Transmission electron microscopy reveals the presence of SARS-CoV-2 in human spermatozoa associated with an ETosis-like response.

BACKGROUND: Severe acute syndrome coronavirus 2 can invade a variety of tissues, including the testis. Even though this virus is scarcely found in human semen polymerase chain reaction tests, autopsy studies confirm the viral presence in all testicular cell types, including spermatozoa and spermatids. OBJECTIVE: To investigate whether the severe acute syndrome coronavirus 2 is present inside the spermatozoa of negative polymerase chain reaction-infected men up to 3 months after hospital discharge. MATERIALS AND METHODS: This cross-sectional study included 13 confirmed moderate-to-severe COVID-19 patients enrolled 30-90 days after the diagnosis. Semen samples were obtained and examined with real-time polymerase chain reaction for RNA detection and by transmission electron microscopy. RESULTS: In moderate-to-severe clinical scenarios, we identified the severe acute syndrome coronavirus 2 inside spermatozoa in nine of 13 patients up to 90 days after discharge from the hospital. Moreover, some DNA-based extracellular traps were reported in all studied specimens. DISCUSSION AND CONCLUSION: Although severe acute syndrome coronavirus 2 was not present in the infected men's semen, it was intracellularly present in the spermatozoa till 3 months after hospital discharge. The Electron microscopy (EM) findings also suggest that spermatozoa produce nuclear DNA-based extracellular traps, probably in a cell-free DNA-dependent manner, similar to those previously described in the systemic inflammatory response to COVID-19. In moderate-to-severe cases, the blood-testes barrier grants little defence against different pathogenic viruses, including the severe acute syndrome coronavirus 2. The virus could also use the epididymis as a post-testicular route to bind and fuse to the mature spermatozoon and possibly accomplish the reverse transcription of the single-stranded viral RNA into proviral DNA. These mechanisms can elicit extracellular cell-free DNA formation. The potential implications of our findings for assisted conception must be addressed, and the evolutionary history of DNA-based extracellular traps as preserved ammunition in animals' innate defence might improve our understanding of the severe acute syndrome coronavirus 2 pathophysiology in the testis and spermatozoa.

Maternal greenness exposure and preterm birth in Brazil: A nationwide birth cohort study.

In the dynamic landscape of maternal and child health, understanding the intricate interplay between environmental factors and pregnancy outcomes is of paramount importance. This study investigates the relationship between maternal greenness exposure and preterm births in Brazil using data spanning from 2010 to 2019. Satellite-derived indices, including the Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI), were employed to assess greenness exposure during whole pregnancy in maternal residential area. Employing Cox proportional hazard models, we calculated the hazard ratios (HRs) with 95% confidence intervals (CIs) for changes in NDVI, while adjusting for individual and area-level covariates. In total, 24,010,250 live births were included. Prevalence of preterm birth was 11.5%, with a modest but statistically significant decreasing trend (p = 0.013) observed across the nation over the study period. The findings reveal a significant association between greenness exposure and a reduced risk of preterm birth. Specifically, for every 0.1 increase in NDVI, there was a 2.0% decrease in the risk of preterm birth (95%CI: 1.9%-2.2%). Stratified analyses based on maternal education and ethnicity indicated potential effect modifications, with stronger protective effects observed among younger mothers and those with less years of education. Sensitivity analyses using EVI yielded consistent results. In conclusion, this study suggests that higher maternal greenness exposure is linked to a decreased risk of preterm birth in Brazil. These findings imply that enhancing residential greenspaces could be a valuable public health strategy to promote maternal and child health in Brazil.

Younger age is associated with cardiovascular pathological phenotype of severe COVID-19 at autopsy.

Introduction: COVID-19 affects patients of all ages. There are few autopsy studies focusing on the younger population. We assessed an autopsy cohort aiming to understand how age influences pathological outcomes in fatal COVID-19. Methods: This study included autopsied patients, aged 6 months to 83 years, with confirmed COVID-19 in 2020-2021. We collected tissue samples from deceased patients using a minimally invasive autopsy protocol and assessed pathological data following a systematic approach. Results: Eighty-six patients were included, with a median age of 55 years (IQR 32.3-66.0). We showed that age was significantly lower in patients with acute heart ischemia (p = 0.004), myocarditis (p = 0.03) and lung angiomatosis (p < 0.001), and significantly higher in patients with exudative diffuse alveolar damage (p = 0.02), proliferative diffuse alveolar damage (p < 0.001), lung squamous metaplasia (p = 0.003) and lung viral atypia (p = 0.03), compared to patients without those findings. We stratified patients by their age and showed that cardiovascular findings were more prevalent in children and young adults. We performed principal component analysis and cluster of pathological variables, and showed that cardiovascular variables clustered and covariated together, and separated from pulmonary variables. Conclusion: We showed that age modulates pathological outcomes in fatal COVID-19. Younger age is associated with cardiovascular abnormalities and older age with pulmonary findings.

Short-term exposure to wildfire-related PM2.5 increases mortality risks and burdens in Brazil.

To assess mortality risks and burdens associated with short-term exposure to wildfire-related fine particulate matter with diameter ≤ 2.5 µm (PM2.5), we collect daily mortality data from 2000 to 2016 for 510 immediate regions in Brazil, the most wildfire-prone area. We integrate data from multiple sources with a chemical transport model at the global scale to isolate daily concentrations of wildfire-related PM2.5 at a 0.25 × 0.25 resolution. With a two-stage time-series approach, we estimate (i) an increase of 3.1% (95% confidence interval [CI]: 2.4, 3.9%) in all-cause mortality, 2.6% (95%CI: 1.5, 3.8%) in cardiovascular mortality, and 7.7% (95%CI: 5.9, 9.5) in respiratory mortality over 0-14 days with each 10 µg/m3 increase in daily wildfire-related PM2.5; (ii) 0.65% of all-cause, 0.56% of cardiovascular, and 1.60% of respiratory mortality attributable to acute exposure to wildfire-related PM2.5, corresponding to 121,351 all-cause deaths, 29,510 cardiovascular deaths, and 31,287 respiratory deaths during the study period. In this study, we find stronger associations in females and adults aged ≥ 60 years, and geographic difference in the mortality risks and burdens.

MUC22, HLA-A, and HLA-DOB variants and COVID-19 in resilient super-agers from Brazil.

Background: Although aging correlates with a worse prognosis for Covid-19, super elderly still unvaccinated individuals presenting mild or no symptoms have been reported worldwide. Most of the reported genetic variants responsible for increased disease susceptibility are associated with immune response, involving type I IFN immunity and modulation; HLA cluster genes; inflammasome activation; genes of interleukins; and chemokines receptors. On the other hand, little is known about the resistance mechanisms against SARS-CoV-2 infection. Here, we addressed polymorphisms in the MHC region associated with Covid-19 outcome in super elderly resilient patients as compared to younger patients with a severe outcome. Methods: SARS-CoV-2 infection was confirmed by RT-PCR test. Aiming to identify candidate genes associated with host resistance, we investigated 87 individuals older than 90 years who recovered from Covid-19 with mild symptoms or who remained asymptomatic following positive test for SARS-CoV-2 as compared to 55 individuals younger than 60 years who had a severe disease or died due to Covid-19, as well as to the general elderly population from the same city. Whole-exome sequencing and an in-depth analysis of the MHC region was performed. All samples were collected in early 2020 and before the local vaccination programs started. Results: We found that the resilient super elderly group displayed a higher frequency of some missense variants in the MUC22 gene (a member of the mucins' family) as one of the strongest signals in the MHC region as compared to the severe Covid-19 group and the general elderly control population. For example, the missense variant rs62399430 at MUC22 is two times more frequent among the resilient super elderly (p = 0.00002, OR = 2.24). Conclusion: Since the pro-inflammatory basal state in the elderly may enhance the susceptibility to severe Covid-19, we hypothesized that MUC22 might play an important protective role against severe Covid-19, by reducing overactive immune responses in the senior population.

Marijuana Is Associated With a Hormonal Imbalance Among Several Habits Related to Male Infertility: A Retrospective Study.

Marijuana is one of the most consumed drugs worldwide. There is increasing evidence of an association between marijuana and male infertility. This study intends to assess the repercussion of marijuana smoking and other habits (sedentary lifestyle, alcohol, and tobacco use) in the testicular function of infertile men seeking andrological evaluation. A retrospective study was performed using medical records data of men aged 18-59 years from 2009 to 2017. Complete semen analyses, sperm functional tests, SHBG, and hormonal levels, testosterone-to-estradiol ratio (T/E2), and testis volume were evaluated. Exclusion criteria included cryptorchidism, infertility caused by genetic or infectious diseases, and cancer. A multiple linear regression analysis was performed to investigate which habit could predict certain parameters using the software SPSS 23.0 (P < 0.05). In a sample of 153 men, semen parameters, testosterone levels, and testis volume were not significantly influenced. Marijuana use had the broader hormonal changes since it influences estradiol (P = 0.000; B = -11.616), prolactin (P = 0.000; B = 3.211), SHBG levels (P = 0.017; B = 7.489), and T/E2 (P = 0.004; B = 14.030). Sedentary lifestyle (P = 0.028; B = 1.279) and tobacco smoking (P = 0.031; B = -2.401) influenced the prolactin levels. Marijuana is associated with hormonal imbalance in this infertile cohort by lowering estradiol levels and inhibiting aromatase function.

Exposure to wildfire-related PM2.5 and site-specific cancer mortality in Brazil from 2010 to 2016: A retrospective study.

BACKGROUND: Long-term exposure to fine particles ≤2.5 µm in diameter (PM2.5) has been linked to cancer mortality. However, the effect of wildfire-related PM2.5 exposure on cancer mortality risk is unknown. This study evaluates the association between wildfire-related PM2.5 and site-specific cancer mortality in Brazil, from 2010 to 2016. METHODS AND FINDINGS: Nationwide cancer death records were collected during 2010-2016 from the Brazilian Mortality Information System. Death records were linked with municipal-level wildfire- and non-wildfire-related PM2.5 concentrations, at a resolution of 2.0° latitude by 2.5° longitude. We applied a variant difference-in-differences approach with quasi-Poisson regression, adjusting for seasonal temperature and gross domestic product (GDP) per capita. Relative risks (RRs) and 95% confidence intervals (CIs) for the exposure for specific cancer sites were estimated. Attributable fractions and cancer deaths were also calculated. In total, 1,332,526 adult cancer deaths (age ≥ 20 years), from 5,565 Brazilian municipalities, covering 136 million adults were included. The mean annual wildfire-related PM2.5 concentration was 2.38 µg/m3, and the annual non-wildfire-related PM2.5 concentration was 8.20 µg/m3. The RR for mortality from all cancers was 1.02 (95% CI 1.01-1.03, p < 0.001) per 1-µg/m3 increase of wildfire-related PM2.5 concentration, which was higher than the RR per 1-µg/m3 increase of non-wildfire-related PM2.5 (1.01 [95% CI 1.00-1.01], p = 0.007, with p for difference = 0.003). Wildfire-related PM2.5 was associated with mortality from cancers of the nasopharynx (1.10 [95% CI 1.04-1.16], p = 0.002), esophagus (1.05 [95% CI 1.01-1.08], p = 0.012), stomach (1.03 [95% CI 1.01-1.06], p = 0.017), colon/rectum (1.08 [95% CI 1.05-1.11], p < 0.001), larynx (1.06 [95% CI 1.02-1.11], p = 0.003), skin (1.06 [95% CI 1.00-1.12], p = 0.003), breast (1.04 [95% CI 1.01-1.06], p = 0.007), prostate (1.03 [95% CI 1.01-1.06], p = 0.019), and testis (1.10 [95% CI 1.03-1.17], p = 0.002). For all cancers combined, the attributable deaths were 37 per 100,000 population and ranged from 18/100,000 in the Northeast Region of Brazil to 71/100,000 in the Central-West Region. Study limitations included a potential lack of assessment of the joint effects of gaseous pollutants, an inability to capture the migration of residents, and an inability to adjust for some potential confounders. CONCLUSIONS: Exposure to wildfire-related PM2.5 can increase the risks of cancer mortality for many cancer sites, and the effect for wildfire-related PM2.5 was higher than for PM2.5 from non-wildfire sources.

High ambient temperature and risk of hospitalization for gastrointestinal infection in Brazil: A nationwide case-crossover study during 2000-2015.

BACKGROUND: The burden of gastrointestinal infections related to hot ambient temperature remains largely unexplored in low-to-middle income countries which have most of the cases globally and are experiencing the greatest impact from climate change. The situation is particularly true in Brazil. OBJECTIVES: Using medical records covering over 78 % of population, we quantify the association between high temperature and risk of hospitalization for gastrointestinal infection in Brazil between 2000 and 2015. METHODS: Data on hospitalization for gastrointestinal infection and weather conditions were collected from 1814 Brazilian cities during the 2000-2015 hot seasons. A time-stratified case-crossover design was used to estimate the association. Stratified analyses were performed by region, sex, age-group, type of infection and early/late study period. RESULTS: For every 5 °C increase in mean daily temperature, the cumulative odds ratio (OR) of hospitalization over 0-9 days was 1.22 [95 % confidence interval (CI): 1.21, 1.23] at the national level, reaching its maximum in the south and its minimum in the north. The strength of association tended to decline across successive age-groups, with infants < 1 year most susceptible. The effect estimates were similar for men and women. Waterborne and foodborne infections were more associated with high temperature than the 'others' and 'idiopathic' groups. There was no substantial change in the association over the 16-year study period. DISCUSSION: Our findings indicate that exposure to high temperature is associated with increased risk of hospitalization for gastrointestinal infection in the hot season, with the strength varying by region, population subgroup and infection type. There was no evidence to indicate adaptation to heat over the study duration.

Post-Mortem Diagnosis of Pediatric Dengue Using Minimally Invasive Autopsy during the COVID-19 Pandemic in Brazil.

We report the first pediatric disease in which the use of minimally invasive autopsy (MIA) confirmed severe dengue as the cause of death. During the COVID-19 pandemic, a previously healthy 10-year-old girl living in north-eastern Brazil presented fever, headache, diffuse abdominal pain, diarrhoea, and vomiting. On the fourth day, the clinical symptoms worsened and the patient died. An MIA was performed, and cores of brain, lungs, heart, liver, kidneys, and spleen were collected with 14G biopsy needles. Microscopic examination showed diffuse oedema and congestion, pulmonary intra-alveolar haemorrhage, small foci of midzonal necrosis in the liver, and tubular cell necrosis in the kidneys. Dengue virus RNA and NS1 antigen were detected in blood and cerebrospinal fluid samples. Clinical, pathological, and laboratory findings, in combination with the absence of other lesions and microorganisms, allowed concluding that the patient had died from complications of severe dengue.

Loss of life expectancy from PM2.5 in Brazil: A national study from 2010 to 2018.

BACKGROUND: Long-term exposure to PM2.5 is proved to be linked with mortality. However, limited studies have estimated the PM2.5 related loss of life expectancy (LLE) and its changing trends. How much life expectancy would be improved if PM2.5 pollution is reduced to the new WHO air quality guideline (AQG) level is unclear. METHODS: Data on deaths from all-causes, cancer, cardiovascular and respiratory diseases were collected from 5,565 Brazilian municipalities during 2010-2018. A difference-in-differences approach with quasi-Poisson regression was applied to examine the PM2.5-years of life lost (YLL) associations and PM2.5 associated LLE. RESULTS: The annual PM2.5 concentration in each municipality from 2010 to 2018 was 7.7 µg/m3 in Brazil. Nationally, with each 10 µg/m3 increase in five-year-average (current and previous four years) concentrations of PM2.5, the relative risks (RRs) were 1.18 (95% CI: 1.15-1.21) for YLL from all-causes, 1.22 (1.16-1.28) from cancer, 1.12 (1.08-1.17) from cardiovascular and 1.17 (1.10-1.25) from respiratory diseases. Life expectancy could be improved by 1.09 (95% CI: 0.92-1.25) years by limiting PM2.5 concentration to the national lowest level (2.9 µg/m3), specifically, 0.20 (0.15-0.24) years for cancer, 0.16 (0.11-0.22) years for cardiovascular and 0.09 (0.05-0.13) years for respiratory diseases, with significant disparities across regions and municipalities. Life expectancy would be improved by 0.78 (0.66-0.90) years by setting the new WHO AQG PM2.5 concentration level of 5 µg/m3 as an acceptable threshold. CONCLUSIONS: Using nationwide death records in Brazil, we found that long-term exposure to PM2.5 was associated with reduced life expectancy from all-causes, cancer, cardiovascular and respiratory diseases with regional inequalities and different trends. PM2.5 pollution abatement to below the WHO AQG level would improve this loss of life expectancy in Brazil.

When One Health Meets the United Nations Ocean Decade: Global Agendas as a Pathway to Promote Collaborative Interdisciplinary Research on Human-Nature Relationships.

Strong evidence shows that exposure and engagement with the natural world not only improve human wellbeing but can also help promote environmentally friendly behaviors. Human-nature relationships are at the heart of global agendas promoted by international organizations including the World Health Organization's (WHO) "One Health" and the United Nations (UN) "Ocean Decade." These agendas demand collaborative multisector interdisciplinary efforts at local, national, and global levels. However, while global agendas highlight global goals for a sustainable world, developing science that directly addresses these agendas from design through to delivery and outputs does not come without its challenges. In this article, we present the outcomes of international meetings between researchers, stakeholders, and policymakers from the United Kingdom and Brazil. We propose a model for interdisciplinary work under such global agendas, particularly the interface between One Health and the UN Ocean Decade and identify three priority research areas closely linked to each other: human-nature connection, conservation-human behavior, and implementation strategies (bringing stakeholders together). We also discuss a number of recommendations for moving forward.

Associations between long-term exposure to PM2.5 and site-specific cancer mortality: A nationwide study in Brazil between 2010 and 2018.

Long-term exposure to PM2.5 has been linked to lung cancer incidence and mortality, but limited evidence existed for other cancers. This study aimed to assess the association between PM2.5 on cancer specific mortality. An ecological study based on the cancer mortality data collected from 5,565 Brazilian cities during 2010-2018 using a difference-in-differences approach with quasi-Poisson regression, was applied to examine PM2.5-cancer mortality associations. Globally gridded annual average surface PM2.5 concentration was extracted and linked with the residential municipality of participants in this study. Sex, age stratified and exposure-response estimations were also conducted. Totalling 1,768,668 adult cancer deaths records of about 208 million population living across 5,565 municipalities were included in this study. The average PM2.5 concentration was 7.63 µg/m3 (standard deviation 3.32) with range from 2.95 µg/m3 to 28.5 µg/m3. With each 10 µg/m3 increase in three-year-average (current year and previous two years) concentrations of PM2.5, the relative risks (RR) of cancer mortality were 1.16 (95% confidence interval [CI]: 1.11-1.20) for all-site cancers. The PM2.5 exposure was significantly associated with several cancer-specific mortalities including oral, nasopharynx, oesophagus, and stomach, colon rectum, liver, gallbladder, larynx, lung, bone, skin, female breast, cervix, prostate, brain and leukaemia. No safe level of PM2.5 exposure was observed in the exposure-response curve for all types of cancer. In conclusion, with nationwide cancer death records in Brazil, we found that long-term exposure to ambient PM2.5 increased risks of mortality for many cancer types. Even low level PM2.5 concentrations had significant impacts on cancer mortality.

Testicular pathology in fatal COVID-19: A descriptive autopsy study.

BACKGROUND: Multi-organ damage is a common feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, going beyond the initially observed severe pneumonia. Evidence that the testis is also compromised is growing. OBJECTIVE: To describe the pathological findings in testes from fatal cases of COVID-19, including the detection of viral particles and antigens, and inflammatory cell subsets. MATERIALS AND METHODS: Postmortem testicular samples were obtained by percutaneous puncture from 11 deceased men and examined by reverse-transcription polymerase chain reaction (RT-PCR) for RNA detection and by light and electron microscopy (EM) for SARS-CoV-2. Immunohistochemistry (IHC) for the SARS-CoV-2 N-protein and lymphocytic and histiocytic markers was also performed. RESULTS: Eight patients had mild interstitial orchitis, composed mainly of CD68+ and TCD8+ cells. Fibrin thrombi were detected in five cases. All cases presented congestion, interstitial edema, thickening of the tubular basal membrane, decreased Leydig and Sertoli cells with reduced spermatogenesis, and strong expression of vascular cell adhesion molecule (VCAM) in vessels. IHC detected SARS-Cov-2 antigen in Leydig cells, Sertoli cells, spermatogonia, and fibroblasts in all cases. EM detected viral particles in the cytoplasm of fibroblasts, endothelium, Sertoli and Leydig cells, spermatids, and epithelial cells of the rete testis in four cases, while RT-PCR detected SARS-CoV-2 RNA in three cases. DISCUSSION AND CONCLUSION: The COVID-19-associated testicular lesion revealed a combination of orchitis, vascular changes, basal membrane thickening, Leydig and Sertoli cell scarcity, and reduced spermatogenesis associated with SARS-CoV-2 local infection that may impair hormonal function and fertility in men.

The impacts of long-term exposure to PM2.5 on cancer hospitalizations in Brazil.

BACKGROUND: Long-term exposure to PM2.5 has been linked to cancer incidence and mortality. However, it was unknown whether there was an association with cancer hospitalizations. METHODS: Data on cancer hospitalizations and annual PM2.5 concentrations were collected from 1,814 Brazilian cities during 2002-2015. A difference-in-difference approach with quasi-Poisson regression was applied to examine State-specific associations. The State-specific associations were pooled at a national level using random-effect meta-analyses. PM2.5 attributable burden were estimated for cancer hospitalization admissions, inpatient days and costs. RESULTS: We included 5,102,358 cancer hospitalizations (53.8% female). The mean annual concentration of PM2.5 was 7.0 µg/m3 (standard deviation: 4.0 µg/m3). With each 1 µg/m3 increase in two-year-average (current year and previous one year) concentrations of PM2.5, the relative risks (RR) of hospitalization were 1.04 (95% confidence interval [CI]: 1.02 to 1.07) for all-site cancers from 2002 to 2015 without sex and age differences. We estimated that 33.82% (95%CI: 14.97% to 47.84%) of total cancer hospitalizations could be attributed to PM2.5 exposure in Brazil during the study time. For every 100,000 population, 1,190 (95%CI: 527 to 1,836) cancer hospitalizations, 8,191 (95%CI: 3,627 to 11,587) inpatient days and US$788,775 (95%CI: $349,272 to $1,115,825) cost were attributable to PM2.5 exposure. CONCLUSIONS: Long-term exposure to ambient PM2.5 was positively associated with hospitalization for many cancer types in Brazil. Inpatient days and cost would be saved if the annual PM2.5 exposure was reduced.

Radiological patterns of incidental epididymitis in mild-to-moderate COVID-19 patients revealed by colour Doppler ultrasound.

The testis is a potential target organ for SARS-CoV-2 infection. Our study intended to investigate any testicular involvement in mild-to-moderate COVID-19 men. We conduct a cross-sectional study in 18 to 55-year-old men hospitalised for confirmed COVID-19. A senior radiologist executed the ultrasound with multi-frequency linear probe in all participants, regardless of any scrotal complaints. Exclusion criteria involved any situation that could impair testicular function. Statistical analysis compared independent groups, classified by any pathological change. Categorical and numerical outcome hypotheses were tested by Fisher's Exact and Mann-Whitney tests, using the Excel for Mac, version 16.29 (p < .05). The sample size was 26 men (mean 33.7 ± 6.2 years; range: 21-42 years), all without scrotal complaints. No orchitis was seen. Eleven men (32.6 ± 5.8 years) had epididymitis (42.3%), bilateral in 19.2%. More than half of men with epididymitis displayed epididymal head augmentation > 1.2 cm (p = .002). Two distinct epididymitis' patterns were reported: (a) disseminated micro-abscesses (n = 6) and (b) inhomogeneous echogenicity with reactional hydrocele (n = 5). Both patterns revealed increased epididymal head, augmented Doppler flow and scrotal skin thickening. The use of colour Doppler ultrasound in mild-to-moderate COVID-19 men, even in the absence of testicular complaints, might be useful to diagnose epididymitis that could elicit fertility complications.

SARS-CoV-2 and its relationship with the genitourinary tract: Implications for male reproductive health in the context of COVID-19 pandemic.

BACKGROUND: The current outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, named coronavirus disease 19 (COVID-19), is not the first well-known spillover of an animal originated virus to infect humans. However, one of the few to make such a fast jump in a powerful evolutionary shortcut. The incredible pattern of aggressiveness worldwide since the beginning of the outbreak is that up to 20% of those infected need hospitalization and 5% evolve to critical conditions, not limited to respiratory-related issues, but rather to systemic involvement. OBJECTIVE: This study aims to summarize the current knowledge about the effects of SARS-CoV-2 infection on the male genitourinary tract. MATERIALS AND METHODS: A narrative review was carried out to identify articles on the SARS-CoV-2 infection on the male genitourinary system. RESULTS: Considerations were made about the molecular characteristics of SARS-CoV-2 and immune response to coronavirus. We discussed the influence of the virus on the urinary system, potential mechanisms of COVID-19- related acute kidney injury (AKI), and the role of cytokine release syndrome on the renal pathophysiology of the disease. In the male reproductive tract, it was discussed the testis' vulnerability to SARS-CoV-2 invasion and the possible adverse effects on its function and the seminal findings of COVID-19. DISCUSSION AND CONCLUSION: During the COVID-19 pandemic, an international coordinated scientific effort must arise to understand the role of the urogenital system in the SARS-CoV-2 infection in the clinical setting.

Socioeconomic inequality in vulnerability to all-cause and cause-specific hospitalisation associated with temperature variability: a time-series study in 1814 Brazilian cities.

BACKGROUND: Exposure to temperature variability has been associated with increased risk of mortality and morbidity. We aimed to evaluate whether the association between short-term temperature variability and hospitalisation was affected by local socioeconomic level in Brazil. METHODS: In this time-series study, we collected city-level socioeconomic data, and daily hospitalisation and weather data from 1814 Brazilian cities between Jan 1, 2000, and Dec 31, 2015. All-cause and cause-specific hospitalisation data was from the Hospital Information System of the Unified Health System in Brazil. City-specific daily minimum and maximum temperatures came from a 0·25° × 0·25° Brazilian meteorological dataset. We represented city-specific socioeconomic level using literacy rate, urbanisation rate, average monthly household income per capita (using the 2000 and 2010 Brazilian census), and GDP per capita (using statistics from the Brazilian Institute of Geography and Statistics for 2000-15), and cities were categorised according to the 2015 World Bank standard. We used quasi-Poisson regression to do time-series analyses and obtain city-specific associations between temperature variability and hospitalisation. We pooled city-specific estimates according to different socioeconomic quartiles or levels using random-effect meta-analyses. Meta-regressions adjusting for demographic and climatic characteristics were used to evaluate the modification effect of city-level socioeconomic indicators on the association between temperature variability and hospitalisation. FINDINGS: We included a total of 147 959 243 hospitalisations (59·0% female) during the study period. Overall, we estimated that the hospitalisation risk due to every 1°C increase in the temperature variability in the current and previous day (TV0-1) increased by 0·52% (95% CI 0·50-0·55). For lower-middle-income cities, this risk was 0·63% (95% CI 0·58-0·69), for upper-middle-income cities it was 0·50% (0·47-0·53), and for high-income cities it was 0·39% (0·33-0·46). The socioeconomic inequality in vulnerability to TV0-1 was especially evident for people aged 0-19 years (effect estimate 1·21% [1·11-1·31] for lower-middle income vs 0·52% [0·41-0·63] for high income) and people aged 60 years or older (0·60% [0·50-0·70] vs 0·43% [0·31-0·56]), and for hospitalisation due to infectious diseases (1·62% [1·46-1·78] vs 0·56% [0·30-0·82]), respiratory diseases (1·32% [1·20-1·44] vs 0·55% [0·37-0·74]), and endocrine diseases (1·21% [0·99-1·43] vs 0·32% [0·02-0·62]). INTERPRETATION: People living in less developed cities in Brazil were more vulnerable to hospitalisation related to temperature variability. This disparity could exacerbate existing health and socioeconomic inequalities in Brazil, and it suggests that more attention should be paid to less developed areas to mitigate the adverse health effects of short-term temperature fluctuations. FUNDING: None.

Socioeconomic level and associations between heat exposure and all-cause and cause-specific hospitalization in 1,814 Brazilian cities: A nationwide case-crossover study.

BACKGROUND: Heat exposure, which will increase with global warming, has been linked to increased risk of a range of types of cause-specific hospitalizations. However, little is known about socioeconomic disparities in vulnerability to heat. We aimed to evaluate whether there were socioeconomic disparities in vulnerability to heat-related all-cause and cause-specific hospitalization among Brazilian cities. METHODS AND FINDINGS: We collected daily hospitalization and weather data in the hot season (city-specific 4 adjacent hottest months each year) during 2000-2015 from 1,814 Brazilian cities covering 78.4% of the Brazilian population. A time-stratified case-crossover design modeled by quasi-Poisson regression and a distributed lag model was used to estimate city-specific heat-hospitalization association. Then meta-analysis was used to synthesize city-specific estimates according to different socioeconomic quartiles or levels. We included 49 million hospitalizations (58.5% female; median [interquartile range] age: 33.3 [19.8-55.7] years). For cities of lower middle income (LMI), upper middle income (UMI), and high income (HI) according to the World Bank's classification, every 5°C increase in daily mean temperature during the hot season was associated with a 5.1% (95% CI 4.4%-5.7%, P < 0.001), 3.7% (3.3%-4.0%, P < 0.001), and 2.6% (1.7%-3.4%, P < 0.001) increase in all-cause hospitalization, respectively. The inter-city socioeconomic disparities in the association were strongest for children and adolescents (0-19 years) (increased all-cause hospitalization risk with every 5°C increase [95% CI]: 9.9% [8.7%-11.1%], P < 0.001, in LMI cities versus 5.2% [4.1%-6.3%], P < 0.001, in HI cities). The disparities were particularly evident for hospitalization due to certain diseases, including ischemic heart disease (increase in cause-specific hospitalization risk with every 5°C increase [95% CI]: 5.6% [-0.2% to 11.8%], P = 0.060, in LMI cities versus 0.5% [-2.1% to 3.1%], P = 0.717, in HI cities), asthma (3.7% [0.3%-7.1%], P = 0.031, versus -6.4% [-12.1% to -0.3%], P = 0.041), pneumonia (8.0% [5.6%-10.4%], P < 0.001, versus 3.8% [1.1%-6.5%], P = 0.005), renal diseases (9.6% [6.2%-13.1%], P < 0.001, versus 4.9% [1.8%-8.0%], P = 0.002), mental health conditions (17.2% [8.4%-26.8%], P < 0.001, versus 5.5% [-1.4% to 13.0%], P = 0.121), and neoplasms (3.1% [0.7%-5.5%], P = 0.011, versus -0.1% [-2.1% to 2.0%], P = 0.939). The disparities were similar when stratifying the cities by other socioeconomic indicators (urbanization rate, literacy rate, and household income). The main limitations were lack of data on personal exposure to temperature, and that our city-level analysis did not assess intra-city or individual-level socioeconomic disparities and could not exclude confounding effects of some unmeasured variables. CONCLUSIONS: Less developed cities displayed stronger associations between heat exposure and all-cause hospitalizations and certain types of cause-specific hospitalizations in Brazil. This may exacerbate the existing geographical health and socioeconomic inequalities under a changing climate.