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

* Context.-An outbreak of severe acute respiratory syndrome (SARS), an infectious disease attributed to a novel coronavirus, occurred in Singapore during the first quarter of 2003 and led to 204 patients with diagnosed illnesses and 26 deaths by May 2, 2003. Twenty-one percent of these patients required admission to the medical intensive care unit. During this period, the Center for Forensic Medicine, Health Sciences Authority, Singapore, performed a total of 14 postmortem examinations for probable and suspected SARS. Of these, a total of 8 were later confirmed as SARS infections.

Objective.-Our series documents the difficulties encountered at autopsy during the initial phases of the SARS epidemic, when the pattern of infection and definitive diagnostic laboratory criteria were yet to be established.

Design.-Autopsies were performed by pathologists affiliated with the Center for Forensic Medicine, Health Sciences Authority, Singapore. Tissue was accessed and read at the Tan Tock Seng Hospital, Singapore, and at the Armed Forces Institute of Pathology, Washington, DC. Autopsy tissue was submitted to the Virology Department, Singapore General Hospital, for analysis, and in situ hybridization for the SARS coronavirus was carried out at the National Institute of Infectious Diseases, Tokyo, Japan.

Results.-Thirteen of 14 patients showed features of diffuse alveolar damage. In 8 patients, no precipitating etiology was identified, and in all of these patients, we now have laboratory confirmation of coronavirus infection. Two of the 8 patients presented at autopsy as sudden unexpected deaths, while the remaining 6 patients had been hospitalized with varying lengths of stay in the intensive care unit. In 3 patients, including the 2 sudden unexpected deaths, in situ hybridization showed the presence of virally infected cells within the lung. In 4 of the 8 SARS patients, pulmonary thromboemboli were also recognized on gross examination, while one patient had marantic cardiac valvular vegetations.

Conclusions.-It is unfortunate that the term atypical pneumonia has been used in conjunction with SARS. Although nonspecific by itself, the term does not accurately reflect the underlying dangers of viral pneumonia, which may progress rapidly to acute respiratory distress syndrome. We observed that the clinical spectrum of disease as seen in our autopsy series included sudden deaths. This is a worrisome finding that illustrates that viral diseases will have a spectrum of clinical presentations and that the diagnoses made for such patients must incorporate laboratory as well as clinical data.

Severe acute respiratory syndrome (SARS), an infectious disease attributed to a novel coronavirus,1,2 was imported into Singapore in March 2003 by a patient who had traveled to Hong Kong3 and who had stayed in the same hotel and same floor as the physician from Guangdong who is believed to be the source of infection for the outbreak in Canada.4 This index case subsequently led to an outbreak of SARS in Singapore, with a total of 204 infections (103 of which were infected by 5 sources5) and 26 deaths by the beginning of May.6

Singapore had 4 clusters of infections during the 2-month period from mid March to the beginning of May.3 Three were centered on hospitals (Tan Tock Seng Hospital with 1163 beds, Singapore General Hospital with 1502 beds, and National University Hospital with 943 beds7), while a fourth group developed around a vegetable wholesale center at Pasir Panjang, Singapore.

Approximately 75% of the SARS infections in Singapore have been traced to hospitals, and about 41% of the SARS patients were health care workers. In our experience, 21% (45) of the SARS patients required admission to the medical intensive care unit (ICU) and, of these, 84% required intubation for acute lung injury (PAO^sub 2^/FIO^sub 2^

During this period, the Center for Forensic Medicine, Health Sciences Authority, Singapore, performed 14 autopsies (Table 1) from different hospitals in Singapore, 6 of which were for probable SARS cases and 8 of which were for suspected SARS cases. Nine of these were mandated by the Director of Medical Services, Singapore, under the Infectious Diseases Act.9 Three of the 14 cases presented as sudden unexpected deaths at the forensic service, 2 of which were later classified as deaths due to SARS.

MATERIALS AND METHODS

All autopsies were carried out by pathologists (P.C., E.S.T., and K.B.T.) at the Health Sciences Authority, Singapore. Twelve were performed using positive air purifying respirators, and 2 were performed using routine precautions currently in place with N95 masks, disposable visors, gloves, protective gowns, and aprons.

Postmortem tissue was sent to the Tan Tock Seng Hospital, Singapore, and the Armed Forces Institute of Pathology, Washington, DC, for histopathology. Stains for macrophages and lymphocytes (CD68 and CDS, Dako Cytomation, Glostrup, Denmark) were also performed using the Ventana detection kit (Ventana Medical Systems, Tucson, Ariz).