ACE2, ACE, DPPIV, PREP and CAT L enzymatic activities in COVID-19: imbalance of ACE2/ACE ratio and potential RAAS dysregulation in severe cases.

OBJECTIVE AND DESIGN: Circulating enzymatic activity and RAAS regulation in severe cases of COVID-19 remains unclear, therefore we measured the serum activity of several proteases as potential targets to control the SARS-CoV-2 infection. MATERIAL OR SUBJECTS: 152 patients with COVID-19-like symptoms were grouped according to the severity of symptoms (COVID-19 negative, mild, moderate and severe). METHODS: Serum samples of COVID-19 patients and controls were subjected to biochemical analysis and enzymatic assays of ACE2, ACE, DPPIV, PREP and CAT L. One-way ANOVA and multivariate logistic regression analysis were used. Statistical significance was accepted at p < 0.05. RESULTS: We detected a positive correlation among comorbidities, higher C-reactive protein (CRP) and D-dimer levels with disease severity. Enzymatic assays revealed an increase in serum ACE2 and CAT L activities in severe COVID-19 patients, while ACE, DPPIV and PREP activities were significantly reduced. Notably, analysis of ACE2/ACE activity ratio suggests a possible imbalance of ANG II/ANG(1-7) ratio, in a positive association with the disease severity. CONCLUSION: Our findings reveal a correlation between proteases activity and the severity of COVID-19. These enzymes together contribute to the activation of pro-inflammatory pathways, trigger a systemic activation of inflammatory mediators, leading to a RAAS dysregulation and generating a significant damage in several organs, contributing to poor outcomes of severe cases.

Thrombomodulin Gene Mutation and Associated Predisposing Factors in Familial Collapsing Glomerulopathy.

Collapsing glomerulopathy (CG) is a rare glomerular disease and its familial form is even rarer. CG and non-collapsing forms of focal segmental glomerulosclerosis may both be caused by pathogenic variants in the same genes, but there is less information on genetics of the former disease. We hypothesized that different hits (viral infection and genetic variants) may be involved in the development of a familial CG here described. We performed renal and etiological routine evaluation, PVB19 serology, genetic tests including whole-exome analysis and dosage of serum thrombomodulin (THBD) in two siblings with CG, one healthy sister, and their mother. The THBD gene variant p.A43T in homozygosity was identified in the proband and her affected brother, both with CG. The same mutation was identified in their mother in heterozygosity. THBD levels were elevated in the serum of both affected siblings. They also had PVB19 positive serology and the G1 high-risk apolipoprotein L1 (APOL1) alleles in homozygosity. Their healthy sister had no PVB19-positive serology and no THBD nor APOL1 gene variants. In this case of familial CG, THBD, and APOL1 gene variants, and a previous PVB19 infection may be associated with the development of CG in a multihit process. In addition, the p.A43T THBD variant, identified in the affected siblings, has never been previously described in homozygosis, pointing to a likely autosomal recessive CG trait caused by this gene mutation.

Face Mask Use During the COVID-19 Outbreak: How Did Educated Brazilians Behave?

PURPOSE: To describe Brazilians' behavior regarding face mask use and health literacy during the COVID-19 pandemic before and after the Ministry of Health of Brazil formal recommendation. DESIGN: Cross-sectional surveys using a web-based questionnaire. Participants were recruited via snowball techniques. SETTING: São Paulo state, the urban epicenter of the COVID-19 pandemic in Brazil at the time of the study. PARTICIPANTS: 2.203 clicks to the survey link and 1.223 surveys completed (55.5% response rate). However, only 1118 surveys were considered after the exclusion criteria (>18 years-old and consent). MEASURES: Demographics, educational status, COVID-19-related symptoms (headache, cough, sore throat, rhinorrhea, fever, asthenia, diarrhea, dyspnea, nausea, vomiting, vertigo, anosmia, and ageusia), and face mask use. ANALYSIS: Self-reports of COVID-19 symptoms were categorized as dichotomous variables (Cohen's h = 0.94). Pearson Chi-square test evaluated differences between T1 and T2 and logistic multiple regression analyzed odds-ratio for the presence of symptoms and independent variables. RESULTS: Face mask use increased from 43.60% in T1 to 90.52% in T2 (P < .0001) as the pandemic went on. Health literacy also changed within 2 weeks and people started to assume everybody should use face masks (62.93% in T1 vs 94.12% in T2; P < .0001; ES = 0.29) during outside activities (43.60% in T1 vs 90.52% in T2; P < .0001; ES = 0.39). Self-reports of face mask use were associated with fewer self-reports of COVID-19 symptoms (OR = 0.65, P = .01, 95% CI 0.48; 0.88). CONCLUSION: Face mask use was already high among educated Brazilians before the formal recommendation by the authorities. This may have contributed to fewer self-reports of COVID-19-related symptoms.

Inflammation and kidney involvement in human viral diseases caused by SARS-CoV-2, HIV, HCV and HBV.

Inflammation is closely related to renal diseases. This is particularly true for renal diseases caused by infections as in viral diseases. In this review, we highlight the inflammatory mechanisms that underlie kidney dysfunction in SARS-CoV-2, human immunodeficiency (HIV), hepatitis C (HCV), and hepatitis B (HBV) infections. The pathophysiology of renal involvement in COVID-19 is complex, but kidney damage is frequent, and the prognosis is worse when it happens. Virus-like particles were demonstrated mostly in renal tubular epithelial cells and podocytes, which suggest that SARS-CoV-2 directly affects the kidneys. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor, which is found in endothelial cells, to infect the human host cells. Critical patients with SARS-CoV-2-associated acute kidney injury (AKI) show an increase in inflammatory cytokines (IL-1ß, IL-8, IFN-γ, TNF-α), known as cytokine storm that favors renal dysfunction by causing intrarenal inflammation, increased vascular permeability, volume depletion, thromboembolic events in microvasculature and persistent local inflammation. Besides AKI, SARS-CoV-2 can also cause glomerular disease, as other viral infections such as in HIV, HBV and HCV. HIV-infected patients present chronic inflammation that can lead to a number of renal diseases. Proinflammatory cytokines and TNF-induced apoptosis are some of the underlying mechanisms that may explain the virus-induced renal diseases that are here reviewed.

Familial Focal Segmental Glomerulosclerosis With Late-Onset Presentation and R229Q/R291W Podocin Mutations.

INTRODUCTION: Pathogenic variants in different genes have been described as involved in the development of familial focal segmental glomerulosclerosis (FSGS). A more precise genotype-phenotype correlation would be helpful to better characterize the clinical and laboratorial manifestations of this disease, as well as response to treatment. We analyzed podocin (NPHS2) gene variants in 50 members of four generations of a family with late-onset presentation of glomerular disease. RESULTS AND DISCUSSION: The NPHS2 gene variants R229Q and/or R291W were detected in several individuals, and the phenotype of FSGS with progressive loss of renal function was observed in all the family members carrying both mutations simultaneously. Patients manifested ongoing proteinuria over the years and progressive loss of renal function, which in three women culminated in renal replacement therapy by the 4th decade of life. In two affected patients with nephrotic syndrome, remission was not reached by the use of corticosteroids and other immunosuppressive drugs. The R229Q variant was pathogenic only when trans-associated with specific mutations, as the R291W variant in this family. CONCLUSION: Coexistence of the two NPHS2 variants R229Q and R291W in compound heterozygosis was a determinant of the FSGS phenotype. The presence of these variants alone in heterozygosis did not cause significant proteinuria.

Inflammation and kidney involvement in human viral diseases caused by SARS-CoV-2, HIV, HCV and HBV

Inflammation is closely related to renal diseases. This is particularly true for renal diseases caused by infections as in viral diseases. In this review, we highlight the inflammatory mechanisms that underlie kidney dysfunction in SARS-CoV-2, human immunodeficiency (HIV), hepatitis C (HCV), and hepatitis B (HBV) infections. The pathophysiology of renal involvement in COVID-19 is complex, but kidney damage is frequent, and the prognosis is worse when it happens. Virus-like particles were demonstrated mostly in renal tubular epithelial cells and podocytes, which suggest that SARS-CoV-2 directly affects the kidneys. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor, which is found in endothelial cells, to infect the human host cells. Critical patients with SARS-CoV-2-associated acute kidney injury (AKI) show an increase in inflammatory cytokines (IL-1β, IL-8, IFN-γ, TNF-α), known as cytokine storm that favors renal dysfunction by causing intrarenal inflammation, increased vascular permeability, volume depletion, thromboembolic events in microvasculature and persistent local inflammation. Besides AKI, SARS-CoV-2 can also cause glomerular disease, as other viral infections such as in HIV, HBV and HCV. HIV-infected patients present chronic inflammation that can lead to a number of renal diseases. Proinflammatory cytokines and TNF-induced apoptosis are some of the underlying mechanisms that may explain the virus-induced renal diseases that are here reviewed.(AU)