HONG KONG—If the severe acute respiratory syndrome (SARS) returns this winter, will physicians know what to expect? A longer follow-up evaluation of SARS patients from Hong Kong suggests that mortality may be even higher than was reported last spring.

In March 2003, Princess Margaret Hospital was dedicated as Hong Kong’s sole quarantine hospital for patients with SARS, and it managed more than 700 SARS patients throughout the course of the outbreak. A retrospective study conducted by the hospital’s SARS Study Group evaluated the clinical characteristics and outcomes of 267 consecutive patients who were hospitalized between February 26 and March 31 for probable or confirmed SARS. All patients were followed for at least three months. The researchers found that the mortality rate in this cohort was 12%; the strongest predictors of mortality were advanced age and high lactate dehydrogenase levels at presentation.[1]

DIAGNOSIS AND TREATMENT

In 227 patients, the diagnosis of SARS was confirmed using reverse transcriptase polymerase chain reaction (RT-PCR) in nasopharyngeal secretions or serologic testing for the SARS coronavirus. The other 40 patients were deemed to have probable SARS.

All patients received amoxicillin-clavulanate plus clarithromycin, or levofloxacin alone. If they did not respond to antibiotics, therapy with ribavirin (24 mg/kg/d) and hydrocortisone (10 mg/kg/d) was initiated. Methylprednisolone was given if symptoms worsened after antiviral treatment.

Sik To Lai, MD, head of the infectious disease team in the Department of Medicine and Geriatrics at Princess Margaret Hospital, noted that antibiotics in themselves “are not useful for treating SARS but are prescribed for the first 72 hours to treat other causes of atypical pneumonia, which may be confused with SARS.” In addition, said Dr. Lai, “Wide-spectrum antibiotics are used to prevent nosocomial infections in patients who are on high doses of corticosteroids.”

Dr. Lai explained that there is no clinical evidence that a combination of antivirals/corticosteroids is the best choice of treatment for SARS and stressed that high-dose corticosteroids should not be given indiscriminately at the onset of disease: “Owing to adverse side effects and their propensity to cause severe sepsis or fungal infection, pulse corticosteroids should only be given to patients with progressive hypoxemia and whitening of the lung fields on chest films.” The most common presenting symptoms were fever (in 99% of patients), chills (74%), malaise (63%), and myalgia (50%). Twenty percent of patients had crackles detected with chest auscultation, but otherwise physical examination was inconclusive.

Nearly all (96%) of the patients had chest-film abnormalities that were indistinguishable from those associated with community-acquired pneumonia. In 12 patients with normal radiographic findings, a high-resolution CT scan revealed patchy ground-glass opacification of the lung parenchyma. In patients with respiratory distress, serial chest radiography showed progressive lung infiltrates with multiple patchy consolidation in both lungs, which either accompanied or preceded clinical deterioration.

According to Dr. Lai, “For rapid diagnosis, the RT-PCR for SARS coronavirus RNA in plasma that was recently developed by the Chinese University of Hong Kong can detect the virus within three days of disease onset with a positivity rate of 80%.” For a definitive diagnosis, serology is preferred.

TWO POSTMORTEM EXAMS

Of the 32 patients who died, two underwent postmortem examinations of the lungs. The first was a 49-year-old man who had not received corticosteroids or ribavirin. He died from respiratory failure 16 days after hospitalization. The main findings were diffuse alveolar damage in both acute and reparative phases in about 80% of the lung tissue. Areas of the lung in the acute phase of damage showed fibrinoid alveolar exudate with mixed acute and chronic inflammatory cells. Focal areas with dilated terminal air space and collapsing alveoli that suggested early honeycomb changes were also identified.

The second patient was a 34-year-old woman who had received ribavirin and corticosteroids immediately, and pulse methylprednisolone after developing respiratory distress. She had a sudden cardiac arrest and died 15 days after hospitalization. A minor pulmonary thromboembolism was identifed. Microscopy showed patchy involvement of the lungs by diffuse acute-phase alveolar damage, representing about 10% of the lung tissue studied. Other areas of the lung were normal. In both patients, RT-PCR was positive for SARS coronavirus.

Sixty-nine patients experienced respiratory failure and required mechanical ventilation. The following complications contributed to mortality most often: respiratory failure (100% of patients), acute renal failure (44%), septicemia (25%), and nosocomial sepsis (19%). The two most powerful independent predictors of mortality were age older than 60 and elevated lactate dehydrogenase levels.

“A presentation of SARS that typically has a worse outcome is low blood oxygen concentration on admission. Other poor prognostic indicators are neutrophilia and high lactate dehydrogenase from the beginning,” Dr. Lai observed.

When asked whether SARS will recur in the coming year, as many other viral infections (eg, influenza) do, Dr. Lai said that SARS is likely to reappear, but probably on a much smaller scale.

—Gale Jurasek

Reference
1. Choi KW, Chau TN, Tsang O, et al. Outcomes and prognostic factors in 267 patients with severe acute respiratory syndrome in Hong Kong. Ann Intern Med. September 11, 2003. [epub ahead of print].

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