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

Low Serum Potassium Levels Increase the Infectious-Caused Mortality in Peritoneal Dialysis Patients: A Propensity-Matched Score Study

<div><p>Background and Objectives</p><p>Hypokalemia has been consistently associated with high mortality rate in peritoneal dialysis. However, studies investigating if hypokalemia is acting as a surrogate marker of comorbidities or has a direct effect in the risk for mortality have not been studied. Thus, the aim of this study was to analyze the effect of hypokalemia on overall and cause-specific mortality.</p><p>Design, Setting, Participants and Measurements</p><p>This is an analysis of BRAZPD II, a nationwide prospective cohort study. All patients on PD for longer than 90 days with measured serum potassium levels were used to verify the association of hypokalemia with overall and cause-specific mortality using a propensity match score to reduce selection bias. In addition, competing risks were also taken into account for the analysis of cause-specific mortality.</p><p>Results</p><p>There was a U-shaped relationship between time-averaged serum potassium and all-cause mortality of PD patients. Cardiovascular disease was the main cause of death in the normokalemic group with 133 events (41.8%) followed by PD-non related infections, n=105 (33.0%). Hypokalemia was associated with a 49% increased risk for CV mortality after adjustments for covariates and the presence of competing risks (SHR 1.49; CI95% 1.01-2.21). In contrast, in the group of patients with K <3.5mEq/L, PD-non related infections were the main cause of death with 43 events (44.3%) followed by cardiovascular disease (n=36; 37.1%). For PD-non related infections the SHR was 2.19 (CI95% 1.52-3.14) while for peritonitis was SHR 1.09 (CI95% 0.47-2.49).</p><p>Conclusions</p><p>Hypokalemia had a significant impact on overall, cardiovascular and infectious mortality even after adjustments for competing risks. The causative nature of this association suggested by our study raises the need for intervention studies looking at the effect of potassium supplementation on clinical outcomes of PD patients.</p></div

Blood pressure behavior along the study period.

<p>Legend: Markers represent mean systolic and diastolic blood pressure whilst error bars represents confidence interval 95%. The bottom box indicates the absolute number of patients included in the analysis per group.</p

All-cause and cause-specific mortality rates for the entire population (n = 5408) using a competing risk analysis.

<p>All-cause and cause-specific mortality rates for the entire population (n = 5408) using a competing risk analysis.</p

Study population.

<p>Study population.</p

Impact of patient training patterns on peritonitis rates in a large national cohort study

Background. Ideal training methods that could ensure best peritoneal dialysis (PD) outcome have not been defined in previous reports. The aim of the present study was to evaluate the impact of training characteristics on peritonitis rates in a large Brazilian cohort.Methods. Incident patients with valid data on training recruited in the Brazilian Peritoneal Dialysis Multicenter Study (BRAZPD II) from January 2008 to January 2011 were included. Peritonitis was diagnosed according to International Society for Peritoneal Dialysis guidelines; incidence rate of peritonitis (episodes/patient-months) and time to the first peritonitis were used as end points.Results. Two thousand two hundred and forty-three adult patients were included in the analysis: 59 +/- 16 years old, 51.8% female, 64.7% with &lt;= 4 years of education. The median training time was 15 h (IQI 10-20 h). Patients were followed for a median of 11.2 months (range 3-36.5). The overall peritonitis rate was 0.29 per year at risk (1 episode/41 patient-months). The mean number of hours of training per day was 1.8 +/- 2.4. Less than 1 h of training/day was associated with higher incidence rate when compared with the intervals of 1-2 h/day (P = 0.03) and &gt; 2 h/day (P = 0.02). Patients who received a cumulative training of &gt; 15 h had significantly lower incidence of peritonitis compared with &lt; 15 h (0.26 per year at risk versus 0.32 per year at risk, P = 0.01). The presence of a caregiver and the number of people trained were not significantly associated with peritonitis incidence rate. Training in the immediate 10 days after implantation of the catheter was associated with the highest peritonitis rate (0.32 per year), compared with training prior to catheter implantation (0.28 per year) or &gt; 10 days after implantation (0.23 per year). More experienced centers had a lower risk for the first peritonitis (P = 0.003).Conclusions. This is the first study to analyze the association between training characteristics and outcomes in a large cohort of PD patients. Low training time (particularly &lt; 15 h), smaller center size and the timing of training in relation to catheter implantation were associated with a higher incidence of peritonitis. These results support the recommendation of a minimum amount of training hours to reduce peritonitis incidence regardless of the number of hours trained per day

Study Population.

<p>Study Population.</p