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AbstractBats are known to be reservoirs of several highly pathogenic viruses. Hence, the interest in bat virus discovery has been increasing rapidly over the last decade. So far, most studies have focused on a single type of virus detection method, either PCR, virus isolation or virome sequencing. Here we present a comprehensive approach in virus discovery, using all three discovery methods on samples from the same bats. By family-specific PCR screening we found sequences of paramyxoviruses, adenoviruses, herpesviruses and one coronavirus. By cell culture we isolated a novel bat adenovirus and bat orthoreovirus. Virome sequencing revealed viral sequences of ten different virus families and orders: three bat nairoviruses, three phenuiviruses, one orbivirus, one rotavirus, one orthoreovirus, one mononegavirus, five parvoviruses, seven picornaviruses, three retroviruses, one totivirus and two thymoviruses were discovered. Of all viruses identified by family-specific PCR in the original samples, none was found by metagenomic sequencing. Vice versa, none of the viruses found by the metagenomic virome approach was detected by family-specific PCRs targeting the same family. The discrepancy of detected viruses by different detection approaches suggests that a combined approach using different detection methods is necessary for virus discovery studies.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2, a new member of the genus Betacoronavirus, is a pandemic virus, which has caused numerous fatalities, particularly in the elderly and persons with underlying morbidities. At present, there are no approved vaccines nor antiviral therapies available. The detection and quantification of SARS-CoV-2-neutralizing antibodies plays a crucial role in the assessment of the immune status of convalescent COVID-19 patients, evaluation of recombinant therapeutic antibodies, and the evaluation of novel vaccines. To detect SARS-CoV-2-neutralizing antibodies, classically, a virus-neutralization test has to be performed at biosafety level 3, considerably limiting the general use of this test. In the present work, a biosafety level 1 pseudotype virus assay based on a propagation-incompetent vesicular stomatitis virus (VSV) has been used to determine the neutralizing antibody titers in convalescent COVID-19 patients. The neutralization titers in serum of two independently analyzed patient cohorts were available within 18 h and correlated well with those obtained with a classical SARS-CoV-2 neutralization test (Pearson correlation coefficients of r = 0.929 and r = 0.939, respectively). Most convalescent COVID-19 patients had only low titers of neutralizing antibodies (ND50 < 320). The sera of convalescent COVID-19 patients also neutralized pseudotype virus displaying the SARS-CoV-1 spike protein on their surface, which is homologous to the SARS-CoV-2 spike protein. In summary, we report a robust virus-neutralization assay, which can be used at low biosafety level 1 to rapidly quantify SARS-CoV-2-neutralizing antibodies in convalescent COVID-19 patients and vaccinated individuals.

A novel series of bis- (Abdelhamid et al., 2017, Banerjee et al., 2018, Bharanidharan et al., 2022)thiadiazoles was synthesized from the reaction of precursor dimethyl 2,2′-(1,2-diphenylethane-1,2-diylidene)-bis(hydrazine-1-carbodithioate) and hydrazonyl chlorides in ethanol under ultrasonic irradiation. Spectral tools (IR. NMR, MS, elemental analyses, molecular dynamic simulation, DFT and LUMO and HOMO) were used to elucidate the structure of the isolated products. Molecular docking for the precursor, 3 and ligands 6a-i to two COVID-19 important proteins M$^{pro}$ and RdRp was compared with two approved drugs, Remdesivir and Ivermectin. The binding affinity varied between the ligands and the drugs. The highest recorded binding affinity of 6c with M$^{pro}$ was (−9.2 kcal/mol), followed by 6b and 6a, (−8.9 and −8.5 kcal/mol), respectively. The lowest recorded binding affinity was (−7.0 kcal/mol) for 6 g. In comparison, the approved drugs showed binding affinity (−7.4 and −7.7 kcal/mol), for Remdesivir and Ivermectin, respectively, which are within the range of the binding affinity of our ligands. The binding affinity of the approved drug Ivermectin against RdRp recoded the highest (−8.6 kcal/mol), followed by 6a, 6 h, and 6i are the same have (−8.2 kcal/mol). The lowest reading was found for compound 3 ligand (−6.3 kcal/mol). On the other side, the amino acids also differed between the compounds studied in this project for both the viral proteins. The ligand 6a forms three H-bonds with Thr 319(A), Sr 255(A) and Arg 457(A), whereas Ivermectin forms three H-bonds with His 41(A), Gly143(A) and Gln 18(A) for viral M$^{pro}$. The RdRp amino acids residues could be divided into four groups based on the amino acids that interact with hydrogen or hydrophobic interactions. The first group contained 6d, 6b, 6 g, and Remdesivir with 1–4 hydrogen bonds and hydrophobic interactions 1 to 10. Group 2 is 6a and 6f exhibited 1 and 3 hydrogen bonds and 15 and 14 hydrophobic interactions. Group 3 has 6e and Ivermectin shows 4 and 3 hydrogen bonds, respectively and 11 hydrophobic interactions for both compounds. The last group contains ligands 3, 6c, 6 h, and 6i gave 1–3 hydrogen bonds and 6c and 3 recorded the highest number of hydrophobic interactions, 14 for both 6c and 6 h. Pro Tox-II estimated compounds’ activities as Hepatoxic, Carcinogenic and Mutagenic, revealing that 6f-h were inactive in all five similar to that found with Remdesivir and Ivermectin. The drug-likeness prediction was carried out by studying physicochemical properties, lipophilicity, size, polarity, insolubility, unsaturation, and flexibility. Generally, some properties of the ligands were comparable to that of the standards used in this study, Remdesivir and Ivermectin.

Abstract Background Experiences from the first wave of the 2019 coronavirus disease (COVID-19) pandemic can aide in the development of future preventive strategies. To date, risk prediction models for COVID-19-related incidence and outcomes in haemodialysis (HD) patients are missing. Methods We developed risk prediction models for COVID-19 incidence and mortality among HD patients. We studied 38 256 HD patients from a multi-national dialysis cohort between March 3rd and July 3rd 2020. Risk prediction models were developed and validated, based on predictors readily available in outpatient haemodialysis units. We compared mortality among patients with and without COVID-19, matched for age, sex, and diabetes. Results During the observational period, 1 259 patients (3.3%) acquired COVID-19. Of these, 62% were hospitalised or died. Mortality was 22% among COVID-19 patients with odds ratios 219.8 (95% CI 80.6-359) to 342.7 (95% CI 60.6-13595.1), compared to matched patients without COVID-19. Since the first wave of the pandemic affected mostly European countries during the study, the risk prediction model for incidence of COVID-19 was developed and validated in European patients only (N = 22 826, AUCDev 0.64, AUCVal 0.69). The model for prediction of mortality was developed in all COVID-19 patients (AUCDev 0.71, AUCVal 0.78). Angiotensin receptor blockers were independently associated with a lower incidence of COVID-19 in European patients. Conclusions We identified modifiable risk factors for COVID-19 incidence and outcome in HD patients. Our risk prediction tools can be readily applied in clinical practice. The current study can aid in the development of preventive strategies for future waves of COVID-19. Graphical Abstract Graphical Abstract

AbstractThe ongoing outbreak of viral pneumonia in China and beyond is associated with a novel coronavirus, provisionally termed 2019-nCoV. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection. Although bats are likely reservoir hosts for 2019-nCoV, the identity of any intermediate host facilitating transfer to humans is unknown. Here, we report the identification of 2019-nCoV related coronaviruses in pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin associated CoVs that belong to two sub-lineages of 2019-nCoV related coronaviruses, including one very closely related to 2019-nCoV in the receptor-binding domain. The discovery of multiple lineages of pangolin coronavirus and their similarity to 2019-nCoV suggests that pangolins should be considered as possible intermediate hosts for this novel human virus and should be removed from wet markets to prevent zoonotic transmission.

STRUCTURED ABSTRACTHyperinflammation is frequently observed in patients with severe COVID-19. Inadequate and defective IFN type I responses against SARS-CoV-2, associated with autoantibodies in a proportion of patients, lead to severe courses of disease. In addition, hyperactive responses of the humoral immune system have been described.In the current study we investigated a possible role of neutralizing autoantibodies against antiinflammatory mediators. Plasma from adult patients with severe and critical COVID-19 was screened by ELISA for antibodies against PGRN, IL-1-Ra, IL-10, IL-18BP, IL-22BP, IL-36-Ra, CD40, IFN-α2, IFN-γ, IFN-ω and serpinB1. Autoantibodies were characterized and the antigens were analyzed for immunogenic alterations.In a discovery cohort with severe to critical COVID-19 high titers of PGRN-autoantibodies were detected in 11 of 30 (36.7%), and of IL-1-Ra-autoantibodies in 14 of 30 (46.7%) patients. In a validation cohort of 64 patients with critical COVID-19 high-titer PGRN-Abs were detected in 25 (39%) and IL-1-Ra-Abs in 32 of 64 patients (50%). PGRN-Abs and IL-1-Ra-Abs belonged to IgM and several IgG subclasses. In separate cohorts with non-critical COVID-19, PGRN-Abs and IL-1-Ra-Abs were detected in low frequency (i.e. in < 5% of patients) and at low titers. Neither PGRN-nor IL-1-Ra-Abs were found in 40 healthy controls vaccinated against SARS-CoV-2 or 188 unvaccinated healthy controls. PGRN-Abs were not cross-reactive against SARS-CoV-2 structural proteins nor against IL-1-Ra. Plasma levels of both free PGRN and free IL-1-Ra were significantly decreased in autoantibody-positive patients compared to Ab-negative and non-COVID-19 controls. In vitro PGRN-Abs from patients functionally reduced PGRN-dependent inhibition of TNF-α signaling, and IL-1-Ra-Abs from patients reduced IL-1-Ra- or anakinra-dependent inhibition of IL-1ß signaling. The pSer81 hyperphosphorylated PGRN isoform was exclusively detected in patients with high-titer PGRN-Abs; likewise, a hyperphosphorylated IL-1-Ra isoform was only found in patients with high-titer IL-1-Ra-Abs. Thr111 was identified as the hyperphophorylated amino acid of IL-1-Ra. In longitudinally collected samples hyperphosphorylated isoforms of both PGRN and IL-1-Ra emerged transiently, and preceded the appearance of autoantibodies. In hospitalized patients, the presence of IL-1-Ra-Abs or IL-1-Ra-Abs in combination with PGRN-Abs was associated with a higher morbidity and mortality.To conclude, neutralizing autoantibodies to IL-1-Ra and PGRN occur in a significant portion of patients with critical COVID-19, with a concomitant decrease in circulating free PGRN and IL-1-Ra, indicative of a misdirected, proinflammatory autoimmune response. The break of self-tolerance is likely caused by atypical hyperphosphorylated isoforms of both antigens, whose appearances precede autoantibody induction. Our data suggest that these immunogenic secondary modifications are induced by the SARS-CoV-2-infection itself or the inflammatory environment evoked by the infection and predispose for a critical course of COVID-19.

This paper discusses Animal Crossing: New Horizons’ (ACNH) release during the COVID-19 pandemic. A combination of the game’s elements, including its comforting aesthetic, participatory community, financial mechanics and goal-setting, promotes the player’s construction of their sense of self and provides crucial stability during the ongoing COVID-19 crisis. In contrast to other life simulator games such as The Sims, the timing of ACNH’s release makes its substitution efforts more adoptable by a wide spectrum of players between casual and hardcore sensibilities. Moreover, the game serves those players as a partial substitute for complex face-to-face interactions during self-isolation. Concurrently, the game’s offer of stability and routine presents a simulacrum of real life (though one that is comparatively exaggerated and narrowed in scope) promoting transference of regularity into the digital space, in contrast to the intense disruption of the everyday by the pandemic, and augmenting that transference with a focus on player agency and self-determination of playstyle. Players’ shared affinities and engagement with the game as a form of serious leisure create personas that offer a divergent range of roles that are not mutually-exclusive – the social player, the turnip trader, the gardener, the artisan – allowing players to adopt multiple specializations within an expansive social environment. In essence, players of ACNH create an array of malleable, interchangeable gaming persona that successfully embody the routine and social play that are forcibly absent from real life during the pandemic. This paper draws upon responses from nearly 2000 ACNH players to frame how the game, a life simulator released during a pandemic curtailing real life, acts as a digital intersection of routine substitution, agency and social connectivity in a disconnected physical world.

Follow-Up-Befragung zur Studie „Homeoffice- und Präsenzkultur im Bereich IT und technische Dienstleistungen in Zeiten der Covid-19-Pandemie“: Durch die Ausbreitung des Coronavirus SARS-CoV-2 und die damit verbundenen Schutzmaßnahmen sind für viele Beschäftigte aus dem Bereich IT und technische Dienstleistungen eine Reihe von Veränderungen im Arbeits- und Privatleben entstanden. Ein Jahr später ist die Homeoffice-Situation für einige Beschäftigte – nicht zuletzt auch durch die Corona-Arbeitsschutzverordnung weiter verstärkt – zum Alltag geworden. Es stellt sich die Frage, wie die Beschäftigten mit ihrer neuen Arbeitssituation umgehen. Die vorliegende Studie zielt darauf ab, die Veränderung der Homeoffice- und Präsenzkultur in Zeiten der Covid-19-Pandemie im Bereich IT und technische Dienstleistungen zu untersuchen. Zudem sollen die wahrgenommenen Veränderungen nach einem Jahr Homeoffice ermittelt sowie der Zusammenhang zwischen Homeoffice- und Präsenzkultur und der mentalen Gesundheit von Beschäftigten untersucht werden. Aufbauend auf einer Online-Umfrage aus April 2020 mit 1.933 Beschäftigten aus dem Bereich IT und technische Dienstleistungen führte das IMVR eine Folgebefragung im Mai 2021 durch. Zum zweiten Befragungszeitpunkt haben 236 Beschäftigte erneut an der Befragung teilgenommen. Die Ergebnisse der zweiten Befragung zeigen, dass die Präsenzkultur nach einem Jahr Homeoffice signifikant abgenommen hat und die Homeofficekultur signifikant gestiegen ist. Zudem werden Empfehlungen für eine gesundheitsförderliche Arbeitsgestaltung im Homeoffice häufiger eingehalten. Wahrgenommene Veränderungen der Arbeitssituation nach einem Jahr im Homeoffice beziehen sich vor allem auf den Kontakt und die Zusammenarbeit, die Akzeptanz von Homeoffice sowie den erhöhten Arbeitsaufwand und Flexibilität im Homeoffice. Des Weiteren zeigt sich ein Zusammenhang zwischen der Homeoffice- bzw. Präsenzkultur und der Gesundheit von Beschäftigten.

Abstract The COVID-19 pandemic has affected human mobility via lockdowns, social distancing rules, home quarantines, and the full or partial suspension of transportation. Evidence-based policy recommendations are urgently needed to ensure that transport systems have resilience to future pandemic outbreaks, particularly within Global South megacities where demand for public transport is high and reduced access can exacerbate socio-economic inequalities. This study focuses on Metro Manila – a characteristic megacity that experienced one of the most stringent lockdowns worldwide. It analyzes aggregated cell phone and GPS data from Google and Apple that provide a comprehensive representation of mobility behavior before and during the lockdown. While significant decreases are observed for all transport modes, public transport experienced the largest drop (−74.5 %, on average). The study demonstrates that: (i) those most reliant on public transport were disproportionately affected by lockdowns; (ii) public transport was unable to fulfil its role as public service; and, (iii) this drove a paradigm shift towards active mobility. Moving forwards, in the short-term policymakers must promote active mobility and prioritize public transport to reduce unequal access to transport. Longer-term, policymakers must leverage the increased active transport to encourage modal shift via infrastructure investment, and better utilize big data to support decision-making.

Home dialysis therapies are flexible kidney replacement strategies with documented clinical benefits. While the incidence of end-stage kidney disease continues to increase globally, the use of home dialysis remains low in most developed countries. Multiple barriers to providing home dialysis have been noted in the published literature. Among known challenges, gaps in clinician knowledge are potentially addressable with a focused education strategy. Recent national surveys in the United States and Australia have highlighted the need for enhanced home dialysis knowledge especially among nephrologists who have recently completed training. Traditional in-person continuing professional educational programmes have had modest success in promoting home dialysis and are limited by scale and the present global COVID-19 pandemic. We hypothesize that the use of a ‘Hub and Spoke’ model of virtual home dialysis mentorship for nephrologists based on project ECHO would support home dialysis growth. We review the home dialysis literature, known educational gaps and plausible educational interventions to address current limitations in physician education Refereed/Peer-reviewed