Genome-wide association studies of COVID-19: Connecting the dots.

Genome-wide association studies (GWASs) are a research approach used to identify genetic variants associated with common diseases, like COVID-19. The lead genetic variants (n = 41) reported by the eleven largest COVID-19 GWASs are mapped to 22 different chromosomal regions. The loci 3q21.31 (LZTFL1 and chemokine receptor genes) and 9q34.2 (ABO), associated with disease severity and susceptibility to infection, respectively, were the most replicated findings across studies. Genes involved with mucociliary clearance (CEP97, FOXP4), viral-entry (ACE2, SLC6A20) and mucosal immunity (MIR6891) are associated with the risk of SARS-CoV-2 infection while genes of antiviral immune response (IFNAR2, OAS1), leukocyte trafficking (CCR9, CXCR6) and lung injury (DPP9, NOTCH4) are associated with severe disease. The biological processes underlying the risk of infection occur prominently, but not exclusively, in the upper airways whereas the severe COVID-19-associated processes in alveolar-capillary interface. The COVID-19 GWASs has unraveled key genetic mechanisms of SARS-CoV-2 pathogenesis, although the genetic basis of other COVID-19 related phenotypes (long COVID and neurological impairment) remains to be elucidated.

CD45RO+ T Cells and T Cell Activation in the Long-Lasting Immunity after Leishmania infantum Infection.

Manifestations of Leishmania infantum infection range from asymptomatic to symptomatic visceral leishmaniasis (VL). People with symptomatic VL (sVL) have suppressed immune responses against Leishmania antigens that are reversed after clinical cure. The intradermal leishmanin skin test (LST) is negative during sVL, but it becomes positive after treatment. The aim of this study was to compare T cell responses in individuals with sVL, recovered VL (RecVL), and endemic controls. Endemic controls were household contacts of a VL case and they were grouped by their LST results, either positive (LST+) or negative (LST-). Mononuclear cells were studied ex vivo or after stimulation with soluble Leishmania antigens (SLA); cell surface markers and cytokines were determined. T cells, ex vivo, from individuals with sVL and from LST+ individuals presented a higher activation for CD4+ and CD8+ cells expressing CD69. However, lymphocytes from sVL stimulated with SLA had lower percentages of CD4+ and CD8+ cells expressing CD69 and CD8+ cells expressing CD25, with no release of interferon-γ or tumor necrosis factor. sVL subjects had lower percentage of memory cells (CD4+ CD45RO+), ex vivo, without SLA stimulation than RecVL, LST+, or LST- (P = 0.0022). However, individuals with sVL had fewer regulatory cells after SLA stimulation (CD4+ CD25HIGH, P = 0.04 and CD4+ FOXP3+, P = 0.02) than RecVL. The decrease in specific memory and activated CD4+ and CD8+ cells, as in response to Leishmania antigens, could explain, in part, the immune impairment during sVL. Finally, protective T cell responses are long lasting because both RecVL or LST+ individuals maintain a specific protective response to Leishmania years after the primary infection.

New challenges in the epidemiology and treatment of visceral leishmaniasis in periurban areas.

Visceral leishmaniasis [VL] represents a major public health problem in many areas of the world. This review focuses on the impact of periurbanization on the epidemiology and treatment of VL, using Brazil as an example. VL continues to be mostly a disease of poverty with impact on families. However, the disease has expanded in Latin America, with foci reported as far south as Argentina. There is an increasing overlap of Leishmania infantum chagasi and HIV infections and other immunosuppressive conditions, resulting in VL emerging as an opportunistic infection. This new setting poses new challenges for VL disease control and patient management.

Impact of socioeconomic status on the quality of life of ESRD patients.

BACKGROUND: Socioeconomic status (SES) has been associated with the incidence of end-stage renal disease (ESRD); however, the impact of SES on the quality of life (QOL) of these patients has not been clearly defined. METHODS: One hundred eighteen patients were prospectively evaluated at the beginning of dialysis treatment and reassessed (n = 90) after an average of 7 months. QOL was measured by means of the Medical Outcomes Survey 36-Item Short Form (SF-36). Classification of SES was according to validated criteria of the Brazilian Association of Research Institutes. RESULTS: Mean scores for SF-36 dimensions were decreased in patients with low compared with high SES, with greater differences noted during follow-up. At this time, mean scores for SF-36 scales for the low- and high-SES groups were as follows: Functional Capacity, 43 +/- 31 versus 68 +/- 26 (P < 0.01); Physical Aspect, 34 +/- 36 versus 56 +/- 38; Pain, 55 +/- 31 versus 80 +/- 28 (P < 0.01); General Health Status, 60 +/- 21 versus 67 +/- 19; Vitality, 42 +/- 25 versus 59 +/- 16 (P < 0.05); Social Aspect, 53 +/- 32 versus 81 +/- 21 (P < 0.01); Emotional Aspect, 49 +/- 44 versus 70 +/- 41; and Mental Health, 51 +/- 27 versus 70 +/- 22 (P < 0.05), respectively. These differences were more pronounced than expected for an age- and sex-matched sample of the Brazilian general population. Multivariate analysis showed that SES continued to significantly affect all QOL dimensions, explaining 5.5% to 14.1% of variation in scales. CONCLUSION: SES is an important factor associated with QOL in patients with ESRD. Further studies to determine optimum interventions and measures in groups with lower SES may be important to improve QOL outcomes and reduce their morbidity.