A living WHO guideline on drugs for covid-19

Clinical question What is the role of drug interventions in the treatment and prevention of covid-19? Recommendations The first version on this living guidance focuses on corticosteroids. It contains a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19, and a weak or conditional recommendation against systemic corticosteroids in patients with non-severe covid-19. Corticosteroids are inexpensive and are on the World Health Organisation list of essential medicines. How this guideline was created This guideline reflects an innovative collaboration between the WHO and the MAGIC Evidence Ecosystem Foundation, driven by an urgent need for global collaboration to provide trustworthy and living covid-19 guidance. A standing international panel of content experts, patients, clinicians, and methodologists, free from relevant conflicts of interest, produce recommendations for clinical practice. The panel follows standards, methods, processes, and platforms for trustworthy guideline development using the GRADE approach. We apply an individual patient perspective while considering contextual factors (that is, resources, feasibility, acceptability, equity) for countries and healthcare systems. The evidence A living systematic review and network meta-analysis, supported by a prospective meta-analysis, with data from eight randomised trials (7184 participants) found that systemic corticosteroids probably reduce 28 day mortality in patients with critical covid-19 (moderate certainty evidence;87 fewer deaths per 1000 patients (95% confidence interval 124 fewer to 41 fewer)), and also in those with severe disease (moderate certainty evidence;67 fewer deaths per 1000 patients (100 fewer to 27 fewer)). In contrast, systemic corticosteroids may increase the risk of death in patients without severe covid-19 (low certainty evidence;absolute effect estimate 39 more per 1000 patients, (12 fewer to 107 more)). Systemic corticosteroids probably reduce the need for invasive mechanical ventilation, and harms are likely to be minor (indirect evidence). Understanding the recommendations The panel made a strong recommendation for use of corticosteroids in severe and critical covid-19 because there is a lower risk of death among people treated with systemic corticosteroids (moderate certainty evidence), and they believe that all or almost all fully informed patients with severe and critical covid-19 would choose this treatment. In contrast, the panel concluded that patients with non-severe covid-19 would decline this treatment because they would be unlikely to benefit and may be harmed. Moreover, taking both a public health and a patient perspective, the panel warned that indiscriminate use of any therapy for covid-19 would potentially rapidly deplete global resources and deprive patients who may benefit from it most as potentially lifesaving therapy. Updates This is a living guideline. Work is under way to evaluate other interventions. New recommendations will be published as updates to this guideline. Readers note This is version 1 of the living guideline, published on 4 September (BMJ 2020;370:m3379) version 1. Updates will be labelled as version 2, 3 etc. When citing this article, please cite the version number. Submitted August 28 Accepted August 31Copyright © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to.

Maackia amurensis Rupr. et Maxim.: Supercritical CO2 Extraction and Mass Spectrometric Characterization of Chemical Constituents.

Three types of extraction were used to obtain biologically active substances from the heartwood of M. amurensis: supercritical CO2 extraction, maceration with EtOH, and maceration with MeOH. The supercritical extraction method proved to be the most effective type of extraction, giving the highest yield of biologically active substances. Several experimental conditions were investigated in the pressure range of 50-400 bar, with 2% of ethanol as co-solvent in the liquid phase at a temperature in the range of 31-70 °C. The most effective extraction conditions are: pressure of 100 bar and a temperature of 55 °C for M. amurensis heartwood. The heartwood of M. amurensis contains various polyphenolic compounds and compounds of other chemical groups with valuable biological activity. Tandem mass spectrometry (HPLC-ESI-ion trap) was applied to detect target analytes. High-accuracy mass spectrometric data were recorded on an ion trap equipped with an ESI source in the modes of negative and positive ions. The four-stage ion separation mode was implemented. Sixty-six different biologically active components have been identified in M. amurensis extracts. Twenty-two polyphenols were identified for the first time in the genus Maackia.

Evolutionary Challenges to Humanity Caused by Uncontrolled Carbon Emissions: The Stockholm Paradigm.

This review paper discusses the Stockholm Paradigm (SP) as a theoretical framework and practical computational instrument for studying and assessing the risk of emerging infectious diseases (EIDs) as a result of climate change. The SP resolves the long-standing parasite paradox and explains how carbon emissions in the atmosphere increase parasites' generalization and intensify host switches from animals to humans. The SP argues that the growing rate of novel EID occurrence caused by mutated zoonotic pathogens is related to the following factors brought together as a unified issue of humanity: (a) carbon emissions and consequent climate change; (b) resettlement/migration of people with hyper-urbanization; (c) overpopulation; and (d) human-induced distortion of the biosphere. The SP demonstrates that, in an evolutionary way, humans now play a role migratory birds once played in spreading parasite pathogens between the three Earth megabiotopes (northern coniferous forest belt; tropical/equatorial rainforest areas; and hot/cold deserts), i.e., the role of "super-spreaders" of parasitic viruses, bacteria, fungi and protozoa. This makes humans extremely vulnerable to the EID threat. The SP sees the +1.0-+1.2 °C limit as the optimal target for the slow, yet feasible curbing of the EID hazard to public health (150-200 years). Reaching merely the +2.0 °C level will obviously be an EID catastrophe, as it may cause two or three pandemics each year. We think it useful and advisable to include the SP-based research in the scientific repository of the Intergovernmental Panel on Climate Change, since EID appearance and spread are indirect but extremely dangerous consequences of climate change.

The oldest unvaccinated Covid-19 survivors in South America.

BACKGROUND: Although older adults are at a high risk of severe or critical Covid-19, there are many cases of unvaccinated centenarians who had a silent infection or recovered from mild or moderate Covid-19. We studied three Brazilian supercentenarians, older than 110 years, who survived Covid-19 in 2020 before being vaccinated. RESULTS: Despite their advanced age, humoral immune response analysis showed that these individuals displayed robust levels of IgG and neutralizing antibodies (NAbs) against SARS-CoV-2. Enrichment of plasma proteins and metabolites related to innate immune response and host defense was also observed. None presented autoantibodies (auto-Abs) to type I interferon (IFN). Furthermore, these supercentenarians do not carry rare variants in genes underlying the known inborn errors of immunity, including particular inborn errors of type I IFN. CONCLUSION: These observations suggest that their Covid-19 resilience might be a combination of their genetic background and their innate and adaptive immunity.

Re-Emergence of Circulation of Seasonal Influenza during COVID-19 Pandemic in Russia and Receptor Specificity of New and Dominant Clade 3C.2a1b.2a.2 A(H3N2) Viruses in 2021-2022.

The circulation of seasonal influenza in 2020-2021 around the world was drastically reduced after the start of the COVID-19 pandemic and the implementation of mitigation strategies. The influenza virus circulation reemerged in 2021-2022 with the global spread of the new genetic clade 3C.2a1b.2a.2 of A(H3N2) viruses. The purpose of this study was to characterize influenza viruses in the 2021-2022 season in Russia and to analyze the receptor specificity properties of the 3C.2a1b.2a.2 A(H3N2) viruses. Clinical influenza samples were collected at the local Sanitary-and-Epidemiological Centers of Rospotrebnadzor. Whole genome sequencing was performed using NGS. The receptor specificity of hemagglutinin was evaluated using molecular modeling and bio-layer interferometry. Clinical samples from 854 cases of influenza A and B were studied; A(H3N2) viruses were in the majority of the samples. All genetically studied A(H3N2) viruses belonged to the new genetic clade 3C.2a1b.2a.2. Molecular modeling analysis suggested a higher affinity of hemagglutinin of 3C.2a1b.2a.2. A(H3N2) viruses to the α2,6 human receptor. In vitro analysis using a trisaccharide 6'-Sialyl-N-acetyllactosamine receptor analog did not resolve the differences in the receptor specificity of 3C.2a1b.2a.2 clade viruses from viruses belonging to the 3C.2a1b.2a.1 clade. Further investigation of the A(H3N2) viruses is required for the evaluation of their possible adaptive advantages. Constant monitoring and characterization of influenza are critical for epidemiological analysis.

Psychotherapy in times of the COVID-19 pandemic in Argentina: Factors associated with the use of telepsychotherapy during social isolation

In Argentina, social isolation during the COVID-19 pandemic has had an impact on the practice of psychotherapy. The goal was to describe factors associated with the use of telepsychotherapy during social isolation. An online survey was conducted among 978 psychologists and psychiatrists from different provinces and the city of Buenos Aires. 77.7% of the participants started using online psychotherapy for the first time at the beginning of social isolation;62.6% of the participants treated half or more of their patients online. Significant relationships were detected between online psychotherapy and various factors that characterize psychotherapeutic practice, but these are weak effects. Participants with a higher percentage of patients in telepsychotherapy reported fewer treatment interruptions and similar or higher levels of income compared to those prior to social isolation. Drastic changes in psychotherapeutic practice during social isolation need to be studied in depth.

Neuropsychological evaluation of cognitive disorders in children after COVID-19.

The article presents the results of neuropsychological remote and face-to-face testing of 25 children aged 12 to 17 years in the nearest (during and 1-2 weeks after the treatment) and later period (2-12 months) after COVID-19 infection with predominant respiratory tract infection, organized in Ekaterinburg in the State Autonomous Institution "Children's Hospital № 8". Indication of family contact with patients with a new coronavirus infection was found in all patients, a positive nasopharyngeal swab for SARS-CoV-2 RNA by PCR was found in 58%, non-focal neurological complaints were found in 54% of children. The control group consisted of 25 pupils of Moscow comprehensive schools (14 girls and 11 boys) aged between 12 and 16 years who were examined before the pandemic. The methods included: investigation of the kinesthetic, spatial, dynamic, graphic praxis; auditory-motor coordination; visual, object-constructive gnosis; auditory-speech, visual memory; voluntary attention; thinking. Significant differences with the results of neuropsychological tests performed in children in the control group were found, allowing us to assert impairment of memory, attention, visual gnosis, visual-spatial function, kinesthetic and dynamic praxis, verbal and non-verbal component of thinking. According to A.R. Luria's theory, the topic of the disorders involves the temporo-parieto-occipital, mediobasal, frontotemporal parts of the brain, the reticular formation and limbic structures. This necessitates the development of corrective educational programs and an in-depth diagnostic algorithm that determines the morphological substrate of cognitive disorders in children, who have undergone COVID-19.

0Effects of the COVID-19 Pandemic on Treatment Adherence in Patients with Chronic Heart Failure.

Background: To assess the influence of the COVID-19 (Coronavirus Disease 2019) pandemic on treatment adherence by patients with CHF (Chronic heart failure) and to determine the factors associated with changing adherence during home-isolation. Methods: The survey was conducted in patients participating in the COMPLIANCE study (ClinicalTrials.gov. NCT04262583). Thirty-one patients, included into in the COMPLIANCE study before March 1, 2020, were interviewed through phone calls. A modified adherence scale of the National Society for Evidence-Based Pharmacotherapy was used, which permits to assess of overall adherence, adherence to particular drugs and the main causes for non-adherence. Results: In the whole group of patients, only a tendency to reduced overall adherence was registered during the COVID-19 pandemic (р=0,256). Significant differences in the rate of adherence deterioration were revealed for angiotensin-converting enzyme (ACE) inhibitors (p=0.031) and for statins (p=0.002). The reasons for non-adherence were lack of opportunity to contact with a physician, inability to perform investigations necessary for correcting prescribed pharmacotherapy, and side effects. Conclusion: A tendency to deterioration of adherence to prescribed pharmacotherapy was revealed during the COVID-19 pandemic. A significant decline in adherence was registered to ACE inhibitors and statins.

Public Policy Measures to Increase Anti-SARS-CoV-2 Vaccination Rate in Russia.

The total vaccination rate remains relatively low in Russia as of March 2022 (around 55%, with around 20% in some regions). In the paper, we study the reasons for it. We communicate the results of our survey aimed at detecting reasons for the relatively low anti-SARS-CoV-2 vaccination rate in Russia (47.1% as of mid-January 2022) and suggest potential measures to increase the level of confidence in the Russian vaccination campaign. A total of 14,310 users exhibited interest to participate in the research (16.84% of the total number of invitations sent in the Russian social network VKontakte). After the sample set repair, only 5822 (40.68% of those who agreed to participate) responses were suitable for the research, and they composed the final set. The age range of the respondents was 16-51 years old (y.o.) with a mean of 29.1 ± 10.6 y.o. The proportion of the female gender in responses was 44.23%. A total of 2454 persons (42.15%) expressed their hesitant, cautious, or negative attitude towards vaccine uptake. Of the 2454 persons with cautious attitude towards vaccination, only 928 (37.82%) were concerned about the quality of the Russian vaccines. A total of 1323 individuals (53.91%) supported one or more conspiracy beliefs. A total of 5064 (86.98% of the whole set) showed cautious or negative attitude towards the planned introduction of a nationwide system of vaccination certification/verification based on QR codes. The main social factors that hinder the Russian vaccination campaign are: vexation over the lack of desire of officials to receive feedback from the general population regarding vaccination, wide support for conspiracy beliefs, and controversy over the QR code-based digital system. To elevate the vaccination rate in Russia, the following steps may be taken: social encouragement of those who support vaccination, increase in transparency of the vaccination campaign, acceptance of both digital and paper vaccination certificates, increase in participation of society in vaccination-related discussions, public disclosure of vaccine composition, and avoidance of excessive digitalization of data in the vaccination campaign.

Cryptocurrency as Epidemiologically Safe Means of Transactions: Diminishing Risk of SARS-CoV-2 Spread

In comparison with other respiratory viruses, the current COVID-19 pandemic’s rapid seizing the world can be attributed to indirect (contact) way of transmission of SARS-CoV-2 virus in addition to the regular airborne way. A significant part of indirect transmission is made through cash bank notes. SARS-CoV-2 remains on cash paper money for period around four times larger than influenza A virus and is absorbed by cash notes two and a half times more effectively than influenza A (our model). During the pandemic, cryptocurrencies have gained attractiveness as an “epidemiologically safe”means of transactions. On the basis of the authors’gallop polls performed online with social networks users in 44 countries in 2020–2021 (the total number of clear responses after the set repair 32,115), around 14.7% of surveyed participants engaged in cryptocurrency-based transactions during the pandemic. This may be one of the reasons of significant rise of cryptocurrencies rates since mid-March 2020 till the end of 2021. The paper discusses the reasons for cryptocurrency attractiveness during the COVID-19 pandemic. Among them, there are fear of SARS-CoV-2 spread via cash contacts and the ability of the general population to mine cryptocurrencies. The article also provides a breakdown of the polled audience profile to determine the nationalities that have maximal level of trust to saving and transacting money as cryptocurrencies.

FORUM SHOPPINGAND REGULATORY COMPETITION IN CROSS-BORDER INSOLVENCIES AND RESTRUCTURINGS

The article covers the subject of forum shopping and regulatory competition in cross-border insolvencies and restructurings due to the impact of Directive of the European Parliament on preventive restructuring frameworks as well as the role of coronavirus pandemic. Looking at the experience of the European Union in handling bankruptcy and pre-bankruptcy forum shopping abuses, authors analyse the EU model of preventive restructuring and its regulatory competition potential. They assess possible impact of COVID-19 on regulatory competition and forum shopping during insolvency and restructuring proceedings. The article draws parallels with Russian judicial practice. Статья посвящена вопросам forum shopping и конкуренции регулирования в сфере трансграничных банкротств и реструктуризаций с учетом влияния событий последнего времени - унификации превентивных реструктуризаций в ЕС и пандемии COVID-19. Авторы рассматривают опыт ЕС по развитию концепций злоупотребления при банкротном и предбанкротном forum shopping, анализируют модель превентивных реструктуризаций в ЕС и заложенный в ней потенциал для конкуренции регулирования. Оценивается возможное влияние пандемии COVID-19 на развитие конкуренции регулирования и forum shopping в сфере банкротств и реструктуризаций. Проводятся параллели с российской правовой действительностью.

Cerebrovascular events and outcomes in hospitalized patients with COVID-19: The SVIN COVID-19 Multinational Registry.

BACKGROUND: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. AIM: To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease. METHODS: Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020-16 June 2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). RESULTS: Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970-1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years. Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920-1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130-280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4-60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63-15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07-2.94, p = 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34-0.98, p = 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19. CONCLUSIONS: COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes.