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Chapter 19 : Severe Acute Respiratory Syndrome: Epidemiology, Pathogenesis, and Animal Models

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Severe Acute Respiratory Syndrome: Epidemiology, Pathogenesis, and Animal Models, Page 1 of 2

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Abstract:

Quantitative studies on viral load in the upper respiratory tract and the feces of patients infected with severe acute respiratory syndrome-coronavirus (SARS-CoV) revealed a progressive increase in viral load, peaking around day 10 after onset of disease symptoms. This explains the epidemiological observation that transmission mainly occurs after the fifth day of illness. Clinical and pathological studies of SARS cases indicate that cells in the lower respiratory tract, particularly type 1 pneumocytes, are the prime targets of SARS, with macrophages subsequently being infected. Although angiotensin-converting enzyme 2 (ACE2) is the primary receptor for SARS, other receptors such as L-SIGN and DC-SIGN may facilitate virus infection, even under circumstances when the virus has not fully adapted to a new host. Epithelial lung damage together with macrophage activation results in increased levels of proinflammatory cytokines. The initial phase of lung disease exists for 10 to 14 days, after which many of the changes present can be attributed to the sequelae of diffuse lung damage, including the effects of mechanical ventilation. As with many other newly emerging infections, SARS had zoonotic origins, highlighting the need for a better understanding of the virus ecology of both wild and domestic animals. As many of these zoonoses do not cause disease in their natural host, surveillance needs to encompass viruses causing unobvious infections as well as those causing overt disease and will require the cooperation of multiple agencies, including those dealing with public health, veterinary medicine, and wildlife or the environment.

Citation: Nicholls J, Peiris J, Perlman S. 2008. Severe Acute Respiratory Syndrome: Epidemiology, Pathogenesis, and Animal Models, p 299-311. In Perlman S, Gallagher T, Snijder E (ed), Nidoviruses. ASM Press, Washington, DC. doi: 10.1128/9781555815790.ch19

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Severe Acute Respiratory Syndrome
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Acute Respiratory Distress Syndrome
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Lower Respiratory Tract Infections
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Figure 1.

Schematic of SARS-CoV infection. SARS-CoV is detected in pneumocytes and in alveolar macrophages (upper left panel). Infection of macrophages results in the secretion of proinflammatory cytokines and chemokines but not IFN-β. Expression of these factors results in tissue damage, increased inflammation, and lung damage, resulting in the nonspecific pulmonary findings observed in patients with SARS (middle panel). As part of the disease process, infected type 1 pneumocytes slough into alveolar spaces and airways; regeneration is evidenced by proliferation of type 2 pneumocytes. Multinucleated giant cells are also observed in SARS-CoV-infected lungs (lower panels). Normal lung tissue is also shown (upper right panel).

Citation: Nicholls J, Peiris J, Perlman S. 2008. Severe Acute Respiratory Syndrome: Epidemiology, Pathogenesis, and Animal Models, p 299-311. In Perlman S, Gallagher T, Snijder E (ed), Nidoviruses. ASM Press, Washington, DC. doi: 10.1128/9781555815790.ch19
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