Booth CM, Matukas LM, Tomlinson GA, Rachlis AR, Rose DB, Dwosh HA, Walmsley SL, Mazzulli T, Avendano M, Derkach P, Ephtimios IE, Kitai I, Mederski BD, Shadowitz SB, Gold WL, Hawryluck LA, Rea E, Chenkin JS, Cescon DW, Poutanen SM, Detsky AS. Clinical Features and Short-term Outcomes of 144 Patients With SARS in the Greater Toronto Area. JAMA. 2003;289(21):2801-2809. doi:10.1001/jama.289.21.JOC30885
Author Affiliations: University of Toronto (Drs Booth, Matukas, Tomlinson, Rachlis, Rose, Dwosh, Walmsley, Mazzulli, Avendano, Derkach, Ephtimios, Kitai, Mederski, Shadowitz, Gold, Hawryluck, Rea, Poutanen, and Detsky and Messrs Chenkin and Cescon), Mount Sinai Hospital (Drs Tomlinson, Walmsley, Mazzulli, Hawryluck, Poutanen, and Detsky), Sunnybrook and Women's College Health Sciences Centre (Drs Rachlis and Shadowitz), Scarborough Hospital (Dr Rose), York Central Hospital (Dr Dwosh), University Health Network (Drs Tomlinson, Walmsley, Gold, Hawryluck, and Detsky), Westpark Healthcare Centre (Drs Avendano and Derkach), Markham-Stouffville Hospital (Dr Ephtimios), RougeValley Health System (Dr Kitai), North York General Hospital (Dr Mederski), and Toronto Public Health (Dr Rea), Toronto, Ontario.
Context Severe acute respiratory syndrome (SARS) is an emerging infectious disease
that first manifested in humans in China in November 2002 and has subsequently
Objectives To describe the clinical characteristics and short-term outcomes of
SARS in the first large group of patients in North America; to describe how
these patients were treated and the variables associated with poor outcome.
Design, Setting, and Patients Retrospective case series involving 144 adult patients admitted to 10
academic and community hospitals in the greater Toronto, Ontario, area between
March 7 and April 10, 2003, with a diagnosis of suspected or probable SARS.
Patients were included if they had fever, a known exposure to SARS, and respiratory
symptoms or infiltrates observed on chest radiograph. Patients were excluded
if an alternative diagnosis was determined.
Main Outcome Measures Location of exposure to SARS; features of the history, physical examination,
and laboratory tests at admission to the hospital; and 21-day outcomes such
as death or intensive care unit (ICU) admission with or without mechanical
Results Of the 144 patients, 111 (77%) were exposed to SARS in the hospital
setting. Features of the clinical examination most commonly found in these
patients at admission were self-reported fever (99%), documented elevated
temperature (85%), nonproductive cough (69%), myalgia (49%), and dyspnea (42%).
Common laboratory features included elevated lactate dehydrogenase (87%),
hypocalcemia (60%), and lymphopenia (54%). Only 2% of patients had rhinorrhea.
A total of 126 patients (88%) were treated with ribavirin, although its use
was associated with significant toxicity, including hemolysis (in 76%) and
decrease in hemoglobin of 2 g/dL (in 49%). Twenty-nine patients (20%) were
admitted to the ICU with or without mechanical ventilation, and 8 patients
died (21-day mortality, 6.5%; 95% confidence interval [CI], 1.9%-11.8%). Multivariable
analysis showed that the presence of diabetes (relative risk [RR], 3.1; 95%
CI, 1.4-7.2; P = .01) or other comorbid conditions
(RR, 2.5; 95% CI, 1.1-5.8; P = .03) were independently
associated with poor outcome (death, ICU admission, or mechanical ventilation).
Conclusions The majority of cases in the SARS outbreak in the greater Toronto area
were related to hospital exposure. In the event that contact history becomes
unreliable, several features of the clinical presentation will be useful in
raising the suspicion of SARS. Although SARS is associated with significant
morbidity and mortality, especially in patients with diabetes or other comorbid
conditions, the vast majority (93.5%) of patients in our cohort survived.
Conclusions Published online May 6, 2003 (doi:10.1001/jama.289.21.JOC30885).
In March 2003, the World Health Organization (WHO) issued a global alert
describing cases of atypical pneumonia of unknown cause appearing in Hong
Kong, China, and Vietnam.1 As of April 28,
2003, severe acute respiratory syndrome (SARS) has been described in 28 countries
involving 5050 individuals and causing 217 deaths.2 Subsequent
information has emerged that suggests that SARS has been present in the Guangdong
province of China since November 2002.3
As defined by WHO, a suspected case of SARS is an individual with fever
(temperature >38°C [100.4°F]), cough or dyspnea, and contact with
an individual believed to have SARS or to have traveled to a region where
there has been documented transmission of the disease. A probable case is
an individual meeting criteria for a suspected case along with radiographic
features of pneumonia, respiratory distress syndrome, or an unexplained respiratory
illness resulting in death with autopsy results demonstrating pathology of
respiratory distress syndrome without an identifiable cause.3
Investigators involved in international collaboration have attempted
to determine a specific viral etiology in order to convert what is currently
best described as a syndrome into a specific disease. At present, a novel
coronavirus is the prime suspect.4,5 Genomic
sequencing of this virus has recently been completed.6,7 Laboratory
assays designed to identify this virus or serologic evidence of exposure to
this virus are being developed.
Initial reports described the clinical features of small numbers of
patients.8,9 Clinical and laboratory
features of a larger Hong Kong cohort have recently been published.10 Anecdotal experience with empirical treatment using
ribavirin and steroids has been described, but none of these regimens has
been studied systematically to determine whether they are effective therapy.10 Further information is urgently needed to better
characterize the clinical features and outcome of this disease. These data
may allow physicians worldwide to anticipate the course of the disease and
risk-stratify patients based on prognostic variables.
This retrospective case series sought to describe the clinical features
and short-term outcomes of patients with SARS in the greater Toronto, Ontario,
area. The current case definition of SARS relies heavily on a history of contact
exposure. At present, contact history is still intact in the greater Toronto
area. However, it is possible that both there and elsewhere, this valuable
component of the clinical assessment may be unavailable for some patients
in the future. Thus, one goal of this study is to describe SARS in the event
that the ability to reliably determine contact is lost before an objective
diagnostic test is found. We also examine which treatments are being used
and their potential toxicities, and we assess clinical and laboratory features
that may predict a combined outcome of death, intubation, or the need for
intensive care unit (ICU) admission.
As described in a recent publication, the first cases of SARS in Canada
involved a family of Hong Kong descent who live in Toronto.8 A
78-year-old woman and her husband traveled to Hong Kong from February 13 through
February 23, 2003, to visit relatives. They stayed at a hotel where a cluster
of 13 persons with suspected or probable SARS are known to have stayed.11 Two days after returning home, the woman developed
fever, myalgia, sore throat, cough, and progressive dyspnea. She died at home
on March 5. Several family members who had close contact with the index case
subsequently developed respiratory symptoms. One family member was subsequently
admitted to a local community hospital that became the epicenter for the Toronto
SARS spread to other patients and health care workers within this hospital
prior to significant awareness of SARS by the Canadian medical community and
before intensive respiratory precautions for patients and contacts were known
to be necessary and were implemented. Other Toronto hospitals were affected
when patients were transferred between institutions. This led to additional
infection of patients, health care workers, and hospital visitors.
As of April 27, 139 probable and 128 suspected cases had been reported
(based on WHO case criteria) in the province of Ontario, accounting for 247
hospital admissions and 21 deaths. These cases were almost exclusively in
the greater Toronto area.12 There is strong
evidence that the outbreak is winding down. There were only 18 new cases of
suspected or probable SARS in Ontario between April 19 and April 27, 2003.
There have been no cases of community spread since April 9, and the only cases
that have occurred outside the health care setting have been among 2 home
contacts of an affected health care worker.12,13
This study included patients with SARS who were admitted to hospitals
in the greater Toronto area between March 7 and April 10, 2003. Nine of the
patients in our cohort have been described previously by Poutanen et al8 and 11 of these patients have been reported recently
by Dwosh et al.14 We included hospitals that
were providing care to the vast majority of SARS patients in the greater Toronto
Adult patients were included if they met the Centers for Disease Control
and Prevention (CDC) criteria for a suspected case as of April 10: fever,
a known exposure to SARS, and either respiratory symptoms or infiltrates observed
on chest radiograph.15 (Note that the CDC criteria
for a suspected case were revised on April 20, 2003.) Known exposure to SARS
was defined as 1 of the following: close contact with (ie, having cared for,
lived with, or had face-to-face contact with) a suspected or probable case
of SARS; travel to Hong Kong, China, Vietnam, Singapore, or Taiwan; or visit
to a SARS-affected hospital in the greater Toronto area. Respiratory symptoms
included cough, dyspnea, or hypoxemia (oxygen saturation <95% with room
air as defined by our study protocol). Patients were excluded if an alternative
medical or microbiological diagnosis explained their clinical presentation.
This retrospective case series was conducted during the SARS outbreak
in the greater Toronto area. Clinicians from participating hospitals identified
patients who met the study inclusion criteria through surveillance of all
patients in their hospitals. The authors of this article include the physicians
who supervised or directly provided care for all of the patients with SARS
in these hospitals during the study period, ensuring complete identification
of all cases. Because of the ongoing outbreak and the restrictions on research
personnel traveling from site to site, patient charts were copied and sent
to 2 data collection centers.
A trained team of physicians and medical students reviewed the patient
charts and recorded demographic, clinical, and laboratory information on a
standardized data collection form (available from the authors on request).
The individual components of all of the definitions of SARS (CDC, WHO, and
Health Canada) were recorded separately and checked by a supervising author.
The proportion of patients who met each of the various definitions was then
determined by computer following an algorithm for each definition. The data
were entered in duplicate into a computerized database. Patient confidentiality
was maintained by recording only date of birth and sex on the data collection
form. The research ethics board at each participating hospital and the University
of Toronto approved the study.
Medians and interquartile ranges (IQRs) were calculated as summaries
of continuous variables. For categorical variables, percentages of patients
in each category were computed. The Wilcoxon rank sum test16 was
used to compare distributions of continuous variables at admission between
patients who subsequently had a poor outcome and patients who did not. Poor
outcome was defined as the earliest of death, need for mechanical ventilation,
or ICU admission. Time to discharge, time to death, and time to a poor outcome
were investigated using survival analysis, with follow-up for all patients
starting at hospital admission and ending on April 17, 2003. Patients were
censored if at the end of follow-up they were still in the hospital (for time
to discharge), still alive (for time to death), and did not have a poor outcome
(for time to poor outcome). The Kaplan-Meier product-limit estimator was used
to estimate survival and for the time-to-event plot.17 Comparisons
between groups of time-to-event data were made using the Cox proportional
hazards model, with graphical and statistical checks for proportionality of
hazards.18,19 With only 30 poor
outcomes, we followed accepted statistical practice and considered only 3
variables in our multiple regression model.20 In
particular, because of a priori hypotheses, we examined 3 binary variables:
diabetes, other comorbidities (chronic obstructive pulmonary disease, cancer,
cardiac disease), and age of 60 years or older. All analyses were carried
out using S-Plus 2000 Professional Release 3 statistical software (Mathsoft,
The initial study cohort comprised 147 adult patients. Three patients
who contracted SARS while in the hospital during the course of a prolonged
stay that began well before the SARS outbreak (eg, for hip fracture) were
excluded from this cohort because of difficulty in determining the inception
of their disease, leaving 144 patients for subsequent analysis. Demographic
details and comorbidities are shown in Table 1. The median (IQR) age of the study population was 45 years
(34-57 years) and 61% were female. Seventy-three patients (51%) were health
care workers (nurses, respiratory therapists, physicians, radiology and electrocardiogram
technicians, housekeepers, clerical staff, security personnel, paramedics,
and research assistants).
A total of 111 patients (77%) were exposed to SARS in the hospital setting
(as health care workers, patients, or visitors). Most exposure occurred in
hospital A, which treated 1 of the sons of the index case early in the outbreak.
Home exposure occurred when family members or friends of hospital-associated
cases had close contact with affected individuals.
The median (IQR) time from self-reported earliest known exposure to
onset of symptoms was 6 days (3-10 days) for prodrome (headache, malaise,
or myalgia), 7 days (4-10 days) for self-reported fever, 8 days (4-11 days)
for diarrhea, and 9 days (5-12 days) for cough or dyspnea. Because this information
relies on patient recall and includes the earliest possible exposure among
cases in which more than 1 possible exposure existed, any inferences about
incubation period must be made with caution.
The earliest symptoms of SARS are shown in Table 2. The majority of individuals reported fever (74%) or prodromal
symptoms (51%) as part of the first constellation of symptoms. Respiratory
symptoms were less frequently reported as the initial symptoms of SARS. Forty-nine
individuals (34%) had been assessed by a physician and sent home prior to
being admitted to the hospital, usually because their initial symptoms did
not suggest SARS at all or because they did meet the case definition requiring
admission. For the latter group, home quarantine and follow-up procedures
were instituted. The median (IQR) time until these individuals were admitted
to the hospital was 3 days (2-5 days).
The relative frequencies of all reported symptoms at the time of admission
are shown in Figure 1. Common clinical
features include fever (99%), nonproductive cough (69%), myalgia (49%), and
dyspnea (42%). Only 2% of patients reported rhinorrhea, all in conjunction
with 1 or more other symptoms.
On admission, 85% of patients had a recorded temperature of 38°C
(100.4°F) or greater. The remaining 15% either developed fever while in
the hospital or reported fever prior to presentation. By day 4 of hospitalization,
only 28% of patients remained febrile. Tachycardia (heart rate >100/min) was
found in 46% of patients on admission, while tachypnea (respiratory rate >20/min)
and rales were noted in 37% and 26% of patients, respectively. No patient
had purpura or rash. One third of patients (34%) were given supplemental oxygen
during their hospital course.
Chest radiography on admission was normal in 25% of individuals, while
unilateral and bilateral infiltrates were observed in 46% and 29% of patients,
respectively. Thirty-one percent of individuals (45/144) had progression of
their pulmonary infiltrates while in the hospital (Table 3). However, 15 patients (10%) never developed an infiltrate.
Some characteristic radiographic features of SARS are shown in Figure 2. Although there was quite a bit of variability in the pattern
of the infiltrates (focal, lobar, diffuse), most patients had multifocal opacities.
Three percent of patients developed a pneumothorax while in the hospital.
Laboratory indices on admission are shown in Table 4. More than half (54%) of the cohort presented with moderate
lymphopenia (<1000/µL). The median (IQR) lymphocyte count was 900/µL
(700-1300/µL) on admission and decreased to a low of 500/µL (400-900/µL)
while in the hospital. Electrolyte and biochemical abnormalities present on
admission worsened the hospital course. These changes are shown in Table 5. During hospitalization, many patients
had hypocalcemia (70%), hypokalemia (43%), hypomagnesemia (57%), and hypophosphatemia
The vast majority of patients (95%) received empirical antibiotic therapy
during the course of their hospitalization. Ribavirin was used in 126/144
(88%) of patients. Ninety-one percent of these individuals received ribavirin
within the first 48 hours of hospitalization. While there was variability
between hospitals, most patients received a loading dose of 2 g intravenously,
followed by 1 g intravenously every 6 hours for 4 days, followed by 500 mg
every 8 hours for 3 days.21 The median (IQR)
treatment course of ribavirin was 6 days (5-7 days). Forty percent of individuals
received steroids; however, less than half of these patients received them
in the first 48 hours. Although there was variability among hospitals, most
patients received approximately 20 to 50 mg/d of hydrocortisone for 10 days.
Only 1 patient received pulse dosages.
The use of ribavirin was temporally associated with significant toxicity.
Seventy-one patients (49%) experienced a decrease in hemoglobin level of at
least 2 g/dL after ribavirin was initiated. Seventy-six percent of these patients
had evidence of hemolysis (defined as a 1.5-fold increase in bilirubin or
decreased haptoglobin level). Many patients with hemolysis were unable to
mount an adequate reticulocyte response. The median (IQR) reticulocyte count
in individuals with hemolysis was 25 000 cells/µL (16 000-35 000
cells/µL). Elevation of transaminases (defined as a 1.5-fold rise in
aspartate aminotransferase or alanine aminotransferase) was observed in 40%
of patients receiving ribavirin, while bradycardia and sore throat were reported
in 14% and 4% of patients, respectively. These toxicities led to the premature
discontinuation of ribavirin in 18% of patients.
There were 8 deaths in our cohort of 144 hospitalized SARS patients
(21-day mortality, 6.5%; 95% confidence interval [CI], 1.9%-11.8% by Kaplan-Meier
analysis). Six of these patients had diabetes. Of the other 2 patients, one
had cancer and the other had no comorbid disease other than being a former
smoker. As of April 17, most individuals (103/144 [72%]) had recovered and
were discharged from the hospital. Among patients who survived, median (IQR)
hospital stay was 10 days (6-15 days), and 74% of patients were discharged
by day 14 (95% CI, 65%-81%). Most of these patients had an uneventful progressive
recovery over the 2 weeks of their hospital stay.
A small proportion (<10%) had a return of fever, other symptoms,
or worsening infiltrates observed by chest radiograph during the second week
of their illness. Some of these patients had not received ribavirin or steroids
at first but were subsequently treated with these regimens. Others had a flare-up
of their symptoms after treatment was stopped. For this latter group, practice
varied, with only some having therapy reinstituted. In any case, all of these
patients recovered thereafter.
As of April 17, 2003, 23% of patients (33/144) were still hospitalized;
8 of these were still receiving mechanical ventilation. Of the entire cohort,
20% of patients (29/144) were admitted to the ICU and 69% (20/29) of these
received mechanical ventilation. Among the 20 patients who received mechanical
ventilation, 7 (35%) died, 2 (1%) were discharged, and 11 (55%) remained hospitalized
as of April 17, 2003. The eighth patient who died declined mechanical ventilation.
At 21 days, 30 patients in our cohort (21%; 95% CI, 14%-28% by Kaplan-Meier
analysis) met the criteria for a poor outcome (death or ICU admission with
or without mechanical ventilation). The majority of these poor outcomes occurred
in the first 6 days of hospitalization, with only 3 occurring after the first
week in the hospital. Table 6 shows
summaries of age, sex, and initial laboratory results classified by poor outcome.
Univariate analysis of these data showed that increased age, male sex, and
increased neutrophil count, creatine kinase, and urea were significantly associated
with poor outcome.
In a univariate Cox proportional hazards model, risk of a poor outcome
was almost doubled for those aged 60 years or older (relative risk [RR], 1.9;
95% CI, 1.3-2.7; P<.001). The presence of any
comorbid disease (diabetes, chronic obstructive pulmonary disease, cancer,
or cardiac disease) was found to increase the risk of a poor outcome (RR,
4.4; 95% CI, 2.1-8.9; P<.001), as was the presence
of diabetes alone (RR, 5.4; 95% CI, 2.5-11.5; P<.001).
Although poor outcomes were more common for those treated with ribavirin,
this was not statistically significant (RR, 1.9; 95% CI, 0.45-8.0; P = .36).
Multivariable Cox proportional hazards analysis was carried out assuming
the a priori hypothesis that age and comorbid diseases would be independently
associated with poor outcome (Table 6).
In a model with diabetes, other comorbid diseases, and age of 60 years or
older, a moderate association was found between advanced age and poor outcome
(RR, 1.4; 95% CI, 0.95-2.10; P = .09). Both diabetes
(RR, 3.1; 95% CI, 1.4-7.2; P = .01) and other comorbid
diseases (chronic obstructive pulmonary disease, cancer, and cardiac disease)
(RR, 2.5; 95% CI, 1.1-5.8; P = .03) were independently
associated with poor outcome.
Although age of 60 years or older, diabetes, and presence of other comorbidities
are all positively associated, a comparison of parameter estimates and SEs
from the single and multivariable models indicated that collinearity was not
a problem. The SE for the age parameter was only marginally larger in the
multiple regression model than in the age-only model, while the parameter
estimate itself was almost 50% smaller. Figure
3 shows Kaplan-Meier survival curves for the 4 groups defined by
the presence and absence of diabetes and other comorbidities. There was no
evidence for nonproportional hazards in any of the Cox model analyses.
Because SARS is an emerging infectious disease, the case definition
is evolving and not consistent among countries. We examined the effect of
varying the definition on our cohort. Prior to April 20, 2003, the CDC case
definition of SARS included 1 category labeled suspected SARS and had no definition
for probable SARS. This differed from the WHO and Health Canada definitions,
which included 2 categories, suspected SARS and probable SARS. As of April
20, 2003, the CDC revised their definition to include both suspected and probable
SARS, and the definition of suspected cases used by all 3 institutions was
identical and consisted of fever, significant contact or travel history, and
respiratory signs or symptoms.3,16,22 Probable
cases defined by WHO and the CDC (after April 20, 2003) include all suspected
cases with a radiographic chest infiltrate, whereas probable cases by Health
Canada criteria include all suspected cases with "severe progressive respiratory
disease." We chose to define severe progressive respiratory disease as having
2 of the following: progressive pulmonary infiltrates, hypoxemia (oxygen saturation
<95% with room air), and need for ICU admission.
Table 7 shows the proportion
of patients in our cohort who met each of these case definition criteria on
hospital admission and subsequently as new clinical features developed in
the hospital. All patients in our cohort did meet the original CDC definition
before it was changed on April 20. However, using the most recent definitions,
16 (11%) of the 144 individuals in our cohort would not meet criteria for
suspected SARS because they had no reported respiratory symptoms despite having
fever, contact history, and chest infiltrates.
We describe a cohort of 144 adult patients who were hospitalized with
SARS in the greater Toronto area. The majority of cases were acquired in hospitals
by health care workers, patients, and visitors. Most cases occurred in 1 hospital
early in the outbreak prior to significant awareness of SARS by the Canadian
medical community and before intensive respiratory precautions were instituted
for patients and their contacts. One third of patients had been seen by a
physician and sent home in the days prior to their admission with early symptoms
These observations have important infection control and public health
implications. Hospitals and clinicians' offices must be prepared to institute
appropriate respiratory precautions when assessing patients with undifferentiated
respiratory conditions and their family members, in order to prevent the introduction
of SARS in the hospital setting. Individuals such as health care workers or
household contacts of cases who are exposed to SARS patients, especially those
with early symptoms, need to be placed in isolation and have appropriate follow-up.
These 2 recommendations may form the basis of containing the disease as it
enters new communities.
We found the clinical features of SARS to be similar to those recently
reported by Lee et al10 in a cohort of 138
SARS patients in Hong Kong. The most common symptoms are fever, nonproductive
cough, myalgia, and dyspnea. Dizziness was less frequently reported in our
cohort than in Hong Kong. Fever is the first symptom as reported by many patients
(74%). The presence of rhinorrhea alone suggests that the diagnosis is unlikely
to be SARS. A significant portion of patients (25%) have normal chest radiograph
results on admission to the hospital. The hallmark laboratory findings include
lymphopenia (88%) and elevated lactate dehydrogenase (94%). These radiographic
and laboratory findings are also consistent with those reported by Lee and
colleagues.10 Many patients also demonstrate
low calcium, phosphorus, magnesium, and potassium levels and elevated creatine
kinase on admission. These electrolyte abnormalities, present on admission,
tend to worsen during hospitalization. It is unclear whether this represents
the natural history of the disease or is secondary to effects of ribavirin
or other therapies on renal tubular function. In patients with SARS, it is
important to closely monitor electrolytes and ensure adequate electrolyte
Given the retrospective nature of our study, it is difficult to determine
whether there is any therapeutic benefit to the treatment regimens used in
treating SARS, specifically ribavirin and steroids. Recent reports suggest
that most patients recover from SARS despite not receiving either ribavirin
or steroids.23 Our study did find numerous
adverse effects associated with ribavirin or other therapies, particularly,
hemolysis and transaminase elevation. Nearly all patients received empirical
antibiotics per the Canadian guidelines for management of community-acquired
Fourteen percent of the patients in our cohort required mechanical ventilation,
which is identical to the experience reported in Hong Kong. Although our overall
crude mortality rate was slightly greater (5.6% vs 3.6%; P = .60 by χ2 test), differences in completeness of
follow-up between the 2 cohorts make comparisons difficult to interpret (eg,
45% of the Hong Kong cohort were still in the hospital at the time that the
article was written compared with 23% of ours). When interpreting variation
in outcome event rates, one must consider which definition was used to define
the cohort. Our study shows that varying the case definition of SARS has an
impact on which patients are included for description.
Univariate analysis showed age of 60 years or older, comorbid disease,
male sex, and several biochemical abnormalities to be associated with poor
outcome. In our multivariable Cox proportional hazards model, diabetes and
other comorbid conditions were independently associated with poor outcome
but age of 60 years older was not. Larger studies are needed to further elucidate
which patients are at most risk of death or requiring mechanical ventilation.
The results of this study must be interpreted in light of several methodological
limitations. This was a retrospective case series study that relied on abstracting
data from clinical notes and patient charts. Accordingly, certain information
was missing for various patients, and certain data that may have been based
on patient memory, such as details concerning exposure history and timing
of onset of symptoms, may be affected by recall bias. This study did not include
patients who were evaluated for possible SARS but did not ultimately meet
any of the case definitions. As such, it cannot provide a decision rule to
distinguish SARS from non-SARS illness but, rather, provides a profile of
patients with SARS (ie, the sensitivities of all of the findings but not the
specificities). Finally, in an effort to quickly disseminate information to
clinicians worldwide, we only assessed short-term outcomes. It will be important
to perform follow-up evaluation of these patients to determine the long-term
repercussions of this illness.
Currently there is no gold standard test for the diagnosis of SARS.
At the current time, SARS is a syndrome, not a specific viral disease. The
results of this study suggest that some features of the history, physical
examination, and laboratory tests should alert clinicians to the possible
diagnosis of SARS, even when the contact history is unreliable. These features
are self-reported fever, prodromal symptoms (headache, malaise, or myalgia),
documented elevated temperature, lymphopenia, elevated lactate dehydrogenase,
and hypocalcemia. In regions where the syndrome enters the community at large
and the contact history is lost (an event that has not happened in the greater
Toronto area), these findings may prove to be important. Where the disease
has never been seen, clinicians should also consider these findings in evaluating
patients with respiratory illness. A chest radiograph should be obtained and
oxygen saturation should also be measured when evaluating such patients, and
a complete assessment to rule out alternative diagnoses or etiologies should
Current case definitions of SARS exclude a significant number of individuals
who have fever, contact history, and pulmonary infiltrates but have no respiratory
symptoms. This has important public health implications. Such individuals
may actually have acquired the virus that causes SARS without developing the
full syndrome. Accordingly, they and their contacts may require quarantine.
At a minimum, these patients require close follow-up.
In conclusion, despite the widespread implications of SARS, overall
21-day survival in our study was 93.5%. The remarkable spirit of international
collaboration among clinicians, researchers, and government agencies needs
to continue in an effort to better understand and control this emerging infectious