-- By .C.W. CHEUNG, M.D., M.W.C. YIU, M.D., L.L.Y. LEONG, M.D., AND F.L. CHAN, M.D.
The outbreak of atypical pneumonia began in February in Asia, including southern China, Hong Kong SAR, and Vietnam, when patients began to present with acute respiratory symptoms (cough, dyspnea, and desaturation) and fever. Chest x-rays revealed nonspecific infiltrates. Efforts to identify a pathogen such as a bacterium or influenza virus were unsuccessful. The World Health Organization coined the term severe acute respiratory syndrome (SARS) in March to describe the condition.
The index patient in Hong Kong was a man from Guangdong province in southern China who had traveled to Hong Kong. He is thought to be the source of infection for some residents of the hotel where he stayed and subsequently for many healthcare workers in a local hospital. Droplet transmission via close personal contact is hypothesized to be responsible for the spread of SARS. Contact with contaminated objects in public use, such as elevator buttons, stair rails, and door handles, has also been suspected.
The initial cases were followed by a community outbreak in a local housing estate where more than 300 people living in a single multistory building were infected. Many of them lived in flats on different floors but with the same orientation, which led to an investigation of an apparently vertical spread. All units on different floors are connected by a single vertical soil stack, and U-traps are present in each flat. Many of the traps were dried up, however, allowing droplets to enter the flats in a retrograde manner. Evidence was also found for a vertical airstream blowing the droplets upward from lower to upper floors. Coupled with a crack in the sewer vent pipe in a lower floor, this may explain the fact that most patients lived in middle and upper levels of the building.
The possibility of airborne spread has not been excluded but is considered unlikely. Many people who stayed in hotel rooms or hospital wards used by infected subjects show no evidence of SARS, making it improbable that the disease is carried through air conditioning systems.
Hong Kong is at present one of the locations most affected by SARS. Between March and early May, 1646 cases of SARS have been reported worldwide, 368 of whom are healthcare workers or medical students, and about 320 of whom resided in the private housing estate mentioned. As of April, 193 patients had died; 73 patients continue to receive intensive care.
DIAGNOSIS
Criteria used for public health case definitions are listed in the accompanying table. The incubation period for SARS is usually less than 10 days. Patients typically present with acute febrile illness with temperature higher than 38° C, although some elderly patients have presented without fever in an early phase of the disease. Chills can be a very pronounced complaint, and myalgia and malaise have also been reported. Diarrhea and upper respiratory tract symptoms, such as sore throat, preceding the acute illness have been noted in some patients. Dry cough and difficulty breathing may follow in two to seven days.
A positive history of close contact with a SARS patient is very helpful. Laboratory tests can show mild derangement of liver function, elevation of creatine phosphokinase and lactate dehydrogenase, and mild thrombocytopenia and lymphopenia. As more patients are being diagnosed, we are seeing a wider spectrum of clinical presentation, including watery diarrhea, confusion, and headache.
Because the clinical picture is nonspecific, universal droplet precaution is now advocated in our location. In some incidences, multiple healthcare workers have contracted the disease from patients not suspected of having SARS. Moreover, early treatment is associated with better outcome, which further stresses the importance of a high level of clinical suspicion.
The causative organism has been identified as a novel corona virus (a single-strand RNA virus) that has not previously been found in animals or humans. Paramyxovirus and chlamydia have also been identified in some specimen; the possibility of a coinfection cannot be excluded at the moment.
Serological tests are available for the corona virus, but they may not be positive in the first few days of the disease. The University of Hong Kong has developed a "quick test" for respiratory secretions, based on polymerase chain reaction technique. Owing to limited experience, however, the positive and negative predictive values have yet to be determined and cannot be used to exclude the diagnosis. Recent evidence suggests a high false negativity.
CHEST RADIOGRAPHS
Plain chest films remain the most commonly used modality for investigation of SARS. Erect radiographs are taken of patients in outpatient or emergency units. Direct digital radiography allows immediate film review by a radiologist. Hospitalized patients present a challenge, however, and we try to minimize their movement within the hospital to reduce exposure of other patients and staff. We use portable x-ray machines in the isolation wards. Erect film holders are set up in the wards to enable posteroanterior projection with less magnification from a standard focus film distance.
The plain film findings as described by the Chinese University of Hong Kong are accessible at www.droid.cuhk.edu.hk. The Web site includes an image gallery that shows the spectrum of imaging findings in SARS patients and recommendations for imaging investigation.
In our experience, ill-defined middle and lower zone infiltrates are the most common presentation. Many of these appear as ground glass opacification or just ill-defined haziness, which may be unilateral or bilateral. Better defined consolidation with air bronchograms are seen in a few patients, but lobar consolidation has not been seen. There is no finding of pleural effusion or hilar enlargement.
Patients presenting with more advanced disease do show patterns of diffuse consolidation involving both the upper and lower zones. This is similar to patients with acute respiratory distress syndrome.
Although useful as a diagnostic tool, plain films may not be the optimal means for following disease progression. Some patients do show increase in extent of lung consolidation with time. We also have patients with worsening saturation and dyspnea whose chest films show little interval change. Whether high-resolution CT (HRCT) would more closely reflect disease progression has yet to be determined.
HRCT OF THORAX
As noted at other centers, HRCT changes usually precede chest x-ray abnormality. HRCT is also used as a problem-solving tool when changes on chest radiographs are equivocal. Apart from earlier diagnosis, we also come across patients with persistent normal radiographs but progressively worsening HRCT changes. HRCT should be used to confirm or exclude lung changes in patients with normal chest x-ray who have clinical findings compatible with SARS.
Changes on HRCT parallel plain-film abnormalities. Ground glass shadowing or air space consolidation is common. Interlobular septum thickening and other interstitial line shadows are also noted. The locations are predominantly lower zone and not uncommonly subpleural.
TREATMENT
No consensus exists regarding the optimal mode of treatment. Supportive care and assisted ventilation when needed are important. Broad-spectrum antibiotics are given to cover the usual organisms. Intravenous administration is preferred, especially in more serious cases.
In the public hospitals in Hong Kong, we are treating patients with typical clinical findings of SARS with a combination of intravenous ribavirin and high-dose steroid (3 mg/kg/day with tapering after the first five days). The empirical experience shows favorable response in the majority of patients. Convalescent patient plasma infusion has been used in a very limited number of cases who failed to respond to the usual treatment. Some are showing signs of favorable response. Other modes of treatment such as immunoglobulin and traditional Chinese medicine are also employed in selected patients with consent obtained.
(1a) (1b)  |
| Case 1. SARS with unilobar involvement revealed by HRCT only. 35-year-old man whose wife was diagnosed with SARS presented to our institute with fever, chills, generalized malaise, myalgia, and severe throbbing headache. A radiologist reviewed the initial chest radiograph (1a) on a PACS diagnostic workstation and called it normal. No neutropenia or deranged liver function was seen on the initial screening. In view of relevant symptoms and the patient's close contact with a SARS patient, however, HRCT was performed the same evening (1b). It showed focal subpleural ground glass opacity with interlobular septal thickening at the superior segment of the left lower lobe. There was significant elevation of serum IgG for corona virus, and polymerase chain reaction for corona virus of the sputum was subsequently positive. |
(2a) (2b)  |
| Case 2. SARS with multilobar involvement on chest x-ray and HRCT. 58-year-old male healthcare worker with recent close contact with a SARS patient presented with fever and generalized myalgia. Earlier chest radiograph at our institution was normal. Repeat chest radiography (2a), taken three days later due to persistent symptoms, revealed ground glass opacity of left middle and lower zones. Again, no pleural effusion or hilar enlargement was found. HRCT performed the same evening (2b) showed multifocal, multilobar involvement, which was far more extensive than indicated on the chest x-ray. Patient's condition rapidly deteriorated and he required intensive care and high oxygen supplement. |
(3a) (3b)  (3c)  |
| Case 3. SARS with unilobar involvement. 29-year-old man presented with chills and severe myalgia. Chest radiograph (3a) showed a patch of ground glass opacity at the periphery of the right middle zone, but lateral view (3b) provided no additional information. HRCT (3c) done the same evening showed a focal ground glass opacity at the lateral segment of the right middle lobe. Sputum was confirmed to have corona virus on polymerase chain reaction. |
(4a) (4b)  (4c)  |
| Case 4. SARS with multilobar involvement. 38-year-old man presented with recurrent fever, dry cough, rigor, and watery diarrhea. Nasal and throat swabs were positive for corona virus polymerase chain reaction. Chest radiograph (4a) taken in emergency department showed ill-defined ground glass opacity at the periphery of the right lower zone and a subtle but similar lesion at the periphery of the left middle and lower zones. No lobar consolidation, hilar enlargement, or pleural effusion was seen. HRCT at the middle zones (4b) showed extensive subpleural ground glass opacity with multilobar involvement. Intensive medical therapy was initiated, and patient showed satisfactory clinical and radiological response. Reassessment HRCT (4c) taken two weeks later showed almost complete resolution of the lesions. |
SUGGESTED READING
1. Tsang KW, Ho PL, Ooi GC, et al. A cluster of cases of severe acute respiratory syndrome in Hong Kong. New Engl J Med 2003 (online): March 31.
2. Hospital Authority guidelines on severe acute respiratory syndrome. Hospital Authority, Hong Kong SAR, China, 2003.
3. Severe acute respiratory syndrome (SARS). Atlanta: Centers for Disease Control and Prevention, 2003.
4. Severe acute respiratory syndrome (SARS) multi-country outbreak -- update 1 to 23. World Health Organization, Geneva, 2003.
5. Radiological appearances of recent cases of atypical pneumonia in Hong Kong. Accessed via Web site of the department of diagnostic radiology and organ imaging of the Chinese University of Hong Kong, Hong Kong SAR. (http://www.droid.cuhk.edu.hk)
6. Outbreak of severe acute respiratory syndrome (SARS) at Amoy Gardens, Kowloon Bay, Hong Kong. Main findings of the investigations. Accessed via Web site http://www.info.gov.hk/dh
TABLE:
| CRITERIA FOR REPORTING TO HOSPITAL AUTHORITY SARS REGISTRY IN HONG KONG ‡ |
|
| EXCLUSION CRITERIA |
| A case should be excluded if an alternative diagnosis can fully explain the patient's illness. |
| SUSPECTED CASES |
| A case that does not completely meet the above criteria should still be considered highly likely of SARS based on clinical judgment. |
| ‡ April 22, 2003 version |
DR. CHEUNG, DR. YIU, DR. LEONG, AND DR. CHAN are radiologists at Queen Mary Hospital in Hong Kong SAR, People's Republic of China.
