Immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) using two-dose primary protocol in children and adolescents (Immunita-002, Brazil): A phase IV six-month follow up.

Introduction: Vaccines are essential for the prevention and control of several diseases, indeed, monitoring the immune response generated by vaccines is crucial. The immune response generated by vaccination against SARS-CoV-2 in children and adolescents is not well defined regarding to the intensity and medium to long-term duration of a protective immune response, which may point out the need of booster doses and might support the decisions in public health. Objective: The study aims to evaluate the immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) in a two-dose primary protocol in children and adolescent aging from 3 to 17 years old in Brazil. Methods: Participants were invited to participate in the research at two public healthcare centers located in Serrana (São Paulo) and Belo Horizonte (Minas Gerais), Brazil. Participants underwent medical interviews to gather their medical history, including COVID-19 history and medical records. Physical exams were conducted, including weight, blood pressure, temperature, and pulse rate measurements. Blood samples were obtained from the participants before vaccination, 1 month after the first dose, and 1, 3, and 6 months after the second dose and were followed by a virtual platform for monitoring post-vaccination reactions and symptoms of COVID-19. SARS-CoV-2 genome from Swab samples of COVID-19 positive individuals were sequenced by NGS. Total antibodies were measured by ELISA and neutralizing antibodies to B.1 lineage and Omicron variant (BA.1) quantified by PRNT and VNT. The cellular immune response was evaluated by flow cytometry by the quantification of systemic soluble immune mediators. Results: The follow-up of 640 participants showed that the CoronaVac vaccine (Sinovac/Butantan Institute) was able to significantly induce the production of total IgG antibodies to SARS-CoV-2 and the production of neutralizing antibodies to B.1 lineage and Omicron variant. In addition, a robust cellular immune response was observed with wide release of pro-inflammatory and regulatory mediators in the early post-immunization moments. Adverse events recorded so far have been mild and transient except for seven serious adverse events reported on VigiMed. Conclusions: The results indicate a robust and sustained immune response induced by the CoronaVac vaccine in children and adolescents up to six months, providing evidences to support the safety and immunogenicity of this effective immunizer.

Hypertension defined by the 2017 ACC/AHA guideline is more accurate than 2018 ESC/ESH for detecting early vascular aging in young adults.

ABSTRACT: Determine the most accurate diagnostic criteria of arterial hypertension (AH) for detecting early vascular aging (EVA) defined by pulse wave velocity (PWV) higher than ≥9.2 m/s.Cross-sectional study of a birth cohort started in 1978/79. The following data were collected between April 6, 2016 and August 31, 2017 from 1775 participants: demographic, anthropometric, office blood pressure (BP) measurement, biochemical risk factors, and PWV. A subsample of 454 participants underwent 24-hour ambulatory BP monitoring. The frequencies of AH, and BP phenotypes were calculated according to both guidelines. BP phenotypes (white-coat hypertension, masked hypertension (MHT), sustained hypertension (SH) and normotension) were correlated with risk factors and subclinical target organ damage after adjustment for confounders by multiple linear regression. Receiver operating characteristic curves were constructed to determine the best BP threshold for detecting EVA.A higher frequency of AH (45.1 vs 18.5%), as well as of SH (40.7 vs 14.8%) and MHT (28.9 vs 25.8%) was identified using the 2017 ACC/AHA criteria comparing with 2018 ESC/ESH. EVA was associated with the higher-risk BP phenotypes (SH and MHT, P < .0001) in both criteria. There was a higher accuracy in diagnosing EVA, with the 2017 ACC/AHA criteria. Analysis of the receiver operating characteristic curves showed office BP cutoff value (128/83 mm Hg) for EVA closer to the 2017 ACC/AHA threshold.The 2017 AHA/ACC guideline for the diagnosis of AH, and corresponding ambulatory BP monitoring values, is more accurate for discriminating young adults with EVA. Clinical application of PWV may help identify patients that could benefit from BP levels <130/80 mm Hg.

Antioxidant Effect of Standardized Extract of Propolis (EPP-AF®) in Healthy Volunteers: A "Before and After" Clinical Study.

BACKGROUND: Propolis is rich in polyphenols, especially flavonoids and phenolic acids, and has significant antioxidant activity, shown mainly in "in vitro" studies. OBJECTIVE: The aim of this study was to evaluate the antioxidant efficacy and safety of a standardized propolis extract in healthy volunteers. DESIGN: A two-phase sequential, open-label, nonrandomized, before and after clinical trial. METHODS: Healthy participants received two EPP-AF® doses (375 and 750 mg/d, P.O, tid) during 7 ± 2 days, starting with the lower doses. Immediately before starting EPP-AF® administration and at the end of each 7-day dosing schedule, blood and urine samples were collected for quantification of 8-OHDG (8-hydroxydeoxyguanosine) and 8-ISO (8-isoprostanes) in urine and GSH (reduced glutathione), GSSG (oxidized glutathione), SOD (superoxide dismutase), FRAP (Ferric Reducing Antioxidant Power), vitamin E, and MDA (malondialdehyde) in plasma. RESULTS: In our study, we had 34 healthy participants (67.7% women, 30 ± 8 years old, 97% white). The 8-ISO, a biomarker of lipid peroxidation, decreased with both doses of EPP-AF® compared to baseline (8-ISO, 1.1 (0.9-1.3) versus 0.85 (0.75-0.95) and 0.89 (0.74-1.0), ng/mg creatinine, P < 0.05, for 375 and 750 mg/d EPP-AF® doses versus baseline, mean and CI 95%, respectively). 8-OHDG, a biomarker of DNA oxidation, was also reduced compared to baseline with 750 mg/d doses (8-OHDG, 15.7 (13.2-18.1) versus 11.6 (10.2-13.0), baseline versus 750 mg/d, respectively, ng/mg creatinine, P < 0.05). Reduction of biomarkers of oxidative stress damage was accompanied by increased plasma SOD activity (68.8 (66.1-73.3) versus 78.2 (72.2-80.5) and 77.7 (74.1-82.6), %inhibition, P < 0.0001, 375 and 750 mg/d versus baseline, median and interquartile range 25-75%, respectively) and by increased GSH for 375 mg/d EPP-AF® doses (1.23 (1.06-1.34) versus 1.33 (1.06-1.47), µmol/L, P < 0.05). CONCLUSION: EPP-AF® reduced biomarkers of oxidative stress cell damage in healthy humans, with increased antioxidant enzymatic capacity, especially of SOD. This trial is registered with the Brazilian Registry of Clinical Trials (ReBEC, RBR-9zmfs9).