SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p

Multidisciplinary approach to metallogenic models and types of primary gold concentration in the Cretaceous arc terranes of the Dominican Republic

Section

PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease

Severe COVID-19 is associated with hyperinflammation and weak T cell responses against SARS-CoV-2. However, the links between those processes remain partially characterized. Moreover, whether and how therapeutically manipulating T cells may benefit patients are unknown. Our genetic and pharmacological evidence demonstrates that the ion channel TMEM176B inhibited inflammasome activation triggered by SARS-CoV-2 and SARS-CoV-2- related murine β-coronavirus. Tmem176b-/- mice infected with murine β-coronavirus developed inflammasome-dependent T cell dysfunction and critical disease, which was controlled by modulating dysfunctional T cells with PD-1 blockers. In critical COVID-19, inflammasome activation correlated with dysfunctional T cells and low monocytic TMEM176B expression, whereas PD-L1 blockade rescued T cell functionality. Here, we mechanistically link T cell dysfunction and inflammation, supporting a cancer immunotherapy to reinforce T cell immunity in critical β-coronavirus disease.Fil: Duhalde Vega, Maite. Institut Pasteur de Montevideo; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Olivera, Daniela. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Davanzo, Gustavo Gastão. Universidade Estadual de Campinas; BrasilFil: Bertullo, Mauricio. Immunoregulation And Inflammation Lab; UruguayFil: Noya, Verónica. Sanatorio Americano; UruguayFil: de Souza, Gabriela Fabiano. Universidade Estadual de Campinas; BrasilFil: Muraro, Stéfanie Primon. Universidade Estadual de Campinas; BrasilFil: Castro, Icaro. Hospital Israelita Albert Einstein; BrasilFil: Arévalo, Ana Paula. Institut Pasteur de Montevideo; UruguayFil: Crispo, Martina. Institut Pasteur de Montevideo; UruguayFil: Galliussi, Germán. Institut Pasteur de Montevideo; UruguayFil: Russo, Sofía. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Charbonnier, David. Institut Pasteur de Montevideo; UruguayFil: Rammauro, Florencia. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Jeldres, Mathías. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Alamón, Catalina. Institut Pasteur de Montevideo; UruguayFil: Varela, Valentina. Institut Pasteur de Montevideo; UruguayFil: Batthyany, Carlos. Institut Pasteur de Montevideo; UruguayFil: Bollati Fogolín, Mariela. Institut Pasteur de Montevideo; UruguayFil: Oppezzo, Pablo. Institut Pasteur de Montevideo; UruguayFil: Pritsch, Otto. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Proença Módena, José Luiz. Universidade Estadual de Campinas; BrasilFil: Nakaya, Helder I.. Hospital Israelita Albert Einstein; BrasilFil: Trias, Emiliano. Institut Pasteur de Montevideo; UruguayFil: Barbeito, Luis. Institut Pasteur de Montevideo; UruguayFil: Anegon, Ignacio. Center For Research In Transplantation And Immunology; FranciaFil: Cuturi, María Cristina. Center For Research In Transplantation And Immunology; FranciaFil: Moraes Vieira, Pedro. Universidade Estadual de Campinas; BrasilFil: Segovia, Mercedes. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Hill, Marcelo. Universidad de la República; Uruguay. Institut Pasteur de Montevideo; Urugua

ECPPA: Randomised trial of low dose aspirin for the prevention of maternal and fetal complications in high risk pregnant women

Objective To determine the effectiveness of low dose aspirin in women at high risk of adverse outcomes associated with pre-eclampsia.Design A collaborative randomised trial comparing the effects of low dose aspirin (60 mg) with placebo on pre-eclampsia and other materno-fetal complications associated with hypertension.Setting Twelve teaching maternity hospitals and 182 obstetricians' offices in Brazil.Subjects One thousand and nine women considered to be at high risk for the development of preeclampsia, or its complications, entered the study between 12 and 32 weeks of gestation. They were randomly allocated to receive aspirin (498 women) or placebo (511 women) until delivery, and follow up was obtained for 96%.Results There were no significant differences between the treatment groups in the incidence of proteinuric pre-eclampsia (6.7% aspirin-allocated compared with 6.0% placebo-allocated women), of preterm delivery (22.3% compared with 26.1%), of intrauterine growth retardation (8.5% compared with 10.1%), or of stillbirth and neonatal death (7.3% compared with 6.0%), nor were there significant differences in the incidence of proteinuric pre-eclampsia in any subgroup of women studied, including those who had systolic blood pressures of 120 mmHg or above at entry (8.5% compared with 7.3%) or those who were chronically hypertensive (10.0% compared with 7.1%). Aspirin was not associated with a significant excess of maternal or fetal bleeding.Conclusion The results of this study do not support the routine prophylactic administration of low dose aspirin in pregnancy to any category of high risk women (even those who have chronic hypertension or who are considered to be especially liable to early onset pre-eclampsia).ESCOLA PAULISTA MED,DEPT MED,MED CLIN D,RUA BOTUCATU 740,BR-04023900 SAO PAULO,BRAZILESCOLA PAULISTA MED,DEPT MED,MED CLIN D,RUA BOTUCATU 740,BR-04023900 SAO PAULO,BRAZILWeb of Scienc