Role of vascular cell adhesion molecules and leukocyte apoptosis in the lymphopenia and thrombocytopenia of patients with severe acute respiratory syndrome (SARS)

Chen, Rong‐Fu; Chang, Jen-Chieh; Yeh, Wen Tien; Lee, Chen Hsiang; Liu, Jien Wei; Eng, Hock Liew; Yang, Kuender D.

doi:10.1016/j.micinf.2005.06.007

Cited by 60 publications

(57 citation statements)

References 39 publications

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“…sVCAM-1 is involved in adhesion and chemotaxis and contributes to early vascular injury and suppression of T cell function. Vascular injury or immunosuppression may explain the poor outcome [17]. By using the Cox regression model for multivariate analysis, we found that platelets and PCT are independent risk factors that predict death.…”

Section: Discussionmentioning

confidence: 88%

Association between platelet parameters and mortality in coronavirus disease 2019: Retrospective cohort study

et al. 2020

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Background: Thrombocytopenia has been implicated in patients infected with severe acute respiratory syndrome coronavirus 2, while the association of platelet count and changes with subsequent mortality remains unclear. Methods: The clinical and laboratory data of 383 patients with the definite outcome by March 1, 2020 in the Central Hospital of Wuhan were reviewed. The association between platelet parameters and mortality risk was estimated by utilizing Cox proportional hazard regression models. Results: Among the 383 patients, 334 (87.2%) were discharged and survived, and 49 (12.8%) died. Thrombocytopenia at admission was associated with mortality of almost three times as high as that for those without thrombocytopenia (P < 0.05). Cox regression analyses revealed that platelet count was an independent risk factor associated with in-hospital mortality in a dose-dependent manner. An increment of per 50 × 10 9 /L in platelets was associated with a 40% decrease in mortality (hazard ratio: 0.60, 95%CI: 0.43, 0.84). Dynamic changes of platelets were also closely related to death during hospitalization. Conclusions: Baseline platelet levels and changes were associated with subsequent mortality.

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Section: Discussionmentioning

confidence: 88%

Association between platelet parameters and mortality in coronavirus disease 2019: Retrospective cohort study

et al. 2020

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“…The cause of the lung T cell decline in our studies is unclear; however, the timing coincides with the observed peak in lung injury following infection. Activation of cytoplasmic caspase 3 has been associated with enhanced T cell death during SARS-CoV infection (5), and SARS-CoV E protein has been shown to induce apoptosis of a T cell line in vitro (55). However, no replicating virus could be recovered from the lung at day 14 postinfection, so the T cell decline may reflect the normal contraction of the effector T cell pool following pathogen clearance.…”

Section: Discussionmentioning

confidence: 99%

Primary Severe Acute Respiratory Syndrome Coronavirus Infection Limits Replication but Not Lung Inflammation upon Homologous Rechallenge

Clay

Donart

Fomukong

et al. 2012

J Virol

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Our knowledge regarding immune-protective and immunopathogenic events in severe acute respiratory syndrome coronavirus (SARS-CoV) infection is limited, and little is known about the dynamics of the immune response at the primary site of disease. Here, an African green monkey (AGM) model was used to elucidate immune mechanisms that facilitate viral clearance but may also contribute to persistent lung inflammation following SARS-CoV infection. During primary infection, SARS-CoV replicated in the AGM lung for up to 10 days. Interestingly, lung inflammation was more prevalent following viral clearance, as leukocyte numbers peaked at 14 days postinfection (dpi) and remained elevated at 28 dpi compared to those of mock-infected controls. Lung macrophages but not dendritic cells were rapidly activated, and both cell types had high activation marker expression at late infection time points. Lung proinflammatory cytokines were induced at 1 to 14 dpi, but most returned to baseline by 28 dpi except interleukin 12 (IL-12) and gamma interferon. In SARS-CoV homologous rechallenge studies, 11 of the 12 animals were free of replicating virus at day 5 after rechallenge. However, incidence and severity of lung inflammation was not reduced despite the limited viral replication upon rechallenge. Evaluating the role of antibodies in immune protection or potentiation revealed a progressive increase in anti-SARS-CoV antibodies in lung and serum that did not correlate temporally or spatially with enhanced viral replication. This study represents one of the first comprehensive analyses of lung immunity, including changes in leukocyte populations, lung-specific cytokines, and antibody responses following SARS-CoV rechallenge in AGMs.

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“…B-lymphocyte count and the ratio of T-helper to T-cytotoxic/suppressor lymphocytes (CD4:CD8) remain normal and stable. Lymphopenia as a result of enhanced cell death during the acute SARS infection is attributed to the activation of cytoplasmic caspase 3 in both CD4 and CD8 lymphocytes (Chen et al 2006). Transfection of SARS E protein in Jurkat T cells could also induce T-cell apoptosis by inactivating antiapoptotic protein Bcl-xL (Yang et al 2005a).…”

Section: T Cell Responsesmentioning

confidence: 99%

Host Immune Responses to SARS Coronavirus in Humans

Xu²

2009

Molecular Biology of the SARS-Coronavirus

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The severe acute respiratory syndrome (SARS) is a newly identified infectious disease caused by a novel zoonotic coronavirus (SARS-CoV) with unknown animal reservoirs. The risk of SARS reemergence in humans remains high due to the large animal reservoirs of SARS-CoV-like coronavirus and the genome instability of RNA coronaviruses. An epidemic in 2003 affected more than 8,000 patients in 29 countries, with 10% mortality. SARS infection is transmitted by air droplets. Clinical and laboratory manifestations include fever, chills, rigor, myalgia, malaise, diarrhea, cough, dyspnoea, pneumonia, lymphopenia, neutrophilia, thrombocytopenia, and elevated serum lactate dehydrogenase, alanine aminotransferase, and creatine kinase activities. Health care workers are a high-risk group, and advanced age is strongly associated with disease severity. Treatment has been empirical, and there is no licensed SARS vaccine for humans so far. However, presence of long-lived neutralizing antibodies and memory T-and B-lymphocytes in convalescent SARS patients raises hope for active immunization. Furthermore, results from preclinical SARS vaccines expressing spike protein to elicit neutralizing antibodies and cellular responses that are protective in mouse and nonhuman primate models are encouraging.Very little is known of the early events in viral clearance and the onset of innate and inflammatory responses during the SARS infection. Regulation of the innate immune response is associated with the development of adaptive immunity and disease severity in SARS infection. Notably, SARS-CoV has evolved evasive strategies to suppress antiviral type I interferon responses in infected cells. In addition, inflammatory responses are characterized by upregulation of proinflammatory cytokines/chemokines such as IL-6, IP-10, and MCP-1 in tissues and serum, and massive infiltrations of inflammatory cells such as macrophages in infected tissues.

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Role of vascular cell adhesion molecules and leukocyte apoptosis in the lymphopenia and thrombocytopenia of patients with severe acute respiratory syndrome (SARS)

Cited by 60 publications

References 39 publications

Association between platelet parameters and mortality in coronavirus disease 2019: Retrospective cohort study

Association between platelet parameters and mortality in coronavirus disease 2019: Retrospective cohort study

Primary Severe Acute Respiratory Syndrome Coronavirus Infection Limits Replication but Not Lung Inflammation upon Homologous Rechallenge

Host Immune Responses to SARS Coronavirus in Humans

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