Clinical, immunological, and microbiological analysis of the association between periodontitis and COVID-19: a case-control study.

PURPOSE: Periodontitis and coronavirus disease (COVID-19) share risk factors and activate similar immunopathological pathways, intensifying systemic inflammation. This study investigated the clinical, immunological and microbiological parameters in individuals with COVID-19 and controls, exploring whether periodontitis-driven inflammation contributes to worsening COVID-19 endpoints. METHODS: Case (positive RT-PCR for SARS-CoV-2) and control (negative RT-PCR) individuals underwent clinical and periodontal assessments. Salivary levels of TNF-α, IL-6, IL-1ß, IL-10, OPG, RANKL, neutrophil extracellular traps, and subgingival biofilm were analyzed at two timepoints. Data on COVID-19-related outcomes and comorbidity information were evaluated from medical records. RESULTS: Ninety-nine cases of COVID-19 and 182 controls were included for analysis. Periodontitis was associated with more hospitalization (p = 0.009), more days in the intensive care unit (ICU) (p = 0.042), admission to the semi-ICU (p = 0.047), and greater need for oxygen therapy (p = 0.042). After adjustment for confounders, periodontitis resulted in a 1.13-fold increase in the chance of hospitalization. Salivary IL-6 levels (p = 0.010) were increased in individuals with COVID-19 and periodontitis. Periodontitis was associated with increased RANKL and IL-1ß after COVID-19. No significant changes were observed in the bacterial loads of the periodontopathogens Porphyromona gingivalis, Aggregatibacter actinomycetemcomitans, Tanerella forsythia, and Treponema denticola. CONCLUSIONS: Periodontitis was associated with worse COVID-19 outcomes, suggesting the relevance of periodontal care to reduce the burden of overall inflammation. Understanding the crosstalk between SARS-CoV-2 infection and chronic conditions such as periodontitis that can influence disease outcome is important to potentially prevent complications of COVID-19.

Can SARS-CoV-2 screening in oral biopsies aid epidemiological surveillance?

BACKGROUND: Three years after the first confirmed COVID-19 case in Brazil, the outcomes of Federal government omissions in managing the crisis and anti-science stance heading into the pandemic have become even more evident. With over 36 million confirmed cases and nearly 700 000 deaths up to January 2023, the country is one of the hardest-hit places in the world. The lack of mass-testing programs was a critical broken pillar responsible for the quick and uncontrolled SARS-CoV-2 spread throughout the Brazilian population. Faced with this situation, we aimed to perform the routine SARS-CoV-2 screening through RT-qPCR of oral biopsies samples to aid in the asymptomatic epidemiological surveillance during the principal outbreak periods. METHODS: We analyzed 649 formalin-fixed paraffin-embedded oral tissue samples from five important oral and maxillofacial pathology laboratories from the north, northeast, and southeast geographic regions of Brazil. We also sequenced the whole viral genome of positive cases to investigate SARS-CoV-2 variants. RESULTS: The virus was detected in 9/649 analyzed samples, of which three harbored the Variant of Concern Alpha (B.1.1.7). CONCLUSION: Although our approach did not value aiding asymptomatic epidemiological surveillance, we could successfully identify a using FFPE tissue samples. Therefore, we suggest using FFPE tissue samples from patients who have confirmed diagnosis of SARS-CoV-2 infection for phylogenetic reconstruction and contraindicate the routine laboratory screening of these samples as a tool for asymptomatic epidemiological surveillance.

Indian food habit & food ingredients may have a role in lowering the severity & high death rate from COVID-19 in Indians: findings from the first nutrigenomic analysis.

Background & objectives: During the COVID-19 pandemic, the death rate was reportedly 5-8 fold lower in India which is densely populated as compared to less populated western countries. The aim of this study was to investigate whether dietary habits were associated with the variations in COVID-19 severity and deaths between western and Indian population at the nutrigenomics level. Methods: In this study nutrigenomics approach was applied. Blood transcriptome of severe COVID-19 patients from three western countries (showing high fatality) and two datasets from Indian patients were used. Gene set enrichment analyses were performed for pathways, metabolites, nutrients, etc., and compared for western and Indian samples to identify the food- and nutrient-related factors, which may be associated with COVID-19 severity. Data on the daily consumption of twelve key food components across four countries were collected and a correlation between nutrigenomics analyses and per capita daily dietary intake was investigated. Results: Distinct dietary habits of Indians were observed, which may be associated with low death rate from COVID-19. Increased consumption of red meat, dairy products and processed foods by western populations may increase the severity and death rate by activating cytokine storm-related pathways, intussusceptive angiogenesis, hypercapnia and enhancing blood glucose levels due to high contents of sphingolipids, palmitic acid and byproducts such as CO2 and lipopolysaccharide (LPS). Palmitic acid also induces ACE2 expression and increases the infection rate. Coffee and alcohol that are highly consumed in western countries may increase the severity and death rates from COVID-19 by deregulating blood iron, zinc and triglyceride levels. The components of Indian diets maintain high iron and zinc concentrations in blood and rich fibre in their foods may prevent CO2 and LPS-mediated COVID-19 severity. Regular consumption of tea by Indians maintains high high-density lipoprotein (HDL) and low triglyceride in blood as catechins in tea act as natural atorvastatin. Importantly, regular consumption of turmeric in daily food by Indians maintains strong immunity and curcumin in turmeric may prevent pathways and mechanisms associated with SARS-CoV-2 infection and COVID-19 severity and lowered the death rate. Interpretation & conclusions: Our results suggest that Indian food components suppress cytokine storm and various other severity related pathways of COVID-19 and may have a role in lowering severity and death rates from COVID-19 in India as compared to western populations. However, large multi-centered case-control studies are required to support our current findings.

Association of 3p21.31 Locus (CXCR6 and LZTFL1) with COVID-19 Outcomes in Brazilian Hospitalyzed Subjects.

The 3p21.31 locus has been associated with severe COVID-19 prognosis in GWAS studies. Here, we evaluated whether three polymorphisms (LZTFL1 rs10490770, CXCR6 rs2234355 and rs2234358) in the reported locus were associated with the need for mechanical ventilation, hospitalization length and death in 102 COVID-19 hospitalized Brazilian subjects. No genetic association was found with the need for mechanical ventilation and hospitalization length. CXCR6 rs2234355 was associated with mortality under the codominance model, with carriers of the A/A genotype having a greater chance of death than A/G (OR: 10.5; 95% CI: 1.55-70.76). Our results further suggest that the CXCR6 genetic variant contributes to COVID-19 outcomes.

Does cell phone use increase the chances of parotid gland tumor development? A systematic review and meta-analysis.

BACKGROUND: Prior epidemiological studies had examined the association between cell phone use and the development of tumors in the parotid glands. However, there is no consensus about the question of whether cell phone use is associated with increased risk of tumors in the parotid glands. We performed a meta-analysis to evaluate the existing literature about the mean question and to determine their statistical significance. METHODS: Primary association studies. Papers that associated cell phone use and parotid gland tumors development were included, with no restrictions regarding publication date, language, and place of publication. Systematic literature search using PubMed, SciELO and Embase followed by meta-analysis. RESULTS AND CONCLUSION: Initial screening included 37 articles, and three were included in meta-analysis. Using three independent samples including 5087 subjects from retrospective case-control studies, cell phone use seems to be associated with greater odds (1.28, 95%- confidence interval: 1.09-1.51) to develop salivary gland tumor. Results should be read with caution due to the limited number of studies available and their retrospective design.

Cohesin subunits, STAG1 and STAG2, and cohesin regulatory factor, PDS5b, in oral squamous cells carcinomas.

BACKGROUND: Cohesin complex is responsible for sister chromatid cohesion. STAG1/STAG2 is part of the complex, which is regulated by PDS5B. Alterations in these genes were described in tumors. PDS5B is a negative regulator of cell proliferation. We aimed to assess molecular alterations in these genes in oral squamous cell carcinoma (OSCC) and predict their expression by the expression of 84 cell cycle genes. In addition, we investigated whether pds5b protein expression impacted ki-67 and p53 immunopositivity. METHODS: We assessed loss of heterozygosity (LOH) at STAG1 and STAG2 loci in 15 OSCC using three polymorphic markers. Associations between the immunoexpression of pds5b and ki-67 and p53 were tested in 62 samples. Differences between transcriptional levels of STAG1, STAG2, and PDS5B between OSCC and normal oral mucosa (NM) were evaluated by qPCR. An 84 cell cycle genes qPCR array was carried with OSCC samples, and STAG1, STAG2, and PDS5B were independently used as response variables in multiple linear regression models. RESULTS: Loss of heterozygosity in at least one marker was observed in three samples. pds5b, p53, and ki-67 were highly expressed, and no association was found between pds5b immunoexpression and ki-67 or p53 (P > 0.05). OSCC and NM showed similar transcriptional levels of STAG1, STAG2, and PDS5B. STAG1 and CUL3 expression seem to be related (P = 0.004). CONCLUSIONS: There is LOH at STAG1 and STAG2 loci in OSCC, but OSCC and NM showed similar transcriptional levels of STAG1, STAG2, and PDS5B. pds5b immunoexpression in OSCC was high, but it was not associated with proliferation cell index.

Cell phone use is associated with an inflammatory cytokine profile of parotid gland saliva.

BACKGROUND: There is controversy on the effects of the non-ionizing radiation emitted by cell phones on cellular processes and the impact of such radiation exposure on health. The purpose of this study was to investigate whether cell phone use alters cytokine expression in the saliva produced by the parotid glands. METHODS: Cytokine expression profile was determined by enzyme linked immuno sorbent assay (ELISA) in the saliva produced by the parotid glands in healthy volunteers, and correlated with self-reported cell phone use and laterality. RESULTS: The following parameters were determined, in 83 Brazilian individuals in saliva produced by the parotid glands comparing the saliva from the gland exposed to cell phone radiation (ipsilateral) to that from the contralateral parotid: salivary flow, total protein concentration, interleukin 1 ß (IL-1 ß), interleukin 6 (IL-6), interleukin 10 (IL-10), interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α) salivary levels by ELISA. After multiple testing correction, decreased IL-10 and increased IL-1ß salivary levels in the ipsilateral side compared with the contralateral side (P < 0.05) were detected. Subjects who used cell phones for more than 10 years presented higher differences between IL-10 levels in ipsilateral versus contralateral parotids (P = 0.0012). No difference was observed in any of the tested parameters in correlation with cell phone monthly usage in minutes. CONCLUSION: The exposure of parotid glands to cell phones can alter salivary IL-10 and IL-1ß levels, consistent with a pro-inflammatory microenvironment that may be related to heat production.

Association between DCHS2 gene and mild cognitive impairment and Alzheimer's disease in an elderly Brazilian sample.

OBJECTIVES: In 2012, Kamboh and colleagues published a genome-wide association study that identified the DCHS2 gene (rs1466662 T/A) influencing the age at onset of Alzheimer's disease (AD). We aimed to investigate if there is association between the DCHS2 gene and amnestic mild cognitive impairment (aMCI) and AD in a sample of the Brazilian population. METHODS: 143 controls, 79 aMCI and 299 AD patients were selected and submitted to the same protocol of tests. Genotyping was performed using the Real Time PCR RESULTS: Amnestic MCI patients showed a higher prevalence of AA than controls and a lower frequency of TT when compared with controls. We also stratified the sample according to the APOE ε4 status. No difference in DCHS2 genotype or allelic frequency occurred in the APOE ε4 allele carrier subgroup. Amnestic MCI patients showed a higher frequency of AA genotype and a lower frequency of TA and TT when compared with controls in APOE ε4 allele non-carrier subgroup. The allelic distribution followed the same pattern. In AD group, we observed a significant difference with a higher A allelic frequency in AD in this subgroup. A multiple logistic regression demonstrated that in APOE ε4 non-carriers, allele rs1466662 was associated to aMCI group. Different variables were associated with aMCI and AD according to APOE ε4 status in our sample. Low level of education was associated with AD, while diabetes mellitus type 2 was associated with aMCI. Copyright © 2016 John Wiley & Sons, Ltd. CONCLUSIONS: Our findings suggest a possible role for DCHS2 gene in aMCI and AD.

Lip cancer and pre-cancerous lesions harbor TP53 mutations, exhibit allelic loss at 9p, 9q, and 17p, but no BRAFV600E mutations.

Molecular mechanisms of lip squamous cell carcinoma (LSCC) and actinic cheilitis (AC) are unclear. We aimed at assessing loss of heterozygosity (LOH) and TP53 and BRAF V600E mutations in these lesions. Formalin-fixed paraffin-embedded (FFPE) samples of 17 LSCC and 16 AC were included, with additional 5 fresh LSCC genotyped for TP53 mutations. LOH was assessed by six polymorphic markers located at 9p22, 9q22, and 17p13 and correlated with cell proliferation (Ki-67) and P53 immunostaining. Direct sequencing of TP53 exons 2-11 (fresh samples), and exons 5-9 (FFPE samples) was carried out. BRAF V600E mutation was genotyped in eight LSCC. LOH occurred in at least one marker in 15/17 LSCC and in 9/16 AC. The marker exhibiting the highest frequency of allelic loss (FAL) in LSCC was D9S157 (8/12 informative cases) and D9S287 in AC (4/11 informative cases). Cell proliferation was not correlated with LOH or with the FAL and no correlation between P53 IHC and 17p LOH was observed. We found TP53 missense mutations in both lesions and nonsense in LSCC, including CC>TT transition, which is a marker of UV damage. BRAF V600E mutation was not detected. LOH and TP53 mutations detected in LSCC and AC may be associated with tumorigenesis, whereas BRAF V600E mutation does not seem to significantly contribute to LSCC pathogenesis.

Evaluation of clinical and genetic factors in obstructive sleep apnoea.

Purpose: To evaluate the correlation between several presumed candidate genes for obstructive sleep apnoea (OSA) and clinical OSA phenotypes and propose a predictive comprehensive model for diagnosis of OSA. Methods: This case-control study compared polysomnographic patterns, clinical data, morbidities, dental factors and genetic data for polymorphisms in PER3, BDNF, NRXN3, APOE, HCRTR2, MC4R between confirmed OSA cases and ethnically matched clinically unaffected controls. A logistic regression model was developed to predict OSA using the combined data. Results: The cohort consisted of 161 OSA cases and 81 controls. Mean age of cases was 53.5 ± 14.0 years, mostly males (57%) and mean body mass index (BMI) of 27.5 ± 4.3 kg/m2. None of the genotyped markers showed a statistically significant association with OSA after adjusting for age and BMI. A predictive algorithm included the variables gender, age, snoring, hypertension, mouth breathing and number of T alleles of PER3 (rs228729) presenting 76.5% specificity and 71.6% sensitivity. Conclusions: No genetic variant tested showed a statistically significant association with OSA phenotype. Logistic regression analysis resulted in a predictive model for diagnosing OSA that, if validated by larger prospective studies, could be applied clinically to allow risk stratification for OSA.

Influence of polymorphisms in CYP2C9, VKORC1, MDR1 and APOE genes on the warfarin maintenance dose in Brazilian patients.

Background: Polymorphisms in the CYP2C9, VKORC1, MDR1 and APOE genes may impact warfarin dose. Aim: To investigate the influence of sociodemographic, clinical factors and polymorphisms *1, *2 and *3 for CYP2C9, -1639G>A for VKORC1, 3435C>T for MDR1, and ϵ2, ϵ3 and ϵ4 for APOE genes on the mean weekly warfarin maintenance dose in adults. Methods: This cross-sectional study recruited a calculated sample of 315 patients in three anticoagulation clinics in Brazil. A model containing the variables significantly associated with warfarin dose was estimated. Results: The mean age of patients was 64.1 ± 13.1 years, with 173 (54.9%) women. Age, use of amiodarone, genotype VKORC1 GA, genotype VKORC1 AA, genotypes CYP2C9*1/*2 or *1/*3 and genotypes CYP2C9*2/*2 or *2/*3 or *3/*3 were associated with a reduced warfarin dose. Conclusion: This study pointed out factors that could impact the management of oral anticoagulation.

Epidemiological Surveillance Reveals the Rise and Establishment of the Omicron SARS-CoV-2 Variant in Brazil.

The introduction of SARS-CoV-2 variants of concern (VOCs) in Brazil has been associated with major impacts on the epidemiological and public health scenario. In this study, 291,571 samples were investigated for SARS-CoV-2 variants from August 2021 to March 2022 (the highest peak of positive cases) in four geographical regions of Brazil. To identify the frequency, introduction, and dispersion of SARS-CoV-2 variants in 12 Brazilian capitals, VOCs defining spike mutations were identified in 35,735 samples through genotyping and viral genome sequencing. Omicron VOC was detected in late November 2021 and replaced the Delta VOC in approximately 3.5 weeks. We estimated viral load differences between SARS-CoV-2 Delta and Omicron through the evaluation of the RT-qPCR cycle threshold (Ct) score in 77,262 samples. The analysis demonstrated that the Omicron VOC has a lower viral load in infected patients than the Delta VOC. Analyses of clinical outcomes in 17,586 patients across the country indicated that individuals infected with Omicron were less likely to need ventilatory support. The results of our study reinforce the importance of surveillance programs at the national level and showed the introduction and faster dispersion of Omicron over Delta VOC in Brazil without increasing the numbers of severe cases of COVID-19.

Botulinum toxin for vaginismus treatment.

BACKGROUND/AIMS: Vaginismus is characterized by recurrent or persistent involuntary contraction of the perineal muscles surrounding the outer third of the vagina when penile, finger, tampon, or speculum penetration is attempted. Recent results have suggested the use of botulinum toxin for the treatment of vaginismus. Here, we assessed previously published data to evaluate the therapeutic effectiveness of botulinum toxin for vaginismus. METHODS: We have carried out a systematic review followed by a meta-analysis. RESULTS: Our results indicate that botulinum toxin is an effective therapeutic option for patients with vaginismus (pooled odds ratio of 8.723 with 95% confidence interval limits of 1.942 and 39.162, p = 0.005). This may hold particularly true in treatment-refractory patients because most of the studies included in this meta-analysis have enrolled these subjects in their primary analysis. CONCLUSION: Botulinum toxin appears to bea reasonable intervention for vaginismus. However, this conclusion should be read carefully because of the deficiency of placebo-controlled randomized clinical trials and the quality issues presented in the existing ones.

IFITM3, FURIN, ACE1, and TNF-α Genetic Association With COVID-19 Outcomes: Systematic Review and Meta-Analysis.

Human polymorphisms may contribute to SARS-CoV-2 infection susceptibility and COVID-19 outcomes (asymptomatic presentation, severe COVID-19, death). We aimed to evaluate the association of IFITM3, FURIN, ACE1, and TNF-α genetic variants with both phenotypes using meta-analysis. The bibliographic search was conducted on the PubMed and Scielo databases covering reports published until February 8, 2022. Two independent researchers examined the study quality using the Q-Genie tool. Using the Mantel-Haenszel weighted means method, odds ratios were combined under both fixed- and random-effect models. Twenty-seven studies were included in the systematic review (five with IFITM3, two with Furin, three with TNF-α, and 17 with ACE1) and 22 in the meta-analysis (IFITM3 n = 3, TNF-α, and ACE1 n = 16). Meta-analysis indicated no association of 1) ACE1 rs4646994 and susceptibility, 2) ACE1 rs4646994 and asymptomatic COVID-19, 3) IFITM3 rs12252 and ICU hospitalization, and 4) TNF-α rs1800629 and death. On the other hand, significant results were found for ACE1 rs4646994 association with COVID-19 severity (11 studies, 692 severe cases, and 1,433 nonsevere controls). The ACE1 rs4646994 deletion allele showed increased odds for severe manifestation (OR: 1.45; 95% CI: 1.26-1.66). The homozygous deletion was a risk factor (OR: 1.49, 95% CI: 1.22-1.83), while homozygous insertion presented a protective effect (OR: 0.57, 95% CI: 0.45-0.74). Further reports are needed to verify this effect on populations with different ethnic backgrounds. Systematic Review Registration: https://www.crd.york.ac.uk/prosperodisplay_record.php?ID=CRD42021268578, identifier CRD42021268578.

SARS-CoV-2 Genomic Surveillance in Brazil: A Systematic Review with Scientometric Analysis.

Several studies have monitored the SARS-CoV-2 variants in Brazil throughout the pandemic. Here, we systematically reviewed and conducted a scientometric analysis of the SARS-CoV-2 genomic surveillance studies using Brazilian samples. A Pubmed database search on October 2022 returned 492 articles, of which 106 were included. Ninety-six different strains were reported, with variant of concern (VOC) gamma (n = 35,398), VOC delta (n = 15,780), and the variant of interest zeta (n = 1983) being the most common. The top three states with the most samples in the published articles were São Paulo, Rio de Janeiro, and Minas Gerais. Whereas the first year of the pandemic presented primary circulation of B.1.1.28 and B.1.1.33 variants, consecutive replacements were observed between them and VOI zeta, VOC gamma, VOC delta, and VOC omicron. VOI mu, VOI lambda, VOC alpha, and VOC beta were also detected but failed to reach significant circulation. Co-infection, re-infection, and vaccine breakthrough reports were found. Article co-citation differed from the co-authorship structure. Despite the limitations, we expect to give an overview of Brazil's genomic surveillance studies and contribute to future research execution.

Negative correlation between ACE2 gene expression levels and loss of taste in a cohort of COVID-19 hospitalized patients: New clues to long-term cognitive disorders.

In early 2020, one of the most prevalent symptoms of SARS-CoV-2 infection was the loss of smell (anosmia), found in 60-70% of all cases. Anosmia used to occur early, concomitantly with other symptoms, and often persisted after recovery for an extended period, sometimes for months. In addition to smell disturbance, COVID-19 has also been associated with loss of taste (ageusia). The latest research suggests that SARS-CoV-2 could spread from the respiratory system to the brain through receptors in sustentacular cells localized to the olfactory epithelium. The virus invades human cells via the obligatory receptor, angiotensin-converting enzyme II (ACE2), and a priming protease, TMPRSS2, facilitating viral penetration. There is an abundant expression of both ACE2 and TMPRSS2 in sustentacular cells. In this study, we evaluated 102 COVID-19 hospitalized patients, of which 17.60% presented anosmia and 9.80% ageusia. ACE1, ACE2, and TMPRSS2 gene expression levels in nasopharyngeal tissue were obtained by RT-qPCR and measured using ΔCT analysis. ACE1 Alu287bp association was also evaluated. Logistic regression models were generated to estimate the effects of variables on ageusia and anosmia Association of ACE2 expression levels with ageusia. was observed (OR: 1.35; 95% CI: 1.098-1.775); however, no association was observed between TMPRSS2 and ACE1 expression levels and ageusia. No association was observed among the three genes and anosmia, and the Alu287bp polymorphism was not associated with any of the outcomes. Lastly, we discuss whetherthere is a bridge linking these initial symptoms, including molecular factors, to long-term COVID-19 health consequences such as cognitive dysfunctions.

Are COMT Val158Met (rs4680), DRD2 TaqIA (rs1800497), and BDNF Val66Met (rs6265) polymorphisms associated with executive functions performance at rest and during physical exercise?

Executive functions (EFs) encompass a wide array of cognitive processes, which appear to be influenced by genetic variants of the COMT, DRD2/ANKK1, and BDNF polymorphisms. The present study aimed to investigate whether COMT Val158Met (rs4680), DRD2/ANKK1 (rs1800497), and BDNF Val66Met (rs6265) polymorphisms were associated with EFs assessed at rest and during moderate acute physical exercise. Sixty physically active individuals underwent four laboratory visits. First, they filled out the pre-exercise survey, researchers collected their anthropometric data, and then performed a maximal cardiopulmonary exercise test. In the second and third sessions, participants performed EFs test in a randomized order: while the individual was seated on a cycle ergometer without pedaling (i.e., rest condition); and during physical exercise (pedaling for 30 minutes at moderate intensity before starting the EFs test during exercising). On the fourth day, blood samples were drawn. Our results showed that the response time of the COMT Val homozygotes group was significantly shorter than the COMT Met-carrier group [t(39.78) = 2.13, p = .039,d = 0.56] at rest condition. No significant association was found for the other analyses (DRD2/ANKK1 and BDNF). In conclusion, the present study suggests that COMT Val158Met (rs4680) polymorphisms may be associated with EFs at rest condition. However, further studies are needed to validate this association.

WGS-Based Lineage and Antimicrobial Resistance Pattern of Salmonella Typhimurium Isolated during 2000-2017 in Peru.

Salmonella Typhimurium is associated with foodborne diseases worldwide, including in Peru, and its emerging antibiotic resistance (AMR) is now a global public health problem. Therefore, country-specific monitoring of the AMR emergence is vital to control this pathogen, and in these aspects, whole genome sequence (WGS)­based approaches are better than gene-based analyses. Here, we performed the antimicrobial susceptibility test for ten widely used antibiotics and WGS-based various analyses of 90 S. Typhimurium isolates (human, animal, and environment) from 14 cities of Peru isolated from 2000 to 2017 to understand the lineage and antimicrobial resistance pattern of this pathogen in Peru. Our results suggest that the Peruvian isolates are of Typhimurium serovar and predominantly belong to sequence type ST19. Genomic diversity analyses indicate an open pan-genome, and at least ten lineages are circulating in Peru. A total of 48.8% and 31.0% of isolates are phenotypically and genotypically resistant to at least one antibiotic, while 12.0% are multi-drug resistant (MDR). Genotype−phenotype correlations for ten tested drugs show >80% accuracy, and >90% specificity. Sensitivity above 90% was only achieved for ciprofloxacin and ceftazidime. Two lineages exhibit the majority of the MDR isolates. A total of 63 different AMR genes are detected, of which 30 are found in 17 different plasmids. Transmissible plasmids such as lncI-gamma/k, IncI1-I(Alpha), Col(pHAD28), IncFIB, IncHI2, and lncI2 that carry AMR genes associated with third-generation antibiotics are also identified. Finally, three new non-synonymous single nucleotide variations (SNVs) for nalidixic acid and eight new SNVs for nitrofurantoin resistance are predicted using genome-wide association studies, comparative genomics, and functional annotation. Our analysis provides for the first time the WGS-based details of the circulating S. Typhimurium lineages and their antimicrobial resistance pattern in Peru.

Persistent symptoms, quality of life, and risk factors in long COVID: a cross-sectional study of hospitalized patients in Brazil.

OBJECTIVES: COVID-19 has been associated with long-term consequences to patient wellness and quality of life. Data on post-COVID-19 conditions are scarce in developing countries. This study aimed to investigate long COVID in a cohort of hospitalized patients in Brazil. METHODS: Surviving patients discharged from the hospital between July 1, 2020 and March 31, 2021 were assessed between 2 and 12 months after acute onset of COVID-19. The outcomes were the prevalence of persistent symptoms, risk factors associated with long COVID, and quality of life as assessed by the EuroQol 5D-3L questionnaire. RESULTS: Of 439 participants, most (84%) reported at least one long COVID symptom, at a median of 138 days (interquartile range [IQR] 90-201) after disease onset. Fatigue (63.1%), dyspnea (53.7%), arthralgia (56.1%), and depression/anxiety (55.1%) were the most prevalent symptoms. In multivariate analysis, dysgeusia (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.18-3.44, P <0.001) and intensive care unit (ICU) admission (OR 2.6, 95% CI 1.19-6.56, P = 0.03) were independently associated with long COVID. Fifty percent of patients reported a worsened clinical condition and quality of life. CONCLUSION: Long-term outcomes of SARS-CoV-2 infection in a low- to middle-income country were relevant. Fatigue was the most common persistent symptom. ICU admission was an independent factor associated with long COVID. Dysgeusia could be a potential predictor of long COVID.

Blockade of interleukin seventeen (IL-17A) with secukinumab in hospitalized COVID-19 patients - the BISHOP study.

BACKGROUND: Patients with severe COVID-19 seem to evolve with a compromised antiviral response and hyperinflammation. Neutrophils are critical players in COVID-19. IL-17A plays a major role in protection against extracellular pathogens and neutrophil attraction/activation. We hypothesized that secukinumab, an anti-IL17A monoclonal antibody, could prevent the deleterious hyperinflammation in COVID-19. METHODS: BISHOP was a randomized, open-label, single-centre, phase-II controlled trial. Fifty adult patients hospitalized with PCR-positive Covid-19, were randomized 1:1 to receive 300 mg of secukinumab subcutaneously at day-0 plus standard of care (group A) or standard of care alone (group B). A second dose of 300 mg of secukinumab could be administered on day-7, according to staff judgement. The primary endpoint was ventilator-free days at day-28 (VFD-28). Secondary efficacy and safety outcomes were also explored. RESULTS: An intention-to-treat analysis showed no difference in VFD-28: 23.7 (95%CI 19.6-27.8) in group A vs. 23.8 (19.9-27.6) in group B, p = .62; There was also no difference in hospitalization time, intensive care unit demand and the incidence of circulatory shock, acute kidney injury, fungal or bacterial co-infections. There was no difference in the incidence of severe adverse events. Pulmonary thromboembolism occurred only in males and was less frequent in secukinumab-treated patients (4.2% vs. 26.2% p = .04). There was one death in each group. Upper airway viral clearance was also similar in both groups. CONCLUSION: The efficacy of secukinumab in the treatment of Covid19 was not demonstrated. Secukinumab decreased pulmonary embolism in male patients. There was no difference between groups in adverse events and no unexpected events were observed.