| Severe Acute Respiratory Syndrome (SARS) is an emerging infectious disease caused by a novel coronavirus. It caused a global outbreak in 2003, resulting in more than 8000 infections, 700 deaths, and major social and economic disruption. In the initial phase of the SARS outbreak, the medical profession had no knowledge regarding the responsible pathogen, nor the clinical manifestations of SARS and the course of illness. There was no reliable diagnostic tool and no known effective therapy. But for the first time in medical history, we witnessed the rapid accumulation of knowledge on a disease as it evolved, which in turn assisted its management and control.;Since conducting randomized-controlled trials during the 2003 crisis was almost impossible, most of the presented studies are either descriptive or case-controlled in design. However, these studies have laid foundations for recent and future research into the clinical diagnosis and management of SARS. Moreover, the construction of the SARS clinical database has contributed to the work of other investigators, which has resulted in over thirty-six publications. It is my hope that these research endeavors can contribute to the understanding of this emerging, deadly disease.;In part ONE of this thesis, including the most up to date information on SARS virology, disease transmission, pathogenesis and laboratory diagnosis will be summarized and presented, including the results of many studies in which I have participated (these references will be underlined as they appear in text). This of course summarizes knowledge that is now known in 2006 but was largely unknown during the initial outbreak. In part TWO, six original clinical studies performed at PWH will be presented: study (1) describes the clinical manifestations and severity of SARS, and its potential to cause major hospital outbreaks; (2) demonstrates the importance of epidemiological linkage in diagnosing SARS; (3) reports the clinical outcomes of a stepwise treatment protocol, which includes the use of corticosteroid therapy as an immunomodulant; (4) demonstrates that corticosteroid therapy can retard viral clearance, and should be used judiciously; (5) demonstrates that a more robust humoral response is associated with severe SARS, thus indicating that passive immunity treatment strategies seem only suitable either during early illness or as prophylaxis; and (6) shows that SARS has few early discriminating laboratory features compared to other causes of community-acquired pneumonia, thus a high index of suspicion is needed to recognize this infection in the absence of worldwide transmission. A thorough review of the relevant published material will be included in the discussion section of each study. |
