SARS-CoV-2 immune complex triggers human monocyte necroptosis.

We analyzed the ability of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) itself and SARS-CoV-2-IgG immune complexes to trigger human monocyte necroptosis. SARS-CoV-2 was able to induce monocyte necroptosis dependently of MLKL activation. Necroptosis-associated proteins (RIPK1, RIPK3 and MLKL) were involved in SARS-CoV-2N1 gene expression in monocytes. SARS-CoV-2 immune complexes promoted monocyte necroptosis in a RIPK3- and MLKL-dependent manner, and Syk tyrosine kinase was necessary for SARS-CoV-2 immune complex-induced monocyte necroptosis, indicating the involvement of Fcγ receptors on necroptosis. Finally, we provide evidence that elevated LDH levels as a marker of lytic cell death are associated with COVID-19 pathogenesis.

Airway Administration of Bacterial Lysate OM-85 Protects Mice Against Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) is a seasonal pathogen responsible for the highest percentage of viral bronchiolitis in pediatric patients. There are currently no vaccine available and therapeutic methods to mitigate the severity of RSV bronchiolitis are limited. OM-85, an oral standardized bacterial lysate isolated from human respiratory strains and widely used to prevent recurrent infections and/or exacerbations in populations at risk, has been shown to be effective and safe in children and adults. Here, we demonstrate that airway administration of OM-85 in Balb/c mice prior to infection prevents RSV-induced disease, resulting in inhibition of viral replication associated with less perivascular and peribronchial inflammation in the lungs. These protective effects are dose and time-dependent with complete protection using 1mg dose of OM-85 only four times intranasally. Mechanistic insights using this topical route in the airways revealed increased alveolar macrophages, a selective set of tolerogenic DCs, Treg and Th1 expansion in the lung, even in the absence of infection, contributing to a better Th1/Th2 balance and preventing ILC2 recruitment in the airways and associated inflammatory sequelae. OM-85 preventive treatment also improved antiviral response by increasing IFNß and its responsive genes in the lung. In vitro, OM-85 protects against RSV infection in a type I interferon pathway. Our animal model data suggest that intranasal use of OM-85 should be considered as a potential prophylactic product to prevent RSV bronchiolitis once human studies confirm these findings.

Short-chain fatty acid acetate triggers antiviral response mediated by RIG-I in cells from infants with respiratory syncytial virus bronchiolitis.

BACKGROUND: Gut microbiota-derived short-chain fatty-acid (SFCA) acetate protects mice against RSV A2 strain infection by increasing interferon-ß production and expression of interferon-stimulated genes (ISGs). However, the role of SFCA in RSV infection using strains isolated from patients is unknown. METHODS: We first used RSV clinical strains isolated from infants hospitalized with RSV bronchiolitis to investigate the effects of in vitro SCFA-acetate treatment of human pulmonary epithelial cells. We next examined whether SCFA-acetate treatment is beneficial in a mouse model of RSV infection using clinical isolates. We sought to investigate the relationship of gut microbiota and fecal acetate with disease severity among infants hospitalized with RSV bronchiolitis, and whether treating their respiratory epithelial cells with SCFA-acetate ex-vivo impacts viral load and ISG expression. We further treated epithelial cells from SARS-CoV-2 infected patients with SCFA-acetate. FINDINGS: In vitro pre-treatment of A549 cells with SCFA-acetate reduced RSV infection with clinical isolates and increased the expression of RIG-I and ISG15. Animals treated with SCFA-acetate intranasally recovered significantly faster, with reduction in the RSV clinical isolates viral load, and increased lung expression of IFNB1 and the RIG-I. Experiments in RIG-I knockout A549 cells demonstrated that the protection relies on RIG-I presence. Gut microbial profile was associated with bronchiolitis severity and with acetate in stool. Increased SCFA-acetate levels were associated with increasing oxygen saturation at admission, and shorter duration of fever. Ex-vivo treatment of patients' respiratory cells with SCFA-acetate reduced RSV load and increased expression of ISGs OAS1 and ISG15, and virus recognition receptors MAVS and RIG-I, but not IFNB1. These SCFA-acetate effects were not found on cells from SARS-CoV-2 infected patients. INTERPRETATION: SCFA-acetate reduces the severity of RSV infection and RSV viral load through modulation of RIG-I expression. FUNDING: FAPERGS (FAPERGS/MS/CNPq/SESRS no. 03/2017 - PPSUS 17/2551-0001380-8 and COVID-19 20/2551-0000258-6); CNPq 312504/2017-9; CAPES) - Finance Code 001.

Prevalence and factors associated with no intention to exclusively breastfeed for the first 6 months of life

Abstract Objective: To investigate the prevalence and factors associated with no intention to exclusively breastfeed for the first 6 months of life in a sample of women in the first 24 h postpartum during the hospital stay. Methods: Cross-sectional study with data from screening phase of a birth cohort. The proportion of mothers who did not intend to breastfeed exclusively for 6 months (primary outcome) derived from a negative response to the question "Would you be willing to try to breastfeed exclusively for the first 6 months?", in an interview conducted by previously trained interviewers. Crude and adjusted prevalence ratios (PR) with 95% confidence intervals were obtained by Poisson regression with robust variance. Results: A total of 2964 postpartum women were interviewed. The overall prevalence of mothers who did not intend to breastfeed exclusively for 6 months was 17.8% (16.4-19.1%). After adjusting for maternal age and type of pregnancy (singleton or multiple), no intention to exclusively breastfeed was higher in mothers with a monthly household income < 3 minimum wages (PR, 1.64; 1.35-1.98) and in those who intended to smoke 4-7 days/week after delivery (PR, 1.42; 1.11-1.83). The presence of significant newborn morbidity (PR, 0.32; 0.19-0.54) and intention to breastfeed up to 12 months (PR, 0.46; 0.38-0.55) had a protective effect against not intending to breastfeed exclusively for 6 months. Conclusions: Approximately 1 in every 5 mothers did not intend to breastfeed exclusively for 6 months. Strategies aimed at promoting exclusive breastfeeding should focus attention on mothers from lower economic strata and smokers.

Prevalence and factors associated with no intention to exclusively breastfeed for the first 6 months of life.

OBJECTIVE: To investigate the prevalence and factors associated with no intention to exclusively breastfeed for the first 6 months of life in a sample of women in the first 24 h postpartum during the hospital stay. METHODS: Cross-sectional study with data from screening phase of a birth cohort. The proportion of mothers who did not intend to breastfeed exclusively for 6 months (primary outcome) derived from a negative response to the question "Would you be willing to try to breastfeed exclusively for the first 6 months?", in an interview conducted by previously trained interviewers. Crude and adjusted prevalence ratios (PR) with 95% confidence intervals were obtained by Poisson regression with robust variance. RESULTS: A total of 2964 postpartum women were interviewed. The overall prevalence of mothers who did not intend to breastfeed exclusively for 6 months was 17.8% (16.4-19.1%). After adjusting for maternal age and type of pregnancy (singleton or multiple), no intention to exclusively breastfeed was higher in mothers with a monthly household income < 3 minimum wages (PR, 1.64; 1.35-1.98) and in those who intended to smoke 4-7 days/week after delivery (PR, 1.42; 1.11-1.83). The presence of significant newborn morbidity (PR, 0.32; 0.19-0.54) and intention to breastfeed up to 12 months (PR, 0.46; 0.38-0.55) had a protective effect against not intending to breastfeed exclusively for 6 months. CONCLUSIONS: Approximately 1 in every 5 mothers did not intend to breastfeed exclusively for 6 months. Strategies aimed at promoting exclusive breastfeeding should focus attention on mothers from lower economic strata and smokers.