Mild illness associated with severe acute respiratory syndrome coronavirus infection: Lessons from a prospective seroepidemiologic study of health-care workers in a teaching hospital in Singapore

Background. Severe acute respiratory syndrome (SARS) is a newly recognized infectious disease that has recently emerged in East Asia and North America. Although the clinical features of acute infection have been well described, mildly symptomatic or asymptomatic infections have not been well characterized. Objective. To assess the spectrum of illness in health-care workers (HCWs). Methods. A prospective seroepidemiologic cohort study was conducted on 372 HCWs in a large teaching hospital in Singapore who were both exposed and not exposed to patients with SARS. Participating HCWs completed a questionnaire and provided paired serum samples, which were analyzed by 2 different laboratories blinded to clinical data, by use of an enzyme-linked immunosorbent assay based on a protocol developed by the Centers for Disease Control and Prevention and a dot-blot immunoassay, with confirmation by a viral neutralization assay. Results. A total of 21 patients with SARS were treated at our hospital. They were associated with transmission to 14 staff members, patients, and visitors in our hospital. Of the 372 HCWs participating in the present study, 8 were found to have positive antibodies to the SARS coronavirus in both samples by use of both test methods, and 6 had pneumonia and had been hospitalized for either probable or suspected SARS infection, whereas 2 had fever but did not have changes on chest radiographs. All seropositive HCWs had been exposed either directly or indirectly to patients with SARS. No asymptomatic, nonexposed staff members were found to be seropositive. There was a trend towards protection for HCWs who, while fully protected, had had contact with patients with SARS. Conclusions. Although the majority of cases of SARS are associated with pneumonia, a small number of mildly symptomatic individuals do seroconvert. HCWs who are exposed to patients with SARS can be infected with SARS, regardless of the intensity of exposure. This has implications for surveillance and infection control planning, in the event that SARS returns next winter.