Molecular identification of Histoplasma capsulatum in patients with disseminated histoplasmosis and acquired immunodeficiency syndrome.

Histoplasmosis is caused by the fungus Histoplasma capsulatum and is often fatal for individuals with acquired immunodeficiency syndrome (AIDS). Delayed diagnosis is a major factor in worsening coinfection, as it can be mistaken for other diseases. Thus, rapid identification of Histoplasma in immunocompromised patients is essential. Molecular techniques, particularly polymerase chain reaction (PCR), were used in this study to identify H. capsulatum in patients coinfected with histoplasmosis and AIDS. Blood samples from 14 individuals with AIDS and disseminated histoplasmosis were collected and analyzed. The PCR method successfully amplified the fungal region in whole blood samples, while PCR-RFLP analysis confirmed a consistent profile in the samples. Genetic sequencing further confirmed the fungal species. Compared to clinical tests such as fungal culture and urinary antigen detection, molecular analysis proved faster, more sensitive, and cost-effective. These molecular markers can potentially be incorporated into routine diagnostics in the future. Further studies are needed to expand and enhance this diagnostic approach, particularly in patients with nonprogressive clinical forms of histoplasmosis.

Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis: A Randomized Trial.

BACKGROUND: Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. METHODS: Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. RESULTS: A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P = .69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P = .82). CONCLUSIONS: One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access.

In vitro antiviral activity of the anti-HCV drugs daclatasvir and sofosbuvir against SARS-CoV-2, the aetiological agent of COVID-19.

BACKGROUND: Current approaches of drug repurposing against COVID-19 have not proven overwhelmingly successful and the SARS-CoV-2 pandemic continues to cause major global mortality. SARS-CoV-2 nsp12, its RNA polymerase, shares homology in the nucleotide uptake channel with the HCV orthologue enzyme NS5B. Besides, HCV enzyme NS5A has pleiotropic activities, such as RNA binding, that are shared with various SARS-CoV-2 proteins. Thus, anti-HCV NS5B and NS5A inhibitors, like sofosbuvir and daclatasvir, respectively, could be endowed with anti-SARS-CoV-2 activity. METHODS: SARS-CoV-2-infected Vero cells, HuH-7 cells, Calu-3 cells, neural stem cells and monocytes were used to investigate the effects of daclatasvir and sofosbuvir. In silico and cell-free based assays were performed with SARS-CoV-2 RNA and nsp12 to better comprehend the mechanism of inhibition of the investigated compounds. A physiologically based pharmacokinetic model was generated to estimate daclatasvir's dose and schedule to maximize the probability of success for COVID-19. RESULTS: Daclatasvir inhibited SARS-CoV-2 replication in Vero, HuH-7 and Calu-3 cells, with potencies of 0.8, 0.6 and 1.1 µM, respectively. Although less potent than daclatasvir, sofosbuvir alone and combined with daclatasvir inhibited replication in Calu-3 cells. Sofosbuvir and daclatasvir prevented virus-induced neuronal apoptosis and release of cytokine storm-related inflammatory mediators, respectively. Sofosbuvir inhibited RNA synthesis by chain termination and daclatasvir targeted the folding of secondary RNA structures in the SARS-CoV-2 genome. Concentrations required for partial daclatasvir in vitro activity are achieved in plasma at Cmax after administration of the approved dose to humans. CONCLUSIONS: Daclatasvir, alone or in combination with sofosbuvir, at higher doses than used against HCV, may be further fostered as an anti-COVID-19 therapy.

The prion protein selectively binds to and modulates the content of purinergic receptor P2X4R.

The GPI-anchored prion protein (PrP(C)) is involved in neurodegeneration, either through misfolding in the Transmissible Spongiform Encephalopathies (TSE), or as a mediator of the neurotoxicity of peptide oligomers in Alzheimer's Disease. PrP(C) has been attributed pleiotropic functions, and appears to scaffold a variety of cell surface signaling modules, for example through its binding to several neurotransmitter receptors. Here we used transfected HEK293 cells to test for an interaction of PrP(C) with purinergic receptor P2X4R. The prion protein bound P2X4R in both overlay and co-immunoprecipitation assays, and co-localized mostly intracellularly, but occasionaly at the cell surface in confocal micrographs. Functional PrP(C):P2X4R interaction was tested by the uptake of a P2X4R-permeant compound, and by modulation of intracellular calcium. Unexpectedly, however, this interaction was traced to a selective effect of PrP(C) upon the content of co-transfected P2X4R. The results suggest a role of PrP(C) in proteostasis, dysfunctions of which may be involved in the pathogenesis of neurodegenerative diseases such as TSE and Alzheimer's Disease.

Anti-inflammatory lipoxin A4 is an endogenous allosteric enhancer of CB1 cannabinoid receptor.

Allosteric modulation of G-protein-coupled receptors represents a key goal of current pharmacology. In particular, endogenous allosteric modulators might represent important targets of interventions aimed at maximizing therapeutic efficacy and reducing side effects of drugs. Here we show that the anti-inflammatory lipid lipoxin A(4) is an endogenous allosteric enhancer of the CB(1) cannabinoid receptor. Lipoxin A(4) was detected in brain tissues, did not compete for the orthosteric binding site of the CB(1) receptor (vs. (3)H-SR141716A), and did not alter endocannabinoid metabolism (as opposed to URB597 and MAFP), but it enhanced affinity of anandamide at the CB1 receptor, thereby potentiating the effects of this endocannabinoid both in vitro and in vivo. In addition, lipoxin A(4) displayed a CB(1) receptor-dependent protective effect against ß-amyloid (1-40)-induced spatial memory impairment in mice. The discovery of lipoxins as a class of endogenous allosteric modulators of CB(1) receptors may foster the therapeutic exploitation of the endocannabinoid system, in particular for the treatment of neurodegenerative disorders.

Behavioral Assessment of Central Auditory Processing in Turner Syndrome.

Introduction Turner syndrome (TS) affects ∼ 1 in 2,500 live births. The presence of hearing alterations is one of the comorbidities found in this syndrome. Objective The present study aimed to evaluate the central auditory abilities in TS and to associate the alterations found with the cytogenetic pattern of the syndrome. Methods We included children and adults aged 9 to 39 years old, diagnosed with TS, with numerical or structural alterations of sex chromosomes in their karyotype. A battery of behavioral tests of central auditory processing (CAP) was performed, including a test within the modalities: monoaural low-redundancy, dichotic listening, binaural interaction, and temporal processing (resolution and ordering). We studied auditory skills in the total sample and in the sample stratified by age, divided into groups: G1 (9 to 13 years old), G2 (14 to 19 years old), and G3 (20 to 31 years old). For the association of the cytogenetic pattern, the division was T1 (chromosome monosomy X), and T2 (other TS cytogenetic patterns). Statistical analysis presented data expressed as median and interquartile range for numerical data and as frequency and percentage for categorical data. Results We found alterations in four auditory skills in the three age groups, but there was a statistically significant difference between the age groups only in the Gaps in Noise Test (GIN) ( p -value = 0.009). Regarding karyotype, a greater number of alterations in the T1 cytogenetic pattern (chromosome monosomy X) was observed in four auditory skills, but without a statistically significant difference. Conclusion The alterations found point to an impairment in CAP in TS.

Saxitoxin potentiates human neuronal cell death induced by Zika virus while sparing neural progenitors and astrocytes.

The Zika virus (ZIKV) epidemic declared in Brazil between 2015 and 2016 was associated with an increased prevalence of severe congenital malformations, including microcephaly. The distribution of microcephaly cases was not uniform across the country, with a disproportionately higher incidence in the Northeast region (NE). Our previous work demonstrated that saxitoxin (STX), a toxin present in the drinking water reservoirs of the NE, exacerbated the damaging effects of ZIKV on the developing brain. We hypothesized that the impact of STX might vary among different neural cell types. While ZIKV infection caused severe damages on astrocytes and neural stem cells (NSCs), the addition of STX did not exacerbate these effects. We observed that neurons subjected to STX exposure were more prone to apoptosis and displayed higher ZIKV infection rate. These findings suggest that STX exacerbates the harmful effects of ZIKV on neurons, thereby providing a plausible explanation for the heightened severity of ZIKV-induced congenital malformations observed in Brazil's NE. This study highlights the importance of understanding the interactive effects of environmental toxins and infectious pathogens on neural development, with potential implications for public health policies.

Cell Cycle Kinetics and Sister Chromatid Exchange in Mosaic Turner Syndrome.

Turner syndrome (TS) is caused by a complete or partial absence of an X or Y chromosome, including chromosomal mosaicism, affecting 1 in 2500 female live births. Sister chromatid exchange (SCE) is used as a sensitive indicator of spontaneous chromosome instability. Cells from mosaic patients constitute useful material for SCE evaluations as they grow under the influence of the same genetic background and endogenous and exogenous factors. We evaluated the proliferation dynamics and SCE frequencies of 45,X and 46,XN cells of 17 mosaic TS patients. In two participants, the 45,X cells exhibited a proliferative disadvantage in relation to 46,XN cells after 72 h of cultivation. The analysis of the mean proliferation index (PI) showed a trend for a significant difference between the 45,X and 46,X+der(X)/der(Y) cell lineages; however, there were no intra-individual differences. On the other hand, mean SCE frequencies showed that 46,X+der(X) had the highest mean value and 46,XX the lowest, with 45,X occupying an intermediate position among the lineages found in at least three participants; moreover, there were intra-individual differences in five patients. Although 46,X+der(X)/der(Y) cell lineages, found in more than 70% of participants, were the most unstable, they had a slightly higher mean PI than the 45,X cell lineages in younger (≤17 years) mosaic TS participants. This suggests that cells with a karyotype distinct from 45,X may increase with time in mosaic TS children and adolescents.

Chromium nicotinate has no effect on insulin sensitivity, glycemic control, and lipid profile in subjects with type 2 diabetes.

OBJECTIVE: To investigate the effect of chromium nicotinate supplementation on insulin sensitivity, glycemic control, and lipid profile in subjects with type 2 diabetes. MATERIALS AND METHODS: In a double-blind clinical trial, 56 overweight individuals with type 2 diabetes were randomized into 3 groups: placebo (NC0), 50 µg (NC50), and 200 µg (NC200) of chromium as chromium nicotinate. Chromium status, sensitivity to insulin, glycemic control, and lipid profile were assessed at the beginning of the study and 45 days and 90 days after. RESULTS: In the beginning, most subjects showed low concentrations of serum chromium (71.88%), regular levels of urinary chromium (80.65%), and insulin resistance (73.80%). The serum chromium concentrations did not differ among the groups over time (p = 0.2549). The changes in serum chromium and urine concentrations did not relate to changes in fasting glucose (p > 0.05). At 90 days of intervention, there was no significant difference between groups in fasting glucose, glycosylated hemoglobin, homeostasis model assessment insulin resistance (HOMA-IR), total cholesterol, and low-density lipoprotein (LDL); there was increase in homeostasis model assessment ß-cell function (HOMA-ß; p = 0.0349) and high-density lipoprotein (HDL; p = 0.0425) in the NC0 group and a reduction of triglycerides in the NC0 (p = 0.0177) and NC50 (p = 0.0336) groups. CONCLUSION: Supplementation at 50 and 200 µg of chromium as chromium nicotinate did not promote glycemic control, increase insulin sensitivity, or change the lipid profile of subjects with diabetes.

Turner syndrome patients' ultrasound profile.

OBJECTIVE: Evaluate the uterus and ovary by ultrasonography, considering the genotype, pubertal development and hormonal levels. MATERIALS AND METHODS: Cross-sectional study of 53 (7-53 years old) patients with Turner syndrome considering pubertal development by Tanner stage, puberty induced or not and the ultrasound examination. RESULTS: The patients were 10 prepubertal and 43 with pubertal signs. Uterus was found adequate in 12 (57.1%) patients and all had spontaneous puberty. Hypoplasic uterus was found in all prepubertal patients and in 28 (52.8%) patients pubescent. The ovaries were visualized bilaterally in 32 (60%) patients and unilaterally in 15 (27.7%). Ovaries were appropriate bilaterally in eight (15.1%). In pubertal patients, the average volume being significantly higher in those with spontaneous puberty (p = 0.04 and 0.03, respectively). We found no significant difference in uterine volume, when considered estrogen route and karyotype. CONCLUSION: The ultrasonographic pattern in patients with spontaneous puberty without secondary failure was appropriate. The karyotype and the route estrogen therapy were not related to the standard of ultrasound study of the uterus and ovary.

Oligomeric α-Synuclein induces skin degeneration in reconstructed human epidermis.

Aged and photoaged skin exhibit fine wrinkles that are signs of epidermal inflammation and degeneration. It has been shown that healthy elderly skin expresses amyloidogenic proteins, including α-Synuclein, which are known to oligomerize and trigger inflammation and neurodegeneration. However, little is known about their putative role in skin physiology and sensitivity. To unravel this possible role, we investigated the impact of oligomeric α-Synuclein (Oα-Syn) in 2D and 3D keratinocyte human models. Exogenous Oα-Syn caused degeneration of reconstructed human epidermis (RHE) by diminishing proliferation and thickness of the stratum basale. Oα-Syn also increased NF-kB nuclear translocation in keratinocytes and triggered inflammation in the RHE, by increasing expression of interleukin-1ß and tumor necrosis factor-alpha, and the release of tumor necrosis factor-alpha in a time-dependent manner. Dexamethasone and an IL-1ß inhibitor partially diminished RHE degeneration caused by Oα-Syn. These findings suggest that Oα-Syn induces epidermal inflammation and decreases keratinocyte proliferation, and therefore might contribute to epidermal degeneration observed in human skin aging.

Efferent Auditory Pathways Inhibition in Turner syndrome. / Efeito inibitório da via auditiva eferente na síndrome de Turner.

PURPOSE: The goal of this study is to investigate the efferent auditory pathways inhibition in Turner's syndrome and to relate it to the cytogenetic profile. METHODS: This is a cross-sectional study with a comparison group. A sample with 94 participants divided into two groups: The study group was a sample of 40 patients diagnosed with Turner's syndrome (17.6 years of age). The control group was composed of 54 volunteers (18.9 years of age), female, without syndrome. The selected individuals were submitted to efferent auditory pathways inhibition research. RESULTS: The mean of the inhibitory effect of the efferent auditory pathway in the study group in the right ear was 0.4 dB and in the comparison group it was 1.9 dB, however in the left ear the mean of the inhibitory effect of the efferent auditory pathway was 1.4 dB in the study group and 0.8 dB in the comparison group. The inhibitory effect of the efferent auditory pathway was present in 14 individuals with monosomy and in 15 with other cytogenetic alterations. CONCLUSIONS: In the study group, the efferent auditory pathways inhibition value was significantly higher in the left ear and significantly lower than the control group in the right ear. There was no significant difference in efferent auditory pathways inhibition of right ear and left ear between the karyotype types.

OBJETIVO: investigar o efeito inibitório da via auditiva eferente na síndrome de Turner e relacionar com o perfil citogenético. MÉTODO: estudo descritivo transversal com grupo de comparação. Amostra: Grupo estudo formado por 40 pacientes com síndrome de Turner (17,6 anos); e Grupo controle constituído por 54 indivíduos (18,9 anos), do sexo feminino sem síndrome. Os indivíduos selecionados foram submetidos à pesquisa do efeito inibitório da via auditiva eferente. RESULTADOS: A média do Efeito inibitório da via auditiva eferente no grupo estudo na orelha direita foi 0,4 dB e no grupo comparação foi de 1,9 dB, entretanto na orelha esquerda a média do efeito inibitório da via auditiva eferente foi 1,4 dB no grupo estudo e 0,8 dB no grupo comparação. O efeito inibitório da via auditiva eferente foi presente em 14 indivíduos com monossomia e em 15 com outras alterações citogenéticas. CONCLUSÃO: No grupo estudo o valor do efeito inibitório da via auditiva eferente foi significantemente maior na orelha esquerda e significativamente menor que o grupo controle na direita. Não houve diferença significativa no efeito inibitório da via auditiva eferente entre os tipos de cariótipo.

Association between cytogenetic alteration and the audiometric profile of individuals with Turner syndrome.

INTRODUCTION: Turner syndrome is a frequent genetic disorder that affects female individuals and covers a large phenotypic variability. Scientific literature suggests an association between hearing loss and Turner syndrome, but it remains a controversial topic. OBJECTIVE: To associate the cytogenetic alteration with the audiometric profile of individuals with Turner syndrome. METHODS: Cross-sectional study, with a hospital-based, convenience sample. Patients diagnosed with Turner syndrome were included and those with difficulty understanding the audiometry and/or other associated syndromes were excluded. The participants were studied with pure tone audiometry. RESULTS: Of the 65 patients included, 36.9% had X chromosome monosomy and 63.0% had other alterations. Regarding the audiometry, 64.6% had normal thresholds and 35.3% had hearing impairment. Of these, 30.4% had hybrid hearing loss, 26.0% alteration at 6 and/or 8kHz, 17.3% had conductive hearing loss, 13.0% sensorineural loss and 13.0% had mixed hearing loss. We observed that the mild degree was the most frequent one. There was no statistically significant association between the cytogenetic type of Turner syndrome and the presence or absence of hearing loss, or with the type and degree of hearing loss. CONCLUSION: The cytogenetic alteration in Turner syndrome was not associated with the audiometric profile, which showed variability regarding the type and degree of hearing loss.

Body composition, but not insulin resistance, influences postprandial lipemia in patients with Turner's syndrome.

OBJECTIVE: The aim of the present study was to examine the influence of body composition and insulin resistance on the magnitude of postprandial lipemia in patients with Turner's syndrome receiving oral versus transdermal estrogen replacement. METHODS: Twenty-five patients with Turner's syndrome receiving oral or transdermal estrogen replacement were evaluated for body mass index, waist-to-hip and waist-to-height ratios, fasting glycemia, insulin, body composition (dual-energy X-ray absorptiometry), and postprandial lipid metabolism. For statistical analysis, we used parametric tests to compare numeric variables between the two subgroups. RESULTS: We observed no difference in postprandial triglyceride levels between patients receiving oral versus transdermal hormone replacement therapy. The postprandial triglycerides increment correlated positively with the percentage of total fat mass (p=0.02) and android fat mass (p=0.02) in the transdermal group. In the oral estrogen group, a positive correlation was observed between the increment in postprandial triglycerides and waist-to-hip (p=0.15) and waist-to-height (p=0.009) ratios. No association was observed between the estrogen replacement route and insulin resistance evaluated by the homeostatic model assessment-insulin resistance (HOMA-IR) index (p=0.19 and p=0.65 for the oral and transdermal groups, respectively). CONCLUSION: We concluded that body composition and anthropometric characteristics possibly affect the extent of postprandial lipemia independently from the route of estrogen replacement.

Quantitative profiling of axonal guidance proteins during the differentiation of human neurospheres.

Axon guidance is required for the establishment of brain circuits. Whether much of the molecular basis of axon guidance is known from animal models, the molecular machinery coordinating axon growth and pathfinding in humans remains to be elucidated. The use of induced pluripotent stem cells (iPSC) from human donors has revolutionized in vitro studies of the human brain. iPSC can be differentiated into neuronal stem cells which can be used to generate neural tissue-like cultures, known as neurospheres, that reproduce, in many aspects, the cell types and molecules present in the brain. Here, we analyzed quantitative changes in the proteome of neurospheres during differentiation. Relative quantification was performed at early time points during differentiation using iTRAQ-based labeling and LC-MS/MS analysis. We identified 6438 proteins, from which 433 were downregulated and 479 were upregulated during differentiation. We show that human neurospheres have a molecular profile that correlates to the fetal brain. During differentiation, upregulated pathways are related to neuronal development and differentiation, cell adhesion, and axonal guidance whereas cell proliferation pathways were downregulated. We developed a functional assay to check for neurite outgrowth in neurospheres and confirmed that neurite outgrowth potential is increased after 10 days of differentiation and is enhanced by increasing cyclic AMP levels. The proteins identified here represent a resource to monitor neurosphere differentiation and coupled to the neurite outgrowth assay can be used to functionally explore neurological disorders using human neurospheres as a model.

Case Report: SARS-CoV-2 Mother-to-Child Transmission and Fetal Death Associated With Severe Placental Thromboembolism.

SARS-CoV-2 infection during pregnancy is not usually associated with significant adverse effects. However, in this study, we report a fetal death associated with mild COVID-19 in a 34-week-pregnant woman. The virus was detected in the placenta and in an unprecedented way in several fetal tissues. Placental abnormalities (MRI and anatomopathological study) were consistent with intense vascular malperfusion, probably the cause of fetal death. Lung histopathology also showed signs of inflammation, which could have been a contributory factor. Monitoring inflammatory response and coagulation in high-risk pregnant women with COVID-19 may prevent unfavorable outcomes, as shown in this case.

WIN 55,212-2 shows anti-inflammatory and survival properties in human iPSC-derived cardiomyocytes infected with SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can infect several organs, especially impacting respiratory capacity. Among the extrapulmonary manifestations of COVID-19 is myocardial injury, which is associated with a high risk of mortality. Myocardial injury, caused directly or indirectly by SARS-CoV-2 infection, can be triggered by inflammatory processes that lead to damage to the heart tissue. Since one of the hallmarks of severe COVID-19 is the "cytokine storm", strategies to control inflammation caused by SARS-CoV-2 infection have been considered. Cannabinoids are known to have anti-inflammatory properties by negatively modulating the release of pro-inflammatory cytokines. Herein, we investigated the effects of the cannabinoid agonist WIN 55,212-2 (WIN) in human iPSC-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2. WIN did not modify angiotensin-converting enzyme II protein levels, nor reduced viral infection and replication in hiPSC-CMs. On the other hand, WIN reduced the levels of interleukins six, eight, 18 and tumor necrosis factor-alpha (TNF-α) released by infected cells, and attenuated cytotoxic damage measured by the release of lactate dehydrogenase (LDH). Our findings suggest that cannabinoids should be further explored as a complementary therapeutic tool for reducing inflammation in COVID-19 patients.

Non-permissive SARS-CoV-2 infection in human neurospheres.

Coronavirus disease 2019 (COVID-19) was initially described as a viral infection of the respiratory tract. It is now known, however, that several other organs are affected, including the brain. Neurological manifestations such as stroke, encephalitis, and psychiatric conditions have been reported in COVID-19 patients, but the neurotropic potential of the virus is still debated. Herein, we sought to investigate SARS-CoV-2 infection in human neural cells. We demonstrated that SARS-CoV-2 infection of neural tissue is non-permissive, however, it can elicit inflammatory response and cell damage. These findings add to the hypothesis that most of the neural damage caused by SARS-CoV-2 infection is due to a systemic inflammation leading to indirect harmful effects on the central nervous system despite the absence of local viral replication.

Non-permissive SARS-CoV-2 infection in human neurospheres.

Coronavirus disease 2019 (COVID-19) was initially described as a viral infection of the respiratory tract. It is now known, however, that several other organs are affected, including the brain. Neurological manifestations such as stroke, encephalitis, and psychiatric conditions have been reported in COVID-19 patients, but the neurotropic potential of the virus is still debated. Herein, we sought to investigate SARS-CoV-2 infection in human neural cells. We demonstrated that SARS-CoV-2 infection of neural tissue is non-permissive, however, it can elicit inflammatory response and cell damage. These findings add to the hypothesis that most of the neural damage caused by SARS-CoV-2 infection is due to a systemic inflammation leading to indirect harmful effects on the central nervous system despite the absence of local viral replication.

Inhibition of SARS-CoV-2 infection in human iPSC-derived cardiomyocytes by targeting the Sigma-1 receptor disrupts cytoarchitecture and beating.

SARS-CoV-2 infects cardiac cells and causes heart dysfunction. Conditions such as myocarditis and arrhythmia have been reported in COVID-19 patients. The Sigma-1 receptor (S1R) is a ubiquitously expressed chaperone that plays a central role in cardiomyocyte function. S1R has been proposed as a therapeutic target because it may affect SARS-CoV-2 replication; however, the impact of the inhibition of S1R in human cardiomyocytes remains to be described. In this study, we investigated the consequences of S1R inhibition in iPSC-derived human cardiomyocytes (hiPSC-CM). SARS-CoV-2 infection in hiPSC-CM was productive and reduced cell survival. S1R inhibition decreased both the number of infected cells and viral particles after 48 hours. S1R inhibition also prevented the release of pro-inflammatory cytokines and cell death. Although the S1R antagonist NE-100 triggered those protective effects, it compromised cytoskeleton integrity by downregulating the expression of structural-related genes and reducing beating frequency. Our findings suggest that the detrimental effects of S1R inhibition in human cardiomyocytes' integrity may abrogate its therapeutic potential against COVID and should be carefully considered.