Role of China in the quest to define and control severe acute respiratory syndrome - Perspectives

Emerging Infectious Diseases, Sept, 2003 by Robert F. Breiman, Meirion R. Evans, Wolfgang Preiser, James Maguire, Alan Schnur, Ailan Li, Henk Bekedam, John S. MacKenzie

If the causative agent can be isolated from stored specimens from the earliest group of patients (from November 2002 to January 2003), how their genetic sequences compare with those from viruses isolated later from various parts of China and elsewhere, and from animals from Guangdong and Guanxi Provinces, would be useful to know. Mutations may be important for a number of reasons. They may affect transmissibility and virulence; they may provide (or frustrate) therapeutic targets for new drugs; and they may pose challenges for development of diagnostic tests and vaccines. Specimens from Chinese patients provide the longest observation window with which mutational tendencies can be evaluated.

An analysis of 14 full-length sequences suggests that two genetic lineages might have arisen from Guangdong. One lineage is represented by the chain of transmission associated with the physician from Guangzhou who traveled to Hong Kong, Special Administrative Region, in February. The other lineage is associated with isolates from Hong Kong, Guangzhou, and Beijing (11). If two genetic lineages arose in Guangdong, were there two separate transmission events from an animal host to humans, or did the lineage diverge within humans? Specimens from early cases in Guangdong may be helpful in addressing this question.

Outcomes of Infection

Epidemiologic, immunologic, and microbiologic factors associated with severe outcome are not fully defined. Clearly, though, a principal determinant for poor outcome is advancing age. As with other respiratory diseases, age-related coexisting conditions reduce the capacity to compensate to conditions associated with severe disease. Understanding other specific factors that result in poor outcome will have value for optimizing therapeutic approaches.

Clinicians disagree about the value of early treatment with ribavirin and high-dose corticosteroids, and some are reticent to ventilate patients because of high risk for transmission to healthcare workers associated with intubation. More data are needed to help define the most effective treatment strategy, particularly for areas with limited resources.

Extraordinary clinical expertise exists among health professionals in Guangdong Province. They have substantial experience with a variety of antivirals, antibiotics, alternative (herbal) medicines, and corticosteroids, and with using assisted ventilation in the treatment of patients with SARS (12). While randomized clinical trials have not been conducted, careful compilations of existing case series data would be helpful in evaluating the potential effectiveness of various management regimens.

The store of clinical data, accumulated from treating hundreds of SARS cases, needs to be put to good use. One priority is to investigate clinical, epidemiologic, and laboratory predictors of poor outcome. Such experience will supplement other recently published data from Hong Kong, Special Administrative Region (1,13-15), and Singapore (16).

Several questions remain unanswered. Do patients exposed to high viral doses (for which a short incubation period may be a surrogate) or to a co-infecting pathogen have poorer outcomes? What is the impact of multiple exposures to SARS-associated coronavirus, like that which occurred among healthcare workers early in the epidemic? Do patients infected early in the transmission cycle perform more poorly than those infected during subsequent cycles of transmission?