SARS-CoV infects not only the upper airway, as do the other human coronaviruses, but also cells lining the lungs, that is, the alveolar epithelium in the lower respiratory tract (7). As a result, these patients have severe difficulty in breathing, causing shortness of breath, respiratory distress, and poor transfer of oxygen from the lungs to the blood. The smallest units of the lungs are the pulmonary alveoli or air cells that form the lung’s alveolar ducts and sacs. In this area, the exchange of gases (intake of oxygen and exit of carbon dioxide) between the lungs and blood takes place. The alveolar lining is composed of epithelial cells that become infected with SARS-CoV. In addition to infecting the lungs, SARS-CoV also nests in the small intestine, liver, and kidneys. The mechanism(s), or pathogenesis, of injury to tissue infected by the virus is not clear. For example, as the clinical disease worsens, the amount of virus present (virus titer) decreases, while the number of infiltrating macrophages and T cells increases greatly. This scenario suggests that a major mediator of this tissue injury and disease may be the host’s own immune response to the virus. Further support for the concept of immune-mediated injury is the heightened levels of proinflammatory chemokines and cytokines, which are factors made primarily by infected macrophages and T cells (7) but known to cause injury. The signifi- cant elevation of these inflammatory products suggests that a “cytokine storm” plays an important part in the disease of SARS.

The lower respiratory track’s involvement in this disease is often serious enough to require the victims’ hospitalization. Of those admitted to the hospital, over 20 percent are so sick that confinement in an intensive care unit is necessary. The fatality rate is about 10 percent, over half of whom are the elderly and/or those having preexisting heart or pulmonary problems. The course of disease after exposure to SARS-CoV is short; within four to six days the infected individuals develop the general symptoms of fever, weakness, muscle pain, and loss of appetite. After a few more days, respiratory symptoms emerge including a dry nonproductive cough and shortness of breath. Thereafter, the disease either resolves or progresses to ongoing respiratory failure within several days, weeks, or occasionally months. For those who recover, complete remission may take months, and for some of these patients, respiratory difficulties remain permanent.

The coronaviruses per se are RNA viruses and contain the largest genome of any RNA virus, as much as 27–32 kb. By comparison, other RNA viruses like Lassa fever virus is 10.7 kb and poliovirus 7.5 kb. The RNA of coronaviruses is of a positive strand type; that is, their RNA is infectious and serves as a virus messenger RNA. Organizationally, the various RNAs of coronaviruses contain seven to fourteen open reading frames and usually encode five structural proteins.

An additional issue still to be resolved is that the genomic sequence of SARS-CoV of humans differs significantly from SARS-CoV of bats. Since viruses usually cannot jump from one species to another without adaptation, and bat SARS-CoV fails to grow in cell cultures that support the growth of both human and civet SARS-CoV, another yet to be discovered animal reservoir(s) may exist. Although bats are a likely candidate as the SARS-CoV reservoir, they probably are not the only one. Most important to the spread of SARS virus among humans is the transmission from one person to others, which spreads the infectious agent and resulting disease. In 2003, a Canadian woman on a visit to Hong Kong became exposed to SARS-CoV and incubated the virus as she traveled by airplane on her return home to Toronto, Canada (2,13,14). She developed fever and respiratory distress, was cared for at home, and died. Her son assisted with her care soon felt ill, found breathing difficult, and went to the hospital emergency room to seek help. The waiting room where he sat for hours was, as usual, crowded with others, so this son of the mother who died from respiratory failure and was later diagnosed as having SARS infected two more people. Those two communicated the disease to many more until the contamination of patients, health-care workers, and visitors resulted in 375 cases of SARS-CoV infection (7,15,24). Among them, 45 percent, or 169 of the individuals infected, were health-care workers; two nurses and one doctor died (2,24). - VPH