MicroRNA -21 expression as an auxiliary diagnostic biomarker of acute brucellosis.

BACKGROUND: This study aimed to measure the expression levels of peripheral blood miRNAs in brucellosis and their involvement in the different phases of the brucellosis. METHODS: The expression levels of miRNAs including miR-210, miR-155, miR-150, miR-146a, miR-139-3p, miR-125a-5p, miR-29 and miR-21 were quantified in 57 brucellosis patients subgrouped into acute, under treatment & relapse phase and 30 healthy controls (HCs) using real-time polymerase chain reaction (RT-PCR). The receiver operating characteristic (ROC) analysis curve analysis was performed to find a biomarker for discrimination of different phases of brucellosis. RESULTS: The expression of miR-155, miR-146a, miR-125a-5p, miR-29, and miR-21 was found to be elevated in the acute brucellosis patients compared to HCs. miR-29 changed in under-treatment patients, while miR-139-3p and miR-125a-5p showed alterations in relapse cases. The ROC curve analysis depicted the potential involvement of miR-21 in the pathogenesis of acute brucellosis. CONCLUSION: The expression level of miR-21 is significantly augmented in acute brucellosis and has the potential to be a contributing diagnostic factor for acute infection.

Investigation of antimicrobial resistance patterns and molecular typing of Pseudomonas aeruginosa isolates among Coronavirus disease-19 patients.

BACKGROUND: Pseudomonas aeruginosa is a common co-infecting pathogen recognized among COVID-19 patients. We aimed to investigate the antimicrobial resistance patterns and molecular typing of Pseudomonas aeruginosa isolates among Coronavirus disease-19 patients. METHODS: Between December 2020 and July 2021, 15 Pseudomonas aeruginosa were isolated from COVID-19 patients in the intensive care unit at Sina Hospital in Hamadan, west of Iran. The antimicrobial resistance of the isolates was determined by disk diffusion and broth microdilution methods. The double-disk synergy method, Modified Hodge test, and polymerase chain reaction were utilized to detect Pseudomonas aeruginosa extended spectrum beta-lactamase and carbapenemase producers. Microtiter plate assay was performed to evaluate the biofilm formation ability of the isolates. The isolates phylogenetic relatedness was revealed using the multilocus variable-number tandem-repeat analysis method. RESULTS: The results showed Pseudomonas aeruginosa isolates had the most elevated resistance to imipenem (93.3%), trimethoprim-sulfamethoxazole (93.3%), ceftriaxone (80%), ceftazidime (80%), gentamicin (60%), levofloxacin (60%), ciprofloxacin (60%), and cefepime (60%). In the broth microdilution method, 100%, 100%, 20%, and 13.3% of isolates showed resistance to imipenem, meropenem, polymyxin B, and colistin, respectively. Ten (66.6%) isolates were identified as multiple drug resistance. Carbapenemase enzymes and extended spectrum beta-lactamases were identified in 66.6% and 20% of the isolates, respectively and the biofilm formation was detected in 100% of the isolates. The blaOXA-48, blaTEM, blaIMP, blaSPM, blaPER, blaVEB, blaNDM, blaSHV, and blaCTX-M genes were detected in 100%, 86.6%, 86.6%, 40%, 20%, 20%, 13.3%, 6.6%, and 6.6% of the isolates, respectively. The blaVIM, blaGIM, blaGES, and blaMCR-1 genes were not identified in any of the isolates. The MLVA typing technique showed 11 types and seven main clusters and most isolates belong to cluster I, V and VII. CONCLUSION: Due to the high rate of antimicrobial resistance, as well as the genetic diversity of Pseudomonas aeruginosa isolates from COVID-19 patients, it is indispensable to monitor the antimicrobial resistance pattern and epidemiology of the isolates on a regular basis.

Circular RNAs in tuberculosis: From mechanism of action to potential diagnostic biomarker.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), continues to be a major global health concern. Understanding the molecular intricacies of TB pathogenesis is crucial for developing effective diagnostic and therapeutic approaches. Circular RNAs (circRNAs), a class of single-stranded RNA molecules characterized by covalently closed loops, have recently emerged as potential diagnostic biomarkers in various diseases. CircRNAs have been demonstrated to modulate the host's immunological responses against TB, specifically by reducing monocyte apoptosis, augmenting autophagy, and facilitating macrophage polarization. This review comprehensively explores the roles and mechanisms of circRNAs in TB pathogenesis. We also discuss the growing body of evidence supporting their utility as promising diagnostic biomarkers for TB. By bridging the gap between fundamental circRNA biology and TB diagnostics, this review offers insights into the exciting potential of circRNAs in combatting this infectious disease.

The quantity and quality of anti-SARS-CoV-2 antibodies show contrariwise association with COVID-19 severity: lessons learned from IgG avidity.

Gaining more appreciation on the protective/damaging aspects of anti-SARS-CoV-2 immunity associated with disease severity is of great importance. This study aimed to evaluate the avidity of serum IgG antibodies against SARS-CoV-2 spike (S) and nucleocapsid (N) in hospitalized symptomatic COVID-19 patients and asymptomatic RT-PCR-confirmed SARS-CoV-2 carriers as well as to compare antibody avidities with respect to vaccination status, vaccination dose and reinfection status. Serum levels of anti-S and anti-N IgG were determined using specific ELISA kits. Antibody avidity was determined by urea dissociation assay and expressed as avidity index (AI) value. Despite higher IgG levels in the symptomatic group, AI values of both anti-S and anti-N IgG were significantly lower in this group compared to asymptomatic individuals. In both groups, anti-S AI values were elevated in one-dose and two-dose vaccinees versus unvaccinated subjects, although significant differences were only detected in the symptomatic group. However, anti-N avidity showed no significant difference between the vaccinated and unvaccinated subgroups. Almost all vaccinated patients of different subgroups (based on vaccine type) had higher anti-S IgG avidity, while the statistical significance was detected only between those receiving Sinopharm compared to the unvaccinated subgroup. Also, statistically significant differences in antibody AIs were only found between primarily infected individuals of the two groups. Our findings indicate a key role for anti-SARS-CoV-2 IgG avidity in protection from symptomatic COVID-19 and calls for the incorporation of antibody avidity measurement into the current diagnostic tests to predict effective immunity toward SARS-CoV-2 infection or even for prognostic purposes.

Polymorphisms in vitamin D receptor genes and its relation with susceptibility to brucellosis: a case-control study.

OBJECTIVE: One of the systemic infections is Brucellosis which is caused by facultative intracellular bacteria of the genus Brucella. Vitamin D is a fat-soluble prohormone, that metabolizes enzymes and its intracellular receptor creates the active hormone and also mediate in responses of immune system. METHODS: Current research consists of 102 patients with brucellosis who were selected based on culture, PCR results serology, and clinical symptoms. The control group composed of 102 healthy people. The polymorphism of genes (Bsm I, Fok I, Taq I, Apa I) encoding Vitamin D receptor (VDR) were assessed by the PCR-RFLP method. RESULTS: The results showed that ff, tt, aa, and bb genotypes in Fok I, ApaI, TaqI, and BsmI were significant in case/control groups (P-value ≤ 0.0001). The genotype frequency AA in the control group is higher than that of the study group, while genotype frequency aa in the study group is more than the control. The odds ratio for brucellosis in individuals with ff genotype is 37 times higher than that of Ff genotype. Also, the odds ratio of brucellosis in individuals with genotype tt, aa, and bb was 12, 53, and 6 times higher than those of the Aa, Bb, and Tt genotypes. CONCLUSION: The genotypes aa and ff in the positions of the ApaI and FokI are of higher importance. The brucellosis risk in individuals accompanied aa genotype at Apa I is 53 times higher than that of the genotype AA, in other words, AA and BB, TT and FF genotypes are protective against the disease.

Comparison of the efficacy of equivalent doses of dexamethasone, methylprednisolone, and hydrocortisone for treatment of COVID-19-related acute respiratory distress syndrome: a prospective three-arm randomized clinical trial.

BACKGROUND: This prospective controlled clinical trial aimed to compare the efficacy of methylprednisolone, dexamethasone, and hydrocortisone at equivalent doses in patients with severe COVID-19. METHODS: In total, 106 patients with mild to moderate COVID-19-related acute respiratory distress syndrome (ARDS) were randomized to receive either dexamethasone (6 mg once a day), methylprednisolone (16 mg twice a day), or hydrocortisone (50 mg thrice a day) for up to 10 days. All participants received a standard of care for COVID-19. The primary and secondary efficacy outcomes included all-cause 28-day mortality, clinical status on day 28 assessed using the World Health Organization (WHO) eight-category ordinal clinical scale, number of patients requiring mechanical ventilation and intensive care unit (ICU) care, number of ventilator-free days, length of hospital and ICU stay, change in PaO2:FiO2 ratios during the first 5 days after treatment, and incidence of serious adverse events. P-values below 0.008 based on Bonferroni's multiple-testing correction method were considered statistically significant. RESULTS: According to the obtained results, there was a trend toward more favorable clinical outcomes in terms of needing mechanical ventilation and ICU care, number of ventilator-free days, change in PaO2:FiO2 ratios during the first 5 days after treatment, clinical status score at day 28, length of ICU and hospital stay, and overall 28-day mortality in patients receiving dexamethasone compared to those receiving methylprednisolone or hydrocortisone; however, likely due to the study's small sample size, the difference between groups reached a significant level only in the case of clinical status score on day 28 (p-value = 0.003). There was no significant difference in the incidence of serious adverse events between the study groups. CONCLUSION: Based on the results, severe cases of COVID-19 treated with dexamethasone might have a better clinical status at 28-day follow-up compared to methylprednisolone and hydrocortisone at an equivalent dose. Larger multicenter trials are required to confirm our findings.

Assessment of Association between miR-146a Polymorphisms and Expression of miR-146a, TRAF-6, and IRAK-1 Genes in Patients with Brucellosis.

BACKGROUND: Brucellosis is a major zoonosis all over the world. MicroRNAs are significant gene expression regulators and could be involved during the infections and also genetic alterations in the miRNAs sequence can affect primary miRNAs and precursor miRNAs processing and thus alter miRNAs expression. Current research studied the impact of the miR-146a polymorphism on miR-146a, TRAF-6, and IRAK-1 genes expression in patients with brucellosis illness. METHODS AND RESULTS: In this research, 25 patients with brucellosis and 25 healthy participants with determined genotypes for miR-SNP rs2910164 and miR-SNP rs57095329 were recruited. IRAK-1, TRAF-6, and miR-146a expressions in peripheral blood mononuclear cells (PBMCs) were specified by quantitative real- time PCR (qRT-PCR). Moreover, interleukin-1ß (IL-1ß) and tumor necrosis factor- alpha (TNF-α) serum levels were assessed by a sandwich enzyme-linked immunosorbent assay (ELISA) technique. There was no significant difference in the expression level of miR-146a, IRAK-1, and TRAF-6, among the patients with brucellosis and control group. TRAF-6 PBMCs expression levels in the distinctive genotypes of rs2910164 were significantly observed in patients (P = 0.048). No significant distinctions were found in miR-146a, IRAK-1, and TRAF-6 expression levels and among the rs57095329 different genotypes in brucellosis patients and controls. Meanwhile, no significant relationship was found between the rs2910164 and rs57095329 genotypes and the serum level of cytokines mentioned between the two groups. We did not find any association between expression of TRAF-6, miR-146a, and IRAK-1 in PBMCs, and cytokines serum levels with two single nucleotide polymorphisms (SNPs) in miR-146a. CONCLUSIONS: To the best of writers' knowledge, this research is the first one evaluating the probable link between the miR-146a rs2910164 and rs57095329 variant with miRNAs, relevant cytokine levels, and target genes in brucellosis.

The current therapeutical strategies in human brucellosis.

Prompt and adequate treatment of human brucellosis continues to be the most important strategy in its management, as eradication of animal brucellosis is not possible so far, and there is no adequate vaccine for humans. The goal of antibrucellar treatment is to alleviate and shorten the symptomatic period and reduce complications, relapses, and chronicity. Contemporary trends in the treatment of human brucellosis are postulated on the ability of Brucellae to persist in host macrophages through the inhibition of phagolysosome fusion and to survive for prolonged periods intracellularly without restricting basic cellular functions. As a result of this and despite satisfactory antibiotic treatment, relapses and therapeutical failures are inevitable to a certain degree. The current principles for the treatment of brucellosis advocate for a long enough treatment duration combined with antimicrobial regimens that possess activity in the intracellular acidic environment. In the future, other antimicrobial agents, immunomodulation, decrease in the intracellular acidic environment, or development of agents that would act on well-defined molecular bacterial targets, might be incorporated to improve the therapeutical effects.

Association between risk of brucellosis and genetic variations in MicroRNA-146a.

BACKGROUND: Single nucleotide polymorphisms (SNPs) are the most common types of DNA changes in the human genome that leading to phenotypic differences in humans. MicroRNAs (miRNAs) are usually affected by various bacterial infections, and they are involved in controlling the immune responses. MicroRNA-146a (miR-146a) plays an essential role in the development of infectious and inflammatory diseases. The aim of the present study was to investigate the association between risk of brucellosis and genetic variations in miR-146a. METHODS: This case-control study was conducted on 108 Brucellosis patients and 108 healthy controls. We genotyped two SNPs (rs2910164 and rs57095329) of the miR-146a using tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) and restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) methods. RESULTS: The rs2910164 SNP was significantly associated with brucellosis in co-dominant [OR = 4.27, 95% CI = (2.35-7.79, P = 0.001] and dominant [OR = 3.52, 95% CI = (1.97-6.30, P = 0.001] models. Co-dominant (P = 0.047) and recessive (P = 0.018) models were significant at position rs57095329 between the two groups of patient and healthy. The A C haplotype (rs2910164 and rs57095329) was associated with brucellosis in the assessed population [OR (95% CI) = 1.98 (1.22-3.20), P = 0.0059]. CONCLUSIONS: Consequently, our study demonstrated significant differences in genotype and haplotype frequencies of miR-146a variants between brucellosis patients and controls. Further studies on the larger sample sizes are required to verify the observed associations.

Predictors of death in patients with COVID-19: A cross-sectional study in West of Iran.

Background: Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a newly identified coronavirus. Our knowledge about the survival rate and prognostic factors of the disease is not established well. The purpose of this study was to evaluate the predictors of COVID-19 mortality in Hamadan province in western Iran. Methods: In this study, we included all laboratory-confirmed COVID-19 cases with known treatment outcomes in Hamadan province, Iran, between 20, 2020, to May 10, 2020. Demographic, clinical, laboratory data, and treatment outcomes were obtained from computerized medical records and compared between survived cases and patients with death outcomes. Univariable and multivariable logistic regression models were used to determine the predictors of death. Results: From 749 investigated patients, 77 patients (10.28%) died during the treatment. The Mean age of patients was 53.97±19.04 years. Multivariable logistic regression showed that males had 2.07 (95% CI: 1.73, 2.54) fold higher odds of death. Those with 60 years old and more had 6.49 (95% CI: 4.53, 7.93) fold higher odds of death. Patients with an underlying disease had 7.14 (95% CI: 6.94, 7.38) fold higher odds of death, and patients who were hospitalized in the ICU ward had 2.24 (95% CI: 1.75, 2.90) times higher odds of COVID-19 related mortality. Conclusion: The potential predictors of death in COVID-19 cases, including the male gender, older age, and having an underlying disease could help physicians to identify patients with poor prognoses at an early stage and better management of them.

Molecular typing of multi-drug resistant Acinetobacter baumannii isolates from clinical and environmental specimens in three Iranian hospitals by pulsed field gel electrophoresis.

BACKGROUND: Multi-drug resistant (MDR) Acinetobacter baumannii is one of the most important causes of nosocomial infections. The purpose of this study was to identify antibiotic resistance patterns, biofilm formation and the clonal relationship of clinical and environmental isolates of A. baumannii by Pulsed Field Gel Electrophoresis method. Forty-three clinical and 26 environmental isolates of the MDR A. baumannii were collected and recognized via API 20NE. Antibiotic resistance of the isolates was assessed by the disk diffusion method, and the biofilm formation test was done by the microtiter plate method. Pulsed Field Gel Electrophoresis (PFGE) was used to assess the genomic features of the bacterial isolates. RESULTS: The resistance rate of clinical and environmental isolates against antibiotics were from 95 to 100%. The difference in antibiotic resistance rates between clinical and environmental isolates was not statistically significant (p > 0.05). Biofilm production capabilities revealed that 31 (44.9%), and 30 (43.5%) isolates had strong and moderate biofilm producer activity, respectively. PFGE typing exhibited eight different clusters (A, B, C, D, E, F, G, and H) with two significant clusters included A and G with 21 (30.4%) and 16 (23.2%) members respectively, which comprises up to 53.6% of all isolates. There was no relationship between biofilm formation and antibiotic resistance patterns with PFGE pulsotypes. CONCLUSIONS: The results show that there is a close relationship between environmental and clinical isolates of A. baumannii. Cross-contamination is also very important that occurs through daily clinical activities between environmental and clinical isolates. Therefore, in order to reduce the clonal contamination of MDR A. baumannii environmental and clinical isolates, it is necessary to use strict infection control strategies.

Association of interleukin-17 gene polymorphisms and susceptibility to brucellosis in Hamadan, western Iran.

IL-17is one of the most important inflammatory cytokines that stimulate immunity responses in humans infected with Brucella species, acting as a regulator that reduces release of γ-IFN, thus increasing resistance to brucellosis. Gene polymorphisms in the regulatory regions of cytokine-encoding genes affect the amountsof cytokines produced and play a fundamental role in infectious diseases. The aim of this study was to determine the association between IL-17 gene polymorphisms and susceptibility to brucellosis. In this case-control study, 86 patients with brucellosis and 86 healthy persons in Hamadan, western Iran, from September 2014 to September 2016, were included. IL-17 genetic variants at positions rs4711998 A/G, rs8193036 C/T, rs3819024 A/G, rs2275913 A/G, rs3819025 A/G, rs8193038 A/G, rs3804513 A/T, rs1974226 A/G and rs3748067 A/G were analyzed by restriction fragment length polymorphism-PCR. Serum IL-17 titers were measured by sandwich ELISA. GG genotypes at positions rs4711998 and rs3748067 were present significantly more frequently in patients with brucellosis than in controls (P < 0.05). The AA genotype at positions rs4711998, rs2275913 and rs3748067 and GG genotype at position rs19744226 were present significantly more frequently in controls than in the patient group. These results suggest that the AA genotype at positions rs3748067, rs3819025 and rs4711998 and GG genotype at position rs3819024 are likely protective factors against brucellosis, whereas the GG genotype at positions rs3748067, rs3819025 and rs4711998 and AA genotype at position rs3819024 may be risk factors against the disease. No significant relationships were found between serum IL-17 titers and genotypes of the single-nucleotide polymorphisms.

Evaluation of the relationship between IL-12, IL-13 and TNF-α gene polymorphisms with the susceptibility to brucellosis: a case control study.

BACKGROUND: The cytokine gene polymorphism is important for the genetic susceptibility of infectious diseases. The aim of the present study was to investigate the relationship between TNF-α, IL-12, and IL-13 gene polymorphisms and predisposition to brucellosis. METHODS: In this study, 107 patients with brucellosis and 107 healthy individuals were evaluated. The SNPs of TNF-α)- 238 G/A) and IL-12 (+ 1188 A/C) were done by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and IL-13 genotyping at positions - 1512 (A/C) and - 1112 (C/T) were analysis by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) methods. IL-12, IL-13 and TNF-α serum levels were measured by a sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: IL-13 (-1512A/C) was associated with Brucellosis risk in dominant model (OR (95% CI) = 2.17 (1.02-4.62)), P-value = 0.041. However, there was no difference in allele and genotype frequencies of TNF-α)- 238 G/A), IL-12 (+ 1188 A/C) and IL-13 [- 1512 (A/C) and - 1112 (C/T)] between patients and controls. Serum levels of IL-12 and TNF-α were significantly more frequent in the patients than in the control groups. CONCLUSIONS: The IL-13 gene polymorphism can be used as a biomarker for detecting susceptibility to Brucella disease.

Highly synergistic activity of melittin with imipenem and colistin in biofilm inhibition against multidrug-resistant strong biofilm producer strains of Acinetobacter baumannii.

The rapid increase of drug resistance and failure of available antibiotics to treat biofilm-associated infections is of great health concern. Accordingly, our study aimed to evaluate the synergistic antibacterial, biofilm inhibitory, and biofilm removal activities of melittin in combination with colistin, imipenem, and ciprofloxacin against multidrug-resistant (MDR) strong biofilm producer Acinetobacter baumannii isolates. The kinetics of biofilm formation were evaluated for the isolates for 144 h. Minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), minimum biofilm inhibitory concentrations (MBICs), and biofilm removal activities for melittin and combinations with antibiotics were determined. Inhibition of biofilm-associated protein (bap) expression by melittin was evaluated with real-time polymerase chain reaction (PCR). Field emission scanning electron microscopy (FE-SEM) was used to visualize the effect of synergism on the inhibition of biofilm production. The geometric means of the fractional inhibitory concentration index (FICi) for melittin-colistin, melittin-imipenem, and melittin-ciprofloxacin combinations were calculated as 0.31, 0.24, and 0.94, respectively. Comparing the geometric means of the removal activity for melittin, colistin, imipenem, and combinations of them in both 6 and 24 h showed a significant difference between the groups (p-value < 0.05). Exposure to melittin induced a statistically significant downregulation of bap mRNA levels in all isolates at sub-MIC doses. Analysis of the FE-SEM results demonstrated that the synergism of melittin-colistin at 0.125-0.25 µg inhibited biofilm formation completely. In conclusion, our findings indicate that melittin possesses considerable potential for use in combination with colistin and imipenem to treat infections caused by MDR strong biofilm producer A. baumannii isolates.

Correlation between ability of biofilm formation with their responsible genes and MDR patterns in clinical and environmental Acinetobacter baumannii isolates.

Acinetobacter baumannii potential to form biofilm and exhibit multiple antibiotic resistances may be responsible in its survival in hospital environment. Accordingly, our study was aimed to determine the correlation between ability of biofilm formation and the frequency of biofilm related genes with antibiotic resistance phenotypes, and also the categorization of their patterns in clinical and environmental isolates. A total of 75 clinical and 32 environmental strains of the A. baumannii were collected and identified via API 20NE. Antibiotic susceptibility was evaluated by disk diffusion and microdilution broth methods. Biofilm formation assay was performed by microtiter plate method. OXA types and biofilm related genes including BlaOXA-51, BlaOXA-23, BlaOXA-24, BlaOXA-58, bap, blaPER-1, and ompA were amplified by PCR. The rate of MDR A. baumannii in clinical isolates (100%) was higher than environmental (81.2%) isolates (p < 0.05). Among 10 antibiotypes, the predominant resistance pattern in clinical and environmental isolates was antibiotypes I (85.3 and 78.1%, respectively). Analysis of the frequency of blaOXA-23 gene revealed a statistically significant difference between clinical (85.3%) and environmental (68.7%) isolates (p < 0.05). The prevalence of strong biofilm producers in clinical and environmental isolates were 31.2%-58.7%, respectively. In the clinical and environmental isolates, the frequencies of ompA, blaRER-1 and bap genes were 100%, 53.3%, 82.7% and 100%, 37.5%, 84.4% respectively. Statistical analysis revealed a significant correlation between the frequency of MDR isolates and biofilm formation ability (p = 0.008). The high frequency of antibiotype I would be indicated that an outbreak has been happened earlier and an endemic strain is currently being settled in the hospital environment. It would be suggested that if there was no difference in the frequency of pattern I and biofilm formation ability between clinical and environmental isolates, it is a critical point representing the higher risk of bacterial transmission from environment to the patients. The resulting data would be assisted in the improvement of disinfection strategies to better control of nosocomial infections. One dominant resistance pattern has shown among clinical and environmental isolates. The frequency of blaOXA-23 had significant difference between clinical and environmental isolates. The presence of bap gene in the A. baumannii isolates was associated with biofilm formation. There was a significant correlation between multiple drug resistance and biofilm formation. The clinical isolates had a higher ability to form strong biofilms compared to the environmental samples.

Comparing the Efficacy and Adverse Events of Available COVID-19 Vaccines Through Randomized Controlled Trials: Updated Systematic Review and Network Meta-analysis.

BACKGROUND: Different vaccines have so far been developed and approved to cope with COVID-19 in the world. The aim of this updated network meta-analysis (NMA) was to compare and rank all available vaccines in terms of efficacy and complications simultaneously. Study Design: A systematic review. METHODS: Three major international databases, including Web of Science, Medline via PubMed, and Scopus, were searched through September 2023. The transitivity assumption was evaluated qualitatively in terms of epidemiologic effect modifiers. The exposure of interest in this study was receiving any available COVID-19 vaccine, and the primary outcome of interest was the incidence of symptomatic COVID-19. In this NMA, the relative risk of symptomatic COVID-19 was used to summarize the efficacy of vaccines in preventing COVID-19. The data were analyzed using the frequentist-based approach, and the results were reported using a random-effects model. Finally, the vaccines were ranked using a P-score. RESULTS: In total, 34 randomized controlled trials (RCTs) met the eligibility criteria for this systematic review and NMA out of 3682 retrieved references. Based on the results of the NMA, mRNA-1273 was the most effective vaccine in preventing COVID-19 and demonstrated the highest P-score (0.93). The relative risk (RR) for mRNA-1273 versus placebo was 0.07 (95% confidence interval [CI]: 0.03, 0.17). The second and third-ranked vaccines were BNT-162b2 (RR=0.08; 95% CI: 0.04, 0.15; P-score=0.93) and Gam-COVID-Vac (0.09; 95% CI: 0.03, 0.25; 0.88). CONCLUSION: Based on the results of this NMA, it seems that all available vaccines were effective in COVID-19 prevention. However, the top three ranked vaccines were mRNA-1273, BNT-162b2, and Gam-COVID-Vac, respectively.

Assessing the Risk of Nephrotoxicity Associated with Aminoglycosides in Brucellosis Patients: A Cross-sectional Study.

OBJECTIVE: The purpose of this study was to investigate renal function in patients with brucellosis before and at the end of gentamicin therapy. To ensure the safety of therapeutic doses of gentamicin, renal functions in brucellosis patients were monitored regarding drug serum levels and check for early detection biomarkers of nephrotoxicity. METHODS: In this cross-sectional study, 41 patients (25 men and 16 women, aged over 15 years) were included, with confirmed acute brucellosis that referred to Brucellosis Research Center in Hamadan, west of Iran between March 2018 to February 2019. At baseline before treatment (first step) and 7 days after gentamicin administration (second step), serum uric acid, blood urea nitrogen (BUN), serum and urine creatinine, erythrocyte sedimentation rate (ESR), quantitative C-reactive protein (CRP) and urinary ß2-microglobulin (ß2M) were measured. Gentamycin serum level due to the highest risk of nephrotoxicity with this drug in aminoglycoside class was also checked by HPLC method. The data were analyzed using SPSS version 22. RESULTS: The mean urinary ß 2M level, serum and urinary creatinine, uric acid, BUN, and quantitative CRP levels in the first step and second step, there were no statistical differences between the two steps. There was a correlation between urinary creatinine and ESR. In addition, a positive correlation was found between urinary ß2M and serum gentamicin level. ESR levels have been significantly reduced in the patients after the treatment compared to before it. CONCLUSION: Our findings confirm that gentamicin is safe at the dose of 5 mg/kg/day for one week intravenously in brucellosis patients.

Evaluation of the Response Rates of Hospitals in the Prevention and Control of COVID-19 in Hamadan Province of Iran.

The COVID-19 pandemic has challenged the capacity of health systems in various countries. This study was designed to evaluate the response rates of hospitals in the prevention and control of COVID-19 in Hamadan province, Iran. In this cross-sectional study, all 20 hospitals in Hamadan province were monitored in February 2020. The instrument used in this study was the WHO checklist, entitled "Infection prevention and control health-care facility response for COVID-19." In each hospital, the hospital infection control officials completed the checklists under the supervision of the hospital managers and were then provided to the project manager. Data analyzed by SPSS 22 software. There were 3482 hospital beds (the average beds of each hospital was 174) in the studied hospitals. Of 15 055 patients admitted to all hospitals, 2196 (14.6%) individuals were COVID-19 patients. The total average score obtained from the checklist was 62.25. Among 7 domains studied, the lowest scores belonged to 2 domains of "infrastructure and equipment" and "patient screening and triage." The scores of domains "IPC programs" and "visitors" were significantly higher in hospitals with ICU beds than other hospitals (P-value = .03 in both domains). A comparison between university-teaching hospitals with other hospitals and those in Hamadan city with other cities revealed no significant differences in any of the domains. The mean response rate (62.25) of hospitals in terms of COVID-19 in Hamadan province indicates their relative readiness to prevent and control the COVID19 pandemic. The shortage of infrastructure and equipment and screening and triage problems of patients were the main challenges of hospitals in managing the COVID-19 pandemic in Hamadan province, Iran.

Efficacy and Safety of a Protein-Based SARS-CoV-2 Vaccine: A Randomized Clinical Trial.

Importance: The protein-based SARS-CoV-2 vaccines FINLAY-FR-2 (Soberana 02) and FINLAY-FR-1A (Soberana Plus) showed good safety and immunogenicity in phase 1 and 2 trials, but the clinical efficacy of the vaccine remains unknown. Objective: To evaluate the efficacy and safety of a 2-dose regimen of FINLAY-FR-2 (cohort 1) and a 3-dose regimen of FINLAY-FR-2 with FINLAY-FR-1A (cohort 2) in Iranian adults. Design, Setting, and Participants: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial was conducted at 6 cities in cohort 1 and 2 cities in cohort 2. Participants included individuals aged 18 to 80 years without uncontrolled comorbidities, coagulation disorders, pregnancy or breastfeeding, recent immunoglobulin or immunosuppressive therapy, and clinical presentation or laboratory-confirmed COVID-19 on enrollment. The study was conducted from April 26 to September 25, 2021. Interventions: In cohort 1, 2 doses of FINLAY-FR-2 (n = 13 857) or placebo (n = 3462) were administered 28 days apart. In cohort 2, 2 doses of FINLAY-FR-2 plus 1 dose of FINLAY-FR-1A (n = 4340) or 3 placebo doses (n = 1081) were administered 28 days apart. Vaccinations were administered via intramuscular injection. Main Outcomes and Measures: The primary outcome was polymerase chain reaction-confirmed symptomatic COVID-19 infection at least 14 days after vaccination completion. Other outcomes were adverse events and severe COVID-19. Intention-to-treat analysis was performed. Results: In cohort 1 a total 17 319 individuals received 2 doses and in cohort 2 5521 received 3 doses of the vaccine or placebo. Cohort 1 comprised 60.1% men in the vaccine group and 59.1% men in the placebo group; cohort 2 included 59.8% men in the vaccine group and 59.9% in the placebo group. The mean (SD) age was 39.3 (11.9) years in cohort 1 and 39.7 (12.0) years in cohort 2, with no significant difference between the vaccine and placebo groups. The median follow-up time in cohort 1 was 100 (IQR, 96-106) days and, in cohort 2, 142 (137-148) days. In cohort 1, 461 (3.2%) cases of COVID-19 occurred in the vaccine group and 221 (6.1%) in the placebo group (vaccine efficacy: 49.7%; 95% CI, 40.8%-57.3%) vs 75 (1.6%) and 51 (4.3%) in cohort 2 (vaccine efficacy: 64.9%; 95% CI, 49.7%-59.5%). The incidence of serious adverse events was lower than 0.1%, with no vaccine-related deaths. Conclusions and Relevance: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of the efficacy and safety of FINLAY-FR-2 and FINLAY-FR-1A, 2 doses of FINLAY-FR-2 plus the third dose of FINLAY-FR-1A showed acceptable vaccine efficacy against symptomatic COVID-19 as well as COVID-19-related severe infections. Vaccination was generally safe and well tolerated. Therefore, Soberana may have utility as an option for mass vaccination of the population, especially in resource-limited settings, because of its storage condition and affordable price. Trial Registration: isrctn.org Identifier: IRCT20210303050558N1.

Implementation of an In-House Platform for Rapid Screening of SARS-CoV-2 Genome Variations.

BACKGROUND: Global real-time monitoring of SARS-CoV-2 variants is crucial to controlling the COVID-19 outbreak. The purpose of this study was to set up a Sanger-based platform for massive SARS-CoV-2 variant tracking in laboratories in low-resource settings. METHODS: We used nested RT-PCR assay, Sanger sequencing and lineage assignment for 930-bp of the SARS-CoV-2 spike gene, which harbors specific variants of concern (VOCs) mutations. We set up our platform by comparing its results with whole genome sequencing (WGS) data on 137 SARS-CoV-2 positive samples. Then, we applied it on 1028 samples from March-September 2021. RESULTS: In total, 125 out of 137 samples showed 91.24% concordance in mutation detection. In lineage assignment, 123 out of 137 samples demonstrated 89.78% concordance, 65 of which were assigned as VOCs and showed 100% concordance. Of 1028 samples screened by our in-house method, 78 distinct mutations were detected. The most common mutations were: S:D614G (21.91%), S:P681R (12.19%), S:L452R (12.15%), S:T478K (12.15%), S:N501Y (8.91%), S:A570D (8.89%), S:P681H (8.89%), S:T716I (8.74%), S:L699I (3.50%) and S:S477N (0.28%). Of 1028 samples, 980 were attributed as VOCs, which include the Delta (B.1.617.2) and Alpha (B.1.1.7) variants. CONCLUSION: Our proposed in-house Sanger-based assay for SARS-CoV-2 lineage assignment is an accessible strategy in countries with poor infrastructure facilities. It can be applied in the rapid tracking of SARS-CoV-2 VOCs in the SARS-CoV-2 pandemic.