A Clinical Prediction Rule for Diagnosing Severe Acute Respiratory Syndrome in the Emergency Department

Context Which characteristics distinguish patients with severe acute respiratory syndrome (SARS)? Contribution These investigators developed a prediction rule for SARS by using data from 2649 consecutive patients seen at 2 Hong Kong triage clinics during the 2003 SARS epidemic. The following characteristics increased the likelihood of SARS: previous contact with a patient with SARS, fever, myalgia, malaise, abnormal chest radiograph, and abnormal lymphocyte and low platelet counts. Age 65 years and older or younger than 18 years, productive sputum, abdominal pain, sore throat, rhinorrhea, and high neutrophil count decreased the likelihood of SARS. Cautions Findings probably are not applicable to isolated cases occurring during an interepidemic period. The Editors The case definition of severe acute respiratory syndrome (SARS) changed numerous times since the first reports on the presenting symptoms of patients with SARS during the 20022003 epidemic (1-3). The definition developed by the World Health Organization (WHO) (4) throughout the main period of spread in 2003 specifies that patients with a history of high fever (body temperature > 38 C), cough or breathing difficulty, and 1 or more exposures (defined as being in close contact with patients with SARS or residing in or traveling through a region affected by SARS) during the 10 days before onset of symptoms would qualify as suspect cases. A probable case of SARS is defined as meeting 2 additional criteria: 1) radiographic evidence of infiltrates consistent with pneumonia or respiratory distress syndrome on chest radiographs, or 2) laboratory-confirmed results that are positive for SARS coronavirus. However, Rainer and colleagues (5) previously concluded that these WHO guidelines for diagnosing suspected cases of SARS may not be sufficiently sensitive for assessing patients before admission to a hospital and could result in substantial underdiagnosis of SARS. In the context of triaging patients in the primary care community setting, such as in emergency departments or special clinics set up during an acute outbreak, the current WHO guidelines are not likely to identify all patients with SARS. This possibility has important consequences not only for affected patients but also for the broader public health because infected persons cannot be rapidly isolated and quarantined. The resurgence of SARS remains a distinct possibility in the coming winter months, given its uncertain origins and possible animal reservoirs (in the form of wild animal markets that are common in Guangdong, China) (6). Accurate, objective models of triage and diagnosis could help physicians and public health authorities assess patients' risks and improve decisions about isolation, quarantine, and treatment in hospitals. We sought to develop a clinical prediction rule for diagnosis that would accurately identify patients with SARS in the emergency department setting during an outbreak and to validate the predictive accuracy of this rule. Methods Sources of Data and Definition of Variables We analyzed an integrated database, the Hospital Authority eSARS system (an electronic Web-based clinical information database developed and used during the 2003 SARS epidemic), that contained clinical and laboratory data from all patients who visited the SARS triage clinics in the emergency departments of the Prince of Wales Hospital and United Christian Hospital in Hong Kong, China. All patients seen in these 2 clinics who were subsequently hospitalized were admitted to the same hospitals; however, after recovering from the acute illness, some were transferred to Hospital Authority convalescent facilities to recuperate before final discharge home. The Hospital Authority is directly responsible for all 44 public hospitals in Hong Kong; it provides 95% of total inpatient bed-days in Hong Kong and provided for clinical care for all patients with SARS in the 2003 outbreak. Although other triage clinics were in operation during the 2003 SARS outbreak, structured, abstracted data from these clinics were unavailable for pooled analysis. Clinical information on the history and physical examination of persons presenting to the emergency departments of the Prince of Wales and United Christian Hospitals was abstracted from chart review by trained nursing and medical officers at each hospital. The reviewers were blinded to the final diagnosis and used a standardized protocol for abstracting information. Candidate variables, collected through standardized recording forms used by triage clinic personnel, included age (<18 years, 18 to 64 years, and 65 years), sex, health care worker (yes vs. no), contact history with patients with SARS (yes vs. no), and history of travel to other SARS-affected areas (as defined by the WHO at the time) within 2 weeks of symptom onset or the time of presentation to the triage clinic (yes vs. no). Additional variables were the presence of fever (defined as either a positive self-reported history or self-measurement at home or a tympanic temperature of at least 38 C at triage), cough, sputum, dyspnea, sore throat, rhinorrhea, chills or rigor, myalgia, anorexia, malaise, diarrhea, vomiting, abdominal pain or headache (coded as dichotomized responses), pulse rate, systolic and diastolic blood pressure, respiratory rate, and oxygen saturation on room air. Investigations consisted of chest radiography (normal, haziness, or unilateral or bilateral pneumonic consolidation as interpreted by the emergency department physician) and simple hematologic and biochemical blood tests, including hemoglobin level, leukocyte count, absolute lymphocyte count, monocyte and neutrophil counts, and platelet count. Because we did not have sufficiently complete data (<60%) on some laboratory determinations for the entire sample (alkaline phosphatase level, alanine aminotransferase level, aspartate aminotransferase level, international normalized ratio, lactate dehydrogenase level, prothrombin time, serum albumin level, and total bilirubin level), we excluded these determinations from the analysis for all patients. According to WHO recommendations for interpreting SARS-related laboratory tests, a final diagnosis of SARS was defined (7) by 1) positive findings on reverse transcriptase polymerase chain reaction (RT-PCR) from 2 or more clinical specimens (from different sites or tested in different laboratories) obtained from patients who were alive or who had died or 2) seroconversion by enzyme-linked immunosorbent assay, immunofluorescent antibody testing, or neutralization assay against SARS coronavirus. Although most of these tests were available during the outbreak, not all patients underwent any or all of them for various reasons, including nonuniform testing protocol (especially in the earlier part of the outbreak), lack of samples because patients died and autopsy examination was not performed, and inadequate and missing specimens. Test variables such as sensitivity and specificity were unknown because no gold standard laboratory or clinicopathologic definitions were available for the diagnosis of this new and emerging disease, against which diagnostic test performance can be benchmarked. Immunoglobulin G antibodies against SARS coronavirus on serologic testing seemed to be the best method for confirming SARS in largely seronegative populations (8) in which the reported seropositivity rate reached 93% to 99% in Hong Kong (5, 9) and 96.2% in Toronto (10). We collected serum samples for paired serologic testing at least 21 to 28 days apart; however, anecdotal reports from longitudinal follow-up of patients with SARS in Hong Kong revealed seroconversion as long as 6 months after acute illness. Overall, Tang and colleagues (10) found that the sensitivity of a single first-generation RT-PCR assay was 54.1% in their Toronto SARS case series, assuming that all of the clinically classified patients truly had SARS. These findings were broadly similar to those reported by Peiris and colleagues (9) for the outbreak at the Amoy Gardens housing estate in Hong Kong during late March and early April 2003. In both the Hong Kong and Toronto epidemics (9, 10), the peak positivity rate of RT-PCR occurred 9 to 11 days after the first appearance of symptoms; gastrointestinal specimens gave higher yields than respiratory samples. Poon and colleagues (11) later produced a second-generation RT-PCR assay capable of detecting SARS coronavirus in up to 88% of respiratory tract samples obtained within the first 3 days after illness onset in confirmed cases of SARS in the Hong Kong outbreak. This test kit had since been adopted in the latter part of the Hong Kong epidemic. We sent all specimens for SARS coronavirus testing in Hong Kong to 3 designated laboratories (Chinese University of Hong Kong, which received most of the samples from the Prince of Wales Hospital; University of Hong Kong; and the government Department of Health, which tested most of the samples from the United Christian Hospital) with rigorous quality control procedures. All 3 facilities were certified as reference laboratories by the WHO and were members of the WHO SARS Reference and Verification Laboratory Network. Derivation Process From the eSARS database, we selected cohorts from the emergency departments of the 2 hospitals for the analysis. The first cohort consisted of new patients who presented to the United Christian Hospital between 10 March 2003 and 10 May 2003; the catchment area included the Amoy Gardens housing estate, a major epicenter of the SARS outbreak in Hong Kong. Most of the patients in the cohort were from Amoy Gardens (821 of 1274 [64.4%]), but patients from the surrounding Kwun Tong district, a densely populated residential and industrial area, were also included. All consecutive patients who presented to the emergency department during the recruitment period with febrile, respiratory, gastrointestinal, infectious, or otherwise constitutional