Preeclampsia in the Context of COVID-19: Mechanisms, Pathophysiology, and Clinical Outcomes.

The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the global COVID-19 pandemic, significantly impacting the health of pregnant women. Obstetric populations, already vulnerable, face increased morbidity and mortality related to COVID-19, aggravated by preexisting comorbidities. Recent studies have shed light on the potential correlation between COVID-19 and preeclampsia (PE), a leading cause of maternal and perinatal morbidity worldwide, emphasizing the significance of exploring the relationship between these two conditions. Here, we review the pathophysiological similarities that PE shares with COVID-19, with a particular focus on severe COVID-19 cases and in PE-like syndrome cases related with SARS-CoV-2 infection. We highlight cellular and molecular mechanistic inter-connectivity between these two conditions, for example, regulation of renin-angiotensin system, tight junction and barrier integrity, and the complement system. Finally, we discuss how COVID-19 pandemic dynamics, including the emergence of variants and vaccination efforts, has shaped the clinical scenario and influenced the severity and management of both COVID-19 and PE. Continued research on the mechanisms of SARS-CoV-2 infection during pregnancy and the potential risk of developing PE from previous infections is warranted to delineate the complexities of COVID-19 and PE interactions and to improve clinical management of both conditions.

SARS-CoV-2 Modulation of HIV Latency Reversal in a Myeloid Cell Line: Direct and Bystander Effects.

Coronavirus disease 2019 (COVID-19) might impact disease progression in people living with HIV (PLWH), including those on effective combination antiretroviral therapy (cART). These individuals often experience chronic conditions characterized by proviral latency or low-level viral replication in CD4+ memory T cells and tissue macrophages. Pro-inflammatory cytokines, such as TNF-α, IL-1ß, IL-6, and IFN-γ, can reactivate provirus expression in both primary cells and cell lines. These cytokines are often elevated in individuals infected with SARS-CoV-2, the virus causing COVID-19. However, it is still unknown whether SARS-CoV-2 can modulate HIV reactivation in infected cells. Here, we report that exposure of the chronically HIV-1-infected myeloid cell line U1 to two different SARS-CoV-2 viral isolates (ancestral and BA.5) reversed its latent state after 24 h. We also observed that SARS-CoV-2 exposure of human primary monocyte-derived macrophages (MDM) initially drove their polarization towards an M1 phenotype, which shifted towards M2 over time. This effect was associated with soluble factors released during the initial M1 polarization phase that reactivated HIV production in U1 cells, like MDM stimulated with the TLR agonist resiquimod. Our study suggests that SARS-CoV-2-induced systemic inflammation and interaction with macrophages could influence proviral HIV-1 latency in myeloid cells in PLWH.

Real-world effectiveness of original BNT162b2 mRNA COVID-19 against symptomatic Omicron infection among children 5-11 years of age in Brazil: A prospective test-negative design study.

OBJECTIVE: To estimate original wild-type BNT162b2 effectiveness against symptomatic Omicron infection among children 5-11 years of age. METHODS: This prospective test-negative, case-control study was conducted in Toledo, southern Brazil, from June 2022 to July 2023. Patients were included if they were aged 5-11 years, sought care for acute respiratory symptoms in the public health system, and were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. In the primary analysis, we determined the effectiveness of two doses of original wild-type BNT162b2 against symptomatic COVID-19. The reference exposure group was the unvaccinated. RESULTS: A total of 757 children were enrolled; of these, 461 (25 cases; 436 controls) were included in the primary analysis. Mean age was 7.4 years, 49.7 % were female, 34.6 % were obese, and 14.1 % had chronic pulmonary disease. Omicron accounted for 100 % of all identified SARS-CoV-2 variants with BA.5, BQ.1, and XBB.1 accounting for 35.7 %, 21.4 % and 21.4 %, respectively. The adjusted estimate of two-dose vaccine effectiveness against symptomatic Omicron was 3.1 % (95 % CI, -133.7 % to 61.8 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 192.5 days (interquartile range, 99 to 242 days). CONCLUSION: In this study with children 5-11 years of age, a two dose-schedule of original wild-type BNT162b2 was not associated with a significant protection against symptomatic Omicron infection after a median time between the second dose and the beginning of COVID-19 symptoms of 192 days, although the study may have been underpowered to detect a clinically important difference. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT05403307 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT05403307).

Submandibular Gland Pathogenesis Following SARS-CoV-2 Infection and Implications for Xerostomia.

Although SARS-CoV-2 induces mucin hypersecretion in the respiratory tract, hyposalivation/xerostomia has been reported by COVID-19 patients. We evaluate the submandibular gland (SMGs) pathogenesis in SARS-CoV-2-infected K18-hACE2 mice, focusing on the impact of infection on the mucin production and structural integrity of acini, ductal system, myoepithelial cells (MECs) and telocytes. The spike protein, the nucleocapsid protein, hACE2, actin, EGF, TNF-α and IL-1ß were detected by immunofluorescence, and the Egfr and Muc5b expression was evaluated. In the infected animals, significant acinar hypertrophy was observed in contrast to ductal atrophy. Nucleocapsid proteins and/or viral particles were detected in the SMG cells, mainly in the nuclear membrane-derived vesicles, confirming the nuclear role in the viral formation. The acinar cells showed intense TNF-α and IL-1ß immunoexpression, and the EGF-EGFR signaling increased, together with Muc5b upregulation. This finding explains mucin hypersecretion and acinar hypertrophy, which compress the ducts. Dying MECs and actin reduction were also observed, indicating failure of contraction and acinar support, favoring acinar hypertrophy. Viral assembly was found in the dying telocytes, pointing to these intercommunicating cells as viral transmitters in SMGs. Therefore, EGF-EGFR-induced mucin hypersecretion was triggered by SARS-CoV-2 in acinar cells, likely mediated by cytokines. The damage to telocytes and MECs may have favored the acinar hypertrophy, leading to ductal obstruction, explaining xerostomia in COVID-19 patients. Thus, acinar cells, telocytes and MECs may be viral targets, which favor replication and cell-to-cell viral transmission in the SMG, corroborating the high viral load in saliva of infected individuals.

Protein C Pretreatment Protects Endothelial Cells from SARS-CoV-2-Induced Activation.

SARS-CoV-2 can induce vascular dysfunction and thrombotic events in patients with severe COVID-19; however, the cellular and molecular mechanisms behind these effects remain largely unknown. In this study, we used a combination of experimental and in silico approaches to investigate the role of PC in vascular and thrombotic events in COVID-19. Single-cell RNA-sequencing data from patients with COVID-19 and healthy subjects were obtained from the publicly available Gene Expression Omnibus (GEO) repository. In addition, HUVECs were treated with inactive protein C before exposure to SARS-CoV-2 infection or a severe COVID-19 serum. An RT-qPCR array containing 84 related genes was used, and the candidate genes obtained were evaluated. Activated protein C levels were measured using an ELISA kit. We identified at the single-cell level the expression of several pro-inflammatory and pro-coagulation genes in endothelial cells from the patients with COVID-19. Furthermore, we demonstrated that exposure to SARS-CoV-2 promoted transcriptional changes in HUVECs that were partly reversed by the activated protein C pretreatment. We also observed that the serum of severe COVID-19 had a significant amount of activated protein C that could protect endothelial cells from serum-induced activation. In conclusion, activated protein C protects endothelial cells from pro-inflammatory and pro-coagulant effects during exposure to the SARS-CoV-2 virus.

Antiviral, anti-inflammatory and antioxidant effects of curcumin and curcuminoids in SH-SY5Y cells infected by SARS-CoV-2.

COVID-19, caused by SARS-CoV-2, affects neuronal cells, causing several symptoms such as memory loss, anosmia and brain inflammation. Curcuminoids (Me08 e Me23) and curcumin (CUR) are derived from Curcuma Longa extract (EXT). Many therapeutic actions have been linked to these compounds, including antiviral action. Given the severe implications of COVID-19, especially within the central nervous system, our study aims to shed light on the therapeutic potential of curcuminoids against SARS-CoV-2 infection, particularly in neuronal cells. Here, we investigated the effects of CUR, EXT, Me08 and Me23 in human neuroblastoma SH-SY5Y. We observed that Me23 significantly decreased the expression of plasma membrane-associated transmembrane protease serine 2 (TMPRSS2) and TMPRSS11D, consequently mitigating the elevated ROS levels induced by SARS-CoV-2. Furthermore, Me23 exhibited antioxidative properties by increasing NRF2 gene expression and restoring NQO1 activity following SARS-CoV-2 infection. Both Me08 and Me23 effectively reduced SARS-CoV-2 replication in SH-SY5Y cells overexpressing ACE2 (SH-ACE2). Additionally, all of these compounds demonstrated the ability to decrease proinflammatory cytokines such as IL-6, TNF-α, and IL-17, while Me08 specifically reduced INF-γ levels. Our findings suggest that curcuminoid Me23 could serve as a potential agent for mitigating the impact of COVID-19, particularly within the context of central nervous system involvement.

SARS-CoV-2 Spike protein triggers gut impairment since mucosal barrier to innermost layers: From basic science to clinical relevance.

Studies have reported the occurrence of gastrointestinal (GI) symptoms, primarily diarrhea, in COVID-19. However, the pathobiology regarding COVID-19 in the GI tract remains limited. This work aimed to evaluate SARS-CoV-2 Spike protein interaction with gut lumen in different experimental approaches. Here, we present a novel experimental model with the inoculation of viral protein in the murine jejunal lumen, in vitro approach with human enterocytes, and molecular docking analysis. Spike protein led to increased intestinal fluid accompanied by Cl- secretion, followed by intestinal edema, leukocyte infiltration, reduced glutathione levels, and increased cytokine levels [interleukin (IL)-6, tumor necrosis factor-α, IL-1ß, IL-10], indicating inflammation. Additionally, the viral epitope caused disruption in the mucosal histoarchitecture with impairment in Paneth and goblet cells, including decreased lysozyme and mucin, respectively. Upregulation of toll-like receptor 2 and toll-like receptor 4 gene expression suggested potential activation of local innate immunity. Moreover, this experimental model exhibited reduced contractile responses in jejunal smooth muscle. In barrier function, there was a decrease in transepithelial electrical resistance and alterations in the expression of tight junction proteins in the murine jejunal epithelium. Additionally, paracellular intestinal permeability increased in human enterocytes. Finally, in silico data revealed that the Spike protein interacts with cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride conductance (CaCC), inferring its role in the secretory effect. Taken together, all the events observed point to gut impairment, affecting the mucosal barrier to the innermost layers, establishing a successful experimental model for studying COVID-19 in the GI context.

Cost-effective 3D lung tissue spheroid as a model for SARS-CoV-2 infection and drug screening.

BACKGROUND: The SARS-CoV-2 pandemic has spurred an unparalleled scientific endeavor to elucidate the virus' structure, infection mechanisms, and pathogenesis. Two-dimensional culture systems have been instrumental in shedding light on numerous aspects of COVID-19. However, these in vitro systems lack the physiological complexity to comprehend the infection process and explore treatment options. Three-dimensional (3D) models have been proposed to fill the gap between 2D cultures and in vivo studies. Specifically, spheroids, composed of lung cell types, have been suggested for studying SARS-CoV-2 infection and serving as a drug screening platform. METHODS: 3D lung spheroids were prepared by coculturing human alveolar or bronchial epithelial cells with human lung stromal cells. The morphology, size, and ultrastructure of spheroids before and after SARS-CoV-2 infection were analyzed using optical and electron microscopy. Immunohistochemistry was used to detect spike protein and, thus, the virus presence in the spheroids. Multiplex analysis elucidated the cytokine release after virus infection. RESULTS: The spheroids were stable and kept their size and morphology after SARS-CoV-2 infection despite the presence of multivesicular bodies, endoplasmic reticulum rearrangement, tubular compartment-enclosed vesicles, and the accumulation of viral particles. The spheroid responded to the infection releasing IL-6 and IL-8 cytokines. CONCLUSION: This study demonstrates that coculture spheroids of epithelial and stromal cells can serve as a cost-effective infection model for the SARS-CoV-2 virus. We suggest using this 3D spheroid as a drug screening platform to explore new treatments related to the cytokines released during virus infection, especially for long COVID treatment.

Prostaglandin E2/Leukotriene B4 balance and viral load in distinct clinical stages of COVID-19: A cross-sectional study.

BACKGROUND: Prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) are eicosanoids involved in modulation of the antiviral immune response. Recent studies have identified increased levels of several eicosanoids in the plasma and bronchoalveolar lavage of patients with coronavirus disease (COVID-19). This study investigated correlations between plasma levels of PGE2 and LTB4 and clinical severity of COVID-19. METHODS: This cross-sectional study involved non-infected (n = 10) individuals and COVID-19 patients classified as cured (n = 13), oligosymptomatic (n = 29), severe (n = 15) or deceased (n = 11). Levels of D-dimer a, known COVID-19 severity marker, PGE2 and LTB4 were measured by ELISAs and data were analysed with respect to viral load. RESULTS: PGE2 plasma levels were decreased in COVID-19 patients compared to the non-infected group. Changes in PGE2 and LTB4 levels did not correlate with any particular clinical presentations of COVID-19. However, LTB4 was related to decreased SARS-CoV-2 burden in patients, suggesting that only LTB4 is associated with control of viral load. CONCLUSIONS: Our data indicate that PGE2/LTB4 plasma levels are not associated with COVID-19 clinical severity. Hospitalized patients with COVID-19 are treated with corticosteroids, which may influence the observed eicosanoid imbalance. Additional analyses are required to fully understand the participation of PGE2 receptors in the pathophysiology of COVID-19.

Host genetics and the profile of COVID-19 in indigenous people from the Brazilian Amazon: A pilot study with variants of the ACE1, ACE2 and TMPRSS2 genes.

This pilot study aimed to investigate genetic factors that may have contributed to the milder clinical outcomes of COVID-19 in Brazilian indigenous populations. 263 Indigenous from the Araweté, Kararaô, Parakanã, Xikrin do Bacajá, Kayapó and Munduruku peoples were analyzed, 55.2% women, ages ranging from 10 to 95 years (average 49.5 ± 20.7). Variants in genes involved in the entry of SARS-CoV-2 into the host cell (ACE1 rs1799752 I/D, ACE2 rs2285666 C/T, ACE2 rs73635825 A/G and TMPRSS2 rs123297605 C/T), were genotyped in indigenous peoples from the Brazilian Amazon, treated during the SARS-CoV-2 pandemic between 2020 and 2021. The distribution of genotypes did not show any association with the presence or absence of IgG antibodies. Additionally, the influence of genetic variations on the severity of the disease was not examined extensively because a significant number of indigenous individuals experienced the disease with either mild symptoms or no symptoms. It is worth noting that the frequencies of risk alleles were found to be lower in Indigenous populations compared to both continental populations and Brazilians. Indigenous Brazilian Amazon people exhibited an ethnic-specific genetic profile that may be associated with a milder disease, which could explain the unexpected response they demonstrated to COVID-19, being less impacted than Brazilians.

Biological evaluation of a mechanical ventilator that operates by controlling an automated manual resuscitator. A descriptive study in swine.

The Covid-19 outbreak challenged health systems around the world to design and implement cost-effective devices produced locally to meet the increased demand of mechanical ventilators worldwide. This study evaluates the physiological responses of healthy swine maintained under volume- or pressure-controlled mechanical ventilation by a mechanical ventilator implemented to bring life-support by automating a resuscitation bag and closely controlling ventilatory parameters. Physiological parameters were monitored in eight sedated animals (t0) prior to inducing deep anaesthesia, and during the next six hours of mechanical ventilation (t1-7). Hemodynamic conditions were monitored periodically using a portable gas analyser machine (i.e. BEecf, carbonate, SaO2, lactate, pH, PaO2, PaCO2) and a capnometer (i.e. ETCO2). Electrocardiogram, echocardiography and lung ultrasonography were performed to detect in vivo alterations in these vital organs and pathological findings from necropsy were reported. The mechanical ventilator properly controlled physiological levels of blood biochemistry such as oxygenation parameters (PaO2, PaCO2, SaO2, ETCO2), acid-base equilibrium (pH, carbonate, BEecf), and perfusion of tissues (lactate levels). In addition, histopathological analysis showed no evidence of acute tissue damage in lung, heart, liver, kidney, or brain. All animals were able to breathe spontaneously after undergoing mechanical ventilation. These preclinical data, supports the biological safety of the medical device to move forward to further evaluation in clinical studies.

An Upgrade on the Surveillance System of SARS-CoV-2: Deployment of New Methods for Genetic Inspection.

SARS-CoV-2 variants surveillance is a worldwide task that has been approached with techniques such as Next Generation Sequencing (NGS); however, this technology is not widely available in developing countries because of the lack of equipment and limited funding in science. An option is to deploy a RT-qPCR screening test which aids in the analysis of a higher number of samples, in a shorter time and at a lower cost. In this study, variants present in samples positive for SARS-CoV-2 were identified with a RT-qPCR mutation screening kit and were later confirmed by NGS. A sample with an abnormal result was found with the screening test, suggesting the simultaneous presence of two viral populations with different mutations. The DRAGEN Lineage analysis identified the Delta variant, but there was no information about the other three mutations previously detected. When the sequenced data was deeply analyzed, there were reads with differential mutation patterns, that could be identified and classified in terms of relative abundance, whereas only the dominant population was reported by DRAGEN software. Since most of the software developed to analyze SARS-CoV-2 sequences was aimed at obtaining the consensus sequence quickly, the information about viral populations within a sample is scarce. Here, we present a faster and deeper SARS-CoV-2 surveillance method, from RT-qPCR screening to NGS analysis.

A Novel Bacterial Protease Inhibitor Adjuvant in RBD-Based COVID-19 Vaccine Formulations Containing Alum Increases Neutralizing Antibodies, Specific Germinal Center B Cells and Confers Protection Against SARS-CoV-2 Infection in Mice.

In this work, we evaluated recombinant receptor binding domain (RBD)-based vaccine formulation prototypes with potential for further clinical development. We assessed different formulations containing RBD plus alum, AddaS03, AddaVax, or the combination of alum and U-Omp19: a novel Brucella spp. protease inhibitor vaccine adjuvant. Results show that the vaccine formulation composed of U-Omp19 and alum as adjuvants has a better performance: it significantly increased mucosal and systemic neutralizing antibodies in comparison to antigen plus alum, AddaVax, or AddaS03. Antibodies induced with the formulation containing U-Omp19 and alum not only increased their neutralization capacity against the ancestral virus but also cross-neutralized alpha, lambda, and gamma variants with similar potency. Furthermore, the addition of U-Omp19 to alum vaccine formulation increased the frequency of RBD-specific geminal center B cells and plasmablasts. Additionally, U-Omp19+alum formulation induced RBD-specific Th1 and CD8+ T-cell responses in spleens and lungs. Finally, this vaccine formulation conferred protection against an intranasal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge of K18-hACE2 mice.

Screening of Natural Products Inhibitors of SARS-CoV-2 Entry.

The COVID-19 pandemic has led to the search for new molecules with antiviral activity against SARS-CoV-2. The entry of the virus into the cell is one of the main targets for inhibiting SARS-CoV-2 infection. Natural products are an important source of new therapeutic alternatives against diseases. Pseudotyped viruses allow the study of SARS-CoV-2 viral entry inhibitors, and due to their simplicity, they allow the screening of a large number of antiviral candidates in Biosafety Level 2 facilities. We used pseudotyped HIV-1 with the D614G SARS-CoV-2 spike glycoprotein to test its ability to infect ACE2-expressing HEK 293T cells in the presence of diverse natural products, including 21 plant extracts, 7 essential oils, and 13 compounds from plants and fungi. The 50% cytotoxic concentration (CC50) was evaluated using the resazurin method. From these analyses, we determined the inhibitory activity of the extract of Stachytarpheta cayennensis, which had a half-maximal inhibitory concentration (IC50) of 91.65 µg/mL, a CC50 of 693.5 µg/mL, and a selectivity index (SI) of 7.57, indicating its potential use as an inhibitor of SARS-CoV-2 entry. Moreover, our work indicates the usefulness of the pseudotyped-virus system in the screening of SARS-CoV-2 entry inhibitors.

Mortality and associated risk factors in patients hospitalized due to COVID-19 in a Peruvian reference hospital.

OBJECTIVES: To determine the risk factors for in-hospital mortality in patients with COVID-19 from a Peruvian national hospital. METHODS: Retrospective cohort study of medical records of patients with COVID-19 hospitalized at Hospital Nacional Hipólito Unanue (HNHU) during the months of April to August 2020. The dependent variable was in-hospital mortality. Independent variables included sociodemographic and clinical characteristics, physical examination findings, oxygen saturation (SaO2) at admission, treatment received during hospitalization and laboratory results at admission. A Cox regression model was used to evaluate the crude and adjusted hazard ratios for associated factors. RESULTS: We included 1418 patients. Median age was 58 years (IQR 47-68 years) and 944 (66.6%) were male. The median length of hospitalization was 7 (4-13) days, and the mortality rate was 46%. The most frequent comorbidities were type 2 diabetes mellitus, hypertension, and obesity. In the adjusted analysis, mortality was associated with age (HR 1.02; 95%CI 1.02-1.03), history of surgery (HR 1.89; 95%CI 1.31-2.74), lower oxygen saturation at admission (HR 4.08; CI95% 2.72-8.05 for SaO2<70% compared to SaO2>94%), the presence of poor general condition (HR 1.81; 95% CI 1.29-2.53), altered state of consciousness (HR 1.58; 95%CI 1.18-2.11) and leukocyte levels (HR 1.01; 95%CI 1.00-1. 02). Treatment with ivermectin (HR 1.44; 95%CI 1.18-1.76) and azithromycin (HR 1.25; 95%CI 1.03-1.52) were associated with higher mortality. Treatment with corticosteroids at low to moderate doses was associated with lower mortality (HR 0.56 95%CI 0. 37-0. 86) in comparison to no steroid use. CONCLUSION: A high mortality was found in our cohort. Low oxygen saturation at admission, age, and the presence of hematological and biochemical alterations were associated with higher mortality. The use of hydroxychloroquine, ivermectin or azithromycin was not useful and was probably associated with unfavorable outcomes. The use of corticosteroids at moderate doses was associated with lower mortality.

A proficient approach to forecast COVID-19 spread via optimized dynamic machine learning models.

This study aims to develop an assumption-free data-driven model to accurately forecast COVID-19 spread. Towards this end, we firstly employed Bayesian optimization to tune the Gaussian process regression (GPR) hyperparameters to develop an efficient GPR-based model for forecasting the recovered and confirmed COVID-19 cases in two highly impacted countries, India and Brazil. However, machine learning models do not consider the time dependency in the COVID-19 data series. Here, dynamic information has been taken into account to alleviate this limitation by introducing lagged measurements in constructing the investigated machine learning models. Additionally, we assessed the contribution of the incorporated features to the COVID-19 prediction using the Random Forest algorithm. Results reveal that significant improvement can be obtained using the proposed dynamic machine learning models. In addition, the results highlighted the superior performance of the dynamic GPR compared to the other models (i.e., Support vector regression, Boosted trees, Bagged trees, Decision tree, Random Forest, and XGBoost) by achieving an averaged mean absolute percentage error of around 0.1%. Finally, we provided the confidence level of the predicted results based on the dynamic GPR model and showed that the predictions are within the 95% confidence interval. This study presents a promising shallow and simple approach for predicting COVID-19 spread.

Assessing the impact of human mobility to predict regional excess death in Ecuador.

COVID-19 outbreaks have had high mortality in low- and middle-income countries such as Ecuador. Human mobility is an important factor influencing the spread of diseases possibly leading to a high burden of disease at the country level. Drastic control measures, such as complete lockdown, are effective epidemic controls, yet in practice one hopes that a partial shutdown would suffice. It is an open problem to determine how much mobility can be allowed while controlling an outbreak. In this paper, we use statistical models to relate human mobility to the excess death in Ecuador while controlling for demographic factors. The mobility index provided by GRANDATA, based on mobile phone users, represents the change of number of out-of-home events with respect to a benchmark date (March 2nd, 2020). The study confirms the global trend that more men are dying than expected compared to women, and that people under 30 show less deaths than expected, particularly individuals younger than 20 with a death rate reduction between 22 and 27%. The weekly median mobility time series shows a sharp decrease in human mobility immediately after a national lockdown was declared on March 17, 2020 and a progressive increase towards the pre-lockdown level within two months. Relating median mobility to excess deaths shows a lag in its effect: first, a decrease in mobility in the previous two to three weeks decreases excess death and, more novel, we found an increase of mobility variability four weeks prior increases the number of excess deaths.

Persistently high hepatitis C rates in haemodialysis patients in Brazil [a systematic review and meta-analysis].

We conducted a systematic review and meta-analysis of studies assessing HCV infection rates in haemodialysis patients in Brazil (Prospero CRD #42021275068). We included studies on patients under haemodialysis, comprising both convenience samples and exhaustive information from selected services. Patients underwent HCV serological testing with or without confirmation by HCV RNA PCR. Exclusion criteria were the following: absence of primary empirical information and studies without information on their respective settings, study year, accurate infection rates, or full specification of diagnostic tests. Studies with samples ≤ 30 and serial assessments with repeated information were also excluded. Reference databases included PubMed, LILACS, Scopus, and Web of Science for the period 1989-2019. A systematic review was carried out, followed by two independent meta-analyses: (i) studies with data on HCV prevalence and (ii) studies with a confirmatory PCR (i.e., active infection), respectively. A comprehensive set of different methods and procedures were used: forest plots and respective statistics, polynomial regression, meta-regression, subgroup influence, quality assessment, and trim-and-fill analysis. 29 studies and 11,290 individuals were assessed. The average time patients were in haemodialysis varied from 23.5 to 56.3 months. Prevalence of HCV infection was highly heterogeneous, with a pronounced decrease from 1992 to 2001, followed by a plateau and a slight decrease in recent years. The summary measure for HCV prevalence was 34% (95% CI 26-43%) for studies implemented before 2001. For studies implemented after 2001, the corresponding summary measure was 11% (95% CI 8-15%). Estimates for prevalence of active HCV infection were also highly heterogeneous. There was a marked decline from 1996 to 2001, followed by a plateau and a slight increase after 2010. The summary measure for active HCV infection was 19% (95% CI 15-25%) in studies carried out before 2001. For studies implemented after 2001, the corresponding summary measure was 9% (95% CI 6-13%). Heterogeneity was pervasive, but different analyses helped to identify its underlying sources. Besides the year each study was conducted, the findings differed markedly between geographic regions and were heavily influenced by the size of the studies and publication biases. Our systematic review and meta-analysis documented a substantial decline in HCV prevalence among Brazilian haemodialysis patients from 1992 to 2015. CKD should be targeted with specific interventions to prevent HCV infection, and if prevention fails, prompt diagnosis and treatment. Although the goal of HCV elimination by 2030 in Brazil remains elusive, it is necessary to adopt measures to achieve micro-elimination and to launch initiatives towards targeted interventions to curb the spread of HCV in people with CKD, among other high-risk groups. This is of particular concern in the context of a protracted COVID-19 pandemic and a major economic and political crisis.

Outbreak of NDM-1-Producing Escherichia coli in a Coronavirus Disease 2019 Intensive Care Unit in a Mexican Tertiary Care Center.

Emergency department areas were repurposed as intensive care units (ICUs) for patients with acute respiratory distress syndrome during the initial months of the coronavirus disease 2019 (COVID-19) pandemic. We describe an outbreak of New Delhi metallo-ß-lactamase 1 (NDM-1)-producing Escherichia coli infections in critically ill COVID-19 patients admitted to one of the repurposed units. Seven patients developed infections (6 ventilator-associated pneumonia [VAP] and 1 urinary tract infection [UTI]) due to carbapenem-resistant E. coli, and only two survived. Five of the affected patients and four additional patients had rectal carriage of carbapenem-resistant E. coli. The E. coli strain from the affected patients corresponded to a single sequence type. Rectal screening identified isolates of two other sequence types bearing blaNDM-1. Isolates of all three sequence types harbored an IncFII plasmid. The plasmid was confirmed to carry blaNDM-1 through conjugation. An outbreak of clonal NDM-1-producing E. coli isolates and subsequent dissemination of NDM-1 through mobile elements to other E. coli strains occurred after hospital conversion during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. This emphasizes the need for infection control practices in surge scenarios. IMPORTANCE The SARS-CoV-2 pandemic has resulted in a surge of critically ill patients. Hospitals have had to adapt to the demand by repurposing areas as intensive care units. This has resulted in high workload and disruption of usual hospital workflows. Surge capacity guidelines and pandemic response plans do not contemplate how to limit collateral damage from issues like hospital-acquired infections. It is vital to ensure quality of care in surge scenarios.

Modeling the Transmission of the SARS-CoV-2 Delta Variant in a Partially Vaccinated Population.

In a population with ongoing vaccination, the trajectory of a pandemic is determined by how the virus spreads in unvaccinated and vaccinated individuals that exhibit distinct transmission dynamics based on different levels of natural and vaccine-induced immunity. We developed a mathematical model that considers both subpopulations and immunity parameters, including vaccination rates, vaccine effectiveness, and a gradual loss of protection. The model forecasted the spread of the SARS-CoV-2 delta variant in the US under varied transmission and vaccination rates. We further obtained the control reproduction number and conducted sensitivity analyses to determine how each parameter may affect virus transmission. Although our model has several limitations, the number of infected individuals was shown to be a magnitude greater (~10×) in the unvaccinated subpopulation compared to the vaccinated subpopulation. Our results show that a combination of strengthening vaccine-induced immunity and preventative behavioral measures like face mask-wearing and contact tracing will likely be required to deaccelerate the spread of infectious SARS-CoV-2 variants.