An acute respiratory distress syndrome drug development collaboration stimulated by the Virginia Drug Discovery Consortium.

The genesis of most older medicinal agents has generally been empirical. During the past one and a half centuries, at least in the Western countries, discovering and developing drugs has been primarily the domain of pharmaceutical companies largely built upon concepts emerging from organic chemistry. Public sector funding for the discovery of new therapeutics has more recently stimulated local, national, and international groups to band together and focus on new human disease targets and novel treatment approaches. This Perspective describes one contemporary example of a newly formed collaboration that was simulated by a regional drug discovery consortium. University of Virginia, Old Dominion University, and a university spinout company, KeViRx, Inc., partnered under a NIH Small Business Innovation Research grant, to produce potential therapeutics for acute respiratory distress syndrome resulting from the ongoing COVID-19 pandemic.

COVID-19 Vaccination and Alcohol Consumption: Justification of Risks.

Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pharmaceutical companies and research institutions have been actively working to develop vaccines, and the mass roll-out of vaccinations against COVID-19 began in January 2021. At the same time, during lockdowns, the consumption of alcoholic beverages increased. During the peak of vaccination, consumption remained at high levels around the world, despite the gradual relaxation of quarantine restrictions. Two of the popular queries on search engines were whether it is safe to drink alcohol after vaccination and whether this will affect the effectiveness of vaccines. Over the past two years, many studies have been published suggesting that excessive drinking not only worsens the course of an acute respiratory distress syndrome caused by the SARS-CoV-2 virus but can also exacerbate post-COVID-19 syndrome. Despite all sorts of online speculation, there is no specific scientific data on alcohol-induced complications after vaccination in the literature. Most of the published vaccine clinical trials do not include groups of patients with a history of alcohol-use disorders. This review analyzed the well-known and new mechanisms of action of COVID-19 vaccines on the immune system and the effects of alcohol and its metabolites on these mechanisms.

Alcohol exacerbates SARS‐CoV‐2 ‐induced ARDS in mice

SARS‐CoV‐2 – induced COVID‐19 causes acute respiratory distress syndrome (ARDS) and multiorgan failure. COVID‐19 can also cause psycho‐social problems, including increased alcohol consumption and consequent complications. Alcohol abuse is recognized as an independent factor that increases by three‐ to four‐fold the incidence of ARDS, a severe form of acute lung injury with a mortality rate of 40 to 50 percent. This translates to tens of thousands of excess deaths in the United States each year from alcohol‐associated lung injury. We developed a combined ARDS and alcohol abuse mouse model by intratracheally instilling the S1 subunit of SARS‐CoV‐2 Spike protein in K18‐hACE2 transgenic mice that express the human angiotensin‐converting enzyme 2 (ACE2) receptor for SARS‐CoV‐2 and which are kept on an ethanol diet. 72 hours after S1SP instillation, mice kept on the ethanol diet exhibited a strong decline in body weight, a dramatic increase in white blood cell content of bronchoalveolar lavage fluid (BALF), and an augmented “cytokine storm”, compared to S1SP treated mice on control diet. Histologic examination of lung tissue demonstrated abnormal recruitment of immune cells in the alveolar space, destructive effects on parenchymal architecture, and an overall worsening of the lung injury score (LIS) of S1SP‐ and alcohol‐treated animals. Along with the activation of pro‐inflammatory biomarkers (NF‐κB, STAT3, NLRP3 inflammasome), lung tissue homogenates from mice on alcohol diet, demonstrated overexpression of ACE2 compared to mice on control diet. In summary, K18‐hACE2 transgenic mice on an alcohol diet exhibit a more severe S1SP‐induced ARDS than corresponding mice on a control diet and may thus represent a useful model for the development of therapeutic interventions against alcohol‐exacerbated COVID‐19.

IMM-BCP-01, a patient-derived anti-SARS-CoV-2 antibody cocktail, is active across variants of concern including Omicron BA.1 and BA.2.

Monoclonal antibodies are an efficacious therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, rapid viral mutagenesis led to escape from most of these therapies, outlining the need for an antibody cocktail with a broad neutralizing potency. Using an unbiased interrogation of the memory B cell repertoire of patients with convalescent COVID-19, we identified human antibodies with broad antiviral activity in vitro and efficacy in vivo against all tested SARS-CoV-2 variants of concern, including Delta and Omicron BA.1 and BA.2. Here, we describe an antibody cocktail, IMM-BCP-01, that consists of three patient-derived broadly neutralizing antibodies directed at nonoverlapping surfaces on the SARS-CoV-2 Spike protein. Two antibodies, IMM20184 and IMM20190, directly blocked Spike binding to the ACE2 receptor. Binding of the third antibody, IMM20253, to its cryptic epitope on the outer surface of RBD altered the conformation of the Spike Trimer, promoting the release of Spike monomers. These antibodies decreased Omicron SARS-CoV-2 infection in the lungs of Syrian golden hamsters in vivo and potently induced antiviral effector response in vitro, including phagocytosis, ADCC, and complement pathway activation. Our preclinical data demonstrated that the three-antibody cocktail IMM-BCP-01 could be a promising means for preventing or treating infection of SARS-CoV-2 variants of concern, including Omicron BA.1 and BA.2, in susceptible individuals.

Alcohol Increases Lung Angiotensin-Converting Enzyme 2 Expression and Exacerbates Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Subunit 1-Induced Acute Lung Injury in K18-hACE2 Transgenic Mice.

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, alcohol consumption increased markedly. Nearly one in four adults reported drinking more alcohol to cope with stress. Chronic alcohol abuse is now recognized as a factor complicating the course of acute respiratory distress syndrome and increasing mortality. To investigate the mechanisms behind this interaction, a combined acute respiratory distress syndrome and chronic alcohol abuse mouse model was developed by intratracheally instilling the subunit 1 (S1) of SARS-CoV-2 spike protein (S1SP) in K18-human angiotensin-converting enzyme 2 (ACE2) transgenic mice that express the human ACE2 receptor for SARS-CoV-2 and were kept on an ethanol diet. Seventy-two hours after S1SP instillation, mice on an ethanol diet showed a strong decrease in body weight, a dramatic increase in white blood cell content of bronchoalveolar lavage fluid, and an augmented cytokine storm, compared with S1SP-treated mice on a control diet. Histologic examination of lung tissue showed abnormal recruitment of immune cells in the alveolar space, abnormal parenchymal architecture, and worsening Ashcroft score in S1SP- and alcohol-treated animals. Along with the activation of proinflammatory biomarkers [NF-κB, STAT3, NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome], lung tissue homogenates from mice on an alcohol diet showed overexpression of ACE2 compared with mice on a control diet. This model could be useful for the development of therapeutic approaches against alcohol-exacerbated coronavirus disease 2019.

HSP90 Inhibitors Modulate SARS-CoV-2 Spike Protein Subunit 1-Induced Human Pulmonary Microvascular Endothelial Activation and Barrier Dysfunction.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused more than 5 million deaths worldwide. Multiple reports indicate that the endothelium is involved during SARS-Cov-2-related disease (COVID-19). Indeed, COVID-19 patients display increased thrombophilia with arterial and venous embolism and lung microcapillary thrombotic disease as major determinants of deaths. The pathophysiology of endothelial dysfunction in COVID-19 is not completely understood. We have investigated the role of subunit 1 of the SARS-CoV-2 spike protein (S1SP) in eliciting endothelial barrier dysfunction, characterized dose and time relationships, and tested the hypothesis that heat shock protein 90 (HSP90) inhibitors would prevent and repair such injury. S1SP activated (phosphorylated) IKBα, STAT3, and AKT and reduced the expression of intercellular junctional proteins, occludin, and VE-cadherin. HSP90 inhibitors (AT13387 and AUY-922) prevented endothelial barrier dysfunction and hyperpermeability and reduced IKBα and AKT activation. These two inhibitors also blocked S1SP-mediated barrier dysfunction and loss of VE-cadherin. These data suggest that spike protein subunit 1 can elicit, by itself, direct injury to the endothelium and suggest a role of HSP90 inhibitors in preserving endothelial functionality.

Preclinical Efficacy of IMM-BCP-01, a Highly Active Patient-Derived Anti-SARS-CoV-2 Antibody Cocktail (preprint)

Using an unbiased interrogation of the anti-viral memory B cell repertoire of convalescent COVID-19 patients, we identified three human antibodies that when combined demonstrated both robust viral suppressive properties against all tested SARS-CoV-2 variants of concern in vitro and profound anti-viral efficacy in vivo. In this report, we describe the pre-clinical characterization of an antibody cocktail, IMM-BCP-01, that consists of three unique, patient-derived recombinant antibodies directed at non-overlapping surfaces on the Spike protein, each with particularly effective antiviral activity. One antibody has a composite epitope blocking ACE2 binding, one antibody bridges two Spike proteins, and one antibody neutralizes virus by binding to a conserved epitope outside of ACE2 binding site. These antibodies, when administered after viral infection, potently decreased viral load in lungs of infected Syrian golden hamsters in a dose-dependent manner, elicited broad anti-viral neutralizing activity against multiple SARS-CoV-2 variants, and induced a robust anti-viral effector function response, including phagocytosis, and activation of classical complement pathway. Our pre-clinical data demonstrate that the unique three antibody cocktail IMM-BCP-01 is a potent and dose-efficient approach to treat early viral infection and prevent SARS-CoV-2 in susceptible individuals.

ТЕОРИЯ И ИСТОРИЯ ПРАВА И ГОСУДАРСТВА

Цель: мониторинг изменения состояния наградного права в Российской Федерации, вызванного противодействием новой коронавирусной инфекции COVJD-19 и определение перспектив его развития. Методы: методологической основой проведенного исследования являются диалектический метод познания и основанные на нем общенаучные (исторические, логические, системные) и частнонаучные методы (группировка, анализ, синтез, сравнение, интерпретация и др.). Результаты: на основе анализа федеральных, региональных, муниципальных и иных нормативных правовых актов автором дан исчерпывающий перечень официальных наград за заслуги в противодействии новой коронавирусной инфекции COVJD-19. Перечислены перечни заслуг для награждения специальными и универсальными наградами лиц, участвовавших в противодействии коронавирусной инфекции, выявлены некоторые недостатки в правовом регулировании наградных отношений на региональном и муниципальном уровне. Обращено внимание на недостатки формирования организационно-правовых основ наградных отношений в отдельных субъектах Российской Федерации, когда награждение медицинских работников и иных лиц универсальными высшими региональными наградами за заслуги в противодействии новой коронавирусной инфекции COVID-19 происходит только посмертно. Научная новизна: впервые в российской юридической науке проведен мониторинг российского наградного права, вызванного противодействием новой коронавирусной инфекции COVID-19. Практическая значимость: в работе предложены меры по совершенствованию правового регулирования наградных отношений за заслуги в противодействии новой коронавирусной инфекции COVID-19, которые могут быть использованы правотворческими органами.Alternate abstract:Objective: to monitor changes in the state of award law in the Russian Federation caused by the counteraction to the new coronavirus infection COVID-19 and to determine the prospects for its development. Methods: the methodological basis of the conducted research is the dialectical method of cognition and the methods based on it: general scientific (historical, logical, systemic) and private scientific (grouping, analysis, synthesis, comparison, interpretation, etc.). Results: based on the analysis of federal, regional, municipal and other regulatory legal acts, the author gives an exhaustive list of official awards for merits in countering the new coronavirus infection COVID-19. The lists of merits for special and universal awards to persons who participated in countering coronavirus infection are presented;some shortcomings in the legal regulation of awarding at the regional and municipal level are identified. Attention is drawn to the shortcomings in he organizational and legal foundations of awarding in some subjects of the Russian Federation, when medical workers and other persons are only posthumously awarded with universal highest regional awards for countering the new coronavirus infection COVID-19. Scientific novelty: for the first time in the Russian legal science, Russian award law was monitored due to the counteraction of the new coronavirus infection COVID-19. Practical significance: the paper proposes measures to improve the legal regulation of awarding for merits in countering the new coronavirus infection COVID-19, which can be used by law-making bodies.

Droplet Microarray Based on Nanosensing Probe Patterns for Simultaneous Detection of Multiple HIV Retroviral Nucleic Acids.

Multiplexed detection of viral nucleic acids is important for rapid screening of viral infection. In this study, we present a molybdenum disulfide (MoS2) nanosheet-modified dendrimer droplet microarray (DMA) for rapid and sensitive detection of retroviral nucleic acids of human immunodeficiency virus-1 (HIV-1) and human immunodeficiency virus-2 (HIV-2) simultaneously. The DMA platform was fabricated by omniphobic-omniphilic patterning on a surface-grafted dendrimer substrate. Functionalized MoS2 nanosheets modified with fluorescent dye-labeled oligomer probes were prepatterned on positively charged amino-modified omniphilic spots to form a fluorescence resonance energy transfer (FRET) sensing microarray. With the formation of separated microdroplets of sample on the hydrophobic-hydrophilic micropattern, prepatterned oligomer probes specifically hybridized with the target HIV genes and detached from the MoS2 nanosheet surface due to weakening of the adsorption force, leading to fluorescence signal recovery. As a proof of concept, we used this microarray with a small sample size (<150 nL) for simultaneous detection of HIV-1 and HIV-2 nucleic acids with a limit of detection (LOD) of 50 pM. The multiplex detection capability was further demonstrated for simultaneous detection of five viral genes (HIV-1, HIV-2, ORFlab, and N genes of SARS-COV-2 and M gene of Influenza A). This work demonstrated the potential of this novel MoS2-DMA FRET sensing platform for high-throughput multiplexed viral nucleic acid screening.

The SARS-CoV-2 spike protein subunit S1 induces COVID-19-like acute lung injury in Κ18-hACE2 transgenic mice and barrier dysfunction in human endothelial cells.

Acute lung injury (ALI) leading to acute respiratory distress syndrome is the major cause of COVID-19 lethality. Cell entry of SARS-CoV-2 occurs via the interaction between its surface spike protein (SP) and angiotensin-converting enzyme-2 (ACE2). It is unknown if the viral spike protein alone is capable of altering lung vascular permeability in the lungs or producing lung injury in vivo. To that end, we intratracheally instilled the S1 subunit of SARS-CoV-2 spike protein (S1SP) in K18-hACE2 transgenic mice that overexpress human ACE2 and examined signs of COVID-19-associated lung injury 72 h later. Controls included K18-hACE2 mice that received saline or the intact SP and wild-type (WT) mice that received S1SP. K18-hACE2 mice instilled with S1SP exhibited a decline in body weight, dramatically increased white blood cells and protein concentrations in bronchoalveolar lavage fluid (BALF), upregulation of multiple inflammatory cytokines in BALF and serum, histological evidence of lung injury, and activation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways in the lung. K18-hACE2 mice that received either saline or SP exhibited little or no evidence of lung injury. WT mice that received S1SP exhibited a milder form of COVID-19 symptoms, compared with the K18-hACE2 mice. Furthermore, S1SP, but not SP, decreased cultured human pulmonary microvascular transendothelial resistance (TER) and barrier function. This is the first demonstration of a COVID-19-like response by an essential virus-encoded protein by SARS-CoV-2 in vivo. This model of COVID-19-induced ALI may assist in the investigation of new therapeutic approaches for the management of COVID-19 and other coronaviruses.

Prosocial Orientation of Russians During the COVID-19 Pandemic: Caring for Others and Yourself.

To mitigate the potentially devastating effects of the COVID-19 pandemic, it is vital to identify psychosocial and moral resources. The care, preservation, protection, and well-being of social communities are attributes of prosocial behavior that can be such a resource. The purpose of the study is to identify the features of prosocial orientation of Russian youth during the COVID-19 pandemic, as well as to identify strategies for prosocial behavior during the COVID-19 pandemic. The sample consisted of 447 people. The study was conducted in May 2020 in the form of an online survey of subjects using Google Forms ("Moral Foundations Questionnaire method" and "Portrait Values Questionnaire"). The research made it possible to establish that Russians were dominated by norms of care, fairness, purity; values of benevolence-universalism, security, and self-direction. During the COVID-19 pandemic, the prosocial orientation of Russians may manifest itself in the following behavioral strategies: proactive prosocial strategy of "caring for others" (true altruism, expressed in forms of volunteering, helping a stranger, and charity despite the risk of contracting a coronavirus infection); egoistic strategy of prosocial behavior "self-care through caring for others" (volunteering based on self-development; helping a stranger to improve your own psychological well-being); conventional prosocial strategy "self-care" (self-isolation and preventive behavior). In the long run, it is necessary to identify personal and environmental resources that allowed people to effectively implement a prosocial self-isolation strategy during the COVID-19 pandemic, as well as various forms of volunteerism.

Unbiased interrogation of memory B cells from convalescent COVID-19 patients reveals a broad antiviral humoral response targeting SARS-CoV-2 antigens beyond the spike protein.

Patients who recover from SARS-CoV-2 infections produce antibodies and antigen-specific T cells against multiple viral proteins. Here, an unbiased interrogation of the anti-viral memory B cell repertoire of convalescent patients has been performed by generating large, stable hybridoma libraries and screening thousands of monoclonal antibodies to identify specific, high-affinity immunoglobulins (Igs) directed at distinct viral components. As expected, a significant number of antibodies were directed at the Spike (S) protein, a majority of which recognized the full-length protein. These full-length Spike specific antibodies included a group of somatically hypermutated IgMs. Further, all but one of the six COVID-19 convalescent patients produced class-switched antibodies to a soluble form of the receptor-binding domain (RBD) of S protein. Functional properties of anti-Spike antibodies were confirmed in a pseudovirus neutralization assay. Importantly, more than half of all of the antibodies generated were directed at non-S viral proteins, including structural nucleocapsid (N) and membrane (M) proteins, as well as auxiliary open reading frame-encoded (ORF) proteins. The antibodies were generally characterized as having variable levels of somatic hypermutations (SHM) in all Ig classes and sub-types, and a diversity of VL and VH gene usage. These findings demonstrated that an unbiased, function-based approach towards interrogating the COVID-19 patient memory B cell response may have distinct advantages relative to genomics-based approaches when identifying highly effective anti-viral antibodies directed at SARS-CoV-2.

Using Pharmacogenetics of Direct Oral Anticoagulants to Predict Changes in Their Pharmacokinetics and the Risk of Adverse Drug Reactions.

Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that are increasingly used worldwide. Taking into account their widespread use for the prevention of thromboembolism in cardiology, neurology, orthopedics, and coronavirus disease 2019 (COVID 19) as well as their different pharmacokinetics and pharmacogenetics dependence, it is critical to explore new opportunities for DOACs administration and predict their dosage when used as monotherapy or in combination with other drugs. In this review, we describe the details of the relative pharmacogenetics on the pharmacokinetics of DOACs as well as new data concerning the clinical characteristics that predetermine the needed dosage and the risk of adverse drug reactions (ADRs). The usefulness of genetic information before and shortly after the initiation of DOACs is also discussed. The reasons for particular attention to these issues are not only new genetic knowledge and genotyping possibilities, but also the risk of serious ADRs (primarily, gastrointestinal bleeding). Taking into account the effect of the carriership of single nucleotide variants (SNVs) of genes encoding biotransformation enzymes and DOACs metabolism, the use of these measures is important to predict changes in pharmacokinetics and the risk of ADRs in patients with a high risk of thromboembolism who receive anticoagulant therapy.

Coronavirus associated molecular mimicry common to SARS-CoV-2 peptide (preprint)

Relationship of COVID-19 and immunity is complex and can involve autoimmune reactions through molecular mimicry. We investigated autoimmunity related pathological mechanisms involving molecular mimicry that are common to certain coronaviruses, including SARS-CoV-2, by means of a selected peptide sequence (CFLGYFCTCYFGLFC). Accordingly, coronavirus-associated sequences that are homologous to that 15mer sequence in the SARS-CoV-2 proteome are attained first. Then, homologous human and coronavirus sequences are obtained, wherein the coronavirus sequences are homologous to the 15mer SARS-CoV-2 peptide. All the identified query-subject sequences contained at least 7 residue matches in the aligned regions. Finally, parts of those coronavirus and host sequences, which are predicted to have high affinity to the same human leukocyte antigen (HLA) alleles as that of the SARS-CoV-2 sequence, are selected among the query and subject epitope-pairs that were both (predicted to be) strongly binding to the same HLA alleles. The proteins or the protein regions with those predicted epitopes include, but not limited to, immunoglobulin heavy chain junction regions, phospholipid phosphatase-related protein type 2, slit homolog 2 protein, and CRB1 isoform I precursor. These proteins are potentially associated with certain pathologies, but especially the possible CRB1 related coronavirus pathogenicity could be furthered by autoimmunity risk in HLA*A24:02 serotypes. Overall, results imply autoimmunity risk in COVID-19 patients with HLA*A02:01 and HLA*A24:02 serotypes in general, through molecular mimicry. This is also common to other coronaviruses than SARS-CoV-2. These results are indicative at the current stage, they need to be validated. Yet, they can pave the way to autoimmunity treatment options to be used in COVID-19 and its associated diseases.

Modeling mutational effects on biochemical phenotypes using convolutional neural networks: application to SARS-CoV-2 (preprint)

Biochemical phenotypes are major indexes for protein structure and function characterization. They are determined, at least in part, by the intrinsic physicochemical properties of amino acids and may be reflected in the protein three-dimensional structure. Modeling mutational effects on biochemical phenotypes is a critical step for understanding protein function and disease mechanism as well as enabling drug discovery. Deep Mutational Scanning (DMS) experiments have been performed on SARS-CoV-2's spike receptor binding domain and the human ACE2 zinc-binding peptidase domain - both central players in viral infection and evolution and antibody evasion - quantifying how mutations impact binding affinity and protein expression. Here, we modeled biochemical phenotypes from massively parallel assays, using convolutional neural networks trained on protein sequence mutations in the virus and human host. We found that neural networks are significantly predictive of binding affinity, protein expression, and antibody escape, learning complex interactions and higher-order features that are difficult to capture with conventional methods from structural biology. Integrating the intrinsic physicochemical properties of amino acids, including hydrophobicity, solvent-accessible surface area, and long-range non-bonded energy per atom, significantly improved prediction (empirical p<0.01) though there was such a strong dependence on the sequence data alone to yield reasonably good prediction. We observed concordance of the DMS data and our neural network predictions with an independent study on intermolecular interactions from molecular dynamics (multiple 500 ns or 1 s all-atom) simulations of the spike protein-ACE2 interface, with critical implications for the use of deep learning to dissect molecular mechanisms. The mutation- or genetically- determined component of a biochemical phenotype estimated from the neural networks has improved causal inference properties relative to the original phenotype and can facilitate crucial insights into disease pathophysiology and therapeutic design.

Early therapy with remdesivir and antibody combinations improves COVID-19 disease in mice (preprint)

Improving the standard of clinical care for coronavirus disease 2019 (COVID-19) is a global health priority. Small molecule antivirals like remdesivir (RDV) and biologics such as human monoclonal antibodies (mAb) have demonstrated therapeutic efficacy against SARS-CoV-2, the causative agent of COVID-19. However, the efficacy of single agent therapies has not been comprehensively defined over the time course of infection and it is not known if combination RDV/mAb will improve outcomes over single agent therapies. In kinetic studies in a mouse-adapted SARS-CoV-2 pathogenesis model, we show that single-agent therapies exert potent antiviral effects even when initiated relatively late after infection, but their efficacy is diminished as a function of time. RDV and a cocktail of two mAbs in combination provided improved outcomes compared to single agents alone extending the therapeutic window of intervention with less weight loss, decreased virus lung titers, reduced acute lung injury, and improved pulmonary function. Overall, we demonstrate that direct-acting antivirals combined with potent mAb can improve outcomes over single agents alone in animal models of COVID-19 thus providing a rationale for the coupling of therapies with disparate modalities to extend the therapeutic window of treatment.

Unbiased interrogation of memory B cells from convalescent COVID-19 patients reveals a broad antiviral humoral response targeting SARS-CoV-2 antigens beyond the spike protein (preprint)

Patients who recover from SARS-CoV-2 infections produce antibodies and antigen-specific T cells against multiple viral proteins. Here, an unbiased interrogation of the anti-viral memory B cell repertoire of convalescent patients has been performed by generating large, stable hybridoma libraries and screening thousands of monoclonal antibodies to identify specific, high-affinity immunoglobulins (Igs) directed at distinct viral components. As expected, a significant number of antibodies were directed at the Spike (S) protein, a majority of which recognized the full-length protein. These full-length Spike specific antibodies included a group of somatically hypermutated IgMs. Further, all but one of the six COVID-19 convalescent patients produced class-switched antibodies to a soluble form of the receptor-binding domain (RBD) of S protein. Functional properties of anti-Spike antibodies were confirmed in a pseudovirus neutralization assay. Importantly, more than half of all of the antibodies generated were directed at non-S viral proteins, including structural nucleocapsid (N) and membrane (M) proteins, as well as auxiliary open reading frame-encoded (ORF) proteins. The antibodies were generally characterized as having variable levels of somatic hypermutations (SHM) in all Ig classes and sub-types, and a diversity of VL and VH gene usage. These findings demonstrated that an unbiased, function-based approach towards interrogating the COVID-19 patient memory B cell response may have distinct advantages relative to genomics-based approaches when identifying highly effective anti-viral antibodies directed at SARS-CoV-2.

P.838Coronavirus information to psychiatric patients

Background: While the Coronavirus-19 pandemic is apparently receding, a second wave is still well possible. Patients diagnosed with a severe mental illness (SMI) have an excess mortality and their lifespan is between 10 to 30 years shorter compared to general population [1]. There are also discrepancies in healthcare access and its utilization in patients with SMI compared to general population [2]. People with SMI are more vulnerable to infectious diseases. What is more, Cov19 mortality seems to be double in males compared to females [3]. Therefore, male SMI patients represent a particularly vulnerable group susceptible to both Cov-19 infection and a severe course of illness. Aims: Our study aims to examine the level of information regarding the new Coronavirus-19 in SMI patients compared to general population. Methods: We applied two questionnaires to male patients with severe mental illness. One of the them was based on the five important affirmations from WHO [4]. There were two possible answers for each question, true or false, with a maximum score of 5 points for each questionnaire. The higher the score, the better the knowledge of preventive measures against infection with coronavirus. Our sample consisted of 42 male inpatients from “Alexandru Obregia Psychiatric Hospital” admitted between March and June 2020 and 42 controls matched by gender, age and education. Prior to filling the questionnaires, patients did not receive any formal information or education upon this topic, other than the instructions from the media. Scores were compared using Mann Whitney test and results were considered statistically significant al alpha 0.05,2-tailed. Results: Mean and median scores for the questions evaluating general information were: 6.95 (±1.75) and 7 (IQR 6-8.25) for SMI patients and 9.07 (±1.46) and 10 (IQR 8.75-10) for controls (U=315, Z=-5.21, p<.001). Mean and median scores for level of knowledge about WHO prevention measures were and 4.38 (±0.96) and 5 (IQR 4-5) for SMI patients and 4.76 (±0.62) and 5 (IQR 5-5) for controls (U=685.5, Z=2.25, p=.025). For fictitious information about COVID-19, SMI patients had a mean score of 2.52 (±1.63) and a median one of 3 (IQR 1-4) while controls had 4.33 (±1.16) and a median of 5 (IQR 4-5) (U=324, Z=-5.19, p<.001). Conclusion: To our best knowledge this is the first study evaluating Cov-10 information in SMI patients. Patients with SMI had a lower knowledge of prevention methods against coronavirus. There are multiple factors that can contribute to these results as the severity of the pathology, cognitive capacities, insight and it might be possible that some patients do not understand simple statements. In addition, the SMI group was less likely to discern erroneous information from genuine advice. For this matter, traditional ways of offering information to SMI patients may need altering and personalization since is of vital importance for infectious prevention and spreading of the virus. No conflict of interest

Disability and the COVID-19 Pandemic: Using Twitter to Understand Accessibility during Rapid Societal Transition

The COVID-19 pandemic has forced institutions to rapidly alter their behavior, which typically has disproportionate negative effects on people with disabilities as accessibility is overlooked. To investigate these issues, we analyzed Twitter data to examine accessibility problems surfaced by the crisis. We identified three key domains at the intersection of accessibility and technology: (i) the allocation of product delivery services, (ii) the transition to remote education, and (iii) the dissemination of public health information. We found that essential retailers expanded their high-risk customer shopping hours and pick-up and delivery services, but individuals with disabilities still lacked necessary access to goods and services. Long-experienced access barriers to online education were exacerbated by the abrupt transition of in-person to remote instruction. Finally, public health messaging has been inconsistent and inaccessible, which is unacceptable during a rapidly-evolving crisis. We argue that organizations should create flexible, accessible technology and policies in calm times to be adaptable in times of crisis to serve individuals with diverse needs. © 2020 Owner/Author.