Targeting IL-6 trans-signalling by sgp130Fc attenuates severity in SARS-CoV-2 -infected mice and reduces endotheliopathy.

BACKGROUND: SARS-CoV-2 infection is considered as a relapsing inflammatory process with a dysregulation of IL-6 signalling. Classic IL-6 signalling is thought to represent a defence mechanism against pathogens. In contrast, IL-6 trans-signalling has pro-inflammatory effects. In severe COVID-19, therapeutic strategies have focused on global inhibition of IL-6, with controversial results. We hypothesized that specific blockade of IL-6 trans-signalling could inhibit inflammatory response preserving the host defence activity inherent to IL-6 classic signalling. METHODS: To test the role of the specific IL-6 trans-signalling inhibition by sgp130Fc in short- and long-term consequences of COVID-19, we used the established K18-hACE2 transgenic mouse model. Histological as well as immunohistochemical analysis, and pro-inflammatory marker profiling were performed. To investigate IL-6 trans-signalling in human cells we used primary lung microvascular endothelial cells and fibroblasts in the presence/absence of sgp130Fc. FINDINGS: We report that targeting IL-6 trans-signalling by sgp130Fc attenuated SARS-CoV-2-related clinical symptoms and mortality. In surviving mice, the treatment caused a significant decrease in lung damage. In vitro, IL-6 trans-signalling induced strong and persisting JAK1/STAT3 activation in endothelial cells and lung fibroblasts with proinflammatory effects, which were attenuated by sgp130Fc. Our data also suggest that in those cells with scant amounts of IL-6R, the induction of gp130 and IL-6 by IL-6:sIL-6R complex sustains IL-6 trans-signalling. INTERPRETATION: IL-6 trans-signalling fosters progression of COVID-19, and suggests that specific blockade of this signalling mode could offer a promising alternative to mitigate both short- and long-term consequences without affecting the beneficial effects of IL-6 classic signalling. These results have implications for the development of new therapies of lung injury and endotheliopathy in COVID-19. FUNDING: The project was supported by ISCIII, Spain (COV-20/00792 to MB, PI23/01351 to MARH) and the European Commission-Next generation EU (European Union) (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global, SGL2103029 to MB). PID2019-110587RB-I00 (MB) supported by MICIN/AEI/10.13039/501100011033/and PID2022-143034OB-I00 (MB) by MICIN/AEI/10.13039/501100011033/FEDER. MAR-H acknowledges support from ISCIII, Spain and the European Commission-Next generation EU (European Union), through CSIC's Global Health PTI.

ISMI-VAE: A deep learning model for classifying disease cells using gene expression and SNV data.

Various studies have linked several diseases, including cancer and COVID-19, to single nucleotide variations (SNV). Although single-cell RNA sequencing (scRNA-seq) technology can provide SNV and gene expression data, few studies have integrated and analyzed these multimodal data. To address this issue, we introduce Interpretable Single-cell Multimodal Data Integration Based on Variational Autoencoder (ISMI-VAE). ISMI-VAE leverages latent variable models that utilize the characteristics of SNV and gene expression data to overcome high noise levels and uses deep learning techniques to integrate multimodal information, map them to a low-dimensional space, and classify disease cells. Moreover, ISMI-VAE introduces an attention mechanism to reflect feature importance and analyze genetic features that could potentially cause disease. Experimental results on three cancer data sets and one COVID-19 data set demonstrate that ISMI-VAE surpasses the baseline method in terms of both effectiveness and interpretability and can effectively identify disease-causing gene features.

Review: N1-methyl-pseudouridine (m1Ψ): Friend or foe of cancer?

Due to the health emergency created by SARS-CoV-2, the virus that causes the COVID-19 disease, the rapid implementation of a new vaccine technology was necessary. mRNA vaccines, being one of the cutting-edge new technologies, attracted significant interest and offered a lot of hope. The potential of these vaccines in preventing admission to hospitals and serious illness in people with comorbidities has recently been called into question due to the vaccines' rapidly waning immunity. Mounting evidence indicates that these vaccines, like many others, do not generate sterilizing immunity, leaving people vulnerable to recurrent infections. Additionally, it has been discovered that the mRNA vaccines inhibit essential immunological pathways, thus impairing early interferon signaling. Within the framework of COVID-19 vaccination, this inhibition ensures an appropriate spike protein synthesis and a reduced immune activation. Evidence is provided that adding 100 % of N1-methyl-pseudouridine (m1Ψ) to the mRNA vaccine in a melanoma model stimulated cancer growth and metastasis, while non-modified mRNA vaccines induced opposite results, thus suggesting that COVID-19 mRNA vaccines could aid cancer development. Based on this compelling evidence, we suggest that future clinical trials for cancers or infectious diseases should not use mRNA vaccines with a 100 % m1Ψ modification, but rather ones with the lower percentage of m1Ψ modification to avoid immune suppression.

Bioinformatics and system biology approaches to determine the connection of SARS-CoV-2 infection and intrahepatic cholangiocarcinoma.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19), has infected millions of individuals worldwide, which poses a severe threat to human health. COVID-19 is a systemic ailment affecting various tissues and organs, including the lungs and liver. Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver cancer, and cancer patients are particularly at high risk of SARS-CoV-2 infection. Nonetheless, few studies have investigated the impact of COVID-19 on ICC patients. METHODS: With the methods of systems biology and bioinformatics, this study explored the link between COVID-19 and ICC, and searched for potential therapeutic drugs. RESULTS: This study identified a total of 70 common differentially expressed genes (DEGs) shared by both diseases, shedding light on their shared functionalities. Enrichment analysis pinpointed metabolism and immunity as the primary areas influenced by these common genes. Subsequently, through protein-protein interaction (PPI) network analysis, we identified SCD, ACSL5, ACAT2, HSD17B4, ALDOA, ACSS1, ACADSB, CYP51A1, PSAT1, and HKDC1 as hub genes. Additionally, 44 transcription factors (TFs) and 112 microRNAs (miRNAs) were forecasted to regulate the hub genes. Most importantly, several drug candidates (Periodate-oxidized adenosine, Desipramine, Quercetin, Perfluoroheptanoic acid, Tetrandrine, Pentadecafluorooctanoic acid, Benzo[a]pyrene, SARIN, Dorzolamide, 8-Bromo-cAMP) may prove effective in treating ICC and COVID-19. CONCLUSION: This study is expected to provide valuable references and potential drugs for future research and treatment of COVID-19 and ICC.

Patients hospitalized with active tuberculosis and Covid-19 coinfection: A matched case-control from the Brazilian Covid-19 Registry.

Although control of Covid-19 has improved, the virus continues to cause infections, such as tuberculosis, that is still endemic in many countries, representing a scenario of coinfection. To compare Covid-19 clinical manifestations and outcomes between patients with active tuberculosis infection and matched controls. This is a matched case-control study based on data from the Brazilian Covid-19 Registry, in hospitalized patients aged 18 or over with laboratory confirmed Covid-19 from March 1, 2020, to March 31, 2022. Cases were patients with tuberculosis and controls were Covid-19 patients without tuberculosis. From 13,636 Covid-19, 36 also had active tuberculosis (0.0026%). Pulmonary fibrosis (5.6% vs 0.0%), illicit drug abuse (30.6% vs 3.0%), alcoholism (33.3% vs 11.9%) and smoking (50.0% vs 9.7%) were more common among patients with tuberculosis. They also had a higher frequency of nausea and vomiting (25.0% vs 10.4%). There were no significant differences in in-hospital mortality, mechanical ventilation, need for dialysis and ICU stay. Patients with TB infection presented a higher frequency of pulmonary fibrosis, abuse of illicit drugs, alcoholism, current smoking, symptoms of nausea and vomiting. The outcomes were similar between them.

Patterns of Non-influenza Respiratory Viruses Among Severe Acute Respiratory Infection Cases in Burkina Faso: A Surveillance Study.

BACKGROUND: Although influenza viruses cause only one-fifth of severe acute respiratory infections (SARI) in Burkina Faso, the other viral causes of SARI remain poorly investigated to inform clinical and preventive decision making. METHODS: Between 2016 and 2019, we prospectively enrolled inpatients meeting the World Health Organization (WHO) case definition of SARI in Burkina Faso. Results of viral etiologies among inpatients tested negative for influenza using the Fast Track Diagnostics Respiratory Kits (FTD-33) were reported. RESULTS: Of 1541 specimens tested, at least one respiratory virus was detected in 76.1% of the 1231 specimens negative for influenza virus. Human rhinoviruses (hRVs) were the most detected pathogens (476; 38.7%), followed by human adenoviruses (hAdV) (17.1%, 210/1231), human respiratory syncytial virus (hRSV) (15.4%, 189/1231), enterovirus (EnV) (11.2%, 138/1231), human bocavirus (hBoV) (7.9%, 97/1231), parainfluenza 3 (hPIV3) (6.1%, 75/1231), human metapneumovirus (hMPV) (6.0%,74/1321), parainfluenza 4 (hPIV4) (4.1%, 51/1231), human coronavirus OC43 (hCoV-OC43) (3.4%, 42/1231), human coronavirus HKU1(hCoV-HKU1) (2.7%, 33/1231), human coronavirus NL63 (hCoV-NL63) (2.5%, 31/1231), parainfluenza 1 (hPIV1) (2.0%, 25/1231), parainfluenza 2 (hPIV2) (1.8%, 22/1231), human parechovirus (PeV) (1.1%, 14/1231), and human coronavirus 229E (hCoV-229E) (0.9%, 11/1231). Among SARI cases, infants aged 1-4 years were mostly affected (50.7%; 622/1231), followed by those <1 year of age (35.7%; 438/1231). Most detected pathogens had year-long circulation patterns, with seasonal peaks mainly observed during the cold and dry seasons. CONCLUSION: Several non-influenza viruses are cause of SARI in Burkina Faso. The integration of the most common pathogens into the routine influenza surveillance system might be beneficial.

Searching for common ground.

The conserved coronavirus fusion peptide is a target of broadly neutralizing antibodies.

Identification and Genetic Characterization of MERS-Related Coronavirus Isolated from Nathusius' Pipistrelle (Pipistrellus nathusii) near Zvenigorod (Moscow Region, Russia).

Being diverse and widely distributed globally, bats are a known reservoir of a series of emerging zoonotic viruses. We studied fecal viromes of twenty-six bats captured in 2015 in the Moscow Region and found 13 of 26 (50%) samples to be coronavirus positive. Of P. nathusii (the Nathusius' pipistrelle), 3 of 6 samples were carriers of a novel MERS-related betacoronavirus. We sequenced and assembled the complete genome of this betacoronavirus and named it MOW-BatCoV strain 15-22. Whole genome phylogenetic analysis suggests that MOW-BatCoV/15-22 falls into a distinct subclade closely related to human and camel MERS-CoV. Unexpectedly, the phylogenetic analysis of the novel MOW-BatCoV/15-22 spike gene showed the closest similarity to CoVs from Erinaceus europaeus (European hedgehog). We suppose MOW-BatCoV could have arisen as a result of recombination between ancestral viruses of bats and hedgehogs. Molecular docking analysis of MOW-BatCoV/15-22 spike glycoprotein binding to DPP4 receptors of different mammals predicted the highest binding ability with DPP4 of the Myotis brandtii bat (docking score -320.15) and the E. europaeus (docking score -294.51). Hedgehogs are widely kept as pets and are commonly found in areas of human habitation. As this novel bat-CoV is likely capable of infecting hedgehogs, we suggest hedgehogs can act as intermediate hosts between bats and humans for other bat-CoVs.

SARS-CoV-2 infections in pediatric and young adult recipients of chimeric antigen receptor T-cell therapy: an international registry report.

BACKGROUND: Immunocompromised patients are at increased risk of SARS-CoV-2 infections. Patients undergoing chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory B-cell malignancies are uniquely immunosuppressed due to CAR T-mediated B-cell aplasia (BCA). While SARS-CoV-2 mortality rates of 33%-40% are reported in adult CAR T-cell recipients, outcomes in pediatric and young adult CAR T-cell recipients are limited. METHODS: We created an international retrospective registry of CAR T recipients aged 0-30 years infected with SARS-CoV-2 within 2 months prior to or any time after CAR T infusion. SARS-CoV-2-associated illness was graded as asymptomatic, mild, moderate, or severe COVID-19, or multisystem inflammatory syndrome in children (MIS-C). To assess for risk factors associated with significant SARS-CoV-2 infections (infections requiring hospital admission for respiratory distress or supplemental oxygen), univariate and multivariable regression analyses were performed. RESULTS: Nine centers contributed 78 infections in 75 patients. Of 70 SARS-CoV-2 infections occurring after CAR T infusion, 13 (18.6%) were classified as asymptomatic, 37 (52.9%) mild, 11 (15.7%) moderate, and 6 (8.6%) severe COVID-19. Three (4.3%) were classified as MIS-C. BCA was not significantly associated with infection severity. Prior to the emergence of the Omicron variant, of 47 infections, 19 (40.4%) resulted in hospital admission and 7 (14.9%) required intensive care, while after the emergence of the Omicron variant, of 23 infections, only 1 (4.3%) required admission and the remaining 22 (95.7%) had asymptomatic or mild COVID-19. Death occurred in 3 of 70 (4.3%); each death involved coinfection or life-threatening condition. In a multivariable model, factors associated with significant SARS-CoV-2 infection included having two or more comorbidities (OR 7.73, CI 1.05 to 74.8, p=0.048) and age ≥18 years (OR 9.51, CI 1.90 to 82.2, p=0.014). In the eight patients infected with SARS-CoV-2 before CAR T, half of these patients had their CAR T infusion delayed by 15-30 days. CONCLUSIONS: In a large international cohort of pediatric and young adult CAR-T recipients, SARS-CoV-2 infections resulted in frequent hospital and intensive care unit admissions and were associated with mortality in 4.3%. Patients with two or more comorbidities or aged ≥18 years were more likely to experience significant illness. Suspected Omicron infections were associated with milder disease.

In vitro and in vivo evaluation of the main protease inhibitor FB2001 against SARS-CoV-2.

FB2001 is a drug candidate that targets the main protease of SARS-CoV-2 via covalently binding to cysteine 145. In this study, we evaluated the inhibitory activities of FB2001 against several SARS-CoV-2 variants in vitro and in vivo (in mice), and we also evaluated the histopathological analysis and immunostaining of FB2001 on lung and brain which have been rarely reported. The results showed that FB2001 exhibited potent antiviral efficacy against several current SARS-CoV-2 variants in Vero E6 cells, namely, B.1.1.7 (Alpha): EC50 = 0.39 ± 0.01 µM, EC90 = 0.75 ± 0.01 µM; B.1.351 (Beta): EC50 = 0.28 ± 0.11 µM, EC90 = 0.57 ± 0.21 µM; B.1.617.2 (Delta): EC50 = 0.27 ± 0.05 µM, EC90 = 0.81 ± 0.20 µM; B.1.1.529 (Omicron): EC50 = 0.26 ± 0.06 µM and EC50 = 0.042 ± 0.007 µM (in the presence of a P-glycoprotein inhibitor). FB2001 remained potent against SARS-CoV-2 replication in the presence of high concentrations of human serum, which indicating that human serum had no significant effect on the in vitro inhibitory activity. Additionally, this inhibitor exhibited an additive effect against SARS-CoV-2 when combined with Remdesivir. Furthermore, FB2001 significantly reduced the SARS-CoV-2 copy numbers and titers in the lungs and brains in vivo, and alleviated the pathological symptoms. In addition, FB2001 could alleviated local bleeding, erythrocyte overflow, edema, and inflammatory cell infiltration in brain tissue, and inhibitors reducing viral titers and improving inflammation in the brain have been rarely reported. A physiologically based pharmacokinetic model was established and verified to predict the FB2001 concentration in human lungs. When FB2001 was administered at 200 mg twice a day for 5 days, the observed Ctrough ss in plasma and predicted Ctrough ss of lung total concentration were 0.163 and 2.5 µg/mL, which were approximately 9 and 132-fold higher than the EC50 of 0.019 µg/mL (0.042 µM) against Omicron variant. Taken together, our study suggests that FB2001 is a promising therapeutic agent in COVID-19 treatment and can be combined with remdesivir to achieve improved clinical outcomes. Owing to its good safety and tolerability in healthy human (NCT05197179 and NCT04766931), FB2001 has been approved for Phase II/III clinical trial (NCT05445934).

Remdesivir-induced emergence of SARS-CoV2 variants in patients with prolonged infection.

We here investigate the impact of antiviral treatments such as remdesivir on intra-host genomic diversity and emergence of SARS-CoV2 variants in patients with a prolonged course of infection. Sequencing and variant analysis performed in 112 longitudinal respiratory samples from 14 SARS-CoV2-infected patients with severe disease progression show that major frequency variants do not generally arise during prolonged infection. However, remdesivir treatment can increase intra-host genomic diversity and result in the emergence of novel major variant species harboring fixed mutations. This is particularly evident in a patient with B cell depletion who rapidly developed mutations in the RNA-dependent RNA polymerase gene following remdesivir treatment. Remdesivir treatment-associated emergence of novel variants is of great interest in light of current treatment guidelines for hospitalized patients suffering from severe SARS-CoV2 disease, as well as the potential use of remdesivir to preventively treat non-hospitalized patients at high risk for severe disease progression.

Long-term survival benefit of male and multimorbid COVID-19 patients with 5-day remdesivir treatment.

Background: Treatment of the coronavirus disease (COVID-19) is still challenging due to the lack of evidence-based treatment protocols and continuously changing epidemiological situations and vaccinations. Remdesivir (RDV) is among the few antiviral medications with confirmed efficacy for specific patient groups. However, real-world data on long-term outcomes for a short treatment course are scarce. Methods: This retrospective observational cohort study included real-life data collected during the second and third wave of the COVID-19 pandemic in Hungary (September 1, 2020-April 30, 2021) from inpatients at a University Center (n = 947). Participants consisted of two propensity score-matched cohorts (370/370 cases): Group RDV including patients receiving RDV and supplementary oxygen and Group standard of care (SOC) as control. The primary outcome was the effect of 5-day RDV treatment on 30- and 60-day all-cause mortality. Multivariate analyses were performed to assess the effect of RDV by different covariates. Results: Group RDV included significantly more patients from the alpha variant wave, with greater frequency of comorbidities diabetes and anemia, and larger degree of parenchymal involvement. All-cause mortality at 30- and 60-day were significantly lower in Group RDV compared to Group SOC. Significant risk reduction of 60-day all-cause mortality was observed for RDV treatment in men and patients with COPD or multiple comorbidities. Conclusions: Hospitalized COVID-19 patients with 5-day RDV treatment had significantly lower 30- and 60-day all-cause mortality, despite their more severe clinical condition. Men and patients with multiple comorbidities, including COPD, profited the most from RDV treatment in the long term. Due to the ongoing COVID-19 pandemic, effective treatment regimens are needed for hospitalized patients.

Nirmatrelvir-remdesivir association for non-hospitalized adults with COVID-19, point of view.

The efforts of the scientific world directed to identifying new antiviral drugs and therapies effective against SARS-CoV-2 continue. New oral antivirals against SARS-CoV-2 such as paxlovid have recently authorized. Evidence shows that these antivirals have good efficacy in reducing the risk of hospitalization in COVID-19 positive patients. Remdesivir is an authorized antiviral for the treatment of SARS-CoV-2 infection. To date, there are still few data in the literature on the safety profile and the risk of generating antiviral-resistant SARS-CoV-2 drug variants. In this manuscript we describe the evidence in the literature on the monotherapy use of paxlovid and monotherapy use of remdesivir, and the scientific hypothesis of using nirmatrelvir and remdesivir in association with the aim of increasing treatment efficacy, reducing the risk of adverse reactions and generating antiviral drug-resistant variants.

Safety and efficacy of convalescent plasma for severe COVID-19: a randomized, single blinded, parallel, controlled clinical study.

BACKGROUND: Convalescent plasma (CP) has been widely used to treat COVID-19 and is under study. However, the variability in the current clinical trials has averted its wide use in the current pandemic. We aimed to evaluate the safety and efficacy of CP in severe coronavirus disease 2019 (COVID-19) in the early stages of the disease. METHODS: A randomized controlled clinical study was conducted on 101 patients admitted to the hospital with confirmed severe COVID-19. Most participants had less than 14 days from symptoms onset and less than seven days from hospitalization. Fifty patients were assigned to receive CP plus standard therapy (ST), and 51 were assigned to receive ST alone. Participants in the CP arm received two doses of 250 mL each, transfused 24 h apart. All transfused plasma was obtained from "super donors" that fulfilled the following criteria: titers of anti-SARS-CoV-2 S1 IgG ≥ 1:3200 and IgA ≥ 1:800 antibodies. The effect of transfused anti-IFN antibodies and the SARS-CoV-2 variants at the entry of the study on the overall CP efficacy was evaluated. The primary outcomes were the reduction in viral load and the increase in IgG and IgA antibodies at 28 days of follow-up. The per-protocol analysis included 91 patients. RESULTS: An early but transient increase in IgG anti-S1-SARS-CoV-2 antibody levels at day 4 post-transfusion was observed (Estimated difference [ED], - 1.36; 95% CI, - 2.33 to - 0.39; P = 0.04). However, CP was not associated with viral load reduction in any of the points evaluated. Analysis of secondary outcomes revealed that those patients in the CP arm disclosed a shorter time to discharge (ED adjusted for mortality, 3.1 days; 95% CI, 0.20 to 5.94; P = 0.0361) or a reduction of 2 points on the WHO scale when compared with the ST group (HR adjusted for mortality, 1.6; 95% CI, 1.03 to 2.5; P = 0.0376). There were no benefits from CP on the rates of intensive care unit admission (HR, 0.82; 95% CI, 0.35 to 1.9; P = 0.6399), mechanical ventilation (HR, 0.66; 95% CI, 0.25 to 1.7; P = 0.4039), or mortality (HR, 3.2; 95% CI, 0.64 to 16; P = 0.1584). Anti-IFN antibodies and SARS-CoV-2 variants did not influence these results. CONCLUSION: CP was not associated with viral load reduction, despite the early increase in IgG anti-SARS-CoV-2 antibodies. However, CP is safe and could be a therapeutic option to reduce the hospital length of stay. Trial registration NCT04332835.

Contribution of nursing research to fighting against COVID-19 pandemic. A systematic review

Introduction: The 2019 coronavirus disease (COVID-19) pandemic, should be an opportunity to ensure greater visibility of nursing in health systems and society worldwide. Objective: Review and synthesize the patterns on COVID-19 and nursing research, identifying the main journals, country of origin, language, topics, designs, and area of applicability of the results. Materials and Methods: Systematic review. Searches in PubMed, CINAHL, LILACS, and EMBASE databases (from the inception of the pandemic to May 15, 2020) were performed. Articles of any language related were related to SARS-CoV-2 infection or COVID-19 disease and nursing in any of its roles (care, management, education, among others) and using any epidemiological design or a scientific report were included. Two reviewers independently selected the studies and extracted the data. The main findings from the included studies were summarized through narrative synthesis and descriptive tables. The characteristics of the studies were presented as absolute values and proportions. Results: Three hundred and sixty-five articles were assessed for eligibility. Thirty-eight were included, published in 28 journals. Of those, 53.57% (n=15) were nursing specific. Most articles were "narrative reviews", accounting for 23.68% (n=9). Most studies were conducted in China (n=18, 47.37%), followed by the United Kingdom and the United States. Thirty-four (89.47%) articles were published in English, followed by Portuguese and Chinese. We identified five areas of application of the results, and the most frequent was the "clinical" setting with 47.00% (n=18). Discussion: These findings are crucial to give visibility to nursing work during the emergency of the COVID-19 pandemic. Mental health was the main research topic, while the clinical setting concentrates the major number of articles. This pattern was aligned with the challenges of the initial phase of the pandemic. Conclusion: Future research should explore the current state of evidence in the main topics identified in this review and continue to give visibility to work carried out by nursing in the emergency of the COVID-19 pandemic.

Introducción: La pandemia de la enfermedad de coronavirus 2019 (COVID-19), debería ser una oportunidad para asegurar una mayor visibilidad de la enfermería en los sistemas de salud y la sociedad en todo el mundo. Objetivo: Revisar y sintetizar los patrones de investigación en enfermería y COVID-19, identificando las principales revistas, país de origen, idioma, temas, diseños y área de aplicabilidad de los resultados. Materiales y Metodos: Una revisión sistemática. Se realizaron búsquedas en las bases de datos PubMed, CINAHL, LILACS y EMBASE (desde el inicio de la pandemia hasta el 15 de mayo de 2020). Se incluyeron artículos de cualquier idioma relacionados con la infección por SARS-CoV-2 o COVID-19 y enfermería en cualquiera de sus roles (cuidado, administración, educación, entre otros) que utilizaron cualquier diseño epidemiológico o informe científico. Dos revisores seleccionaron de forma independiente los estudios y extrajeron los datos. Los principales hallazgos de los estudios incluidos se resumieron mediante una síntesis narrativa y tablas descriptivas. Las características de los estudios se presentaron como valores absolutos y proporciones. Resultados: En 325 artículos se evaluaron los criterios de elegibilidad y se incluyeron 38 publicados en 28 revistas. De ellos, el 53,57% (n=15) eran específicos de enfermería. La mayoría de los artículos fueron "revisiones narrativas", que representan el 23,68% (n=9). La mayoría de los estudios se realizaron en China (n=18, 47,37%), seguido de Reino Unido y Estados Unidos. Treinta y cuatro (89,47%) artículos se publicaron en inglés, seguidos de portugués y chino. Identificamos cinco áreas de aplicación de los resultados y la más frecuente fue el ámbito "clínico" con un 47,00% (n=18). Discusión: Estos hallazgos son cruciales para dar visibilidad al trabajo de enfermería en la emergencia de la pandemia COVID-19. Se destaca que la salud mental fue el principal tópico de investigación mientras que el escenario clínico concentró el mayor número de artículo. Este patrón estuvo alineado con los desafíos impuestos por la fase inicial de la pandemia. Conclusión: Las investigaciones futuras deberán explorar el estado actual de la evidencia en los principales temas identificados en esta revisión y continuar dando visibilidad al trabajo realizado por enfermería en la emergencia de la pandemia por COVID-19.

Introdução: A pandemia da doença coronavírus (COVID-19) de 2019 deve ser uma oportu-nidade para garantir maior visibilidade da enfermagem nos sistemas de saúde e na sociedade em todo o mundo. Objetivo: Revisar e sintetizar os padrões de pesquisa em enfermagem e COVID-19, identificando as principais revistas, país de origem, língua, tópicos, desenhos e área de aplicabilidade dos resultados. Materiais e Métodos: Uma revisão sistemática. As ba-ses de dados PubMed, CINAHL, LILACS e EMBASE foram pesquisadas (Do início da pan-demia até 15 de maio de 2020). Artigos de qualquer língua relacionados à infecção por SARS-CoV-2 ou COVID-19 e enfermagem foram incluídos em qualquer das suas funções (assistên-cia, administração, educação, entre outras) que utilizassem qualquer desenho epidemiológico ou relatório científico. Dois revisores selecionaram independentemente estudos e extraíram os dados. As principais conclusões dos estudos incluídos foram resumidas através de uma síntese narrativa e tabelas descritivas. As características dos estudos foram apresentadas em valores absolutos e proporções. Resultados: Em 325 artigos foram avaliados os critérios de elegibili-dade e incluídos 38 publicados em 28 revistas. Destes, 53,57% (n=15) eram específicos da enfermagem. A maioria dos artigos eram "revisões narrativas", representando 23,68% (n=9). A maioria dos estudos foi realizada na China (n=18, 47,37%), seguida do Reino Unido e dos Estados Unidos. Trinta e quatro (89,47%) artigos foram publicados em inglês, seguidos de português e chinês. Identificamos cinco áreas de aplicação dos resultados e a mais frequente foi a área "clínica" com 47,00% (n=18). Discussão: Estas conclusões são cruciais para dar vi-sibilidade ao trabalho de enfermagem durante a emergência da pandemia da COVID-19. A saúde mental foi o principal tema de investigação, enquanto que o cenário clínico concentra o maior número de artigos. Este padrão foi alinhado com os desafios da fase inicial da pande-mia. Conclusão: A investigação futura deve explorar o estado atual das provas nos principais tópicos identificados nesta revisão e continuar a dar visibilidade ao trabalho realizado pela enfermagem na emergência da pandemia da COVID-19.

Mental Health of Postpartum Women During the COVID-19 Pandemic: An Integrative Review / Saúde mental de puérperas durante a pandemia covid-19: revisão integrativa / Salud mental de puérperas durante la pandemia de covid-19: revisión integradora

Objective: To identify and analyze the scientific evidence on the mental health of postpartum women during the COVID-19 pandemic. Method: This integrative review was carried out using the VHL, CINAHL, PubCovid, Scopus, and Web of Science databases, whose research question was "What is the scientific evidence on the mental health of postpartum women during the SARS-CoV-2 pandemic?" Results: Ten articles in English were included, identifying a higher frequency of cross-sectional research (n = 4), publications in November 2020 (n = 3), conducted in Italy (n = 3), with level VI evidence (n = 6). The study found that postpartum women feel depressed, lonely, and afraid; attention is drawn to the worsening risk of postpartum depression with significant prevalence values. It points out factors that negatively influence the mental health of this population in the current pandemic and discloses care measures. Conclusions: In addition to previous characteristics, socioeconomic conditions (e.g., living in highly infected areas, unemployment) and elements inherent to this pandemic (e.g., distance and fear of contagion) negatively influence the mental health of postpartum women. Means of dealing with the conditions imposed by the COVID-19 pandemic are available, such as relaxation techniques, physical exercise, and professional support. The relevance and need for research on this theme, mostly nationally, are highlighted.

Objetivo: identificar e analisar as evidências científicas sobre a saúde mental de puérperas durante a pandemia da covid-19. Método: revisão integrativa nas bases de dados BVS, CINAHL, PubCovid, Scopus e Web of Science, na qual se considerou a pergunta de pesquisa "Quais as evidências científicas sobre a saúde mental das puérperas na pandemia do Sars-CoV-2?" Resultados: foram incluídos 10 artigos, em língua inglesa, e foi identificada maior frequência em pesquisas transversais (n = 4), publicações em novembro de 2020 (n = 3), realizadas na Itália (n = 3), com nível VI de evidência (n = 6). Demonstrou-se que as puérperas se sentem deprimidas, solitárias e com medo; atentam para a piora no risco de depressão pós-parto com valores importantes de prevalência. Apontam fatores que influenciam negativamente a saúde mental dessa população na atual pandemia e revelam ações de cuidado. Conclusões: além de características pregressas, há condições socioeconômicas ­ como residir em áreas de maior contaminação, desemprego ­ e elementos inerentes a essa pandemia ­ como distanciamento e medo da contaminação ­ que influenciam negativamente a saúde mental de puérperas. Há meios de lidar com as condições impostas pela pandemia da covid-19, como técnicas de relaxamento, prática de exercício físico e apoio profissional. Salientam-se a importância e a necessidade de pesquisas nacionais, principalmente, e internacionais nessa temática.

Objetivo: identificar y analizar las evidencias científicas sobre la salud mental de puérperas durante la pandemia de la covid-19. Método: revisión integradora en las bases de datos BVS, CINAHL, PubCovid, Scopus y Web of Science, en la que se consideró la pregunta de investigación "¿Cuáles son las evidencias científicas sobre la salud mental de las puérperas en la pandemia del SARS-CoV-2?" Resultados: se incluyeron diez artículos, en inglés, y se identificó más frecuencia en investigaciones trasversales (n = 4), publicaciones en noviembre de 2020 (n = 3), realizadas en Italia (n = 3), con nivel VI de evidencia (n = 6). Se demostró que las puérperas se sienten deprimidas, solitarias y con miedo, lo cual agrava el riesgo de depresión posparto con valores importantes de prevalencia. Se señalan factores que influyen de forma negativa en la salud mental de esta población y se evidencian acciones de cuidado. Conclusiones: además de las características anteriores, algunas condiciones socio-económicas (como vivir en áreas de más infección, desempleo) y elementos inherentes a esta pandemia (como distanciamiento y miedo de contagiarse) influyen de forma negativa en la salud mental de puérperas. Hay formas de manejar las condiciones impuestas por la pandemia de covid-19, como técnicas de relajación, práctica de ejercicio físico y soporte profesional. Se destacan la importancia y la necesidad de investigaciones nacionales, principalmente, e internacionales en esta temática.

Functional binding dynamics relevant to the evolution of zoonotic spillovers in endemic and emergent Betacoronavirus strains.

Comparative functional analysis of the dynamic interactions between various Betacoronavirus mutant strains and broadly utilized target proteins such as ACE2 and CD26, is crucial for a more complete understanding of zoonotic spillovers of viruses that cause diseases such as COVID-19. Here, we employ machine learning to replicated sets of nanosecond scale GPU accelerated molecular dynamics simulations to statistically compare and classify atom motions of these target proteins in both the presence and absence of different endemic and emergent strains of the viral receptor binding domain (RBD) of the S spike glycoprotein. A multi-agent classifier successfully identified functional binding dynamics that are evolutionarily conserved from bat CoV-HKU4 to human endemic/emergent strains. Conserved dynamics regions of ACE2 involve both the N-terminal helices, as well as a region of more transient dynamics encompassing residues K353, Q325 and a novel motif AAQPFLL 386-92 that appears to coordinate their dynamic interactions with the viral RBD at N501. We also demonstrate that the functional evolution of Betacoronavirus zoonotic spillovers involving ACE2 interaction dynamics are likely pre-adapted from two precise and stable binding sites involving the viral bat progenitor strain's interaction with CD26 at SAMLI 291-5 and SS 333-334. Our analyses further indicate that the human endemic strains hCoV-HKU1 and hCoV-OC43 have evolved more stable N-terminal helix interactions through enhancement of an interfacing loop region on the viral RBD, whereas the highly transmissible SARS-CoV-2 variants (B.1.1.7, B.1.351 and P.1) have evolved more stable viral binding via more focused interactions between the viral N501 and ACE2 K353 alone.Communicated by Ramaswamy H. Sarma.

Innate Immune Training with Bacterial Extracts Enhances Lung Macrophage Recruitment to Protect from Betacoronavirus Infection.

Training of the innate immune system with orally ingested bacterial extracts was demonstrated to have beneficial effects on infection clearance and disease outcome. The aim of our study was to identify cellular and molecular processes responsible for these immunological benefits. We used a murine coronavirus (MCoV) A59 mouse model treated with the immune activating bacterial extract Broncho-Vaxom (BV) OM-85. Tissue samples were analysed with qPCR, RNA sequencing, histology, and flow cytometry. After BV OM-85 treatment, interstitial macrophages accumulated in lung tissue leading to a faster response of type I interferon (IFN) signalling after MCoV infection resulting in overall lung tissue protection. Moreover, RNA sequencing showed that lung tissue from mice receiving BV OM-85 resembled an intermediate stage between healthy and viral infected lung tissue at day 4, indicating a faster return to normal tissue homoeostasis. The pharmacologic effect was mimicked by adoptively transferring naive lung macrophages into lungs from recipient mice before virus infection. The beneficial effect of BV OM-85 was abolished when inhibiting initial type I IFN signalling. Overall, our data suggest that BV OM-85 enhances lung macrophages allowing for a faster IFN response towards a viral challenge as part of the oral-induced innate immune system training.

Breve reflexão sobre a aferição de temperatura em ambientes públicos para controle da COVID-19 / Notes on temperature measurement in public environments for COVID-19 control / Breve reflexión sobre medición de temperatura en ambientes públicos para el control de COVID-19

A Covid-19 é uma doença causada pelo betacoronavírus SARS-CoV-2. O vírus é transmitido pelo contato interpessoal próximo, por meio de gotículas respiratórias. Dentre as medidas de prevenção contra contágio e disseminação da doença, é recomendado a higienização das mãos com água e sabão e/ou álcool em gel e o afastamento social, uso de máscaras de pano e a aferição da temperatura utilizando termômetro digital infravermelho para o controle de acesso nos ambientes públicos, a fim de impedir possíveis portadores sintomáticos do vírus. Temos por objetivo, refletir sobre a eficácia da aferição da temperatura em ambientes públicos utilizando termômetro digital com sensor de infravermelho. Baseado nos conhecimentos da fisiologia da temperatura corporal e processos febris, apresentados na literatura especializada, e na experiência da identificação de portadores utilizando o procedimento de aferição de temperatura descrito, é evidente a necessidade de uma elaboração de políticas públicas de combate à pandemia mais abrangente, que enfatize a necessidade do conjunto das medidas sanitárias. Aliado a isso, é necessário um programa de testagem contínuo e em massa, permitindo o mapeamento e a busca por auxílio e orientação médica especializada, bem como um programa de educação e conscientização da população para a necessidade de quarentena e isolamento social em casos suspeitos que apresentem sintomas de pirexia.

Covid-19 is a disease caused by the betacoronavirus SARS-CoV-2, which is transmitted through close interpersonal contact through respiratory droplets. Among the preventive measures against contagion and dissemination, the guidelines recommend hand hygiene with water and soap or hand sanitizer, social withdrawal, use of cloth masks and temperature measurement using digital infrared thermometer for access control in public environments to prevent possible symptomatic carriers. This study sought to reflect on the effectiveness of measuring temperature in public environments using a digital infrared thermometer. Based on specialized literature on body temperature physiology and febrile response, as well as on the practice of carrier identification by temperature measurement, the research point to the need of elaborating more comprehensive public policies to combat the pandemic, emphasizing a combination of health measures. Moreover, a continuous and mass testing program is needed, allowing the mapping and search for specialized medical help, as well as an education and awareness program on the need for quarantine and social isolation is symptomatic carriers.

Covid-19 es la enfermedad causada por el betacoronavirus SARS-CoV-2. El virus se transmite por contacto interpersonal cercano, a través de gotitas respiratorias. Entre las medidas preventivas contra el contagio y propagación de la enfermedad, se recomiendan la higiene de manos con agua y jabón y / o gel de alcohol y el retraimiento social, el uso de mascarillas de tela y la medición de la temperatura mediante un termómetro digital infrarrojo para su control. para prevenir posibles portadores sintomáticos del virus. Nuestro objetivo es reflexionar sobre la efectividad de medir la temperatura en entornos públicos utilizando un termómetro digital con sensor de infrarrojos. Con base en el conocimiento de la fisiología de la temperatura corporal y los procesos febriles, presentado en la literatura especializada, y en la experiencia de identificación de portadores mediante el procedimiento de medición de temperatura descrito, se evidencia la necesidad de la elaboración de una política pública más integral para combatir la pandemia., que enfatiza la necesidad de todas las medidas sanitarias. A ello se suma un programa de pruebas continuas y masivas, que permitan el mapeo y búsqueda de asistencia y orientación médica especializada, así como un programa de educación y sensibilización de la población sobre la necesidad de cuarentena y aislamiento social en casos sospechosos, que presentan síntomas del pirexia.