Clinical Signs and Symptoms

The median incubation period for SARS appears to be approximately 4–6 days; most patients become ill within 2 to 10 days after exposure (8,12,17,18). Some evidence suggests that the incubation period may be as long as 14 days in some persons (17).

The most common initial symptom is fever, often accompanied by headache, myalgia, malaise, chills, and rigor (1,11,17–22). In some patients, headache, myalgia, and malaise precede the onset of fever by up to 1 day, and fever may have resolved by the time respiratory symptoms appear (1,18,19,22). Respiratory symptoms typically do not begin until 2–7 days after illness onset, although they are among the initial symptoms in up to 30% of patients (1,18–20). The most common respiratory complaints are lower respiratory tract symptoms, including nonproductive cough and dyspnea; productive cough is reported in up to 25% of patients (1,11,17–22). In some series, <10% of patients reported upper respiratory complaints (18,20,23), but in others the reported prevalence of rhinorrhea or sore throat is as high as 25% among patients with SARS (11,17,19). The prevalence of gastrointestinal symptoms has varied by report, but nausea, vomiting, diarrhea, or a combination of these symptoms has been reported in up to 25% of patients with SARS at the time of initial evaluation (1,11,17–22,24). In one series, diarrhea developed in 73% of patients at some point in the course of illness (22). Fever and diarrhea have been the dominant initial symptoms in some patients (13). Asymptomatic infection with SARS-CoV appears to be uncommon (25,26).

Elderly patients and those with underlying chronic illnesses such as renal failure may not have typical symptoms of SARS (12,13,27). For patients in this group who have strong epidemiologic risk factors for SARS, the diagnosis should be considered in almost any change in health status, even if the patients do not exhibit typical clinical features.

Physical Findings

Tachypnea, tachycardia, and hypoxemia have been reported in 40% to 75% of patients upon admission to the hospital (1,18–20) but may be less common in patients who are evaluated earlier in the course of illness as outpatients (21). Upon auscultation of the lungs, rales or rhonchi have been detectable in most patients in some series, and less commonly in others (18,20,21,28). Some researchers have observed a lack of lung sounds despite marked infiltration on chest radiography (21,28). As many as 15%–44% of patients may have a normal measured body temperature when first evaluated (18,19).

Laboratory Findings

Hematologic abnormalities are among the most consistent laboratory findings reported in patients with SARS; most patients have total leukocyte counts that are normal or slightly low, and 70%–95% of patients have lymphopenia (11,18–20,22,29). Platelet counts are mildly depressed in 30% to 50% of patients (11,19,22,29). Prolongation of the activated partial thromboplastin time can be observed in 40% to 60% of patients, but disseminated intravascular coagulation is uncommon (11,29).

Other common abnormal laboratory findings include elevated lactate dehydrogenase levels in 70% to 90% of patients (11,18,19), elevated alanine aminotransferase or aspartate aminotransferase levels in 20% to 30% (11,22), elevated creatine phosphokinase in 30% to 40% (11,22,30), and elevated C-reactive protein (1,31).

Radiographic Findings

While the full understanding of the spectrum of radiographic manifestations of SARS will require additional information, available data suggest that almost all reported patients with laboratory evidence of SARS-CoV infection have radiographic evidence of pneumonia documented at some point during their illness (19,21,31). Chest radiographs may be normal in up to 30% of patients with the clinical diagnosis of SARS at the time when first evaluated (18,22,32–34). In reports from China, radiographic changes consistent with pneumonia were detected in 67% to 80% of SARS patients by day 3 of illness, 97%-100% by day 7, and in 100% by day 10 (33,34). A lesion typically begins as an isolated focal lesion found in a peripheral location, often in the lower lobes. In 75% of patients, the lesions progress over several days to involve additional lobes or both lungs (32,34).

Computed tomography (CT) of the chest appears to be more sensitive than conventional chest radiography for detecting pneumonia; SARS patients who have normal chest radiographic findings early in their clinical course often have evidence of pneumonia by CT (11,35). Common CT findings are ground-glass opacification and a lower lobe and peripheral distribution (35).

Distinguishing SARS from Other Illnesses

As with other causes of bacterial and viral pneumonia, clinical findings in patients with SARS cannot accurately predict the causative agent. Further study is required to determine whether a constellation of clinical findings alone can be used to discriminate accurately between SARS and other (especially viral) respiratory illnesses. Many of the clinical and laboratory features of SARS are similar to those in other forms of viral pneumonia (28,36). Several clinical features, however, may be helpful in facilitating recognition of patients with SARS (Table 1).

Epidemiologic Linkage to Cases or SARS-affected Areas

The predominant mode of transmission of SARS-CoV appears to be through large respiratory droplets or direct contact (7,8). This mode of transmission is consistent with the observation that most patients can be linked, either directly or indirectly, to persons with SARS or places where transmission is either suspected or documented (17,37). In the Toronto and Singapore outbreaks, >94% of cases had documented contact with a SARS patient or with a hospital ward where there was a known SARS patient (8,38). Therefore, determining if persons with symptoms compatible with SARS have an epidemiologic linkage either to other persons with known or suspected SARS or to places with known or suspected transmission of SARS-CoV is important.

Whether a history of travel to areas previously affected by SARS will be a useful epidemiologic clue for recognizing future outbreaks depends in part on whether SARS-CoV currently exists within a human or an animal reservoir. If the virus exists within a human reservoir, the virus could reemerge anywhere on the globe, although the areas of highest activity during the recent outbreaks are most likely to harbor persistent infection in humans. Alternatively, if SARS-CoV currently exists primarily within the animal reservoir from which it originated, future outbreaks may more likely originate in Southeast Asia. Given that China appears to have been the origin of the most recent outbreak (4,39) and neighboring areas are at greatest risk, persons traveling in Southeast Asia, especially in China, Hong Kong, and Taiwan, may be at increased risk for infection if SARS recurs.

Case Clustering

The major limitation of relying on linkage to settings of known transmission to identify persons at risk for SARS is identifying the first cases acquired in an area not previously known to have circulation of SARS-CoV. Because SARS-CoV infections tend to appear in clusters, one potential strategy for early recognition in such areas is to seek evidence for clustering of pneumonia cases. Early recognition of clusters requires clinicians evaluating patients with pneumonia to routinely seek a history of exposure to others with pneumonia.

Healthcare Association

Healthcare facilities have played a central role in the epidemiology of SARS. Persons who work in healthcare settings were among the earliest and most severely affected group in almost every major outbreak reported, particularly during the earliest phases of the outbreak (8,11,13). For example, in the Toronto and Singapore outbreaks, 43% and 41%, respectively, of the SARS cases occurred in healthcare workers (40). Therefore, atypical pneumonia among healthcare workers should raise the suspicion for SARS, particularly if there are multiple cases among healthcare workers in the same facility. In addition, atypical pneumonia in a person who works in a laboratory that contains live SARS-CoV should raise the possibility of SARS.

Alternative Diagnoses

Documenting the presence of other diseases does not exclude the possibility of SARS because patients with SARS-CoV infection can be co-infected with other respiratory pathogens (19,47). If the presence of an alternative diagnosis is to be used as justification for discontinuing SARS-specific isolation precautions, the alternative diagnoses should be based only upon tests with high positive predictive value, and the clinical illness should be fully explainable by the diagnosis. The possibility of secondary infection should be considered if the diagnosis of bacterial pneumonia is confirmed, since bacterial pneumonia is a well-known complication of viral respiratory tract infection and may occur following SARS-CoV infection.

Particular care should be taken in completely attributing the illness to an alternative diagnosis if the epidemiologic link to others known to have SARS-CoV infection is strong, or if the patient is part of an epidemiologic cluster of similar illnesses. In the latter instance, confirming an alternative diagnosis among more than one person within the cluster may be used as evidence against SARS, particularly if the clinical findings are not typical of SARS (e.g., upper respiratory symptoms).

Ruling out SARS

The only currently available laboratory method for excluding the diagnosis of SARS-CoV infection is to obtain a negative result on serologic testing of a convalescent-phase serum sample obtained >28 days after onset of symptoms. For patients without evidence of pneumonia at the initial evaluation, serial observations over time may be helpful in identifying those in whom isolation precautions can be safely discontinued (21). Resolution of symptoms and lack of development of radiographic evidence of pneumonia by the 2nd week of illness argue against the diagnosis of SARS. Some patients with mild illness may be missed when this approach is used, but if that is the case, they likely will not play an epidemiologically important role in transmission.

Patients with documented pneumonia who have been given the provisional diagnosis of SARS should be treated as if they have SARS-CoV infection, unless there is convincing evidence for an alternative diagnosis or new epidemiologic information excludes the possibility that the patient was exposed to SARS