This document, from the Centers for Disease Control provides guidance on the clinical evaluation and management of patients who present from the community with fever and/or respiratory illnesses. Recommendations supercede those in the draft, Public Health Guidance for Community-Level Preparedness and Response to Severe Acute Respiratory Syndrome (SARS), which is currently being revised and finalized. Recommendations also supercede other SARS-related CDC materials on relevant topics that are under review.

I. Introduction

Severe acute respiratory syndrome (SARS) is a recently recognized febrile severe lower respiratory illness that is caused by infection with a novel coronavirus, SARS-associated coronavirus (SARS-CoV). During the winter of 2002 through the spring of 2003, WHO received reports of >8,000 SARS cases and nearly 800 deaths. No one knows if SARS-CoV will recur, but it is important to be prepared for that possibility. Early recognition of cases and application of appropriate infection control measures will be critical in controlling future outbreaks.

Many studies have been undertaken or are underway to evaluate whether there are specific laboratory and/or clinical parameters that can distinguish SARS-CoV disease from other febrile respiratory illnesses. Researchers are also working on the development of laboratory tests to improve diagnostic capabilities for SARS-CoV and other respiratory pathogens. To date, however, no specific clinical or laboratory findings can distinguish with certainty SARS-CoV disease from other respiratory illnesses rapidly enough to inform management decisions that must be made soon after the patient presents to the healthcare system. Therefore, early clinical recognition of SARS-CoV disease still relies on a combination of clinical and epidemiologic features.

II. Identification of Potential Cases of SARS-CoV Disease

The diagnosis of SARS-CoV disease and the implementation of control measures should be based on the risk of exposure. In the absence of any documented cases of SARS-CoV disease worldwide, the overall likelihood that a given patient being evaluated for fever or respiratory illness has SARS-CoV disease will be exceedingly low unless there are both typical clinical findings and some accompanying epidemiologic evidence that raises the suspicion of exposure to SARS-CoV. Therefore, one approach in this setting would be to consider the diagnosis only for patients who require hospitalization for unexplained pneumonia and who have an epidemiologic history that raises the suspicion of exposure, such as recent travel to a previously SARS-affected area (or close contact with an ill person with such a travel history), employment as a healthcare worker with direct patient contact or as a worker in a laboratory that contains live SARS-CoV, or an epidemiologic link to a cluster of cases of unexplained pneumonia. Once SARS-CoV transmission has been documented anywhere in the world, the positive predictive value of even early clinical symptoms (e.g., fever or respiratory symptoms in the absence of pneumonia), while still low, may be improved if used in combination with an epidemiologic link to settings in which SARS-CoV has been documented.

In that context, the guidance that follows should be considered in the evaluation and management of patients who present from the community with febrile respiratory illnesses. For more detailed guidance on infection control, see Public Health Guidance for Community-Level Preparedness and Response to Severe Acute Respiratory Syndrome (SARS).

III. Guidelines for Evaluation of SARS-CoV Disease among Persons Presenting with Community-Acquired Illness (Figures 1 and 2)

The following is an approach for the evaluation of possible SARS-CoV disease among persons presenting with community-acquired illness. As part of the work-up, in addition to identification of suggestive clinical features, clinicians should routinely incorporate into the medical history questions that may provide epidemiologic clues to identify patients with SARS-CoV disease.

IV. Additional Considerations

In some settings, early recognition of SARS-CoV disease may require additional measures. The following guidance is provided to assist in the evaluation of patients in settings or with characteristics not detailed/outlined in Figures 1 and 2. These include SARS outbreaks in the surrounding community, management of patients who become ill while already in the hospital, workers from laboratories that contain live SARS-CoV, pediatric patients, the elderly, and persons with chronic underlying diseases.

A. Additional epidemiologic risk factors to consider in community outbreak settings

The risk factors that should trigger suspicion for SARS-CoV may vary depending on the level of SARS-CoV transmission occurring in the community. Specifically, as outbreaks become more widespread, the types of epidemiologic characteristics that are considered as risk factors for SARS-CoV disease should be broadened appropriately. Two examples are given below.

1. Evaluating patients in the midst of a community outbreak in which more extensive secondary transmission of SARS-CoV is occurring in well-defined settings with all cases linked to other cases (e.g., an outbreak in a local hospital)

• Continue the activities for evaluation of persons with 'fever and/or respiratory illness' outlined in Figure 2, but in addition:
• Consider the diagnosis of SARS-CoV disease among all persons with radiographic evidence of pneumonia (even if not requiring hospitalization) if they:
  • Have had exposure to hospitals in the 10 days before onset of symptoms (e.g., patient, visitor, or staff), or
  • Are employed in an occupation at particular risk for SARS-CoV exposure, including a healthcare worker with or without direct patient contact or a worker in a clinical or research virology laboratory, or
  • Have close contact with a patient with documented pneumonia.

This document is focused on the evaluation and management of patients who present from the community, although many of the same principles apply to hospitalized patients who develop nosocomial fever or respiratory symptoms. The diagnosis of nosocomial SARS-CoV disease may be particularly challenging, however, since many inpatients may have other reasons for developing nosocomial fever, respiratory symptoms, and pneumonia. Therefore, in hospitals known to have or suspected of having patients with SARS-CoV disease, clinicians and public health officials must be particularly vigilant about evaluating fever and respiratory illnesses among inpatients. Additional guidance on when to apply Figure 2 in the evaluation of patients who develop fever and/or respiratory illness while hospitalized is provided in Public Health Guidance for Community-Level Preparedness and Response to Severe Acute Respiratory Syndrome (SARS), Supplement C: Preparedness and Response In Healthcare Facilities (460 KB/35 pages).

C. Laboratory workers

Breaks in technique in laboratories that contain live SARS-CoV could result in laboratory-acquired cases of SARS-CoV disease. Personnel working in laboratories that contain live SARS-CoV should report any febrile and/or respiratory illnesses to the supervisor, be evaluated for possible exposures, and be closely monitored for clinical features and course of illness. If laboratory workers with fever and/or respiratory illness are found to have an exposure to SARS-CoV, they should be managed according to the guidance in Figure 2. More detailed information for persons who work in laboratories that contain live SARS-CoV is provided in the guidance for medical surveillance of laboratory personnel who work with SARS-CoV, to be posted soon at the CDC SARS web site.

D. Considerations for the pediatric population

The document does not specifically address the evaluation and management of infants and children. Much less is known about SARS-CoV disease in pediatric patients than in adults. During the 2003 outbreaks, infants and children accounted for only a small percentage of patients and had much milder disease with better outcome. Their role in transmission is not well described but is likely much less significant than the role of adults. Taking these factors into account, the following guidance may change as more information becomes available on SARS-CoV disease in the pediatric population:

• In the absence of SARS-CoV transmission in the world, evaluation and management for possible SARS-CoV disease should be considered only for adults, unless special circumstances make the clinician and health department consider a child to be of potentially high risk for having SARS-CoV disease.
• In the presence of SARS-CoV transmission in the world, the evaluation algorithm established for adults can be used in children with the following caveats:
  • Both the rate of development of radiographically confirmed pneumonia and the timing of development of such radiographic changes in children are unknown.
  • The positive predictive value of rapid virus antigen detection tests (e.g., RSV) "in season" will be higher in a pediatric population.
  • Pneumococcal and legionella urinary antigen testing are not recommended for routine diagnostic use in children.

Typical symptoms of SARS-CoV disease may not always be present in elderly patients and those with underlying chronic illnesses, such as renal failure. Therefore, the diagnosis should be considered for almost any change in health status, even in the absence of typical clinical features of SARS-CoV disease, when such patients have epidemiologic risk factors for SARS-CoV disease (e.g., close contact with someone suspected to have SARS-CoV disease or exposure to a location [domestic or international] with documented or suspected recent transmission of SARS-CoV).

Figure 1. Algorithm for evaluation and management of patients requiring hospitalization for radiographically confirmed pneumonia, in the absence of SARS-CoV disease transmission worldwide

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FOOTNOTES FOR FIGURE 1

¹ Or Acute Respiratory Distress Syndrome (ARDS) of unknown etiology

² Guidance for the management of community-acquired pneumonia is available from the Infectious Diseases Society of America (IDSA) and can be found online.

³ The 2003 SARS-CoV outbreak likely originated in mainland China, and neighboring areas such as Taiwan and Hong Kong are thought to be at higher risk due to the high volume of travelers from mainland China. Although less likely, SARS-CoV may also reappear from other previously affected areas. Therefore, clinicians should obtain a complete travel history. If clinicians have concerns about the possibility of SARS-CoV disease in a patient with a history of travel to other previously affected areas (e.g., while traveling abroad, had close contact with another person with pneumonia of unknown etiology or spent time in a hospital in which patients with acute respiratory disease were treated), they should contact the health department.

Figure 2: Algorithm for management of fever or respiratory symptoms when SARS-CoV transmission is occurring in the world

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FOOTNOTES FOR FIGURE 2:

¹Clinical description of SARS-CoV disease and approach to treatment: Clinical judgment should be used to determine when symptoms trigger initiation of the algorithm in Figure 2. The earliest symptoms of SARS-CoV disease usually include fever, chills, rigors, myalgia, and headache. In some patients, myalgia and headache may precede the onset of fever by 12-24 hours. Diarrhea may also be an early manifestation. Respiratory symptoms often do not appear until 2-7 days after the onset of illness, and most often include shortness of breath and/or dry cough.

Although not diagnostic, the following laboratory abnormalities have been seen in some patients with laboratory-confirmed SARS-CoV disease:

• Lymphopenia with normal or low white blood cell count
• Elevated hepatic transaminases
• Elevated creatine phosphokinase
• Elevated lactate dehydrogenase
• Elevated C-reactive protein
• Prolonged activated partial thromboplastin time

²Exposure history for SARS-CoV, once SARS-CoV transmission is documented in the world:
In settings of no or limited local secondary transmission of SARS-CoV, patients are considered exposed to SARS if, within 10 days of symptom onset, the patient has:

• Close contact with someone suspected of having SARS-CoV disease, OR
• A history of foreign travel (or close contact with an ill person with a history of travel) to a location with documented or suspected SARS-CoV, OR
• Exposure to a domestic location with documented or suspected SARS-CoV (including a laboratory that contains live SARS-CoV), or close contact with an ill person with such an exposure history.

³Clinical work-up: Clinicians should work up patients as clinically indicated. Depending on symptoms and exposure history, initial diagnostic testing for patients with suspected SARS-CoV disease may include:

• Complete blood count (CBC) with differential
• Chest radiograph
• Pulse oximetry
• Blood cultures
• Sputum Gram's stain and culture
• Testing for viral respiratory pathogens, notably influenza A and B and respiratory syncytial virus
• Legionella and pneumococcal urinary antigen testing if radiographic evidence of pneumonia (adults only)

SARS-CoV testing may be considered as part of the initial work-up if there is a high level of suspicion for SARS-CoV disease based on exposure history. For additional details on specialized laboratory testing options available through the health department and the Laboratory Response Network (LRN), see CDC's SARS website.

⁴Alternative diagnosis:
An alternative diagnosis should be based only on laboratory tests with high positive-predictive value (e.g., blood culture, viral culture, Legionella urinary antigen, pleural fluid culture, transthoracic aspirate). In some settings, PCR testing for bacterial and viral pathogens can also be used to help establish alternative diagnoses. The presence of an alternative diagnosis does not necessarily rule out co-infection with SARS-CoV.

⁵Radiographic testing:
Chest CT may show evidence of an infiltrate before a chest radiograph (CXR). Therefore, a chest CT should be considered in patients with a strong epidemiologic link to a known case of SARS-CoV disease and a negative CXR 6 days after onset of symptoms. Alternatively, the patient should remain in SARS isolation, and the CXR should be repeated on day 9 after symptom onset.

⁶Discontinuation of SARS isolation precautions:
SARS isolation precautions should be discontinued only after consultation with the local public health authorities and the evaluating clinician. Factors that might be considered include the strength of the epidemiologic exposure to SARS-CoV, the nature of contact with others in the residential or work setting, the strength of evidence for an alternative diagnosis, and evidence for clustering of pneumonia among close contacts. Isolation precautions should be discontinued on the basis of an alternative diagnosis only when the following criteria are met:

• Absence of strong epidemiologic link to known cases of SARS-CoV disease
• Alternative diagnosis confirmed using a test with a high positive-predictive value
• Clinical manifestations entirely explained by the alternative diagnosis
• No evidence of clustering of pneumonia cases among close contacts (unless >1 case in the cluster is confirmed to have the same alternative diagnosis)
• All cases of presumed SARS-CoV disease identified in the surrounding community can be epidemiologically linked to known cases or locations in which transmission is known to have occurred.