SARS: clinical virology and pathogenesis

Abstract

SARS: clinical virology and pathogenesis JOHN NICHOLLS, XIAO-PING DONG, GU JIANG, MALIK PEIRIS. Respirology 2003; 8 : S6-S8Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus, called the SARS coronavirus (SARS-CoV). Over 95% of well characterized cohorts of SARS have evidence of recent SARSCoV infection. The genome of SARS-CoV has been sequenced and it is not related to any of the previously known human or animal coronaviruses. It is probable that SARS-CoV was an animal virus that adapted to human-human transmission in the recent past. The virus can be found in nasopharyngeal aspirate, urine and stools of SARS patients. Second generation reverse transcriptase polymerase chain reaction assays are able to detect SARS-CoV in nasopharyngeal aspirates of approximately 80% of patients with SARS within the first 3 days of illness. Seroconversion for SARSCoV using immunofluorescence on infected cells is an excellent method of confirming the diagnosis, but antibody responses only appear around day 10 of the illness. Within the first 10 days the histological picture is that of acute phase diffuse alveolar damage (DAD) with a mixture of inflammatory infiltrate, oedema and hyaline membrane formation. Desquamation of pneumocytes is prominent and consistent. After 10 days of illness the picture changes to one of organizing DAD with increased fibrosis, squamous metaplasia and multinucleated giant cells. The role of cytokines in the pathogenesis of SARS is still unclear.

SARS-CoV replication and pathogenesis in an in vitro model of the human conducting airway epithelium

“…Previously, the reported receptor for SARS-CoV, the angiotensin 1 converting enzyme 2 (hACE2) had only been localized to alveolar cells in the lung although recent evidence indicates that hACE2 is present throughout the human airway epithelium suggesting additional cellular targets of infections (Jia et al, 2005) SARS-CoV specific RNA has also been localized in pulmonary macrophages although whether viable virus was present was not determined (Lu et al, 2005). In another study based on six patients who died from SARS the most pronounced morphological features were giant cell formation (predominately macrophages) and pneumocyte hyperplasia suggesting that proinflammatory cytokines released by stimulated macrophages in the alveolus were a predominant cause of pathogenesis (Nicholls et al, 2003a;Nicholls et al, 2003b). Histological samples for determining SARSCoV infection of airways have been less rigorously studied as pathological analyses is usually performed on late stage fatal cases (Chow et al, 2004;.…”

Synthetic Reconstruction of Zoonotic and Early Human Severe Acute Respiratory Syndrome Coronavirus Isolates That Produce Fatal Disease in Aged Mice

“…Two phases have been identified during SARS-CoV infection in humans (41). ARDS develops within the first 10 days with DAD, edema, and hyaline membrane formation (39,40). After the acute phase, organizing DAD with increased fibrosis is observed (40).…”

“…ARDS develops within the first 10 days with DAD, edema, and hyaline membrane formation (39,40). After the acute phase, organizing DAD with increased fibrosis is observed (40). ARDS has been shown to be the major cause of death in cases of human infection by SARS-CoV and avian influenza A (H5N1) (39) and likely the 1918 influenza virus (25).…”

Severe Acute Respiratory Syndrome (SARS): A Brief Review With Exploration of the Outcomes, Prognostic Factors and Sequelae

“…[60,61]. No specific pathological patterns have been identified that is characteristic of SARS and appearances might be complicated with superimposed infections and immunomodulatory treatment modalities [62]. anaemia) and high-dose potent corticosteroids (hyperglycaemia, nosocomial infections and hypokalaemia).…”