Safety and immunogenicity of influenza A(H3N2) component vaccine in juvenile systemic lupus erythematosus

Abstract Introduction Seasonal influenza A (H3N2) virus is an important cause of morbidity and mortality in the last 50 years in population that is greater than the impact of H1N1. Data assessing immunogenicity and safety of this virus component in juvenile systemic lupus erythematosus (JSLE) is lacking in the literature. Objective To evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in JSLE. Methods 24 consecutive JSLE patients and 29 healthy controls (HC) were vaccinated with influenza A/Singapore/ INFIMH-16-0019/2016(H3N2)-like virus. Influenza A (H3N2) seroprotection (SP), seroconversion (SC), geometric mean titers (GMT), factor increase in GMT (FI-GMT) titers were assessed before and 4 weeks post-vaccination. Disease activity, therapies and adverse events (AE) were also evaluated. Results JSLE patients and controls were comparable in current age [14.5 (10.1-18.3) vs. 14 (9-18.4) years, p = 0.448] and female sex [21 (87.5%) vs. 19 (65.5%), p = 0.108]. Before vaccination, JSLE and HC had comparable SP rates [22 (91.7%) vs. 25 (86.2%), p = 0.678] and GMT titers [102.3 (95% CI 75.0-139.4) vs. 109.6 (95% CI 68.2-176.2), p = 0.231]. At D30, JSLE and HC had similar immune response, since no differences were observed in SP [24 (100%) vs. 28 (96.6%), p = 1.000)], SC [4 (16.7%) vs. 9 (31.0%), p = 0.338), GMT [162.3 (132.9-198.3) vs. 208.1 (150.5-287.8), p = 0.143] and factor increase in GMT [1.6 (1.2-2.1) vs. 1.9 (1.4-2.5), p = 0.574]. SLEDAI-2K scores [2 (0-17) vs. 2 (0-17), p = 0.765] and therapies remained stable throughout the study. Further analysis of possible factors influencing vaccine immune response among JSLE patients demonstrated similar GMT between patients with SLEDAI < 4 compared to SLEDAI ≥ 4 ( p = 0.713), as well as between patients with and without current use of prednisone ( p = 0.420), azathioprine ( p = 1.0), mycophenolate mofetil ( p = 0.185), and methotrexate ( p = 0.095). No serious AE were reported in both groups and most of them were asymptomatic (58.3% vs. 44.8%, p = 0.958). Local and systemic AE were alike in both groups ( p > 0.05). Conclusion This is the first study that identified adequate immune protection against H3N2-influenza strain with additional vaccine-induced increment of immune response and an adequate safety profile in JSLE. ( www.clinicaltrials.gov , NCT03540823).

Inflammasome Genetic Variants Are Associated with Protection to Clinical Severity of COVID-19 among Patients from Rio de Janeiro, Brazil.

COVID-19 has a broad spectrum of clinical manifestations, from asymptomatic or mild/moderate symptoms to severe symptoms and death. The mechanisms underlying its clinical evolution are still unclear. Upon SARS-CoV-2 infection, host factors, such as the inflammasome system, are activated by the presence of the virus inside host cells. The search for COVID-19 risk factors is of relevance for clinical management. In this study, we investigated the impact of inflammasome single-nucleotide polymorphisms (SNPs) in SARS-CoV-2-infected individuals with distinct severity profiles at clinical presentation. Patients were divided into two groups according to disease severity at clinical presentation based on the WHO Clinical Progression Scale. Group 1 included patients with mild/moderate disease (WHO < 6; n = 76), and group 2 included patients with severe/critical COVID-19 (WHO ≥ 6; n = 357). Inpatients with moderate to severe/critical profiles were recruited and followed-up at Hospital Center for COVID-19 Pandemic - National Institute of Infectology (INI)/FIOCRUZ, RJ, Brazil, from June 2020 to March 2021. Patients with mild disease were recruited at Oswaldo Cruz Institute (IOC)/FIOCRUZ, RJ, Brazil, in August 2020. Genotyping of 11 inflammasome SNPs was determined by real-time PCR. Protection and risk estimation were performed using unconditional logistic regression models. Significant differences in NLRP3 rs1539019 and CARD8 rs2043211 were observed between the two groups. Protection against disease severity was associated with the A/A genotype (ORadj = 0.36; P = 0.032), allele A (ORadj = 0.93; P = 0.010), or carrier-A (ORadj = 0.45; P = 0.027) in the NLRP3 rs1539019 polymorphism; A/T genotype (ORadj = 0.5; P = 0.045), allele T (ORadj = 0.93; P = 0.018), or carrier-T (ORadj = 0.48; P = 0.029) in the CARD8 rs2043211 polymorphism; and the A-C-G-C-C (ORadj = 0.11; P = 0.018), A-C-G-C-G (ORadj = 0.23; P = 0.003), C-C-G-C-C (ORadj = 0.37; P = 0.021), and C-T-G-A-C (ORadj = 0.04; P = 0.0473) in NLRP3 genetic haplotype variants. No significant associations were observed for the other polymorphisms. To the best of our knowledge, this is the first study demonstrating an association between CARD8 and NLRP3 inflammasome genetic variants and protection against COVID-19 severity, contributing to the discussion of the impact of inflammasomes on COVID-19 outcomes.

The influence of the marine Bacillus cereus over carbon steel, stainless corrosion, and copper coupons.

The present study evaluated the influence of the marine bacteria Bacillus cereus Mc-1 on the corrosion of 1020 carbon steel, 316L stainless steel, and copper alloy. The Mc-1 strain was grown in a modified ammoniacal citrate culture medium (CFA.ico-), CFA.ico- with sodium nitrate supplementation (NO3-), and CFA.ico- with sodium chloride supplementation (NaCl). The mass loss and corrosion rate were evaluated after the periods of 7, 15, and 30 days. The results showed that in CFA.ico- and CFA.ico- medium added NO3- the corrosion rates of carbon steel and copper alloy were high when compared to the control. Whereas the medium was supplemented with NaCl, despite the rates being above the averages of the control system, they were considerably below the previous results. In general, the corrosion rates induced by Mc-1 on 316L coupons were below the results compared to carbon steel and copper alloy. When analyzing the corrosion rate measurements, regardless of the culture medium, the corrosion levels decreased consistently after 15 days, being below the levels evaluated after 7 days of the experiment. Our analyses suggest that B. cereus Mc-1 has different influences on corrosion in different metals and environmental conditions, such as the presence of NO3- and NaCl. These results can help to better understand the influence of this bacteria genus on the corrosion of metals in marine environments.

Marine bacterial community analysis on 316L stainless steel coupons by Illumina MiSeq sequencing.

In order to evaluate the corrosive action of microorganisms on 316L metal exposed directly to a marine environment, a system was designed to immerse coupons in seawater. After periods of 30, 60 and 90 days, the coupons were recovered, the corrosion rates evaluated and the biofilm samples on their surface were analyzed by 16S rRNA gene sequencing. The results of the corrosion rate showed an acceleration over the entire experimental period. Alpha diversity measurements showed higher rates after 60 days of the experiment, while abundance measurements showed higher rates after 90 days of exposure to the marine environment. The beta-diversity results showed a clear separation between the three conditions and proximity in the indices between replicates of the same experimental condition. The results of 16S rRNA gene sequencing showed that after 30 days of exposure to seawater, there was massive representativeness of the pioneer bacteria, Gamma and Alphaproteobacteria, with emphasis on the genera Alcanivorax, Oceanospirillum and Shewanella. At the 60-day analysis, the Gammaproteobacteria class remained dominant, followed by Alphaproteobacteria and Flavobacteria, and the main representatives were Flexibacter and Pseudoalteromonas. In the last analysis, after 90 days, a change in the described bacterial community profile was observed. The Gammaproteobacteria class was still the largest in diversity and OTUs. The most predominant genera in number of OTUs were Alteromonas, Bacteriovorax and, Nautella. Our results describe a change in the microbial community over coupons directly exposed to the marine environment, suggesting a redirection to the formation of a mature biofilm. The conditions created by the biofilm structure suggest said condition favor biocorrosion on the analyzed coupons.

The influence of surface microbial diversity and succession on microbiologically influenced corrosion of steel in a simulated marine environment.

To explore how a succession of bacteria grown on steel coupons in a marine environment can influence their corrosion process, we designed a microcosm in laboratory to evaluate corrosion kinetics and microbial diversity over 30 days. The results described a clear influence of corrosion by a succession of different bacterial groups. During the initial period, 2-7 days, a sharp increase in the rate of corrosion was detected accompanied by the presence of Alteromonadaceae, Vibrionaceae, Oceanospirillaceae, Rhodobacteraceae, Rhodospirillaceae and Flavobacteriaceae bacteria families. After 15 days, representatives of families Piscirickettsiaceae and Pseudomonadaceae were also described, accompanied by a continuous corrosion process over the coupons. After 30 days, there was a sudden change in the profile of the bacteria present on the steel coupons, with a prevalence of Halomonadaceae family species, and establishment and continuity of the corrosion process by the biofilm grown on the coupons. The results describe differences in microbial diversity over the time, highlighting certain bacterial lithotrophic species that persisted for most of the experiment, through a complex association between bacteria and metal surfaces, which can be a new starting point for development and maintenance of a favorable microenvironment to accelerate corrosion processes.