Obesity in Severe COVID-19 Patients Has a Distinct Innate Immune Phenotype.

Obesity alters the capacity of effective immune responses in infections. To further address this phenomenon in the context of COVID-19, this study investigated how the immunophenotype of leukocytes was altered in individuals with obesity in severe COVID-19. This cross-sectional study enrolled 27 ICU COVID-19 patients (67% women, 56.33 ± 19.55 years) that were assigned to obese (BMI ≥ 30 kg/m2, n = 9) or non-obese (BMI < 30kg/m2, n = 18) groups. Monocytes, NK, and both Low-Density (LD) and High-Density (HD) neutrophils were isolated from peripheral blood samples, and surface receptors' frequency and expression patterns were analyzed by flow cytometry. Clinical status and biochemical data were additionally evaluated. The frequency of monocytes was negatively correlated with BMI, while NK cells and HD neutrophils were positively associated (p < 0.05). Patients with obesity showed a significant reduction of monocytes, and these cells expressed high levels of PD-L1 (p < 0.05). A higher frequency of NK cells and increased expression of TREM-1+ on HD neutrophils were detected in obese patients (p < 0.05). The expression of receptors related to antigen-presentation, phagocytosis, chemotaxis, inflammation and suppression were strongly correlated with clinical markers only in obese patients (p < 0.05). Collectively, these outcomes revealed that obesity differentially affected, and largely depressed, innate immune response in severe COVID-19.

sTREM-1 and TNF-α levels are associated with the clinical outcome of leprosy patients.

Leprosy reaction (LR) and physical disability (PD) are the most significant clinical complications of leprosy. Herein, we assessed the circulating serum-sTREM-1 and TNF-α levels and their genetic polymorphisms in leprosy. Serum-sTREM-1 and TNF-α levels were measured in leprosy patients (LP) before treatment (n = 51) and from their household contacts (HHCs; n = 25). DNA samples were genotyped using TREM-1 rs2234246 and TNF-α rs1800629-SNP in 210 LPs and 168 endemic controls. The circulating sTREM-1 and TNF-α levels are higher in the multibacillary form. The ROC curve of the serum-sTREM-1 levels was able to differentiate LR from non-LR and PD from non-PD. Similarly, LPs with serum-sTREM-1 levels >210 pg/ml have 3-fold and 6-fold higher chances of presenting with LR and PD, respectively. Genotypes CC+CT of the TREM-1 were associated with leprosy. Taken together, our analyses indicated that sTREM-1 and TNF-α play an important role in the pathogenesis of leprosy and provide promising biomarkers to assist in the diagnosis of leprosy complications.

A single-set functional training program increases muscle power, improves functional fitness, and reduces pro-inflammatory cytokines in postmenopausal women: A randomized clinical trial.

Introduction: Aging can be associated with reduced muscle power, functional decline, and increased plasma concentrations of proinflammatory cytokines. Functional training (FT) can improve muscle power, functional fitness and reduce plasma cytokines. However, the functional training optimal volume required to produce these adaptations must be clarified. Our study analyzed the effects of multiple-set functional training (MSFT) and single-set functional training (SSFT) on postmenopausal women's muscle power, functional fitness, and inflammatory profile. Methods: Forty-three women were randomly allocated into three groups: multiple-set functional training (n = 16, age 64.13 ± 5.17), single-set functional training (n = 14, age 63.79 ± 4.88), and control group (CG, n = 13, age 64.62 ± 5.44). The bench press and squat exercises evaluated upper and lower limb muscle power. The following tests assessed functional fitness: putting on and taking off a T-shirt, gallon-jug shelf-transfer, standing up and walking around the house, five times sit-to-stand, and 400-m walk. Plasma cytokine (TNF-α, IL-6, and IL 10) concentrations were measured by flow cytometry. Results: Single-set functional training and multiple-set functional training increased upper and lower limbs muscle power and improved functional fitness, except for the putting on and taking off a T-shirt test. Multiple-set functional training reduced TNF-α and IL-6, while single-set functional training reduced only TNF-α. IL-10 was unaffected by exercise. Discussion: Single-set functional training and multiple-set functional training, therefore, promoted similar muscle power and functional fitness improvements over 24 weeks. Multiple-set functional training was more effective than single-set functional training, reducing both TNF and IL-6, while single-set functional training only decreased TNF-α.

Prevalence of SARS-CoV-2 infection among urban cleaning and solid waste management workers during transmission of the Omicron variant in Brazil.

This study estimated the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in urban cleaning and solid waste management workers during the transmission of the Omicron variant in one of the poorest regions of Brazil (the state of Sergipe). Nasopharyngeal swabs were collected from 494 workers, and the presence of SARS-CoV-2 RNA was tested by quantitative reverse-transcriptase polymerase chain reaction. Data on socio-demographic characteristics, comorbidities, vaccination status, mask use, and use of public transport to commute to the workplace were collected. The prevalence with a 95% confidence interval (CI) was calculated from the proportion of SARS-CoV-2 positive cases among the total number of individuals tested. The prevalence ratio (PR) with a 95% CI was the measure of association used to evaluate the relationship between SARS-CoV-2 infection and the exposure variables. The prevalence of SARS-CoV-2 infection was 22.5% (95% CI, 19.0 to 26.4). Individuals under the age of 40 had a higher prevalence of infection (PR, 1.53; 95% CI, 1.03 to 2.30) as well as those who did not believe in the protective effect of vaccines (PR, 1.78; 95% CI, 1.05 to 2.89). Our results indicate the need for better guidance on preventive measures against coronavirus disease 2019 among urban cleaning and solid waste management workers.

Dynamics of SARS-CoV-2 seroprevalence during the first year of the COVID-19 pandemic in the Northeast region of Brazil.

In this household-based seroepidemiological survey, we analyzed the dynamics of SARS-CoV-2 seroprevalence during the first year of the COVID-19 pandemic in Sergipe State, Northeast Brazil, the poorest region of the country. A total of 16,547 individuals were tested using a rapid IgM-IgG antibody test and fluorescence immunoassay (FIA). Seroprevalence rates were presented according to age, sex, and geographic region. A comparative analysis was performed between the results obtained in July 2020 (peak of the first wave), August - November 2020 (end of the first wave), and February - March 2021 (beginning of the second wave). Seroprevalence rates in the three phases were estimated at 9.3% (95% CI 8.5-10.1), 12.0% (95% CI 11.2-12.9) and 15.4% (95% CI 14.5-16.4). At the end of the first wave, there was a rise in seroprevalence in the countryside (p < 0.001). At the beginning of the second wave, we found an increase in seroprevalence among women (p < 0.001), adults aged 20 to 59 years (p < 0.001), and the elderly (p < 0.001). In this phase, we found an increase in estimates both in metropolitan areas and in the countryside (p < 0.001). This study showed an increase in SARS-CoV-2 seroprevalence over the first year of the pandemic, with approximately one in six people having anti-SARS-CoV-2 antibodies at the beginning of the second wave of COVID-19. Furthermore, our results suggest a rapid spread of COVID-19 from metropolitan areas to the countryside during the first months of the pandemic.

The increase in SARS-CoV-2 lineages during 2020-2022 in a state in the Brazilian Northeast is associated with a number of cases.

SARS-CoV-2 has caused a high number of deaths in several countries. In Brazil, there were 37 million confirmed cases of COVID-19 and 700,000 deaths caused by the disease. The population size and heterogeneity of the Brazilian population should be considered in epidemiological surveillance due to the varied tropism of the virus. As such, municipalities and states must be factored in for their unique specificities, such as socioeconomic conditions and population distribution. Here, we investigate the spatiotemporal dispersion of emerging SARS-CoV-2 lineages and their dynamics in each microregion from Sergipe state, northeastern Brazil, in the first 3 years of the pandemic. We analyzed 586 genomes sequenced between March 2020 and November 2022 extracted from the GISAID database. Phylogenetic analyses were carried out for each data set to reconstruct evolutionary history. Finally, the existence of a correlation between the number of lineages and infection cases by SARS-CoV-2 was evaluated. Aracaju, the largest city in northeastern Brazil, had the highest number of samples sequenced. This represented 54.6% (320) of the genomes, and consequently, the largest number of lineages identified. Studies also analyzed the relationship between mean lineage distributions and mean monthly infections, daily cases, daily deaths, and hospitalizations of vaccinated and unvaccinated patients. For this, a correlation matrix was created. Results revealed that the increase in the average number of SARS-CoV-2 variants was related to the average number of SARS-CoV-2 cases in both unvaccinated and vaccinated individuals. Thus, our data indicate that it is necessary to maintain epidemiological surveillance, especially in capital cities, since they have a high rate of circulation of resident and non-resident inhabitants, which contributes to the dynamics of the virus.

Bodyweight and Combined Training Reduce Chronic Low-Grade Inflammation and Improve Functional Fitness of Postmenopausal Women.

Exercise is an important tool against the deleterious effects of aging. Among the possibilities of exercise, bodyweight training (BWT) has been highlighted in the last years as a safe option to improve the health of older people. We compared the effects of 24 weeks of BWT and combined training (CT) on low-grade systematic inflammation and functional fitness in postmenopausal women. For this, 40 women were allocated and submitted to CT (n = 20, 64.43 ± 3.13 years, 29.56 ± 4.80 kg/m²) and BWT (n = 20, 65.10 ± 4.86 years, 28.76 ± 4.26 kg/m²). We measured inflammation by the interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) assessments. For functional fitness, we used tests similar to activities of daily living. At the end of the 16 weeks, data from 24 women were analyzed, CT (n = 14) and BT (n = 10). Both groups reduced TNF-α and IL-6 levels, without differences in IL-10. Regarding functional fitness, both groups demonstrated improvements in all tests after 24 weeks, except for rise from prone position and the 400-meter walk test for CT. In summary, CT and BWT are effective in reducing the plasma concentration of pro-inflammatory cytokines and improving functional fitness in postmenopausal women.

Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and other inflammatory mediators in malaria by Plasmodium vivax during enteroparasites coinfection.

Malaria is a major health issue with more than 200 million cases occurring annually. Moreover, in Malaria endemic area are frequently observed Malaria-enteroparasite co-infections associated with the modulation of inflammatory response. In this aspect, biomarkers play an important role in the disease prognosis. This study aimed to evaluate inflammatory mediators in malaria during coinfection with enteroparasites. A subset of serum samples already collected was analyzed and divided into four groups: Malaria (n = 34), Co-infected (n = 116), Enteroparasite (n = 120) and Control (n = 95). The serum levels of sTREM-1 and IL-6 were measured by ELISA. TNF-α, and IL-10 levels were previously carried out by flow cytometry. Higher serum levels of sTREM-1 and IL-6 were showed in malaria patients compared to healthy controls. In co-infected malarial patients sTREM-1 serum levels were similar to control group. Interestingly, co-infected malaria patients showed IL-6 serum levels decreased compared to individuals only infected with P. vivax. However, in Malaria patients and co-infected there was a positive correlation between the IL-6 and IL-10 levels (P < 0.0001). This is the first report of sTREM-1 levels in P. vivax infected. Moreover, the results revealing a divergent effect of co-infection with the increased balance between pro-and anti-inflammatory cytokines and reduced IL-6 levels but increases the anemia occurrence. The results also highlight the potential use of IL-6 as a biomarker for P. vivax and enteroparasites coinfection.

TREM-1 Expression on the Surface of Neutrophils in Patients With Visceral Leishmaniasis Is Associated With Immunopathogenesis.

Visceral leishmaniasis (VL) is a systemic chronic and potentially fatal disease for humans. Mechanisms related to the dysregulation of the inflammatory response may be involved in both the pathogenesis and prognosis of VL. Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) is a receptor constitutively expressed on neutrophils and monocyte subsets. The protein serves to regulate and amplify inflammatory responses. This study aimed to evaluate the expression profile of TREM-1 on the surface of neutrophils from patients with VL at varying time points during leishmanicidal treatment. For this purpose, neutrophils were isolated from the peripheral blood of patients with VL at different stages of treatment, which include 0, 7, and 30 days after treatment. Surface TREM-1 expression was assessed by immunophenotyping neutrophil populations. In addition, the association of TREM-1 expression on the surface of neutrophils with clinical and laboratory parameters and serum levels of inflammatory mediators was also evaluated. Results demonstrate a lower surface expression of TREM-1 in VL patients in the absence of treatment. However, increased levels of TREM-1 expression were observed 7 and 30 days after the start of treatment, with levels similar to those of healthy controls. TREM-1 expression was directly correlated with lymphocyte and erythrocyte count and indirectly correlated with spleen and liver size. Furthermore, elevated levels of TREM-1 expression were also correlated with lower serum levels of interleukin (IL)-22. Taken together, these results suggest that infection by Leishmania infantum leads to depressed TREM-1 expression on the neutrophil surface and may contribute to the inflammatory imbalance that characterizes active VL disease.

Role of triggering receptor expressed on myeloid cells-1 (TREM-1) in COVID-19 and other viral pneumonias: a systematic review and meta-analysis of clinical studies.

BACKGROUND: Triggering receptor expressed on myeloid cells-1 (TREM-1) has emerged as an important inflammatory marker of immune response associated with severity and mortality outcomes in infection diseases, including viral pneumonias. AIM: (1) To evaluate the expression of TREM-1 in patients with COVID-19 and other viral pneumonias compared to healthy individuals; and (2) to analyze the levels of these biomarkers according to disease severity. MATERIALS AND METHODS: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Searches were performed in PubMed, Scopus, Embase, and Google Scholar. Studies were considered eligible if they were observational studies that provided data on the levels of TREM-1 in humans with viral pneumonia compared to healthy controls. The results of the meta-analysis were expressed as standardized mean difference (SMD) and an effect size of 0.8 was considered a large effect. A subgroup analysis was performed according to the disease severity. RESULTS: Seven studies were included in this systematic review. Four studies included patients with COVID-19 and three analyzed patients with different viruses. The meta-analysis was performed only with patients with COVID-19, which showed increased levels of soluble form of TREM-1 (sTREM-1) among patients with COVID-19 compared to healthy controls (SMD 1.53; 95% CI 0.53-2.52; p < 0.01). No differences were found between patients with mild-to-moderate COVID-19 and healthy controls, but higher levels of sTREM-1 were shown among patients with severe COVID-19 (SMD 1.83; 95% CI 0.77-2.88; p < 0.01). All three studies including patients with other viral pneumonias showed that TREM-1 levels were significantly elevated in infected patients compared with controls. CONCLUSION: These findings may provide evidence on the pro-inflammatory role of TREM-1 in these infections, contributing to the inflammatory profile and disease progression.

Magnitude of visceral leishmaniasis and HIV coinfection and association with social determinants of health in the Northeast region of Brazil: a retrospective, spatiotemporal model (2010-2018).

The Northeast region of Brazil (NRB) includes the states with the highest prevalence of visceral leishmaniasis (VL), as well as those with significant increases in HIV cases. This study aims to analyze the spatiotemporal patterns of VL-HIV coinfection and its association with the social determinants of health (SDH) in the NRB. Time trend analysis and Bayesian spatial statistical inferences, Moran's autocorrelation, and retrospective space-time scanning were performed. Spatial regression modelling was used to build an explanatory model for the occurrence of VL-HIV coinfection within NRB. A total of 1550 cases of VL-HIV coinfection were confirmed. We observed a higher prevalence among males (1232; 83%), individuals aged from 20 to 59 years (850; 54.8%), non-white skin color (1,422; 91.7%), and with low education (550; 35.48%). NRB showed an increasing and significant trend in the detection rate of coinfection (APC, 5.3; 95% CI, 1.4 to 9.4). The states of Maranhão and Piauí comprised the high-risk cluster. The SDH that most correlated with the occurrence of coinfection were poor housing, low income, and low education. VL-HIV is dispersed in the NRB but chiefly affects states with greater social vulnerability. Taken together, these findings reinforce the necessity to implement surveillance strategies that will contribute to the reduction of cases in these populations.

Oxidative stress and inflammatory markers in patients with COVID-19: Potential role of RAGE, HMGB1, GFAP and COX-2 in disease severity.

BACKGROUND: SARS-CoV-2 infection can lead to the abnormal induction of cytokines and a dysregulated hyperinflammatory state that is implicated in disease severity and risk of death. There are several molecules present in blood associated with immune cellular response, inflammation, and oxidative stress that could be used as severity markers in respiratory viral infections such as COVID-19. However, there is a lack of clinical studies evaluating the role of oxidative stress-related molecules including glial fibrillary acidic protein (GFAP), the receptor for advanced glycation end products (RAGE), high mobility group box-1 protein (HMGB1) and cyclo-oxygenase-2 (COX-2) in COVID-19 pathogenesis. AIM: To evaluate the role of oxidative stress-related molecules in COVID-19. METHOD: An observational study with 93 Brazilian participants from September 2020 to April 2021, comprising 23 patients with COVID-19 admitted to intensive care unit (ICU), 19 outpatients with COVID-19 with mild to moderate symptoms, 17 individuals reporting a COVID-19 history, and 34 healthy controls. Blood samples were taken from all participants and western blot assay was used to determine the RAGE, HMGB1, GFAP, and COX-2 immunocontent. RESULTS: We found that GFAP levels were higher in patients with severe or critical COVID-19 compared to outpatients (p = 0.030) and controls (p < 0.001). A significant increase in immunocontents of RAGE (p < 0.001) and HMGB1 (p < 0.001) were also found among patients admitted to the ICU compared to healthy controls, as well as an overexpression of the inducible COX-2 (p < 0.001). In addition, we found a moderate to strong correlation between RAGE, GFAP and HMGB1 proteins. CONCLUSION: SARS-CoV-2 infection induces the upregulation of GFAP, RAGE, HMGB1, and COX-2 in patients with the most severe forms of COVID-19.

Antimony resistance associated with persistence of Leishmania (Leishmania) infantum infection in macrophages.

Visceral leishmaniasis is a severe disease caused by protozoan parasites that include Leishmania (L.) infantum. The disease is established when parasites subvert the immune response of the host. Notably, chemotherapy-based use of antimonial compounds can partially alleviate disease burden. Unfortunately, the resistance to drug treatments is increasing in areas endemic to the disease. In this report, we investigated immune responses within macrophages infected with antimony-resistant L. infantum isolates from patients with a relapse in the disease. Results revealed that antimony-resistant parasites persist in the first 24 h of infection. Activation of macrophage or blocking of thiol production during infection shows enhanced clearance of parasites, which is coordinately associated with increased production of pro-inflammatory cytokines. Taken together, these results suggest that the mechanism of antimony resistance in L. infantum isolates may be related to a decrease in macrophage microbicidal functions.

Seroprevalence of SARS-CoV-2 antibodies in the poorest region of Brazil: results from a population-based study.

Population-based seroprevalence studies on coronavirus disease 2019 (COVID-19) in low- and middle-income countries are lacking. We investigated the seroprevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibodies in Sergipe state, Northeast Brazil, using rapid IgM-IgG antibody test and fluorescence immunoassay. The seroprevalence was 9.3% (95% CI 8.5-10.1), 10.2% (95% CI 9.2-11.3) for women and 7.9% (IC 95% 6.8-9.1) for men (P = 0.004). We found a decline in the prevalence of SARS-CoV-2 antibodies according to age, but the differences were not statistically significant: 0-19 years (9.9%; 95% CI 7.8-12.5), 20-59 years (9.3%; 95% CI 8.4-10.3) and ≥60 years (9.0%; 95% CI 7.5-10.8) (P = 0.517). The metropolitan area had a higher seroprevalence (11.7%, 95% CI 10.3-13.2) than outside municipalities (8.0%, 95% CI 7.2-8.9) (P < 0.001). These findings highlight the importance of serosurveillance to estimate the real impact of the COVID-19 outbreak and thereby provide data to better understand the spread of the virus, as well as providing information to guide stay-at-home measures and other policies. In addition, these results may be useful as basic data to follow the progress of COVID-19 outbreak as social restriction initiatives start to be relaxed in Brazil.

Spatial and spatiotemporal dynamics of visceral leishmaniasis in an endemic North-eastern region of Brazil.

Visceral Leishmaniasis (VL) is a neglected disease with increasing incidence in Brazil, particularly in the North-eastern. The aim of this study was to analyze the spatial and spatiotemporal dynamics of VL in an endemic region of North-eastern Brazil, between 2009 and 2017. Using spatial analysis techniques, an ecological and time series study was made regarding VL cases in Sergipe filed as notifiable disease events. With data from the Brazilian Institute of Geography and Statistics (Instituto Brasileiro de Geografia e Estatística, IBGE), a digital population and cartographic baseline was established. Segmented linear regression was used to examine the temporal trends. The statistical analysis methods of Global and Local Moran' I, local Bayesian empirical methodology and spatial-temporal scanning were used to produce thematic maps. High instances were found among adults, males, urban residents, non-Whites and persons with low levels of education. A decrease in the recovery rate and an increase in the proportion of urban cases and lethality was found. A heterogeneous VL distribution with spatiotemporal agglomeration on the seaside of the state was seen in Sergipe. To better manage the disease, new research is encouraged together with development of public health strategies. Further, improving health care networks, especially primary care, is suggested as this approach has a key role in health promotion, prevention and monitoring of the most prevalent diseases.

CXCL10 immunomodulatory effect against infection caused by an antimony refractory isolate of Leishmania braziliensis in mice.

Leishmania braziliensis is the main causative agent of American tegumentary leishmaniasis in Brazil. Current treatment includes different drugs that have important side effects and identification of cases of parasite resistance to treatment support the search for new therapeutic strategies. Recent findings have indicated that CXCL10, a chemokine that recruits and activates Th1 cells, NK cells, macrophages, dendritic cells and B lymphocytes, is a potential alternative to treat Leishmania infection. Here, we tested CXCL10 immunotherapy against experimental infection caused by an antimony-resistant isolate of Leishmania braziliensis. Following infection, mice were treated with CXCL10 for 7 days after onset of lesions. We demonstrate that mice treated with CXCL10 controlled lesion progression and parasite burden more efficiently comparing to controls. An increased IFN-γ, IL-10, TGF-ß and low IL-4 production combined with a distinct inflammatory infiltrate composed by activated macrophages, lymphocytes and granulomas was observed in the CXCL10-treated group comparing to controls. However, CXCL10 and Glucantime combined therapy did not improve CXCL10-induced protective effect. Our findings reinforce the potential of CXCL10 immunotherapy as an alternative treatment against infection caused by L. braziliensis resistant to conventional chemotherapy.

Family COVID-19 cluster analysis of an infant without respiratory symptoms.

Diagnosing cases of coronavirus disease (COVID-19) with only non-respiratory symptoms has been challenging. We reported the diagnosis of a child who tested positive for COVID-19 with abdominal pain/diarrhea and tracked his family cluster. One member of the family tested positive for COVID-19 on real-time reverse-transcription polymerase chain reaction assay and three other family members had anti-SARS-CoV-2 antibodies.