MTOR gene variants are associated with severe COVID-19 outcomes: A multicenter study.

BACKGROUND: The worst outcomes linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been attributed to the cytokine storm, which contributes significantly to the immunopathogenesis of the disease. The mammalian target of rapamycin (mTOR) pathway is essential for orchestrating innate immune cell defense including cytokine production and is dysregulated in severe Coronavirus Disease 2019 (COVID-19) individuals. The individual genetic background might play a role in the exacerbated immune response. OBJECTIVE: In this study, we aimed to investigate the association between MTOR genetic variants and COVID-19 outcomes. METHODS: This study enrolled groups of individuals with severe (n = 285) and mild (n = 207) COVID-19 from Brazilian states. The MTOR variants, rs1057079 and rs2536, were genotyped. A logistic regression analysis and Kaplan-Meier survival curves were performed. We applied a genotyping risk score to estimate the cumulative contribution of the risk alleles. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) plasma levels were also measured. RESULTS: The T allele of the MTOR rs1057079 variant was associated with a higher likelihood of developing the most severe form of COVID-19. In addition, higher levels of IL-6 and COVID-19 death was linked to the T allele of the rs2536 variant. These variants exhibited a cumulative risk when inherited collectively. CONCLUSIONS: These results show a potential pathogenetic role of MTOR gene variants and may be useful for predicting severe outcomes following COVID-19 infection, resulting in a more effective allocation of health resources.

Comparison of Urinary Protein/Creatinine Ratio as an Alternative to 24-h Proteinuria in Lupus Nephritis: TUNARI Study.

BACKGROUND: Lupus nephritis (LN) occurs in approximately 50% of people with systemic lupus erythematosus (SLE). The 24-h proteinuria (gold standard) is measured among other tests for the control and monitoring of LN activity. This study investigates the use of the protein/creatinine ratio (PCR) as an alternative for the detection of proteinuria and its accuracy compared to the gold standard in a predominantly non-white population. METHODS: This was a prospective study conducted in Salvador, Brazil, between December 2021 and May 2022. We invited adult patients diagnosed with SLE and LN, regardless of their disease activity. The estimation of the PCR and 24-h proteinuria was performed using conventional methods. The analysis used was Spearman's r correlation coefficient (rs), coefficient of determination (r2), and concordance by the Bland-Altman method. A specific sensitivity was measured by the ROC curve with its respective cut-off by the Youden Index. RESULTS: We compared 112 samples of 75 patients with LN, with a mean age of 34.5 ± 11.8 years. Of these patients, 85% were women, 87.9% were non-white. A high degree of correlation was observed between PCR with 24-h proteinuria (rs = 0.77 and r2 = 0.59). The ROC analysis shows an area under the curve of 0.92 and the cut-off point calculated by the Youden Index was 0.78 with a sensitivity of 90.0% and specificity of 82%. However, the Bland-Altman graph indicated decreasing concordance as the degree of proteinuria increased, despite showing concordance at high levels of proteinuria. CONCLUSION: The PCR shows high sensitivity to follow-up patients with LN when compared with 24-h proteinuria. Our findings suggest that PCR is a useful parameter for the evaluating and monitoring patients in complete remission. However, in cases of partial remission, the utility of PCR is limited.

Lambda light chain-induced monoclonal gammopathy of renal significance, manifesting with Fanconi Syndrome and osteomalacia.

BACKGROUND: Monoclonal gammopathy of renal significance (MGRS) encompasses a heterogeneous group of kidney diseases in which a monoclonal immunoglobulin secreted by a clone of B cells or plasma cells causes kidney damage without meeting the hematological criteria for malignancy. Among the various forms of involvement, MGRS can manifest as a proximal tubule disorder, such as Fanconi syndrome (FS), characterized by urinary loss of phosphate, glucose, amino acids, uric acid and bicarbonate. Few cases of MGRS have been described in the literature, manifesting as FS and monoclonal production of lambda light chains, almost all of which are secondary to the production of kappa light chains. CASE PRESENTATION: Here we report a clinical case of a 45-year-old Brazilian male, African descent, with proximal weakness of the lower limbs, whose initial assessment showed a urine summary with the presence of proteinuria and glycosuria without hyperglycemia, associated with mild worsening of renal function, hypouricemia, hypocalcemia and phosphaturia. Evolution was characterized by a MGRS manifesting as FS and osteomalacia. CONCLUSION: The diagnosis of MGRS is not always easy, it requires knowledge of the clinical characteristics, diagnostic criteria and prognosis of each case. Therefore, all possible efforts should be made for multidisciplinary diagnosis.

SARS-CoV-2 Incidence, signs and symptoms and main risk factors for COVID-19 infection in Health Care Workers: A hospital-wide survey in Salvador, Brazil.

BACKGROUND: Brazil is the third country most affected by Coronavirus Disease 2019 (COVID-19) in the world. Health care workers (HCWs) are at higher risk of infection. Despite the increasing numbers of studies on the topic, There are gaps in the knowledge of characteristics and risk factors for infection of HCWS. This information is important to design preventive strategies and to mitigate the disease impact. The objective of this study was to estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, to identify factors associated, and to describe symptoms reported by healthcare workers at a tertiary hospital in Salvador, Brazil. METHODS: All HCWs were evaluated in a cross-sectional study conducted between May and September 2020, using self-administered questionnaires, and screening all participants for SARS-COV-2 IgG and IgM antibodies by rapid tests. Reactive IgG samples were retested by ELISA and IgM-positive test had a saliva sample retest by RT-PCR. Univariate associations were estimated by a non-adjusted incidence proportion ratio. Variables associated with COVID-19 incidence at p < 0.20 were selected for inclusion in a binary logistic regression model. RESULTS: A total of 2083 HCWs were included, mean age 41±10 years, 71.8% women, and 77.8% non-white. Of these, 271 (13.0%) and 25 (1.2%) HCWs tested positive for IgG and IgM SARS-CoV-2 antibodies, respectively, and three had a positive RT-PCR. Ancillary work [Odds Ratio (OR): 4.96], elementary education (OR: 2.91), high school education (OR: 2.89), and catholic religion (OR: 2.16) were associated with an increased likelihood of a positive IgG antibodies against SARS-CoV-2. Anosmia [Incidence Proportion Ratio (IPR): 7.41] and ageusia (IPR:8.51) were the most frequent associated symptoms. CONCLUSION: HCWs with low mean family income, lower level of schooling, ancillary workor being black had a significantly higher likelihood of testing positive for SARS-CoV-2 antibodies. Social vulnerability was an important risk factor for COVID-19 infection.

Clinical and Laboratory Outcomes in HIV-1 and HTLV-1/2 Coinfection: A Systematic Review.

Aim: To perform a systematic review to describe the available findings on clinical outcomes in HIV-1 and HTLV-1/HTLV-2 co-infected individuals since 1995. Design: This Systematic Review used PECO criteria follow by PRISMA reporting guidelines and registered as CRD42021279062 (Prospero database). The Newcastle-Ottawa Scale assessed the methodological quality of included studies. Data Collection and Analysis: A systematical search in PubMed/MEDLINE, Embase, Web of Sciences databases for cross-sectional, case-control, or cohort studies design to identify clinical and laboratorial outcomes related to HIV-1 and HTLV-1/2 coinfection. Search strategy: [("HIV-1" AND "HTLV-1" OR "HTLV-2") AND ("Coinfection") AND (1990/01/01:2021/12/31[Date- Publication])]. Results: A total of 15 articles were included on this systematic review describing data of 2,566 mono and coinfected patients, 58% male, with mean age was 35.7 ± 5.7 years. HIV-1 and HTLV-1 coinfected patients were more likely to had shorter survival and faster progression to death or mortality than monoinfected ones. Coinfected had higher CD4 cell counts and less likelihood of ART use. In addition, higher frequency of diseases like ichthyosis (22.2 vs. 6.8%), scabies (18.6 vs. 0%), candidiasis (42 vs. 12%), Strongyloidiasis (15.4 vs. 2%) and neurological manifestations like encephalopathy, peripheral neuropathy and HAM/TSP were more frequently reported in coinfected patients. Conclusions: HIV-1 and HTLV-1 coinfection and HIV-1 and HTLV-1 /2 triple coinfection were related to shorter survival, higher mortality rate, and faster progression to death, while coinfection by HIV-1/HTLV-2 seems to have neutral association with longer survival, slower AIDS progression, and lower mortality rate. The available evidence indicates an urgent need for prevention and control measures, including screening, diagnosis, and treatment of HIV-1 and HTLV-1/2 coinfected patients. Test-and-treat strategy for patients living with HIV in areas endemic for HTLV infection is mandatory, to avoid the risks of delayed therapy and death for coinfected patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021279062.

SARS-CoV-2 Incidence, signs and symptoms and main risk factors for COVID-19 infection in Health Care Workers: A hospital-wide survey in Salvador, Brazil

ABSTRACT Background: Brazil is the third country most affected by Coronavirus Disease 2019 (COVID-19) in the world. Health care workers (HCWs) are at higher risk of infection. Despite the increasing numbers of studies on the topic, There are gaps in the knowledge of characteristics and risk factors for infection of HCWS. This information is important to design preventive strategies and to mitigate the disease impact. The objective of this study was to estimate the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, to identify factors associated, and to describe symptoms reported by healthcare workers at a tertiary hospital in Salvador, Brazil. Methods: All HCWs were evaluated in a cross-sectional study conducted between May and September 2020, using self-administered questionnaires, and screening all participants for SARS-COV-2 IgG and IgM antibodies by rapid tests. Reactive IgG samples were retested by ELISA and IgM-positive test had a saliva sample retest by RT-PCR. Univariate associations were estimated by a non-adjusted incidence proportion ratio. Variables associated with COVID-19 incidence at p < 0.20 were selected for inclusion in a binary logistic regression model. Results: A total of 2083 HCWs were included, mean age 41±10 years, 71.8% women, and 77.8% non-white. Of these, 271 (13.0%) and 25 (1.2%) HCWs tested positive for IgG and IgM SARS-CoV-2 antibodies, respectively, and three had a positive RT-PCR. Ancillary work [Odds Ratio (OR): 4.96], elementary education (OR: 2.91), high school education (OR: 2.89), and catholic religion (OR: 2.16) were associated with an increased likelihood of a positive IgG antibodies against SARS-CoV-2. Anosmia [Incidence Proportion Ratio (IPR): 7.41] and ageusia (IPR:8.51) were the most frequent associated symptoms. Conclusion: HCWs with low mean family income, lower level of schooling, ancillary workor being black had a significantly higher likelihood of testing positive for SARS-CoV-2 antibodies. Social vulnerability was an important risk factor for COVID-19 infection.

High Prevalence of Frailty and Prefrailty Status in Brazilian Patients Living with HIV.

Frailty is associated with an increased probability of serious adverse health outcomes in the geriatric general population. People living with HIV have a higher prevalence of frailty. However, the magnitude of this problem in younger patients in South America is unknown. We aimed to determine the prevalence and factors associated with frailty. This is a cross-sectional study from the Brazilian cohort HIV-AIDS (CoBRA) developed between March and November of 2018, on patients ≥18 years of age. Frailty phenotype was assessed by original Fried criteria. The results were analyzed using descriptive statistics, while identification of factors related to frailty was assessed by using multivariate logistic regression. We enrolled 231 patients; all, but 2 were on antiretroviral therapy (ART). Median age was 45.6 interquartile range (36.7-52.1) years, 136 (58.9%) were male, and 86.7% self-identified as non-white. Mean CD4 count was 660 (±345) cells/mm3 and 83.5% had undetectable HIV plasma viral load (<50 copies/mL). Prevalence of frailty and prefrailty was 10.4% and 52.4%, respectively. A CD4 count <200 cells/mm3, depression, low income, and use of third-line ART were variables significantly associated with a greater risk to present frail or prefrail status. Frailty prevalence increases with age and is an important health problem to health care in HIV aging patients. It requires proper strategies to its early detection, prevention, and management.