Multiple organ infection and the pathogenesis of SARS

By Jiang Gu, E. Gong, Bo Zhang, Jie Zheng, Zi-fen Gao, Yanfeng Zhong, W. Zou, J. Zhan, Sheng-lan Wang, Zhi-gang Xie and 13 more. Journal of Experimental Medicine, 2005

1,325 citations recorded by the source corpus.

After >8,000 infections and >700 deaths worldwide, the pathogenesis of the new infectious disease, severe acute respiratory syndrome (SARS), remains poorly understood. We investigated 18 autopsies of patients who had suspected SARS; 8 cases were confirmed as SARS. We evaluated white blood cells from 22 confirmed SARS patients at various stages of the disease. T lymphocyte counts in 65 confirmed and 35 misdiagnosed SARS cases also were analyzed retrospectively. SARS viral particles and genomic sequence were detected in a large number of circulating lymphocytes, monocytes, and lymphoid tissues, as well as in the epithelial cells of the respiratory tract, the mucosa of the intestine, the epithelium of the renal distal tubules, the neurons of the brain, and macrophages in different organs. SARS virus seemed to be capable of infecting multiple cell types in several organs; immune cells and pulmonary epithelium were identified as the main sites of injury. A comprehensive theory of pathogenesis is proposed for SARS with immune and lung damage as key features.

Subfields: Infectious Diseases, Neurology

View Paper: https://www.semanticscholar.org/paper/b85dff4c588035f8d217ebd4077e5865e106c7fa

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Citations in the corpus

Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China (2020, background): “SARS-CoV was able to infect multiple cell types in several organs, including circulating lymphocytes, the epithelial cells of the respiratory tract, and the mucosa of the intestine [17].”
Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies (2020, background): “Histopathological studies have shown lung consolidation and edema with pleural effusions and focal hemorrhage, all of which resemble COVID-19 features (13, 24).”
Hypothesis for potential pathogenesis of SARS-CoV-2 infection–a review of immune changes in patients with viral pneumonia (2020, background): “[36] hypothesized that the marked T lymphocytes (CD3+, CD4+, and CD8+ cells) decline weakened immune system and aggravated the SARS infection of the respiratory tract.”
Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2 (2020, neutral): “Pathology due to SARS, MERS, and now COVID-19 is not limited to the lung; damage can occur in multiple organs (Gu et al., 2005; Wu and McGoogan, 2020; Yeung et al., 2016).”
Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients (2020, background): “In patients infected with SARS-CoV, it has been reported that the severity of pulmonary immune injury correlated with extensive infiltration of neutrophils and macrophages in the lungs 18, 19 , accompanied with increased numbers of neutrophils and monocytes and lower CD8 + and CD4 + T cell counts in”
SARS-CoV-2 and viral sepsis: observations and hypotheses (2020, result): “Previous studies have shown that SARS-like viral particles and SARS-CoV RNA were detected in T lymphocytes isolated from peripheral blood sample, spleen, lymph nodes, and lymphoid tissue of various organs, 22, 23 suggesting that SARS-CoV might be able to infect T cells directly.”
Postmortem examination of COVID‐19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction (2020, background): “One patient with superimposed bronchopneumonia showed florid vasculitis of small veins and capillaritis, which has previously been described in individual SARS cases.(14,15) However, vasculitic changes of other organs or clinical findings related to systemic vasculitis were not seen, implying that t”
Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice (2016, neutral): “Cell Host & renchyma with intense antigen distribution in type II and to a lesser extent in type I pneumocytes (Figure 2B), similar to findings in SARS-CoV-infected human autopsy samples (Gu et al., 2005; Nicholls et al., 2003).”
Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19 (2020, neutral): “Autopsy studies in SARS showed atrophy of lymphoid organs, including lymph nodes, spleen, and Peyer’s patches, and loss of germinal centers (Gu et al., 2005).”
Severe Acute Respiratory Syndrome Coronavirus Infection Causes Neuronal Death in the Absence of Encephalitis in Mice Transgenic for Human ACE2 (2008, background): “In one report, examination of autopsy samples from eight patients with SARS revealed the presence of SARS-CoV in brain samples by immunohistochemistry, electron microscopy, and real-time reverse transcription-PCR (20).”
Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? (2019, background): “It is now accepted that HCoV are not always confined to the upper respiratory tract and that they can invade the CNS [220, 245, 248, 270] .”
Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients (2020, background): “infection of lymphocytes was barely detected in SARS patients [48].”
SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor (2020, background): “However, ACE2 expression is not limited to the lung, and extrapulmonary spread of SARS-CoV in ACE2 tissues was observed (Ding et al., 2004; Gu et al., 2005; Hamming et al., 2004).”
The Coronavirus Nucleocapsid Is a Multifunctional Protein (2014, background): “Since actively dividing lymphocytes are a major cell target of SARS-CoV [154], SARS-CoV N may decelerate lymphocyte proliferation and therefore interfere with immune system function [75].”