Analysis of Deaths During the Severe Acute Respiratory Syndrome (SARS) Epidemic in Singapore: Challenges in Determining a SARS Diagnosis

Archives of Pathology & Laboratory Medicine, Feb 2004 by Chong, Pek Yoon, Chui, Paul, Ling, Ai E, Franks, Teri J, Et al

Tissue was taken at autopsy for immunofluorescent antigen detection of respiratory viruses using the following methods: (1) polymerase chain reaction for coronavirus with a range of primers, including SAR1a/as and BNIoutS2/As2^sup 2^ and Cor1/2 (sense 5'-CAC CGT TTC TAC AGG TTA GCT AAC GA-3' and antisense 5'-AAA TGT TTA CGC AGG TAA GCG TAA AA-3') from the Government Virus Unit, Hong Kong,10 and (2) viral isolation on a variety of cell lines, including Vero cells. Immunoglobulin M and G (IgM and IgG) antibodies to the coronavirus were detected using an immunofluorescent antibody assay. These assays were performed in the Virology Department, Singapore General Hospital (A.E.L., K.P.C., and L.L.E.Q).

In an attempt to localize the virus, unstained sections of the lung from the 8 cases with a positive polymerase chain reaction for the SARS coronavirus were submitted to the National Institute of Infectious Diseases, Tokyo, Japan, for detection of SARS using the recently described in situ hybridization-AT tailing technique with catalyzed signal amplification (T.S. and N.N.).11

Data from the Tan Tock Seng Hospital were collated by the Department of Diagnostic Radiology (G.J.L.K. and G.W.), the Medical ICU (D.Y.H.T.), and the Communicable Disease Center (Y.S.L.).

RESULTS

Table 1 summarizes the clinical diagnoses and significant pathology findings with special reference to the pulmonary system in SARS and non-SARS cases. Table 2 gives the clinical profile of the SARS patients, and Table 3 details the virology and other microbiology findings in SARS and non-SARS cases. Table 4 gives details of the in situ hybridization-AT tailing-catalyzed signal amplification staining in the SARS cases.

Clinical Findings

Eleven inpatients with progressive pulmonary symptoms subsequently underwent an autopsy for a clinical diagnosis of SARS or suspected SARS. Nine either had a history of exposure to SARS or had traveled to an affected area. Two (patients 9 and 11) were referred for autopsy because of a short history of fever, a rapid progression of disease, and radiologic findings that were suggestive of SARS. Three were routine coroner autopsies at which the forensic pathologist thought the pulmonary findings were suggestive of ARDS12 but for which there was no apparent risk factor.

Eight patients (6 males and 2 females; mean age, 50 years) subsequently had laboratory confirmation of SARS infections, while 6 patients (5 males and 1 female; mean age, 56 years, including a pediatric patient, or 67 years, if the pediatric patient was excluded) were negative for coronavirus. Both groups had patients with comorbid conditions (Table 2).

The clinical course for the 8 SARS patients of our study varied (see Figures 1 through 5). Patients 1, 2, and 3 stayed a mean average of 10 days (range, 10-13) in the hospital, received mechanical ventilation for 7 days (range, 4-8), and died about 3 weeks into their illness. Patients 4 and 5 died within 5 to 8 days of the detection of fever. Patient 4 had significant comorbid factors such as end-stage renal failure and ischemic heart disease. His last admission was for an elevated temperature of 38.5�C. Patient 5 had hypertension and was admitted with a temperature of 35�C and a blood pressure level of 80/50 mm Hg. Patient 6 was febrile, deteriorated rapidly for 2 days, and collapsed 10 days after the onset of fever. Patient 8 saw his general practitioner twice for 1 week for fever (37.7�C) but collapsed at home on day 8. The most rapid onset documented was in case 7, in which the patient had visited a physician 2 days before she died with complaints of fever and a runny nose. Her temperature was recorded on the 2 days preceding her death as 38�C and, without the use of antipyretics, as 37.4�C.