Molecular dynamics analysis of fast-spreading severe acute respiratory syndrome coronavirus 2 variants and their effects in the interaction with human angiotensin-converting enzyme 2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is evolving with mutations in the Spike protein, especially in the receptor-binding domain (RBD). The failure of public health measures to contain the spread of the disease in many countries has given rise to novel viral variants with increased transmissibility. However, key questions about how quickly the variants can spread and whether they can cause a more severe disease remain unclear. Herein, we performed a structural investigation using molecular dynamics simulations and determined dissociation constant (KD) values using surface plasmon resonance (SPR) assays of three fastspreading SARS-CoV-2 variants, Alpha, Beta and Gamma ones, as well as genetic factors in the host cells that may be related to the viral infection. Our results suggest that the SARS-CoV-2 variants facilitate their entry into the host cell by moderately increased binding affinities to the human ACE2 receptor, different torsions in hACE2 mediated by RBD variants, and an increased Spike exposure time to proteolytic enzymes. We also found that other host cell aspects, such as gene and isoform expression of key genes for the infection (ACE2, FURIN and TMPRSS2), may have few contributions to the SARS-CoV-2 variants infectivity. In summary, we concluded that a combination of viral and host cell factors allows SARS-CoV-2 variants to increase their abilities to spread faster than wild-type. O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

Spatio-temporal analysis between the incidence of COVID-19 and human development in Mato Grosso do Sul, Brazil.

ObjetiveTo analyze the spatial distribution of the Covid-19 incidence and its correlation with the municipal human development index (IDHM) in the state of Mato Grosso do Sul (MS), Brazil. MethodsThis is an ecological, exploratory and analytical study whose units of analysis were the 79 municipalities that make up the state of MS. Covid-19 incidence coefficients, death numbers, lethality rate, mortality rate and Human Development Index for municipalities (IDHM) in the period from March 2020 to December 31, 2020 were used. spatial correlations between the variables mentioned above. ResultsThe incidence of Covid-19 has spatial dependence with moderate positive correlation and formation of clusters located in the Metropolitan Region of Campo Grande (RMCG) and municipalities in the region. ConclusionThe uneven mapping of Covid-19 and its relationship with IDHM in the Ministry of Health can contribute to actions to address the regional pandemic.

The aging whole blood transcriptome reveals a potential role of FASLG in COVID-19

The risk for severe illness from COVID-19 increases with age as older patients are at the highest risk. Although it is still unclear whether the virus is blood-transmitted, the viral RNA is detected in serum. Identifying how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) interacts with specific blood components during aging is expected to guide proper therapies. Considering that all human coronavirus require host cellular molecules to promote infection, we investigated the aging whole blood transcriptome from the Genotype-Tissue Expression (GTEx) database to explore differentially expressed genes (DEGs) translated into proteins potentially interacting with viral proteins. From a total of 22 DEGs in aged blood, five genes (FASLG, CTSW, CTSE, VCAM1, and BAG3) changed expression during aging. These age-related genes are involved in immune response, inflammation, cell component and cell adhesion, and platelet activation/aggregation. Both males and females older than 50 overexpress FASLG compared with younger adults (20-30 years old), possibly inducing a hyper-inflammatory cascade that activates specific immune cells. Furthermore, the expression of cathepsins (CTSW and CTSE) and the anti-apoptotic co-chaperone molecule BAG3 was significantly increased throughout aging in both gender. By exploring publicly available Single-Cell RNA-Sequencing (scRNA-Seq) data on peripheral blood of SARS-CoV-2-infected patients, we found FASLG and CTSW expressed mainly in natural killer (NK) cells and CD8+ (cytotoxic) T lymphocytes whereas BAG3 was expressed in CD4+ T cells, naive T cells, and CD14+ monocytes. The increased expression of FASLG in blood during aging may explain why older patients are more prone to severe acute viral infection complications. These results indicate FASLG as a prognostic candidate and potential therapeutic target for more aggressive clinical manifestation of COVID-19.

Population-based seroprevalence of SARS-CoV-2 is more than halfway through the herd immunity threshold in the State of Maranhao, Brazil

BackgroundFew population-based studies on the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been performed to date, and most of them have used lateral flow immunoassays with finger-prick, which may yield false-negative results and thus underestimate the true infection rate. MethodsA population-based household survey was performed in the State of Maranhao, Brazil, from 27 July 2020 to 8 August 2020 to estimate the seroprevalence of SARS-CoV-2 using a serum testing electrochemiluminescence immunoassay. A three-stage cluster sampling stratified by four state regions was used. The estimates took clustering, stratification, and non-response into account. Qualitative detection of IgM and IgG antibodies was performed in a fully-automated Elecsys(R) Anti-SARS-CoV-2 electrochemiluminescence immunoassay on the Cobas(R) e601 analyser (Roche Diagnostics). FindingsA total of 3156 individuals were interviewed. Seroprevalence of total antibodies against SARS-CoV-2 was 40{middle dot}4% (95%CI 35{middle dot}6-45{middle dot}3). Population adherence to non-pharmaceutical interventions was higher at the beginning of the pandemic than in the last month. SARS-CoV-2 infection rates were significantly lower among mask wearers and among those who maintained social and physical distancing in the last month compared to their counterparts. Among the infected, 62{middle dot}2% had more than three symptoms, 11{middle dot}1% had one or two symptoms, and 26{middle dot}0% were asymptomatic. The infection fatality rate was 0{middle dot}17%, higher for males and advanced age groups. The ratio of estimated infections to reported cases was 22{middle dot}2. InterpretationTo the best of our knowledge, the seroprevalence of SARS-CoV-2 estimated in this population-based survey was the highest and the closest to the herd immunity threshold reported to date. Our results suggest that the herd immunity threshold is not as low as 20%, but at least higher than or equal to around 40%. The infection fatality rate was one of the lowest reported so far, and the proportion of asymptomatic cases was low.

Anti-SARS-CoV-2 IgM and IgG antibodies in health workers in Sergipe, Brazil

BackgroundThe exponential growth of COVID-19 cases in Brazil is overloading health systems with overcrowding of hospitals and overflowing intensive care units. Increasing infection rates in health professionals can lead to the collapse of the health system and further worsen the pandemic. The aim of this study was to evaluate the seroprevalence of IgM and IgG for SARS-CoV-2 in health workers in Sergipe, Brazil. MethodsThe targeted tests involved health professionals working on the front line to combat COVID-19. The samples were collected in the month of June, in six hospital units in the state of Sergipe. Results471 health professionals were tested. Of these, 28 workers (5.95%) tested positive for IgM and 64 (13.59%) tested positive for IgG. 9 workers (1.91%) tested positive for IgM and were also positive for IgG. DiscussionHealth workers must be monitored constantly, because if they are infected, they can spread the virus to colleagues, hospitalized patients and even family members. ConclusionKnowing the prevalence of antibodies to the virus in health workers is an important measure of viral spread control.

Assessment of genotoxicity of aluminium acetate in bone marrow, male germ cells and fetal liver cells of Swiss albino mice.

Aluminium acetate (AA) has many pharmaceutical applications, which necessitates a thorough evaluation of its toxicity. Dose- and time-dependent genotoxic effects of AA were investigated in Swiss albino mice after exposure via intraperitoneal (i.p.) injection, by employing assays to detect chromosomal aberrations (CA) and micronuclei (MN) in bone marrow, MN in fetal liver, and abnormalities in sperm. Animals were treated with single doses of 50, 100 and 150mg/kg body weight (bw), and with daily doses of 50mg/kg bw for seven consecutive days, in order to study the effects of acute and cumulative doses, respectively. Post-treatment sampling was done at 24, 48 and 72h for bone-marrow CA and MN tests, to study time-dependent effects. Both single and repeated exposures of AA induced chromosomal aberrations, which were dose and time-dependent. The MN test failed to demonstrate genotoxicity after the single-dose exposures, indicating that a higher threshold dose is required for MN induction. Repeated treatment of AA, however, induced MN formation even at the low dose (P<0.05), reflecting genotoxicity following chronic/sub-chronic exposure. A significant reduction in mitotic index and in the P/N (polychromatic/normochromatic erythrocytes) ratio suggests that AA also has a mitodepressive effect in bone-marrow cells. AA-induced germinal genotoxicity was evident from a significant and dose-dependent increase in the percentage of abnormal spermatozoa and a reduction in sperm count. Transplacental exposure of AA resulted in the dose-dependent increase in the frequency of micronucleated erythrocytes in the developing fetus. Thus, the current in vivo study revealed genotoxic effects of AA both on somatic and germ cells of Swiss albino mice.

El enfermero asistencial y educador en una unidad de trasplante renal: un desafío / No disponible

Este es un estudio descriptivo, retrospectivo, de revisión bibliográfica, de carácter exploratorio relacionado con el papel asistencial y educador del enfermero en el trasplante renal. El estudio pretende hacer un levantamiento bibliográfico sobre el tema; discutir la importancia de las orientaciones del personal de enfermería durante el pre y pos-operatorio del trasplante renal y hacer el levantamiento de las principales orientaciones de enfermería en una unidad de trasplante renal en la literatura consultada. Hay una preocupación muy importante por parte de la enfermería para mantener el cuidado al trasplantado renal dentro y fuera del hospital. Las directrices abordan desde las cuestiones más simples a las más complejas, lo que es extremadamente importante durante el pre y postrasplante en un intento por lograr el éxito de las acciones (AU)

This is a descriptive retrospective study, literature review, exploratory and related to the welfare assistance and educational role of the nurse in renal transplantation. The study intends to do a survey on the subject, to discuss the importance of the orientations of the nursery personnel during the preoperative and postoperative renal transplantation period and to survey the main orientations of nursing in a renal transplant unit found in the consulted literature. There is a very significant concern on the part of nursing to keep the well care of the transplanted kidney patients within and outside the hospital. The guidelines tackle from the most complex to the easiest issues, which is extremely important during the pre and post-transplant period in an attempt to achieve success of the actions (AU)