Immunomodulatory markers and therapies for the management of infant respiratory syncytial virus infection.

INTRODUCTION: The human respiratory syncytial virus (hRSV) is one of childhood diseases' most common respiratory pathogens and is associated with lower respiratory tract infections. The peak in disease that this virus can elicit during outbreaks is often a significant burden for healthcare systems worldwide. Despite theapproval of treatments against hRSV, this pathogen remains one the most common causative agent of infant mortality around the world. AREAS COVERED: This review focuses on the key prognostic and immunomodulatory biomarkers associated with hRSV infection, as well as prophylactic monoclonal antibodies and vaccines. The goal is to catalyze a paradigm shift within the scientific community toward the discovery of novel targets to predict the clinical outcome of infected patients, as well as the development of novel antiviral agents targeting hRSV. The most pertinent research on this topic was systematically searched and analyzed using PubMed ISI Thomson Scientific databases. EXPERT OPINION: Despite advances in approved therapies against hRSV, it is crucial to continue researching to develop new therapies and to find specific biomarkers to predict the severity of infection. Along these lines, the use of multi-omics data, artificial intelligence and natural-derived compounds with antiviral activity could be evaluated to fight hRSV and develop methods for rapid diagnosis of severity.

Co-administration of recombinant BCG and SARS-CoV-2 proteins leads to robust antiviral immunity.

SARS-CoV-2 is the causative virus of COVID-19, which has been responsible for millions of deaths worldwide since its discovery. After its emergence, several variants have been identified that challenge the efficacy of the available vaccines. Previously, we generated and evaluated a vaccine based on a recombinant Bacillus Calmette-Guérin (rBCG) expressing the nucleoprotein (N) of SARS-CoV-2 (rBCG-N-SARS-CoV-2). This protein is a highly immunogenic antigen and well conserved among variants. Here, we tested the administration of this vaccine with recombinant N and viral Spike proteins (S), or Receptor Binding Domain (RBD-Omicron variant), plus a booster with the recombinant proteins only, as a novel and effective strategy to protect against SARS-CoV-2 variants. METHODS: BALB/c mice were immunized with rBCG-N-SARS-CoV-2 and recombinant SARS-CoV-2 proteins in Alum adjuvant, followed by a booster with recombinant proteins to assess the safety and virus-specific cellular and humoral immune responses against SARS-CoV-2 antigens. RESULTS: Immunization with rBCG-N-SARS-CoV-2 + recombinant proteins as a vaccine was safe and promoted the activation of CD4+ and CD8+ T cells that recognize SARS-CoV-2 N, S, and RBD antigens. These cells were able to secrete cytokines with an antiviral profile. This immunization strategy also induced robust titers of specific antibodies against N, S, and RBD and neutralizing antibodies of SARS-CoV-2. CONCLUSIONS: Co-administration of the rBCG-N-SARS-CoV-2 vaccine with recombinant SARS-CoV-2 proteins could be an effective alternative to control particular SARS-CoV-2 variants. Due to its safety and capacity to induce virus-specific immune responses, we believe the rBCG-N-SARS-CoV-2 + Proteins vaccine could be an attractive candidate to protect against this virus, especially in newborns.

Immunogenicity and Safety of a Quadrivalent Influenza Vaccine in Population Aged 3 Years and Older in Chile and the Philippines: A Phase 3, Non-Inferiority, Double-Blind, Randomized Controlled Clinical Trial.

OBJECTIVES: In this study, we aimed to evaluate the non-inferiority of a quadrivalent influenza vaccine (QIV) developed by Sinovac Biotech Co., Ltd. (Sinovac, Beijing, China) by comparing its immunogenicity and safety with a comparator QIV (Vaxigrip Tetra®) in a population aged 3 years and older in Chile and the Philippines. METHODS: A phase 3, non-inferiority, double-blind, randomized controlled, multicenter clinical trial was conducted in the southern hemisphere (SH) 2023 influenza season. Participants aged ≥ 3 years old with stable health were randomized 1:1 to receive either Sinovac QIV or comparator QIV. The co-primary outcomes were immunological non-inferiority for Sinovac QIV versus the comparator against each strain contained in the vaccines in terms of seroconversion rates (SCRs) and geometric mean titers (GMTs) of hemagglutination inhibition (HI) antibodies 28 days after final vaccination. RESULTS: A total of 2039 participants were vaccinated (1019 Sinovac QIV; 1020 comparator QIV). Sinovac QIV induced non-inferior immune responses to all four strains as compared to comparator QIV, with slightly higher GMTs than those of comparator QIV: GMT ratios (lower limit 95% confidence interval (CI)) were 1.8 (1.6) for A(H1N1), 1.4 (1.3) for A (H3N2), 1.3 (1.1) for B Victoria and 1.2 (1.1) for B Yamagata; observed seroconversion rate differences (lower limit 95% CI) were 9.6% (6.7) for A(H1N1), 7.0% (3.5) for A(H3N2), 2.4% (-0.03) for B Victoria and 6.8% (3.0) for B Yamagata. Adverse reactions were similar across the two groups and no vaccine-related serious adverse events were reported. CONCLUSIONS: The immunogenicity of Sinovac QIV was non-inferior to that of the comparator QIV in these populations aged 3 years and older, and safety was comparable.

Advancement in the development of mRNA-based vaccines for respiratory viruses.

Acute respiratory infections are the leading cause of death and illness in children under 5 years old and represent a significant burden in older adults. Primarily caused by viruses infecting the lower respiratory tract, symptoms include cough, congestion, and low-grade fever, potentially leading to bronchiolitis and pneumonia. Messenger ribonucleic acid (mRNA)-based vaccines are biopharmaceutical formulations that employ mRNA molecules to induce specific immune responses, facilitating the expression of viral or bacterial antigens and promoting immunization against infectious diseases. Notably, this technology had significant relevance during the COVID-19 pandemic, as these formulations helped to limit SARS-CoV-2 virus infections, hospitalizations, and deaths. Importantly, mRNA vaccines promise to be implemented as new alternatives for fighting other respiratory viruses, such as influenza, human respiratory syncytial virus, and human metapneumovirus. This review article analyzes mRNA-based vaccines' main contributions, perspectives, challenges, and implications against respiratory viruses.

Partial long-term clinical improvement after a BCG challenge in systemic lupus erythematosus-prone mice.

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder that causes a breakdown of immune tolerance. Current treatments mainly involve general immunosuppression, increasing the risk of infections. On the other hand, Bacillus Calmette-Guérin (BCG) has been investigated as a potential therapy for autoimmune diseases in recent years, prompting an ongoing investigation. This study aimed to evaluate the effect of BCG vaccination on early and late clinical presentation of SLE in a murine disease model. MRL/MPJ-Faslpr mice were immunized with BCG or treated with PBS as a control. The progress of the disease was evaluated at 27 days post-immunization (dpi) (early) and 56 dpi (late). Clinical parameters and proteinuria were monitored. Blood samples were collected for measurement of antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), and cytokine determination was performed using ELISA. Samples collected from mice were analyzed by flow cytometry and histopathology. We observed a clinical improvement in BCG-treated mice, reduced proteinuria in the latter stages of the disease, and decreased TNF-α. However, BCG did not elicit significant changes in ANAs, anti-dsDNA, histopathological scores, or immune cell infiltration. BCG was only partially beneficial in an SLE mouse model, and further research is needed to determine whether the immunity induced by this vaccine can counteract lupus's autoimmune response.

Asymptomatic herpes simplex virus brain infection elicits cellular senescence phenotypes in the central nervous system of mice suffering multiple sclerosis-like disease.

Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease affecting the central nervous system (CNS) in animals that parallels several clinical and molecular traits of multiple sclerosis in humans. Herpes simplex virus type 1 (HSV-1) infection mainly causes cold sores and eye diseases, yet eventually, it can also reach the CNS, leading to acute encephalitis. Notably, a significant proportion of healthy individuals are likely to have asymptomatic HSV-1 brain infection with chronic brain inflammation due to persistent latent infection in neurons. Because cellular senescence is suggested as a potential factor contributing to the development of various neurodegenerative disorders, including multiple sclerosis, and viral infections may induce a premature senescence state in the CNS, potentially increasing susceptibility to such disorders, here we examine the presence of senescence-related markers in the brains and spinal cords of mice with asymptomatic HSV-1 brain infection, EAE, and both conditions. Across all scenarios, we find a significant increases of senescence biomarkers in the CNS with some differences depending on the analyzed group. Notably, some senescence biomarkers are exclusively observed in mice with the combined conditions. These results indicate that asymptomatic HSV-1 brain infection and EAE associate with a significant expression of senescence biomarkers in the CNS.

New insights into the pathogenesis of SARS-CoV-2 during and after the COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the respiratory distress condition known as COVID-19. This disease broadly affects several physiological systems, including the gastrointestinal, renal, and central nervous (CNS) systems, significantly influencing the patient's overall quality of life. Additionally, numerous risk factors have been suggested, including gender, body weight, age, metabolic status, renal health, preexisting cardiomyopathies, and inflammatory conditions. Despite advances in understanding the genome and pathophysiological ramifications of COVID-19, its precise origins remain elusive. SARS-CoV-2 interacts with a receptor-binding domain within angiotensin-converting enzyme 2 (ACE2). This receptor is expressed in various organs of different species, including humans, with different abundance. Although COVID-19 has multiorgan manifestations, the main pathologies occur in the lung, including pulmonary fibrosis, respiratory failure, pulmonary embolism, and secondary bacterial pneumonia. In the post-COVID-19 period, different sequelae may occur, which may have various causes, including the direct action of the virus, alteration of the immune response, and metabolic alterations during infection, among others. Recognizing the serious adverse health effects associated with COVID-19, it becomes imperative to comprehensively elucidate and discuss the existing evidence surrounding this viral infection, including those related to the pathophysiological effects of the disease and the subsequent consequences. This review aims to contribute to a comprehensive understanding of the impact of COVID-19 and its long-term effects on human health.

Immune responses during COVID-19 breakthrough cases in vaccinated children and adolescents.

Background: Vaccine effectiveness against SARS-CoV-2 infection has been somewhat limited due to the widespread dissemination of the Omicron variant, its subvariants, and the immune response dynamics of the naturally infected with the virus. Methods: Twelve subjects between 3-17 years old (yo), vaccinated with two doses of CoronaVac®, were followed and diagnosed as breakthrough cases starting 14 days after receiving the second dose. Total IgGs against different SARS-CoV-2 proteins and the neutralizing capacity of these antibodies after infection were measured in plasma. The activation of CD4+ and CD8+ T cells was evaluated in peripheral blood mononuclear cells stimulated with peptides derived from the proteins from the wild-type (WT) virus and Omicron subvariants by flow cytometry, as well as different cytokines secretion by a Multiplex assay. Results: 2 to 8 weeks post-infection, compared to 4 weeks after 2nd dose of vaccine, there was a 146.5-fold increase in neutralizing antibody titers against Omicron and a 38.7-fold increase against WT SARS-CoV-2. Subjects showed an increase in total IgG levels against the S1, N, M, and NSP8 proteins of the WT virus. Activated CD4+ T cells showed a significant increase in response to the BA.2 subvariant (p<0.001). Finally, the secretion of IL-2 and IFN-γ cytokines showed a discreet decrease trend after infection in some subjects. Conclusion: SARS-CoV-2 infection in the pediatric population vaccinated with an inactivated SARS-CoV-2 vaccine produced an increase in neutralizing antibodies against Omicron and increased specific IgG antibodies for different SARS-CoV-2 proteins. CD4+ T cell activation was also increased, suggesting a conserved cellular response against the Omicron subvariants, whereas Th1-type cytokine secretion tended to decrease. Clinical Trial Registration: clinicaltrials.gov #NCT04992260.

Gestational hypothyroxinemia induces ASD-like phenotypes in behavior, proinflammatory markers, and glutamatergic protein expression in mouse offspring of both sexes.

Background: The prevalence of autism spectrum disorder (ASD) has significantly risen in the past three decades, prompting researchers to explore the potential contributions of environmental factors during pregnancy to ASD development. One such factor of interest is gestational hypothyroxinemia (HTX), a frequent condition in pregnancy associated with cognitive impairments in the offspring. While retrospective human studies have linked gestational HTX to autistic traits, the cellular and molecular mechanisms underlying the development of ASD-like phenotypes remain poorly understood. This study used a mouse model of gestational HTX to evaluate ASD-like phenotypes in the offspring. Methods: To induce gestational HTX, pregnant mice were treated with 2-mercapto-1-methylimidazole (MMI), a thyroid hormones synthesis inhibitor, in the tap-drinking water from embryonic days (E) 10 to E14. A separate group received MMI along with a daily subcutaneous injection of T4, while the control group received regular tap water during the entire pregnancy. Female and male offspring underwent assessments for repetitive, anxious, and social behaviors from postnatal day (P) 55 to P64. On P65, mice were euthanized for the evaluation of ASD-related inflammatory markers in blood, spleen, and specific brain regions. Additionally, the expression of glutamatergic proteins (NLGN3 and HOMER1) was analyzed in the prefrontal cortex and hippocampus. Results: The HTX-offspring exhibited anxious-like behavior, a subordinate state, and impaired social interactions. Subsequently, both female and male HTX-offspring displayed elevated proinflammatory cytokines in blood, including IL-1ß, IL-6, IL-17A, and TNF-α, while only males showed reduced levels of IL-10. The spleen of HTX-offspring of both sexes showed increased Th17/Treg ratio and M1-like macrophages. In the prefrontal cortex and hippocampus of male HTX-offspring, elevated levels of IL-17A and reduced IL-10 were observed, accompanied by increased expression of hippocampal NLGN3 and HOMER1. All these observations were compared to those observed in the Control-offspring. Notably, the supplementation with T4 during the MMI treatment prevents the development of the observed phenotypes. Correlation analysis revealed an association between maternal T4 levels and specific ASD-like outcomes. Discussion: This study validates human observations, demonstrating for the first time that gestational HTX induces ASD-like phenotypes in the offspring, highlighting the need of monitoring thyroid function during pregnancy.

Respiratory Syncytial Virus Vaccines: Analysis of Pre-Marketing Clinical Trials for Immunogenicity in the Population over 50 Years of Age.

Immunosenescence refers to age-related alterations in immune system function affecting both the humoral and cellular arm of immunity. Understanding immunosenescence and its impact on the vaccination of older adults is essential since primary vaccine responses in older individuals can fail to generate complete protection, especially vaccines targeting infections with increased incidence among the elderly, such as the respiratory syncytial virus. Here, we review clinical trials of both candidate and approved vaccines against respiratory syncytial virus (RSV) that include adults aged ≥50 years, with an emphasis on the evaluation of immunogenicity parameters. Currently, there are 10 vaccine candidates and 2 vaccines approved for the prevention of RSV in the older adult population. The number of registered clinical trials for this age group amounts to 42. Our preliminary evaluation of published results and interim analyses of RSV vaccine clinical trials indicates efficacy in older adult participants, demonstrating immunity levels that closely resemble those of younger adult participants.

Human metapneumovirus respiratory infection affects both innate and adaptive intestinal immunity.

Introduction: Respiratory infections are one of the leading causes of morbidity and mortality worldwide, mainly in children, immunocompromised people, and the elderly. Several respiratory viruses can induce intestinal inflammation and alterations in intestinal microbiota composition. Human metapneumovirus (HMPV) is one of the major respiratory viruses contributing to infant mortality in children under 5 years of age worldwide, and the effect of this infection at the gut level has not been studied. Methods: Here, we evaluated the distal effects of HMPV infection on intestinal microbiota and inflammation in a murine model, analyzing several post-infection times (days 1, 3, and 5). Six to eight-week-old C57BL/6 mice were infected intranasally with HMPV, and mice inoculated with a non-infectious supernatant (Mock) were used as a control group. Results: We did not detect HMPV viral load in the intestine, but we observed significant changes in the transcription of IFN-γ in the colon, analyzed by qPCR, at day 1 post-infection as compared to the control group. Furthermore, we analyzed the frequencies of different innate and adaptive immune cells in the colonic lamina propria, using flow cytometry. The frequency of monocyte populations was altered in the colon of HMPV -infected mice at days 1 and 3, with no significant difference from control mice at day 5 post-infection. Moreover, colonic CD8+ T cells and memory precursor effector CD8+ T cells were significantly increased in HMPV-infected mice at day 5, suggesting that HMPV may also alter intestinal adaptive immunity. Additionally, we did not find alterations in antimicrobial peptide expression, the frequency of colonic IgA+ plasma cells, and levels of fecal IgA. Some minor alterations in the fecal microbiota composition of HMPV -infected mice were detected using 16s rRNA sequencing. However, no significant differences were found in ß-diversity and relative abundance at the genus level. Discussion: To our knowledge, this is the first report describing the alterations in intestinal immunity following respiratory infection with HMPV infection. These effects do not seem to be mediated by direct viral infection in the intestinal tract. Our results indicate that HMPV can affect colonic innate and adaptive immunity but does not significantly alter the microbiota composition, and further research is required to understand the mechanisms inducing these distal effects in the intestine.

A molecular perspective for the development of antibodies against the human respiratory syncytial virus.

The human respiratory syncytial virus (hRSV) is the leading etiologic agent causing respiratory infections in infants, children, older adults, and patients with comorbidities. Sixty-seven years have passed since the discovery of hRSV, and only a few successful mitigation or treatment tools have been developed against this virus. One of these is immunotherapy with monoclonal antibodies against structural proteins of the virus, such as Palivizumab, the first prophylactic approach approved by the Food and Drug Administration (FDA) of the USA. In this article, we discuss different strategies for the prevention and treatment of hRSV infection, focusing on the molecular mechanisms against each target that underly the rational design of antibodies against hRSV. At the same time, we describe the latest results regarding currently approved therapies against hRSV and the challenges associated with developing new candidates.

Subinhibitory antibiotic concentrations promote the excision of a genomic island carried by the globally spread carbapenem-resistant Klebsiella pneumoniae sequence type 258.

The ICEKp258.2 genomic island (GI) has been proposed as an important factor for the emergence and success of the globally spread carbapenem-resistant Klebsiella pneumoniae sequence type (ST) 258. However, a characterization of this horizontally acquired element is lacking. Using bioinformatic and experimental approaches, we found that ICEKp258.2 is not confined to ST258 and ST512, but also carried by ST3795 strains and emergent invasive multidrug-resistant pathogens from ST1519. We also identified several ICEKp258.2-like GIs spread among different K. pneumoniae STs, other Klebsiella species and even other pathogen genera, uncovering horizontal gene transfer events between different STs and bacterial genera. Also, the comparative and phylogenetic analyses of the ICEKp258.2-like GIs revealed that the most closely related ICEKp258.2-like GIs were harboured by ST11 strains. Importantly, we found that subinhibitory concentrations of antibiotics used in treating K. pneumoniae infections can induce the excision of this GI and modulate its gene expression. Our findings provide the basis for the study of ICEKp258.2 and its role in the success of K. pneumoniae ST258. They also highlight the potential role of antibiotics in the spread of ICEKp258.2-like GIs among bacterial pathogens.

SEN1990 is a predicted winged helix-turn-helix protein involved in the pathogenicity of Salmonella enterica serovar Enteritidis and the expression of the gene oafB in the SPI-17.

Excisable genomic islands (EGIs) are horizontally acquired genetic elements that harbor an array of genes with diverse functions. ROD21 is an EGI found integrated in the chromosome of Salmonella enterica serovar Enteritidis (Salmonella ser. Enteritidis). While this island is known to be involved in the capacity of Salmonella ser. Enteritidis to cross the epithelial barrier and colonize sterile organs, the role of most ROD21 genes remains unknown, and thus, the identification of their function is fundamental to understanding the impact of this EGI on bacterium pathogenicity. Therefore, in this study, we used a bioinformatical approach to evaluate the function of ROD21-encoded genes and delve into the characterization of SEN1990, a gene encoding a putative DNA-binding protein. We characterized the predicted structure of SEN1990, finding that this protein contains a three-stranded winged helix-turn-helix (wHTH) DNA-binding domain. Additionally, we identified homologs of SEN1990 among other members of the EARL EGIs. Furthermore, we deleted SEN1990 in Salmonella ser. Enteritidis, finding no differences in the replication or maintenance of the excised ROD21, contrary to what the previous Refseq annotation of the protein suggests. High-throughput RNA sequencing was carried out to evaluate the effect of the absence of SEN1990 on the bacterium's global transcription. We found a downregulated expression of oafB, an SPI-17-encoded acetyltransferase involved in O-antigen modification, which was restored when the deletion mutant was complemented ectopically. Additionally, we found that strains lacking SEN1990 had a reduced capacity to colonize sterile organs in mice. Our findings suggest that SEN1990 encodes a wHTH domain-containing protein that modulates the transcription of oafB from the SPI-17, implying a crosstalk between these pathogenicity islands and a possible new role of ROD21 in the pathogenesis of Salmonella ser. Enteritidis.

Different Safety Pattern of an Inactivated SARS-CoV-2 Vaccine (CoronaVac®) According to Age Group in a Pediatric Population from 3 to 17 Years Old, in an Open-Label Study in Chile.

During the COVID-19 pandemic, the importance of vaccinating children against SARS-CoV-2 was rapidly established. This study describes the safety of CoronaVac® in children and adolescents between 3- and 17-years-old in a multicenter study in Chile with two vaccine doses in a 4-week interval. For all participants, immediate adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were registered throughout the study. In the safety subgroup, AEs were recorded 28 days after each dose. COVID-19 surveillance was performed throughout the study. A total of 1139 individuals received the first and 1102 the second dose of CoronaVac®; 835 were in the safety subgroup. The first dose showed the highest number of AEs: up to 22.2% of participants reported any local and 17.1% systemic AE. AEs were more frequent in adolescents after the first dose, were transient, and mainly mild. Pain at the inoculation site was the most frequent AE for all ages. Fever was the most frequent systemic AE for 3-5 years old and headache in 6-17 years old. No SAEs or AESIs related to vaccination occurred. Most of the COVID-19 cases were mild and managed as outpatients. CoronaVac® was safe and well tolerated in children and adolescents, with different safety patterns according to age.

Characterization of the humoral and cellular immunity induced by a recombinant BCG vaccine for the respiratory syncytial virus in healthy adults.

Introduction: The human respiratory syncytial virus (hRSV) is responsible for most respiratory tract infections in infants. Even though currently there are no approved hRSV vaccines for newborns or infants, several candidates are being developed. rBCG-N-hRSV is a vaccine candidate previously shown to be safe in a phase I clinical trial in adults (clinicaltrials.gov identifier #NCT03213405). Here, secondary immunogenicity analyses were performed on these samples. Methods: PBMCs isolated from immunized volunteers were stimulated with hRSV or mycobacterial antigens to evaluate cytokines and cytotoxic T cell-derived molecules and the expansion of memory T cell subsets. Complement C1q binding and IgG subclass composition of serum antibodies were assessed. Results: Compared to levels detected prior to vaccination, perforin-, granzyme B-, and IFN-γ-producing PBMCs responding to stimulus increased after immunization, along with their effector memory response. N-hRSV- and mycobacterial-specific antibodies from rBCG-N-hRSV-immunized subjects bound C1q. Conclusion: Immunization with rBCG-N-hRSV induces cellular and humoral immune responses, supporting that rBCG-N-hRSV is immunogenic and safe in healthy individuals. Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/, identifier NCT03213405.

Differential Severe Acute Respiratory Syndrome Coronavirus 2-Specific Humoral Response in Inactivated Virus-Vaccinated, Convalescent, and Breakthrough-Infected Subjects.

BACKGROUND: We sought to identify potential antigens for discerning between humoral responses elicited after vaccination with CoronaVac (a severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] inactivated vaccine), natural infection, or breakthrough infection. METHODS: Serum samples obtained from volunteers immunized with CoronaVac (2 and 3 doses), breakthrough case patients, and from convalescent individuals were analyzed to determine the immunoglobulin (Ig) G responses against 3 structural and 8 nonstructural SARS-CoV-2 antigens. RESULTS: Immunization with CoronaVac induced higher levels of antibodies against the viral membrane (M) protein compared with convalescent subjects both after primary vaccination and after a booster dose. Individuals receiving a booster dose displayed equivalent levels of IgG antibodies against the nucleocapsid (N) protein, similar to convalescent subjects. Breakthrough case patients produced the highest antibody levels against the N and M proteins. Antibodies against nonstructural viral proteins were present in >50% of the convalescent subjects. CONCLUSIONS: Vaccinated individuals elicited a different humoral response compared to convalescent subjects. The analysis of particular SARS-CoV-2 antigens could be used as biomarkers for determining infection in subjects previously vaccinated with CoronaVac.

Gut microbiota short-chain fatty acids and their impact on the host thyroid function and diseases.

Thyroid disorders are clinically characterized by alterations of L-3,5,3',5'-tetraiodothyronine (T4), L-3,5,3'-triiodothyronine (T3), and/or thyroid-stimulating hormone (TSH) levels in the blood. The most frequent thyroid disorders are hypothyroidism, hyperthyroidism, and hypothyroxinemia. These conditions affect cell differentiation, function, and metabolism. It has been reported that 40% of the world's population suffers from some type of thyroid disorder and that several factors increase susceptibility to these diseases. Among them are iodine intake, environmental contamination, smoking, certain drugs, and genetic factors. Recently, the intestinal microbiota, composed of more than trillions of microbes, has emerged as a critical player in human health, and dysbiosis has been linked to thyroid diseases. The intestinal microbiota can affect host physiology by producing metabolites derived from dietary fiber, such as short-chain fatty acids (SCFAs). SCFAs have local actions in the intestine and can affect the central nervous system and immune system. Modulation of SCFAs-producing bacteria has also been connected to metabolic diseases, such as obesity and diabetes. In this review, we discuss how alterations in the production of SCFAs due to dysbiosis in patients could be related to thyroid disorders. The studies reviewed here may be of significant interest to endocrinology researchers and medical practitioners.

Influence of SARS-CoV-2 mRNA Vaccine Booster among Cancer Patients on Active Treatment Previously Immunized with Inactivated versus mRNA Vaccines: A Prospective Cohort Study.

Cancer patients on chemotherapy have a lower immune response to SARS-CoV-2 vaccines. Therefore, through a prospective cohort study of patients with solid tumors receiving chemotherapy, we aimed to determine the immunogenicity of an mRNA vaccine booster (BNT162b2) among patients previously immunized with an inactivated (CoronaVac) or homologous (BNT162b2) SARS-CoV-2 vaccine. The primary outcome was the proportion of patients with anti-SARS-CoV-2 neutralizing antibody (NAb) seropositivity at 8-12 weeks post-booster. The secondary end points included IgG antibody (TAb) seropositivity and specific T-cell responses. A total of 109 patients were included. Eighty-four (77%) had heterologous vaccine schedules (two doses of CoronaVac followed by the BNT162b2 booster) and twenty-five had (23%) homologous vaccine schedules (three doses of BNT162b2). IgG antibody positivity for the homologous and heterologous regimen were 100% and 96% (p = 0.338), whereas NAb positivity reached 100% and 92% (p = 0.13), respectively. Absolute NAb positivity and Tab levels were associated with the homologous schedule (with a beta coefficient of 0.26 with p = 0.027 and a geometric mean ratio 1.41 with p = 0.044, respectively). Both the homologous and heterologous vaccine regimens elicited a strong humoral and cellular response after the BNT162b2 booster. The homologous regimen was associated with higher NAb positivity and Tab levels after adjusting for relevant covariates.

Novel evidence on sepsis-inducing pathogens: from laboratory to bedside.

Sepsis is a life-threatening condition and a significant cause of preventable morbidity and mortality globally. Among the leading causative agents of sepsis are bacterial pathogens Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pyogenes, along with fungal pathogens of the Candida species. Here, we focus on evidence from human studies but also include in vitro and in vivo cellular and molecular evidence, exploring how bacterial and fungal pathogens are associated with bloodstream infection and sepsis. This review presents a narrative update on pathogen epidemiology, virulence factors, host factors of susceptibility, mechanisms of immunomodulation, current therapies, antibiotic resistance, and opportunities for diagnosis, prognosis, and therapeutics, through the perspective of bloodstream infection and sepsis. A list of curated novel host and pathogen factors, diagnostic and prognostic markers, and potential therapeutical targets to tackle sepsis from the research laboratory is presented. Further, we discuss the complex nature of sepsis depending on the sepsis-inducing pathogen and host susceptibility, the more common strains associated with severe pathology and how these aspects may impact in the management of the clinical presentation of sepsis.