Immunogenicity of RV1 and RV5 vaccines administered in standard and interchangeable mixed schedules: a randomized, double-blind, non-inferiority clinical trial in Mexican infants.

Introduction: Rotavirus-associated diarrheal diseases significantly burden healthcare systems, particularly affecting infants under five years. Both Rotarix™ (RV1) and RotaTeq™ (RV5) vaccines have been effective but have distinct application schedules and limited interchangeability data. This study aims to provide evidence on the immunogenicity, reactogenicity, and safety of mixed RV1-RV5 schedules compared to their standard counterparts. Methods: This randomized, double-blind study evaluated the non-inferiority in terms of immunogenicity of mixed rotavirus vaccine schedules compared to standard RV1 and RV5 schedules in a cohort of 1,498 healthy infants aged 6 to 10 weeks. Participants were randomly assigned to one of seven groups receiving various combinations of RV1, and RV5. Standard RV1 and RV5 schedules served as controls of immunogenicity, reactogenicity, and safety analysis. IgA antibody levels were measured from blood samples collected before the first dose and one month after the third dose. Non-inferiority was concluded if the reduction in seroresponse rate in the mixed schemes, compared to the standard highest responding scheme, did not exceed the non-inferiority margin of -0.10. Reactogenicity traits and adverse events were monitored for 30 days after each vaccination and analyzed on the entire cohort. Results: Out of the initial cohort, 1,365 infants completed the study. Immunogenicity analysis included 1,014 infants, considering IgA antibody titers ≥20 U/mL as seropositive. Mixed vaccine schedules demonstrated non-inferiority to standard schedules, with no significant differences in immunogenic response. Safety profiles were comparable across all groups, with no increased incidence of serious adverse events or intussusception. Conclusion: The study confirms that mixed rotavirus vaccine schedules are non-inferior to standard RV1 and RV5 regimens in terms of immunogenicity and safety. This finding supports the flexibility of rotavirus vaccination strategies, particularly in contexts of vaccine shortage or logistic constraints. These results contribute to the global effort to optimize rotavirus vaccination programs for broader and more effective pediatric coverage.Clinical trial registration: ClinicalTrials.gov, NCT02193061.

Metabolic Reprogramming in SARS-CoV-2 Infection Impacts the Outcome of COVID-19 Patients.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection triggers inflammatory clinical stages that affect the outcome of patients with coronavirus disease 2019 (COVID-19). Disease severity may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. The aim of this study was to characterize the profile of amino acids and acylcarnitines in COVID-19 patients. A multicenter, cross-sectional study was carried out. A total of 453 individuals were classified by disease severity. Levels of 11 amino acids, 31 acylcarnitines, and succinylacetone in serum samples were analyzed by electrospray ionization-triple quadrupole tandem mass spectrometry. Different clusters were observed in partial least squares discriminant analysis, with phenylalanine, alanine, citrulline, proline, and succinylacetone providing the major contribution to the variability in each cluster (variable importance in the projection >1.5). In logistic models adjusted by age, sex, type 2 diabetes mellitus, hypertension, and nutritional status, phenylalanine was associated with critical outcomes (odds ratio=5.3 (95% CI 3.16-9.2) in the severe vs. critical model, with an area under the curve of 0.84 (95% CI 0.77-0.90). In conclusion the metabolic imbalance in COVID-19 patients might affect disease progression. This work shows an association of phenylalanine with critical outcomes in COVID-19 patients, highlighting phenylalanine as a potential metabolic biomarker of disease severity.

ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing the death of more than 5 million people worldwide. The genetic background represents a factor that predisposes the way the host responds to SARS-CoV-2 infection. In this sense, genetic variants of ACE and ACE2 could explain the observed interindividual variability to COVID-19 outcomes. In order to improve the understanding of how genetic variants of ACE and ACE2 are involved in the severity of COVID-19, we included a total of 481 individuals who showed clinical manifestations of COVID-19 and were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood and saliva samples. ACE insertion/deletion polymorphism was evaluated by the high-resolution melting method; ACE single-nucleotide polymorphism (SNP) (rs4344) and ACE2 SNPs (rs2285666 and rs2074192) were genotyped using TaqMan probes. We assessed the association of ACE and ACE2 polymorphisms with disease severity using logistic regression analysis adjusted by age, sex, hypertension, type 2 diabetes, and obesity. The severity of the illness in our study population was divided as 31% mild, 26% severe, and 43% critical illness; additionally, 18% of individuals died, of whom 54% were male. Our results showed in the codominant model a contribution of ACE2 gene rs2285666 T/T genotype to critical outcome [odds ratio (OR) = 1.83; 95%CI = 1.01-3.29; p = 0.04] and to require oxygen supplementation (OR = 1.76; 95%CI = 1.01-3.04; p = 0.04), in addition to a strong association of the T allele of this variant to develop critical illness in male individuals (OR = 1.81; 95%CI = 1.10-2.98; p = 0.02). We suggest that the T allele of rs2285666 represents a risk factor for severe and critical outcomes of COVID-19, especially for men, regardless of age, hypertension, obesity, and type 2 diabetes.