Pathogenetic mechanisms of severe acute respiratory syndrome

Abstract

Severe acute respiratory syndrome (SARS) is an acute respiratory disease with significant morbidity and mortality. While its clinical manifestations have been extensively studied, its pathogenesis is not yet fully understood. A limited number of autopsy studies have revealed that the lungs and the immune system are the organs that sustain the most severe damage. Other organs affected include the kidneys, brain, digestive tract, heart, liver, thyroid gland and urogenital tract. The primary target cells are pneumocytes and enterocytes, both cell types abundantly expressing angiotensin-converting enzyme 2 which is the main SARS-CoV receptor. Other cell types infected include the epithelial cells of renal tubules, cerebral neurons, and immune cells. The pathology of this disease results from both direct and indirect injury. Direct injury is caused by infection of the target cells by the virus. Indirect injury mainly results from immune responses, circulatory dysfunction, and hypoxia. In this review, we summarize the major pathological findings at the gross, cellular and molecular levels and discuss the various possible mechanisms that may contribute to the pathogenesis of SARS. The implications of the proposed pathogenesis for prevention, diagnosis and therapy of the disease are discussed.

Human coronaviruses: Viral and cellular factors involved in neuroinvasiveness and neuropathogenesis

“…Our results indicate that HCoV are able to infect human endothelial cells of the BBB in culture (unpublished data). It has also been speculated that SARS-CoV could do the same after viremia (Guo et al, 2008). Therefore, neuroinvasive coronaviruses that infect humans could use the hematogenous route to penetrate into the CNS.…”

Recently Discovered Human Coronaviruses

“…41 By means of droplet inhalation, SARS-CoV reaches the respiratory tract and invades epithelial cells of trachea, bronchi, bronchioles, and alveoli. 42 SARS-CoV typically causes a broad spectrum of disease, starting with an influenza-like syndrome, including symptoms such as high fever, malaise, rigors, and fatigue. 41 After disease onset, infections may progress to a nonsevere variant of disease or cough variant, characterized by relatively moderate symptoms.…”

“…44 Symptoms may worsen even further into an acute respiratory distress syndrome (ARDS), as a result of progressive pulmonary immune infiltration, formation of hyaline membranes, diffuse alveolar damage (DAD), and a high viral burden. 42,45,46 ARDS is the most severe form of acute lung injury (ALI) and is regarded as the leading cause of death in SARS-CoV infected individuals. 47,48 Lung injury in patients who have SARS is supposed to occur directly, by viral-mediated destruction of alveolar and bronchial epithelial cells, as well as indirectly, through extensive production of immune mediators.…”

Literature-related discovery: Potential treatments and preventatives for SARS

“…A careful reading of these reviews shows that the humoral and cellular components of the adaptive immune system of those who succumbed were deficient on presentation and deteriorated thereafter. There is controversy about whether adequate antiviral interferons were generated during the innate response, but there is common agreement that the switch from innate to adaptive immunity was defective [10][11][12][13][14][15][16][17][18][19][20][21][22][23].…”