Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS‐CoV) in SARS patients: implications for pathogenesis and virus transmission pathways

By Yanqing Ding, Li He, Qingling Zhang, Zhong-Xi Huang, X. Che, J. Hou, Hui-jun Wang, Hong Shen, Li-wen Qiu, Zhuguo Li and 8 more. Journal of Pathology, 2004

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We previously identified the major pathological changes in the respiratory and immune systems of patients who died of severe acute respiratory syndrome (SARS) but gained little information on the organ distribution of SARS‐associated coronavirus (SARS‐CoV). In the present study, we used a murine monoclonal antibody specific for SARS‐CoV nucleoprotein, and probes specific for a SARS‐CoV RNA polymerase gene fragment, for immunohistochemistry and in situ hybridization, respectively, to detect SARS‐CoV systematically in tissues from patients who died of SARS. SARS‐CoV was found in lung, trachea/bronchus, stomach, small intestine, distal convoluted renal tubule, sweat gland, parathyroid, pituitary, pancreas, adrenal gland, liver and cerebrum, but was not detected in oesophagus, spleen, lymph node, bone marrow, heart, aorta, cerebellum, thyroid, testis, ovary, uterus or muscle. These results suggest that, in addition to the respiratory system, the gastrointestinal tract and other organs with detectable SARS‐CoV may also be targets of SARS‐CoV infection. The pathological changes in these organs may be caused directly by the cytopathic effect mediated by local replication of the SARS‐CoV; or indirectly as a result of systemic responses to respiratory failure or the harmful immune response induced by viral infection. In addition to viral spread through a respiratory route, SARS‐CoV in the intestinal tract, kidney and sweat glands may be excreted via faeces, urine and sweat, thereby leading to virus transmission. This study provides important information for understanding the pathogenesis of SARS‐CoV infection and sheds light on possible virus transmission pathways. This data will be useful for designing new strategies for prevention and treatment of SARS. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Citations in the corpus

• Lethal Infection of K18-hACE2 Mice Infected with Severe Acute Respiratory Syndrome Coronavirus (2006, methodology): “We also analyzed the brain for evidence of SARS-CoV, since the virus has been detected in patient brains in some studies (5, 11, 42) (Fig.”
• Autopsy Findings and Venous Thromboembolism in Patients With COVID-19 (2020, result): “As in patients with SARS–CoV-1, in whom viral replication could be detected in other organs, including the liver, kidney, spleen, and cerebrum (30), we detected viral RNA at high titers in other organs (liver, kidney, and heart) in 5 patients.”
• Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study (2020, background): “However, SARS-CoV, using the same receptor, was not detected in skeletal muscle by post-mortem examination [15].”
• Severe Acute Respiratory Syndrome Coronavirus Infection Causes Neuronal Death in the Absence of Encephalitis in Mice Transgenic for Human ACE2 (2008, background): “In all studies that examined brain sections from SARS patients, virus was detected almost exclusively in neurons (14, 20, 53), consistent with studies showing a marked neuronal tropism in infected hACE2 Tg mice (32, 49).”
• Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2 (2005, background): “Tissue expression of the receptor corresponds to the localization of virus in infected individuals and animals (Harmer et al, 2002; Chan et al, 2004; Ding et al, 2004; Hamming et al, 2004) .”
• Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target (2020, background): “Expression of the ACE2 receptor is also found in many extrapulmonary tissues including heart, kidney, endothelium, and intestine [15] [16] [17] [18] [19] .”
• Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System (2020, background): “39, 47, 54, 55, 59, 60 In addition to the direct impact of the virus on the microbiome, the predisposing disease states such as diabetes mellitus 61 and pulmonary disease have their own adverse effects on the gut microbiome, 62,63 which may be worsened by SARS-CoV-2 infection.”
• Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2 (2020, unknown): “910 Cell 181, 905–913, May 14, 2020 ACE2 is expressed in various tissues including the heart, kidney tubules, the luminal surface of the small intestine, and blood vessels (Crackower et al., 2002; Danilczyk and Penninger, 2006; Ding et al., 2004; Gu et al., 2005; Hamming et al., 2004; Zhang et al., ”
• The Novel Coronavirus 2019 epidemic and kidneys (2020, background): “Viral RNA has been identified in kidney tissue and urine in both infections.(17,18) Recently, Zhong’s lab in Guangzhou successfully isolated SARS-CoV-2 from the urine sample of an infected patient, suggesting the kidney as the target of this novel coronavirus.”
• COVID-19 and Multiorgan Response (2020, unknown): “11 It also shares the same cellular receptor as SARS-CoV which is the angiotensin-converting enzyme 2 (ACE2) receptor. 12 ACE2 receptors are enriched in alveolar epithelial type II cells of lung tissues 13 , as well as extrapulmonary tissues such as the heart, endothelium, kidneys and intestines 14,”
• Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment (2020, result): “Distribution of ACE-2 receptor expression intensely on the surface of alveolar epithelial type II cells, cardiac, renal, intestinal, and endothelial cells is consistent with the target organs involved and the clinical picture in COVID19 infection [2, 4].”
• Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes (2009, background): “Interestingly, ACE2 mRNA was detectable at low levels in rat liver and increased following bile duct ligation (363-fold).”