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Introduction: Evidence on the association of biomarkers of host response to infection with COVID-19 clinical outcomes has focused mainly on hospitalized patients. We investigated the prognostic performance of 39 immune and endothelial activation markers measured early in the course of disease to predict the development of severe COVID-19 and hospitalization. Methods: We conducted a nested case-control study from a randomized clinical trial evaluating the efficacy of COVID-19 convalescent plasma in outpatients aged 50 years or older presenting with mild-to-moderate COVID-19. We selected participants who were hospitalized within 28 days (cases) and who were not (controls) to compare their biomarker levels in plasma samples collected at enrolment. Results: A total of 42 cases and 42 controls were included in this study. The levels of CRP, IL6, IP10, ferritin, IFNα, IL8, IL1RA, MCP1, and RANTES, determined within 7 days of symptoms onset, showed good individual prognostic performance for COVID-19 associated hospitalization by day 28. The biomarkers CRP, IL6, IP10, IL8, IL1RA, and suPAR showed good individual prognostic performance for severe COVID-19. CRP, IL6 and IP10 had the most robust association with both hospitalization and severe COVID-19, with CRP having the highest discriminatory capacity with hospitalization, and IL6 for severe COVID-19. Discussion: Our study shows good prognostic performance of CRP and IL6 for 28-day hospitalization in patients with mild-to-moderate COVID-19, in the absence of clinical criteria for admission upon enrolment. These findings confirm the value of these biomarkers at early stages of COVID-19 disease in the outpatient setting to support management decisions. [ABSTRACT FROM AUTHOR]

RTS,S/AS01E, the first approved malaria vaccine, demonstrated moderate efficacy during the phase 3 pediatric trial. We previously investigated cell-mediated immune (CMI) responses following the primary 3-dose immunization and now report responses to the booster dose given 18 months later. Thirty CMI markers were measured by Luminex in supernatants of peripheral blood mononuclear cells from 709 children and infants after RTS,S/AS01E antigen stimulation, and their associations with malaria risk and antibodies one month post-booster and one year later were assessed. IL-2, IFN-γ, IL-17, IL-5, and IL-13 were associated with RTS,S/AS01E booster vaccination, and IL-2 responses to the circumsporozoite protein (CSP) remained higher after one year. IL-2 was associated with reduced malaria risk in one site, and IL-10 was associated with increased risk in infants. Anti-CSP IgG and IL-2 were moderately correlated one year after booster. This study highlights the moderate cell-mediated immunogenicity of the RTS,S/AS01E booster dose that aligns with partial recovery of RTS,S/AS01E vaccine efficacy. [ABSTRACT FROM AUTHOR]

Background: Ambient air pollution has been associated with COVID-19 disease severity and antibody response induced by infection. Objectives: We examined the association between long-term exposure to air pollution and vaccine-induced antibody response. METHODS: This study was nested in an ongoing population-based cohort, COVICAT, the GCAT-Genomes for Life cohort, in Catalonia, Spain, with multiple follow-ups. We drew blood samples in 2021 from 1,090 participants of 2,404 who provided samples in 2020, and we included 927 participants in this analysis. We measured immunoglobulin M (IgM), IgG, and IgA antibodies against five viral-target antigens, including receptor-binding domain (RBD), spike-protein (S), and segment spike-protein (S2) triggered by vaccines available in Spain. We estimated prepandemic (2018-2019) exposure to fine particulate matter [PM [less than or equal to] 2.5 [micro]m in aerodynamic diameter (P[M.sub.2.5])], nitrogen dioxide (N[O.sub.2]), black carbon (BC), and ozone ([O.sub.3]) using Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE) models. We adjusted estimates for individual- and area-level covariates, time since vaccination, and vaccine doses and type and stratified by infection status. We used generalized additive models to explore the relationship between air pollution and antibodies according to days since vaccination. Results: Among vaccinated persons not infected by SARS-CoV-2 (n = 632), higher prepandemic air pollution levels were associated with a lower vaccine antibody response for IgM (1 month post vaccination) and IgG. Percentage change in geometric mean IgG levels per interquartile range of P[M.sub.2.5] (1.7 [micro]g/[m.sup.3]) were -8.1 (95% CI: - 15.9, 0.4) for RBD, -9.9 (-16.2, -3.1) for S, and -8.4 (-13.5, -3.0) for S2. We observed a similar pattern for N[O.sub.2] and BC and an inverse pattern for [O.sub.3]. Differences in IgG levels by air pollution levels persisted with time since vaccination. We did not observe an association of air pollution with vaccine antibody response among participants with prior infection (n = 295). Discussion: Exposure to air pollution was associated with lower COVID-19 vaccine antibody response. The implications of this association on the risk of breakthrough infections require further investigation. https://doi.org/10.1289/EHP11989, Introduction Air pollution has been associated with COVID-19 disease initially in ecological studies and later in cohort studies using individual data. (1-6) There are some differences between findings of individual-based [...]

Limited research suggests that certain viruses reactivate in severe‐acute‐respiratory‐syndrome‐coronavirus 2 infection, contributing to the development of postacute sequelae of COVID‐19 (PASC). We examined 1083 infected individuals from a population‐based cohort, and assessed differences in plasma immunoglobulin (Ig)G and immunoglobulin A levels against Epstein‐Barr virus (EBV), cytomegalovirus, varicella zoster virus (VZV), BK polyomavirus, KI polyomavirus, WU polyomavirus (WUPyV), respiratory syncytial virus, and Adv‐36 according to the severity of previous COVID‐19 and PASC history. Individuals who had experienced severe COVID‐19 had higher antibody responses to latent viruses. Ever PASC, active persistent PASC, and PASC with neuropsychiatric symptoms were associated with higher immnoglobulin G to EBV early antigen‐diffuse, VZV, and WUPyV even among individuals without previous severe COVID‐19. [ABSTRACT FROM AUTHOR]

Despite clear associations between vitamin D deficiency and obesity and/or type 2 diabetes, a causal relationship is not established. Vitamin D receptors (VDRs) are found within multiple tissues, including the brain. Given the importance of the brain in controlling both glucose levels and body weight, we hypothesized that activation of central VDR links vitamin D to the regulation of glucose and energy homeostasis. Indeed, we found that small doses of active vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D3) (calcitriol), into the third ventricle of the brain improved glucose tolerance and markedly increased hepatic insulin sensitivity, an effect that is dependent upon VDR within the paraventricular nucleus of the hypothalamus. In addition, chronic central administration of 1,25D3 dramatically decreased body weight by lowering food intake in obese rodents. Our data indicate that 1,25D3-mediated changes in food intake occur through action within the arcuate nucleus. We found that VDR colocalized with and activated key appetite-regulating neurons in the arcuate, namely proopiomelanocortin neurons. Together, these findings define a novel pathway for vitamin D regulation of metabolism with unique and divergent roles for central nervous system VDR signaling. Specifically, our data suggest that vitamin D regulates glucose homeostasis via the paraventricular nuclei and energy homeostasis via the arcuate nuclei.

Anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) seroprevalence is used to estimate the proportion of individuals within a population previously infected, to track viral transmission, and to monitor naturally and vaccine‐induced immune protection. However, in sub‐Saharan African settings, antibodies induced by higher exposure to pathogens may increase unspecific seroreactivity to SARS‐CoV‐2 antigens, resulting in false positive responses. To investigate the level and type of unspecific seroreactivitiy to SARS‐CoV‐2 in Africa, we measured immunoglobulin G (IgG), IgA, and IgM to a broad panel of antigens from different pathogens by Luminex in 602 plasma samples from African and European subjects differing in coronavirus disease 2019, malaria, and other exposures. Seroreactivity to SARS‐CoV‐2 antigens was higher in prepandemic African than in European samples and positively correlated with antibodies against human coronaviruses, helminths, protozoa, and especially Plasmodium falciparum. African subjects presented higher levels of autoantibodies, a surrogate of polyreactivity, which correlated with P. falciparum and SARS‐CoV‐2 antibodies. Finally, we found an improved sensitivity in the IgG assay in African samples when using urea as a chaotropic agent. In conclusion, our data suggest that polyreactive antibodies induced mostly by malaria are important mediators of the unspecific anti‐SARS‐CoV‐2 responses, and that the use of dissociating agents in immunoassays could be useful for more accurate estimates of SARS‐CoV‐2 seroprevalence in African settings. [ABSTRACT FROM AUTHOR]

Milk and dairy products are known to have a significant role in human development and tissue maintenance due to their high nutritional value. With the higher incidence of obesity and metabolic diseases, nutrition and public health authorities have recommended the intake of fat‐free or low‐fat dairy due to the saturated fatty acid content of whole‐fat products and their effect on serum cholesterol levels. However, recent studies have questioned the association between milk fat consumption and cardiometabolic risk. This literature review aims to compile the scientific evidence of the metabolic effects of milk fatty acids in clinical and basic research studies, as well as their relationship with metabolic disorders and gut microbiota composition. Research shows that various milk fatty acids exert effects on metabolic alterations (obesity, type 2 diabetes and cardiovascular diseases) by modifying glucose homeostasis, inflammation and lipid profile‐related factors. Additionally, recent studies have associated the consumption of milk fatty acids with the production of metabolites and the promotion of healthy gut microbiota. From mainly observational studies, evidence suggests that milk and dairy fatty acids are not directly linked to cardiometabolic risk, but further controlled research is necessary to clarify such findings and to assess whether dietary recommendations to choose low‐fat dairy foods are necessary for the population for the prevention of obesity and cardiometabolic disease. [ABSTRACT FROM AUTHOR]

ETV5 has been described to be involved in the epithelial to mesenchymal transition (EMT) mainly in cancer. It is known that EMT provokes cytoskeleton remodeling, improving cellular migratory, and invasive capabilities. Moreover, overexpression of ETV5 has been correlated to cancer development and this gene has been implicated in cell proliferation. However, little is known about the downregulation of ETV5 expression in a pancreatic cell line and the inverse mesenchymal to epithelial transition (MET). Therefore, we studied the implications of ETV5 silencing over the phenotype of the insulinoma INS-1 (832/13) cell line and described the MET by partial ETV5 silencing in the INS-1 (832/13) cell line. The downregulation of ETV5 expression was obtained by using ETV5 siRNA in the insulinoma rat cell line, INS-1 (832/13). Then, ETV5 knockdown provoked a MET phenotype observed by crystal violet staining and verified by immunohistochemistry against E-cadherin. Wound healing assay showed no migration, and F-actin stain revealed rearrangement of actin microfilaments. In addition, TGFβ1 and TGFβ3 were downregulated in the absence of ETV5. ETV5 silencing induces epithelial phenotype by downregulating TGFβ1 and TGFβ3 in INS-1 (832/13) cell line. [ABSTRACT FROM AUTHOR]