Aetiology

The newly recognised SARS coronavirus (CoV) has been identified as the probable causal agent of SARS.[3][5] SARS-CoV is an enveloped, positive-strand RNA virus in the Coronaviridae family. Human coronaviruses such as OC43 and 229E have definitively been associated with upper respiratory tract illness, while the recently discovered agents NL63 and HKU1 are recognised as common causes of community-acquired respiratory infections.

The origin of SARS-CoV is still being investigated. The fact that SARS-like viruses have been identified in a number of different animals supports the hypothesis that SARS-CoV was first transmitted to humans from wild animals used for food, with subsequent person-to-person transmission.[6] Furthermore, genotypic evidence suggests that SARS-CoV evolved from a positive selective pressure acting on animal SARS-like viruses, finally leading to the emergence of the SARS-CoV genotype responsible for the pandemic of 2002-2003. While animal reservoirs of animal SARS-like viruses exist, human or animal reservoirs of SARS-CoV have not been found. Research laboratories are recognised as the only reservoirs of SARS-CoV, highlighting the importance of biosafety. Recent findings that horseshoe bats are the natural reservoir of a SARS-like CoV and that civet cats are the amplification host explain how these animals may serve as the source and amplification focuses for emerging infections.[7][8]

Pathophysiology

SARS coronavirus (CoV) is transmitted primarily through droplets, entering the human body via the respiratory tract mucosa and causing viraemia. Angiotensin-converting enzyme 2 (ACE2) has been identified as a functional receptor for SARS-CoV.[9] The incubation period is 2 to 10 days and the risk of transmission is greater during the second week of illness, which correlates with the timing of peak viral load.[10][11] The possibility of fomite transmission and airborne transmission cannot be excluded, although the role of faecal-oral or faecal-respiratory spread seems to be of minor importance.[12] Although each SARS case is expected to infect 2 to 4 people,[13] it is thought that, in the pandemic of 2002-2003, a small number of infected individuals were responsible for a disproportionate number of transmissions in so-called 'superspreading events', and that it was through this mechanism that the SARS outbreak disseminated globally.[14][15]

There are 3 phases in the course of the disease: viral replication, inflammatory pneumonitis, and pulmonary fibrosis.[16] Pathological findings of the lungs include diffuse alveolar damage, desquamation of pneumocytes, hyaline membrane formation, and inflammatory infiltrates.[17] The longer the course of the disease, the more extensive the fibrous organisation of the lung tissue.

Clinical deterioration in some patients during the third week of illness, despite a fall in viral load, suggests that immune dysregulation may play a role.[18][19] Furthermore, the HLA-B*4601 haplotype has been associated with the severity of SARS infection, suggesting the existence of a genetic predisposition.[20]

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