pleural-based opacity (ranging from ground-glass opacification to frank consolidation) may be the only abnormality. High-resolution computed tomography (HRCT) scanning of the chest during this time may reveal an infiltrate in the retrocardiac region. (See the image below.)
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. 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.[48]
Findings consistent with SARS include ground-glass opacification, with or without thickening of the intralobular or interlobular interstitium, or frank consolidation. Indeed, a combination of ground-glass opacification (with or without thickening of the interstitium) and frank consolidation may be noted.[48]
Fouchier RA, Kuiken T, Schutten M, van Amerongen G, van Doornum GJ, van den Hoogen BG, et al. Aetiology: Koch's postulates fulfilled for SARS virus. Nature. May 15 2003;423(6937):240. [Medline].
Lee N, Hui D, Wu A, Chan P, Cameron P, Joynt GM, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med. May 15 2003;348(20):1986-94. [Medline].
Tsang KW, Ho PL, Ooi GC, Yee WK, Wang T, Chan-Yeung M, et al. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N Engl J Med. May 15 2003;348(20):1977-85. [Medline].
Centers for Disease Control and Prevention. 2003. Severe Acute Respiratory Syndrome. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/ncidod/sars/. Accessed November 07, 2011.
Booth CM, Matukas LM, Tomlinson GA, Rachlis AR, Rose DB, Dwosh HA, 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].
Severe acute respiratory syndrome (SARS) and coronavirus testing--United States, 2003. MMWR Morb Mortal Wkly Rep. Apr 11 2003;52(14):297-302. [Medline].
Lim PL, Kurup A, Gopalakrishna G, Chan KP, Wong CW, Ng LC, et al. Laboratory-acquired severe acute respiratory syndrome. N Engl J Med. Apr 22 2004;350(17):1740-5. [Medline].
Liang G, Chen Q, Xu J, Liu Y, Lim W, Peiris JS, et al. Laboratory diagnosis of four recent sporadic cases of community-acquired SARS, Guangdong Province, China. Emerg Infect Dis. Oct 2004;10(10):1774-81. [Medline].
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.
Liang WN, Liu M, Chen Q, Liu ZJ, He X, Pan Y, 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].
Hui DS, Chan PK. Clinical features, pathogenesis and immunobiology of severe acute respiratory syndrome. Curr Opin Pulm Med. May 2008;14(3):241-7. [Medline].
Lo AW, Tang NL, To KF. How the SARS coronavirus causes disease: host or organism?. J Pathol. Jan 2006;208(2):142-51. [Medline].
Hui DS, Chan PK. Severe acute respiratory syndrome and coronavirus. Infect Dis Clin North Am. Sep 2010;24(3):619-38. [Medline].
Tan YJ, Fielding BC, Goh PY, Shen S, Tan TH, Lim SG, et al. Overexpression of 7a, a protein specifically encoded by the severe acute respiratory syndrome coronavirus, induces apoptosis via a caspase-dependent pathway. J Virol. Dec 2004;78(24):14043-7. [Medline]. [Full Text].
Jiang Y, Xu J, Zhou C, Wu Z, Zhong S, Liu J, et al. Characterization of cytokine/chemokine profiles of severe acute respiratory syndrome. Am J Respir Crit Care Med. Apr 15 2005;171(8):850-7. [Medline].
Peiris JS, Lai ST, Poon LL, Guan Y, Yam LY, Lim W, et al. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet. Apr 19 2003;361(9366):1319-25. [Medline].
Hui DS, Sung JJ. Severe acute respiratory syndrome. Chest. Jul 2003;124(1):12-5. [Medline].
Wong GW, Hui DS. Severe acute respiratory syndrome (SARS): epidemiology, diagnosis and management. Thorax. Jul 2003;58(7):558-60. [Medline]. [Full Text].
Wang LF, Shi Z, Zhang S, Field H, Daszak P, Eaton BT. Review of bats and SARS. Emerg Infect Dis. Dec 2006;12(12):1834-40. [Medline].
Rota PA, Oberste MS, Monroe SS, Nix WA, Campagnoli R, Icenogle JP, et al. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science. May 30 2003;300(5624):1394-9. [Medline].
Tripet B, Howard MW, Jobling M, Holmes RK, Holmes KV, Hodges RS. Structural characterization of the SARS-coronavirus spike S fusion protein core. J Biol Chem. May 14 2004;279(20):20836-49. [Medline].
Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. Nov 27 2003;426(6965):450-4. [Medline].
Frieman M, Baric R. Mechanisms of severe acute respiratory syndrome pathogenesis and innate immunomodulation. Microbiol Mol Biol Rev. Dec 2008;72(4):672-85, Table of Contents. [Medline]. [Full Text].
Yang ZY, Huang Y, Ganesh L, Leung K, Kong WP, Schwartz O, et al. pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN. J Virol. Jun 2004;78(11):5642-50. [Medline]. [Full Text].
Samuel CE. Antiviral actions of interferons. Clin Microbiol Rev. Oct 2001;14(4):778-809, table of contents. [Medline]. [Full Text].
Stertz S, Reichelt M, Spiegel M, Kuri T, Martínez-Sobrido L, García-Sastre A, et al. The intracellular sites of early replication and budding of SARS-coronavirus. Virology. May 10 2007;361(2):304-15. [Medline].
Versteeg GA, Bredenbeek PJ, van den Worm SH, Spaan WJ. Group 2 coronaviruses prevent immediate early interferon induction by protection of viral RNA from host cell recognition. Virology. Apr 25 2007;361(1):18-26. [Medline].
Kuri T, Weber F. Interferon interplay helps tissue cells to cope with SARS-coronavirus infection. Virulence. Jul-Aug 2010;1(4):273-5. [Medline].
Cervantes-Barragan L, Züst R, Weber F, Spiegel M, Lang KS, Akira S, et al. Control of coronavirus infection through plasmacytoid dendritic-cell-derived type I interferon. Blood. Feb 1 2007;109(3):1131-7. [Medline].
Cameron MJ, Ran L, Xu L, Danesh A, Bermejo-Martin JF, Cameron CM, et al. Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome. J Virol. Aug 2007;81(16):8692-706. [Medline]. [Full Text].
Fang X, Gao J, Zheng H, Li B, Kong L, Zhang Y, et al. The membrane protein of SARS-CoV suppresses NF-kappaB activation. J Med Virol. Oct 2007;79(10):1431-9. [Medline].
Yu IT, Li Y, Wong TW, Tam W, Chan AT, Lee JH, et al. Evidence of airborne transmission of the severe acute respiratory syndrome virus. N Engl J Med. Apr 22 2004;350(17):1731-9. [Medline].
Cyranoski D, Abbott A. Apartment complex holds clues to pandemic potential of SARS. Nature. May 1 2003;423(6935):3-4. [Medline].
Chan JW, Ng CK, Chan YH, Mok TY, Lee S, Chu SY, et al. Short term outcome and risk factors for adverse clinical outcomes in adults with severe acute respiratory syndrome (SARS). Thorax. Aug 2003;58(8):686-9. [Medline]. [Full Text].
Tansey CM, Louie M, Loeb M, Gold WL, Muller MP, de Jager J, et al. One-year outcomes and health care utilization in survivors of severe acute respiratory syndrome. Arch Intern Med. Jun 25 2007;167(12):1312-20. [Medline].
Tang NL, Chan PK, Wong CK, To KF, Wu AK, Sung YM, et al. Early enhanced expression of interferon-inducible protein-10 (CXCL-10) and other chemokines predicts adverse outcome in severe acute respiratory syndrome. Clin Chem. Dec 2005;51(12):2333-40. [Medline].
Hui DS, Wong KT, Ko FW, Tam LS, Chan DP, Woo J, et al. The 1-year impact of severe acute respiratory syndrome on pulmonary function, exercise capacity, and quality of life in a cohort of survivors. Chest. Oct 2005;128(4):2247-61. [Medline].
Tsai LK, Hsieh ST, Chao CC, Chen YC, Lin YH, Chang SC, et al. Neuromuscular disorders in severe acute respiratory syndrome. Arch Neurol. Nov 2004;61(11):1669-73. [Medline].
Tsui PT, Kwok ML, Yuen H, Lai ST. Severe acute respiratory syndrome: clinical outcome and prognostic correlates. Emerg Infect Dis. Sep 2003;9(9):1064-9. [Medline]. [Full Text].
Centers for Disease Control and Prevention. Updated Interim U.S. Case Definition for Severe Acute Respiratory Syndrome (SARS). Centers for Disease Control and Prevention. Available at http://www.cdc.gov/ncidod/sars/casedefinition.htm. Accessed Oct 26 2011.
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.
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].
Armed Forces Institute of Pathology. Severe Acute Respiratory Syndrome (SARS). Armed Forces Institute of Pathology..
Ng LF, Wong M, Koh S, Ooi EE, Tang KF, Leong HN, et al. Detection of severe acute respiratory syndrome coronavirus in blood of infected patients. J Clin Microbiol. Jan 2004;42(1):347-50. [Medline]. [Full Text].
Chen X, Zhou B, Li M, Liang X, Wang H, Yang G, et al. Serology of severe acute respiratory syndrome: implications for surveillance and outcome. J Infect Dis. Apr 1 2004;189(7):1158-63. [Medline].
Sui J, Li W, Murakami A, Tamin A, Matthews LJ, Wong SK, et al. Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association. Proc Natl Acad Sci U S A. Feb 24 2004;101(8):2536-41. [Medline]. [Full Text].
Hsu LY, Lee CC, Green JA, Ang B, Paton NI, Lee L, et al. Severe acute respiratory syndrome (SARS) in Singapore: clinical features of index patient and initial contacts. Emerg Infect Dis. Jun 2003;9(6):713-7. [Medline]. [Full Text].
Nicolaou S, Al-Nakshabandi NA, Müller NL. SARS: imaging of severe acute respiratory syndrome. AJR Am J Roentgenol. May 2003;180(5):1247-9. [Medline].
Ho W. Guideline on management of severe acute respiratory syndrome (SARS). Lancet. Apr 19 2003;361(9366):1313-5. [Medline].
Lapinsky SE, Hawryluck L. ICU management of severe acute respiratory syndrome. Intensive Care Med. Jun 2003;29(6):870-5. [Medline].
Taccone P, Pesenti A, Latini R, Polli F, Vagginelli F, Mietto C, et al. Prone positioning in patients with moderate and severe acute respiratory distress syndrome: a randomized controlled trial. JAMA. Nov 11 2009;302(18):1977-84. [Medline].
Lee N, Allen Chan KC, Hui DS, Ng EK, Wu A, Chiu RW, et al. Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. J Clin Virol. Dec 2004;31(4):304-9. [Medline].
Sung JJ, Wu A, Joynt GM, Yuen KY, Lee N, Chan PK, et al. Severe acute respiratory syndrome: report of treatment and outcome after a major outbreak. Thorax. May 2004;59(5):414-20. [Medline]. [Full Text].
Ho JC, Ooi GC, Mok TY, Chan JW, Hung I, Lam B, et al. High-dose pulse versus nonpulse corticosteroid regimens in severe acute respiratory syndrome. Am J Respir Crit Care Med. Dec 15 2003;168(12):1449-56. [Medline].
Tan EL, Ooi EE, Lin CY, Tan HC, Ling AE, Lim B, et al. Inhibition of SARS coronavirus infection in vitro with clinically approved antiviral drugs. Emerg Infect Dis. Apr 2004;10(4):581-6. [Medline].
Chu CM, Cheng VC, Hung IF, Wong MM, Chan KH, Chan KS, et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax. Mar 2004;59(3):252-6. [Medline]. [Full Text].
Chan KS, Lai ST, Chu CM, Tsui E, Tam CY, Wong MM, et al. Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: a multicentre retrospective matched cohort study. Hong Kong Med J. Dec 2003;9(6):399-406. [Medline].
Ströher U, DiCaro A, Li Y, Strong JE, Aoki F, Plummer F, et al. Severe acute respiratory syndrome-related coronavirus is inhibited by interferon- alpha. J Infect Dis. Apr 1 2004;189(7):1164-7. [Medline].
Haagmans BL, Kuiken T, Martina BE, Fouchier RA, Rimmelzwaan GF, van Amerongen G, et al. Pegylated interferon-alpha protects type 1 pneumocytes against SARS coronavirus infection in macaques. Nat Med. Mar 2004;10(3):290-3. [Medline].
Loutfy MR, Blatt LM, Siminovitch KA, Ward S, Wolff B, Lho H, et al. Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: a preliminary study. JAMA. Dec 24 2003;290(24):3222-8. [Medline].
Das D, Kammila S, Suresh MR. Development, characterization, and application of monoclonal antibodies against severe acute respiratory syndrome coronavirus nucleocapsid protein. Clin Vaccine Immunol. Dec 2010;17(12):2033-6. [Medline]. [Full Text].
ter Meulen J, Bakker AB, van den Brink EN, Weverling GJ, Martina BE, Haagmans BL, et al. Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets. Lancet. Jun 26 2004;363(9427):2139-41. [Medline].
Lew TW, Kwek TK, Tai D, Earnest A, Loo S, Singh K, et al. Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome. JAMA. Jul 16 2003;290(3):374-80. [Medline].
Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, Ng MH, et al. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. Jan 2005;24(1):44-6. [Medline].
Chen L, Liu P, Gao H, Sun B, Chao D, Wang F, et al. Inhalation of nitric oxide in the treatment of severe acute respiratory syndrome: a rescue trial in Beijing. Clin Infect Dis. Nov 15 2004;39(10):1531-5. [Medline].
Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr HW. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet. Jun 14 2003;361(9374):2045-6. [Medline].
Pogrebnyak N, Golovkin M, Andrianov V, Spitsin S, Smirnov Y, Egolf R, et al. Severe acute respiratory syndrome (SARS) S protein production in plants: development of recombinant vaccine. Proc Natl Acad Sci U S A. Jun 21 2005;102(25):9062-7. [Medline]. [Full Text].
Schulze K, Staib C, Schätzl HM, Ebensen T, Erfle V, Guzman CA. A prime-boost vaccination protocol optimizes immune responses against the nucleocapsid protein of the SARS coronavirus. Vaccine. Dec 2 2008;26(51):6678-84. [Medline].
Chen Z, Zhang L, Qin C, Ba L, Yi CE, Zhang F, et al. Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region. J Virol. Mar 2005;79(5):2678-88. [Medline]. [Full Text].
He Y, Li J, Heck S, Lustigman S, Jiang S. Antigenic and immunogenic characterization of recombinant baculovirus-expressed severe acute respiratory syndrome coronavirus spike protein: implication for vaccine design. J Virol. Jun 2006;80(12):5757-67. [Medline]. [Full Text].
Mandavilli A. SARS epidemic unmasks age-old quarantine conundrum. Nat Med. May 2003;9(5):487. [Medline].
Yang W. Severe acute respiratory syndrome (SARS): infection control. Lancet. Apr 19 2003;361(9366):1386-7. [Medline].

