A 74-year-old male was admitted to the Intensive Care Unit of our hospital with respiratory failure and was diagnosed with SARS. He was 9.5 years post orthotopic liver transplant for alcoholic cirrhosis. His current immunosuppression was cyclosporin 100 mg twice daily and prednisone 5 mg/day. His other medication included insulin and trimethoprim/sulfamethoxazole prophylaxis. The patient visited Hospital A for an outpatient podiatry appointment 5 days prior to the onset of his illness. He spent most of the day in the hospital but no specific exposure to an ill person was recounted. Hospital A was subsequently quarantined by the Public Health authority due to an unrecognized exposure and outbreak of SARS in this facility. Numerous people, of whom the majority were health care workers, developed SARS at this facility. Approximately 5 days after his outpatient appointment at Hospital A, the patient developed high fever, chills, nonproductive cough, and myalgias. He subsequently developed progressive shortness of breath and, after visiting his family physician, presented again to the Hospital A emergency. Due to impending respiratory failure, he was immediately transferred to the intensive care unit of another facility (Hospital B). In Hospital B, he required mechanical ventilation and was commenced on Ceftriaxone and levofloxacin for community-acquired pneumonia. Full isolation precautions were not used at this time as SARS was not suspected. Within 24 h, since he was a transplant patient, he was transferred to our facility's intensive care unit for ongoing care. On arrival at our hospital, the patient was placed in negative-pressure isolation with full precautions due to the suspicion of SARS.
On admission, he was febrile (38.8  C) and hypotensive, requiring inotropic therapy for blood pressure support. His initial laboratory investigations were as follows: hemoglobin was 87 g/L; total white blood cell count was 2.0 bil/L with a lymphocyte count of 0.2 bil/L; platelets were 74 bil/L. His AST was slightly elevated at 51 U/L but ALT and bilirubin were normal. His arterial blood gas on 100% FiO2 was pH 7.45, PO2 57 mmHg, PCO2 34 mmHg. Chest radiograph demonstrated bilateral airspace and interstitial disease, more prominent on the right side ( Figure 1). Investigations including a broncho-alveolar lavage (BAL) were performed and he was treated with ceftriaxone and azithromycin. In addition, he received ribavirin 2 g intravenously loading and 1 g every 6 h intravenously for presumptive SARS. His cyclosporin was discontinued. The hospital course was complicated by progressive hypoxemia, and multisystem organ failure. Death occurred on day 18 of his illness.
A BAL at the time of admission was negative for routine bacterial, fungal and mycobacterial stains and culture. Direct fluorescent antibody stains of BAL fluid were negative for influenza, parainfluenza, respiratory syncytial virus and adenovirus. Culture was negative for routine respiratory viruses, cytomegalovirus, and Legionella. Special stains for Legionella and Pneumocystis were negative, as were PCR for Mycoplasma and Chlamydia. CMV antigenemia, and urine Legionella antigen were negative.
A coronavirus-specific RT-PCR was performed on BAL fluid and was positive. We obtained an amplicon of the expected size of 216 bp, which was sequenced. The sequence was identical to that found in another patient with SARS reported previously. The sequence internal to the primers was 100% homologous to the expected segment of the pol 1b coding region of the SARS coronavirus complete sequence from a Canadian isolate (BCCA Genome Science Center, British Columbia; GenBank accession number AY274119). We also performed RT-PCR for coronaviruses on plasma samples and peripheral blood mononuclear cells purified by buffy coat obtained on the first and fifth day of hospitalization, but coronavirus was not detected in these samples.
The patient had not been in isolation until reaching our facility. During the course of his illness, several persons were exposed. These included his wife and two children, family physician (FP), FP's office staff and several other patients in the waiting room. At Hospital A, due to a large outbreak, it was not possible to determine those exposed as a direct result of this patient as several other SARS exposures had occurred at the same time. However, hundreds of individuals from this hospital were placed in isolation. The patient had two visitors during his emergency visit at Hospital A. Exposure also occurred in 11 individuals involved in transfer of the patient to hospital B and 68 staff at Hospital B, primarily those involved in the patient's ICU care. Subsequent illness compatible with suspect or probable SARS occurred in 10 persons: the patient's wife, family physician, two visitors at Hospital A, and six staff at Hospital B, resulting in one death due to SARS. This is likely an underestimate as we were unable to determine how many at Hospital A were exposed specifically due to this patient.
Due to this outbreak of SARS in the greater Toronto area, all transplant programs in the city were temporarily closed. Prior to re-starting the transplant program, concern arose about unrecognized SARS in potential cadaveric organ donors, with the largely unknown potential for spread to multiple recipients. A donor may be at risk of incubating SARS or have active SARS due to exposure in a health care facility or specific epidemiological exposure within the community. Therefore, a donor SARS screening tool was developed and is shown in Figure 2. The screening tool is based on information regarding potential hospital exposure, clinical symptoms, and contact history. In section A, the category of the donor institution is listed. Hospital categorization is based on Canada's Ministry of Health guidelines and ranges from category 0 (no SARS cases in institution) to category 3 (SARS exposure and further spread from the exposed person to others) (Figure 2). This information is readily available from the infection control practitioner at a given institution. Section B is based on determining if any clinical or radiological evidence of SARS is present. Section C evaluates contact exposure to either someone with SARS (suspected or probable) or due to travel to areas with high risk of SARS exposure based on current governmental travel advisories (available at www.cdc.gov in the United States). With the above information, donors can be classified into high risk, intermediate (or indeterminate) risk, or low risk, based on categories shown at the bottom of Figure 2. Since implementation of the screening tool, our practice has been to accept low-risk donors and intermediate-risk donors, and generally exclude high-risk donors. This is done in discussion with the transplant team and the recipient. The screening tool can be modified for living related donors by labeling section A as category 0 if the donor has not visited any hospital within the previous 10 days. We have also implemented a modified version of this screening tool for potential recipients, to ensure that a patient incubating SARS is not inadvertently transplanted.