Neutralization activity in chronic HIV infection is characterized by a distinct programming of follicular helper CD4 T cells.

A subset of people living with HIV (PLWH) can produce broadly neutralizing antibodies (bNAbs) against HIV, but the lymph node (LN) dynamics that promote the generation of these antibodies are poorly understood. Here, we explored LN-associated histological, immunological, and virological mechanisms of bNAb generation in a cohort of anti-retroviral therapy (ART)-naïve PLWH. We found that participants who produce bNAbs, termed neutralizers, have a superior LN-associated B cell follicle architecture compared with PLWH who do not. The latter was associated with a significantly higher in situ prevalence of Bcl-6hi follicular helper CD4 T cells (TFH), expressing a molecular program that favors their differentiation and stemness, and significantly reduced IL-10 follicular suppressor CD4 T cells. Furthermore, our data reveal possible molecular targets mediating TFH- B cell interactions in neutralizers. Together, we identify cellular and molecular mechanisms that contribute to the development of bNAbs in PLWH.

High-flow nasal cannula therapy for hypoxemic respiratory failure in patients with COVID-19.

INTRODUCTION: High-flow nasal cannula (HFNC) therapy in patients with hypoxemic respiratory failure due to COVID-19 is poorly understood and remains controversial. METHODS: We evaluated a large cohort of patients with COVID-19-related hypoxemic respiratory failure at the temporary COVID-19 hospital in Mexico City. The primary outcome was the success rate of HFNC to prevent the progression to invasive mechanical ventilation (IMV). We also evaluated the risk factors associated with HFNC success or failure. RESULTS: HFNC use effectively prevented IMV in 71.4% of patients [270 of 378 patients; 95% confidence interval (CI) 66.6-75.8%]. Factors that were significantly different at admission included age, the presence of hypertension, and the Charlson comorbidity index. Predictors of therapy failure (adjusted hazard ratio, 95% CI) included the comorbidity-age-lymphocyte count-lactate dehydrogenase (CALL) score at admission (1.27, 1.09-1.47; p < 0.01), Rox index at 1 hour (0.82, 0.7-0.96; p = 0.02), and no prior steroid treatment (0.34, 95% CI 0.19-0.62; p < 0.0001). Patients with HFNC success rarely required admission to the intensive care unit and had shorter lengths of hospital stay [19/270 (7.0%) and 15.0 (interquartile range, 11-20) days, respectively] than those who required IMV [104/108 (96.3%) and 26.5 (20-36) days, respectively]. CONCLUSION: Treating patients with HFNC at admission led to improvement in respiratory parameters in many patients with COVID-19.