Severe Acute Respiratory Syndrome: What Do We Know About This Disease?

Prof. Joseph J. Y. Sung
Department of Medicine & Therapeutic, Prince of Wales Hospital, The Chinese University of Hong Kong

The outbreak of SARS in early March 2003 has shocked the world. In less than 2 months, this emerging disease has affected over 3,000 people from 27 countries. The high infectivity of the virus, the rapid deterioration of pulmonary function, the high death toll of this disease and the predilection for health care workers have created much anxiety of the public as well as the medical profession.

What do we know about this disease? Thanks to the hard work of our virologists, we now know that SARS is caused by a novel Coronavirus. The evidence is compelling and there should be little dispute. We still do not know from which animal(s) did this virus come from. We are not sure about its mode of transmission, although droplet and fomite transmission are likely to be the most important ones. We know that there is a polymorphism within the genome of this virus. We have speculated a lot about its mutations and related this to the different clinical presentations. There is a lot to be explored about this virus. We need the two universities in Hong Kong, indeed the scientific community of the whole world, to work together to study this infection.

What do we know about this disease? From our experience in looking after over 270 patients in the Prince of Wales Hospital and my personal communications with local experts, I believe that SARS can be represented as a tri-phasic disease. In the first week of the illness, most patients presented with fever, myalgia and chills. There is usually no or minimal respiratory symptoms. This is likely to be a viral replicative phase. The virus multiplies in the host cells and being released into the blood stream. Damage in the lung by the virus itself is limited at this stage but cytokines are being produced by the macrophages. The disease progresses relatively slowly in the first week. Some patients may recover spontaneously in this phase of the disease. At least 70% of patients then proceed to the second phase which is an immune hyperactive phase. At this stage of the disease, early response cytokines such as TNFa, IL-1, IL-6 and IL-8 are produced in large quantities. While these cytokines are meant to eradicate the virus, it is also producing a lot of tissue damage in the lung. Patient start to develop respiratory symptoms: shortness of breath (especially in the standing or sitting position), cough with pinkish sputum and chest radiograph shows multiple areas of consolidation involving both lungs. This is a critical period in the illness. If nothing has been done to stop the so-called "cytokine storm", the lung will be permanently damaged and progress to the development of acute respiratory distress syndrome (ARDS). In the third week of disease, the patient will go into the pulmonary destruction phase. Ground-glass appearance of the lung will appear on chest radiograph, arterial blood oxygenation will decline, supplementary oxygen requirement will go up. Eventually, a reasonable oxygenation saturation level cannot be maintained with oxygen therapy, patients will require positive pressure ventilation. For some reasons not entirely clear at this point, patients at this stage of the disease are prone to develop spontaneous pneumothorax or pneumo-mediastinum. If they require assisted positive pressure ventilation, they are also more prone to barotraumas which poses further difficulties to look after these patents. The three phases of the disease are illustrated by the diagram below (Figure 1).

The treatment of SARS is still evolving. Ribavirin is chosen as the anti-viral agent of choice because of its wide-spectrum activities, especially against RNA viruses. To date, the optimal dose of ribavirin to inhibit this Coronavirus is still not known. The major problems of using ribavirin are its teratogenicity and its hemolytic activity. Yet, we have little choices. Corticosteroids are used to combat the cytokines storm. It is prescribed in the second phase of the disease to avoid further lung damage. Corticosteroid should not be used as an antipyretic agent, and obviously not an anti-viral agent. Methylprednisolone in the form of pulse therapy is effective. Detail protocol can be found in the Hospital Authority Guideline (www.ha.org.hk). Although these recommendations are based on anecdotal experience, controlled randomized study in a life-threatening situation, especially during the crisis, would be difficult. We believe that the key to successful therapy is timing of these medication and prevention of ARDS development. Newer agents, including antiviral agents and immunomodulators, are under investigation. It will take some time before their efficacy can be proven by clinical trials.


Figure 1. Severe Acute Respiratory Syndrome (SARS): a tri-phasic disease.

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