Hepatitis E virus (HEV) was considered the only member of the Hepeviridae family with zoonotic potential. Nevertheless, this consideration has been reassessed owing to several reported cases of acute ...and chronic hepatitis linked to the Orthohepevirus C genus. Because the circulation of Orthohepevirus C in rodents has been described worldwide, the risk of zoonotic transmission is plausibly global.
Orthohepevirus C RNA was retrospectively evaluated in 2 cohorts of patients in Spain. The first cohort included patients with acute hepatitis without etiological diagnosis after screening for hepatotropic virus infection. The second cohort included patients diagnosed with acute HEV infection, defined as positivity for anti-HEV-IgM antibodies and/or detectable HEV RNA in serum.
Cohort 1 comprised 169 patients (64.4% male, median age 43 years) and cohort 2 comprised 98 individuals (68.3% male, median age 45 years). Of the individuals included in Cohort 1, two (1.18%; 95% CI 0.2-3.8) had detectable Orthohepevirus C RNA in serum. In Cohort 2, of the 98 included patients, 58 showed detectable HEV RNA, while 40 only showed positivity for IgM antibodies. Among those bearing only IgM antibodies, Orthohepevirus C RNA was detected in 1 (2.5%; 95% CI 0.06-13.1) individual. All strains were consistent with genotype C1. The infection resulted in mild self-limiting acute hepatitis in 2 patients. Infection caused severe acute hepatitis in the remaining patient who died as a result of liver and renal failure.
We described 3 cases of Orthohepevirus C in patients with acute hepatitis, resulting in the first description of this infection in Europe. The prevalence obtained in our study suggests that Orthohepevirus C could be an emerging disease in Europe.
We describe the first cases of acute hepatitis related to rat hepatitis E virus in Europe. The prevalence found in our study suggest that rat hepatitis E virus could be considered an emerging disease in Europe.
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•First cases of acute hepatitis related to Orthohepevirus C infection in Europe.•Second registered death related to Orthohepevirus C infection worldwide in an immunosuppressed individual.•Screening for Orthohepevirus C RNA should be evaluated in all patients with acute hepatitis.
Nipah virus (NiV) is an emerging zoonotic paramyxovirus to which is attributed numerous high mortality outbreaks in South and South-East Asia; Bangladesh's Nipah belt accounts for the vast majority ...of human outbreaks, reporting regular viral emergency events. The natural reservoir of NiV is the Pteropus bat species, which covers a wide geographical distribution extending over Asia, Oceania, and Africa. Occasionally, human outbreaks have required the presence of an intermediate amplification mammal host between bat and humans. However, in Bangladesh, the viral transmission occurs directly from bat to human mainly by ingestion of contaminated fresh date palm sap. Human infection manifests as a rapidly progressive encephalitis accounting for extremely high mortality rates. Despite that, no therapeutic agents or vaccines have been approved for human use. An updated review of the main NiV infection determinants and current potential therapeutic and preventive strategies is exposed.
Reliable serological tests are required to determine the prevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to characterize immunity to the disease in ...order to address key knowledge gaps in the coronavirus disease 2019 (COVID-19) pandemic. Quantitative suspension array technology (qSAT) assays based on the xMAP Luminex platform overcome the limitations of rapid diagnostic tests and enzyme-linked immunosorbent assays (ELISAs) with their higher precision, dynamic range, throughput, miniaturization, cost-efficiency, and multiplexing capacity. We developed three qSAT assays for IgM, IgA, and IgG against a panel of eight SARS-CoV-2 antigens, including spike protein (S), nucleocapsid protein (N), and membrane protein (M) constructs. The assays were optimized to minimize the processing time and maximize the signal-to-noise ratio. We evaluated their performances using 128 prepandemic plasma samples (negative controls) and 104 plasma samples from individuals with SARS-CoV-2 diagnosis (positive controls), of whom 5 were asymptomatic, 51 had mild symptoms, and 48 were hospitalized. Preexisting IgG antibodies recognizing N, M, and S proteins were detected in negative controls, which is suggestive of cross-reactivity to common-cold coronaviruses. The best-performing antibody/antigen signatures had specificities of 100% and sensitivities of 95.78% at ≥14 days and 95.65% at ≥21 days since the onset of symptoms, with areas under the curve (AUCs) of 0.977 and 0.999, respectively. Combining multiple markers as assessed by qSAT assays has the highest efficiency, breadth, and versatility to accurately detect low-level antibody responses for obtaining reliable data on the prevalence of exposure to novel pathogens in a population. Our assays will allow gaining insights into antibody correlates of immunity and their kinetics, required for vaccine development to combat the COVID-19 pandemic.
COVID-19 patients elicit strong responses to the nucleocapsid (N) protein of SARS-CoV-2 but binding antibodies are also detected in prepandemic individuals, indicating potential crossreactivity with ...common cold human coronaviruses (HCoV) and questioning its utility in seroprevalence studies. We investigated the immunogenicity of the full-length and shorter fragments of the SARS-CoV-2 N protein, and the crossreactivity of antibodies with HCoV. We identified a C-terminus region in SARS-CoV2 N of minimal sequence homology with HCoV that was more specific for SARS-CoV-2 and highly immunogenic. IgGs to the full-length SARS-CoV-2 N also recognized N229E N, and IgGs to HKU1 N recognized SARS-CoV-2 N. Crossreactivity with SARS-CoV-2 was stronger for alpha- rather than beta-HCoV despite having less sequence identity, revealing the importance of conformational recognition. Higher preexisting IgG to OC43 N correlated with lower IgG to SARS-CoV-2 N in rRT-PCR negative individuals, reflecting less exposure and indicating a potential protective association. Antibodies to SARS-CoV-2 N were higher in patients with more severe and longer duration of symptoms and in females. IgGs remained stable for at least 3 months, while IgAs and IgMs declined faster. In conclusion, N protein is a primary target of SARS-CoV-2-specific and HCoV crossreactive antibodies, both of which may affect the acquisition of immunity to COVID-19.
Abstract
Scarce data have been reported about cellular immunity and longevity for different COVID-19 vaccination schedules. We carried out a prospective study enrolling 709 healthcare workers ...receiving two doses of mRNA-1273, BNT162b2, ChAdOx1, ChAdOx1/BNT162b2 or ChAdOx1 single dose to compare humoral and cellular immunogenicity across 9 months. Higher SARS-CoV-2 spike antibody levels were observed among individuals with hybrid immunity with one dose of any vaccine in comparison to uninfected individuals receiving two doses (mRNA-1273: 20,145 vs 4295 U/mL; BNT162b2: 15,659 vs 1959 U/mL; ChAdOx1: 5344 vs 2230 U/mL), except for ChAdOx1/BNT162b2 heterologous schedule (12,380 U/mL). Naturally infected individuals did not increase substantially the titers after the second dose and showed higher levels throughout the 9 months follow-up. The mean elimination half-life of antibodies among COVID-19 naïve participants was 98, 111, 60 and 36 days, for mRNA-1273, BNT162b2, ChAdOx1/ChAdOx1 and ChAdOx1/BNT162b2, respectively. Cellular immunity was preserved in 96%, 98%, 88% and 92% of uninfected individuals who received mRNA-1273, BNT162b2, ChAdOx1/ChAdOx1 and ChAdOx1/BNT162b2 after 6/9 months. Individuals with specific T cells showed robust long lasting protection, especially when m-RNA based vaccines are inoculated. These data may influence the validity of the vaccination passport and the need for booster vaccinations.
The widespread critical evidence surrounding executive compensation of listed corporations has boosted shareholder activism in recent decades. The say‐on‐pay (SOP) mechanism—a vote in which ...shareholders express their (dis)agreement with executive pay designs—is one of the corporate governance mechanisms that has led to this activism among listed firms. Merging agency and socioemotional wealth (SEW) arguments, this paper analyzes how effective SOP voting results are among listed family firms in terms of CEO compensation efficiency and equity. Using a sample of UK listed firms from 2011 to 2018, our results show that SOP effectiveness is positively influenced by family ownership and is strongly moderated by family involvement in management and in governance as well as by family generation. Our findings stress the strong family effect and the ethical perceptions of family shareholders on SOP voting, showing how family participation in the firm encourages fairer and more aligned CEO compensation packages. SOP institutional and practical implications oriented to preserve shareholder value and family wealth are finally outlined.
The inadequacy of HIV viraemia and resistance monitoring in Africa leads to uncontrolled circulation of HIV strains with drug resistance mutations (DRM), compromising antiretroviral therapy (ART) ...effectiveness. This study describes the DRM prevalence and its therapeutic impact in HIV-infected pediatric patients from Kinshasa (Democratic Republic of Congo, DRC).
From 2016-2018, dried blood were collected from 71 HIV-infected children and adolescents under ART in two hospitals in Kinshasa for HIV-1 DRM pol analysis, predicted ARV-susceptibility by Stanford and phylogenetic characterization.
HIV-1 sequences were recovered from 55 children/adolescents with 14 years of median-age. All had received nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTI, NNRTI), 9.1% protease inhibitors (PI) and only one integrase inhibitor (INI). Despite the use of ART, 89.1% showed virological failure and 67.3% carried viruses with major-DRM to one (12.7%), two (47.3%), or three (5.5%) ARV-families. Most children/adolescents harbored DRM to NNRTI (73.5%) or NRTI (61.2%). Major-DRM to PI was present in 8.3% and minor-DRM to INI in 15%. Dual-class-NRTI+NNRTI resistance appeared in 53.1% of patients. Viruses presented high/intermediate resistance to nevirapine (72.9% patients), efavirenz (70.9%), emtricitabine/lamivudine (47.9%), rilpivirine (41.7%), etravirine (39.6%), doravidine (33.3%), zidovudine (22.9%), among others. Most participants were susceptible to INI and PI. Great diversity of variants was found, with a high rate (40%) of unique recombinants.
The high DRM prevalence observed among HIV-infected children and adolescents in Kinshasa could compromise the 95-95-95-UNAIDS targets in the DRC. It also reinforces the need for routine resistance monitoring for optimal rescue therapy election in this vulnerable population to control the spread of resistant HIV in the country.
The development of tools that provide early triage of COVID-19 patients with minimal use of diagnostic tests, based on easily accessible data, can be of vital importance in reducing COVID-19 ...mortality rates during high-incidence scenarios. This work proposes a machine learning model to predict mortality and risk of hospitalization using both 2 simple demographic features and 19 comorbidities obtained from 86,867 electronic medical records of COVID-19 patients, and a new method (LR-IPIP) designed to deal with data imbalance problems. The model was able to predict with high accuracy (90-93%, ROC-AUC = 0.94) the patient's final status (deceased or discharged), while its accuracy was medium (71-73%, ROC-AUC = 0.75) with respect to the risk of hospitalization. The most relevant characteristics for these models were age, sex, number of comorbidities, osteoarthritis, obesity, depression, and renal failure. Finally, to facilitate its use by clinicians, a user-friendly website has been developed ( https://alejandrocisterna.shinyapps.io/PROVIA ).
Interleukin (IL)-36 is a recently described cytokine with well-known functions in the regulation of multiple inflammatory diseases. Since no data exists on how this cytokine regulates adipose tissue ...(AT) homeostasis, we aimed to explore the function of a specific isoform, IL-36γ, an agonist, in human obesity and obesity-associated type 2 diabetes as well as in AT inflammation and fibrosis. Plasma IL-36γ was measured in 91 participants in a case-control study and the effect of weight loss was evaluated in 31 patients with severe obesity undergoing bariatric surgery. Gene expression levels of
and its receptor were analyzed in relevant human metabolic tissues. The effect of inflammatory factors and IL-36γ was determined
in human adipocytes and macrophages. We found, for the first time, that the increased (
<0.05) circulating levels of IL-36γ in patients with obesity decreased (
<0.001) after weight and fat loss achieved by Roux-en-Y gastric bypass and that gene expression levels of
were upregulated in the visceral AT (
<0.05) and in the peripheral blood mononuclear cells (
<0.01) from patients with obesity. We also demonstrated increased (
<0.05) expression levels of
in the epididymal AT from diet-induced obese mice.
was significantly enhanced (
<0.001) by LPS in human adipocytes and monocyte-derived macrophages, while no changes were found after the incubation with anti-inflammatory cytokines. The addition of IL-36γ for 24 h strongly induced (
<0.01) its own expression as well as key inflammatory and chemoattractant factors with no changes in genes associated with fibrosis. Furthermore, adipocyte-conditioned media obtained from patients with obesity increased (
<0.01) the release of IL-36γ and the expression (
<0.05) of cathepsin G (
) in monocyte-derived macrophages. These findings provide, for the first time, evidence about the properties of IL-36γ in the regulation of AT-chronic inflammation, emerging as a link between AT biology and the obesity-associated comorbidities.
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