The Impact of COVID-19 Routine Life - A Survey

The COVID-19 pandemic, caused by the novel coronavirus, has had a significant impact on daily life, education, business, and trade. The virus spreads quickly through direct contact with droplets, fecal-oral transmission, and water contamination. The consequences of the pandemic can be classified into three categories: health, economic, and social. The physical, mental, and psychological behaviors of individuals have also changed due to the pandemic. This study aimed to assess the impact of COVID-19 on the general population. A survey questionnaire with ten questions was distributed through an online portal, and the responses were analyzed using SPSS software. The results showed that healthcare workers were among the most affected, with the primary impact on their social and psychological well-being. Although previous research suggested that all fields were equally affected, this study found that healthcare workers were the most impacted group. The study concluded that the COVID-19 pandemic had a significant impact on the social and psychological well-being of the general population, with healthcare workers being the most affected. © 2023 IEEE.

Are You with Us or Against Us?

When the COVID-19 pandemic hit, two contrasting images quickly became repre-sentative of the crisis. On the one hand, there were heroic doctors working day and night with the novel virus, risking their lives and making sacrifices to save others. On the other, there were 'anti-maskers' and 'anti-vaxxers': people doubting if the virus is real, questioning the ef-fectiveness of protective measures, suspicious that the crisis is nothing more than an elaborate plot, a scam aimed to redesign their world and to destroy the values they hold dear. Reflecting on research conducted in Ireland with people separated by the conspiratorial divide, this pa-per examines some methodological and analytical challenges of doing simultaneous research with opposing stakeholders. Analysing my own entanglements in the conflicts over vaccines and conspiracy theories in this paper I argue that the pandemic was not just a battle to secure the acceptability of specific medical technology (the COVID-19 vaccine) but was also about safeguarding respectability of science and maintaining the rule of experts. It was about pre-venting ontological turn, the end of the era of reason, a dawn of modernity.

Immunosuppressants exert differential effects on pan-coronavirus infection and distinct combinatory antiviral activity with molnupiravir and nirmatrelvir.

BACKGROUND: Immunocompromised populations, such as organ transplant recipients and patients with inflammatory bowel disease (IBD) receiving immunosuppressive/immunomodulatory medications, may be more susceptible to coronavirus infections. However, little is known about how immunosuppressants affect coronavirus replication and their combinational effects with antiviral drugs. OBJECTIVE: This study aims to profile the effects of immunosuppressants and the combination of immunosuppressants with oral antiviral drugs molnupiravir and nirmatrelvir on pan-coronavirus infection in cell and human airway organoids (hAOs) culture models. METHODS: Different coronaviruses (including wild type, delta and omicron variants of SARS-CoV-2, and NL63, 229E and OC43 seasonal coronaviruses) were used in lung cell lines and hAOs models. The effects of immunosuppressants were tested. RESULTS: Dexamethasone and 5-aminosalicylic acid moderately stimulated the replication of different coronaviruses. Mycophenolic acid (MPA), 6-thioguanine (6-TG), tofacitinib and filgotinib treatment dose-dependently inhibited viral replication of all tested coronaviruses in both cell lines and hAOs. The half maximum effective concentration (EC50) of tofacitinib against SARS-CoV-2 was 0.62 µM and the half maximum cytotoxic concentration (CC50) was above 30 µM, which resulted in a selective index (SI) of about 50. The anti-coronavirus effect of the JAK inhibitors tofacitinib and filgotinib is dependent on the inhibition of STAT3 phosphorylation. Combinations of MPA, 6-TG, tofacitinib, and filgotinib with the oral antiviral drugs molnupiravir or nirmatrelvir exerted an additive or synergistic antiviral activity. CONCLUSIONS: Different immunosuppressants have distinct effects on coronavirus replication, with 6-TG, MPA, tofacitinib and filgotinib possessing pan-coronavirus antiviral activity. The combinations of MPA, 6-TG, tofacitinib and filgotinib with antiviral drugs exerted an additive or synergistic antiviral activity. Thus, these findings provide an important reference for optimal management of immunocompromised patients infected with coronaviruses.

E-learning enhancement through educational data mining with Covid-19 outbreak period in backdrop: A review.

E-learning is fast becoming an integral part of the teaching- learning process, particularly after the outbreak of Covid-19 pandemic. Educational institutions across the globe are striving to enhance their e-learning instructional mechanism in accordance with the aspirations of present-day students who are widely using numerous technological tools - computers, tablets, mobiles, and Internet for educational purposes. In the wake of the evident incorporation of e-learning into the educational process, research related to the application of Educational Data Mining (EDM) techniques for enhancing e-learning systems has gained significance in recent times. The various data mining techniques applied by researchers to study hidden trends or patterns in educational data can provide valuable insights for educational institutions in terms of making the learning process adaptive to student needs. The insights can help the institutions achieve their ultimate goal of improving student academic performance in technology-assisted learning systems of the modern world. This review paper aims to comprehend EDM's role in enhancing e-learning environments with reference to commonly-used techniques, along with student performance prediction, the impact of Covid-19 pandemic on e-learning and priority e-learning focus areas in the future.

Revealing the roles of TLR7, a nucleic acid sensor for COVID-19 in pan-cancer.

Recent studies suggested that cancer was a risk factor for coronavirus disease 2019 (COVID-19). Toll-like receptor 7 (TLR7), a severe acute respiratory syndrome 2 (SARS-CoV-2) virus's nucleic acid sensor, was discovered to be aberrantly expressed in many types of cancers. However, its expression pattern across cancers and association with COVID-19 (or its causing virus SARS-CoV-2) has not been systematically studied. In this study, we proposed a computational framework to comprehensively study the roles of TLR7 in COVID-19 and pan-cancers at genetic, gene expression, protein, epigenetic, and single-cell levels. We applied the computational framework in a few databases, including The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), Human Protein Atlas (HPA), lung gene expression data of mice infected with SARS-CoV-2, and the like. As a result, TLR7 expression was found to be higher in the lung of mice infected with SARS-CoV-2 than that in the control group. The analysis in the Opentargets database also confirmed the association between TLR7 and COVID-19. There are also a few exciting findings in cancers. First, the most common type of TLR7 was "Missense" at the genomic level. Second, TLR7 mRNA expression was significantly up-regulated in 6 cancer types and down-regulated in 6 cancer types compared to normal tissues, further validated in the HPA database at the protein level. The genes significantly co-expressed with TLR7 were mainly enriched in the toll-like receptor signaling pathway, endolysosome, and signaling pattern recognition receptor activity. In addition, the abnormal TLR7 expression was associated with mismatch repair (MMR), microsatellite instability (MSI), and tumor mutational burden (TMB) in various cancers. Mined by the ESTIMATE algorithm, the expression of TLR7 was also closely linked to various immune infiltration patterns in pan-cancer, and TLR7 was mainly enriched in macrophages, as revealed by single-cell RNA sequencing. Third, abnormal expression of TLR7 could predict the survival of Brain Lower Grade Glioma (LGG), Lung adenocarcinoma (LUAD), Skin Cutaneous Melanoma (SKCM), Stomach adenocarcinoma (STAD), and Testicular Germ Cell Tumors (TGCT) patients, respectively. Finally, TLR7 expressions were very sensitive to a few targeted drugs, such as Alectinib and Imiquimod. In conclusion, TLR7 might be essential in the pathogenesis of COVID-19 and cancers.

Interactive Distance Learning for Virtual Capacity Building Development Intra-Pandemic Experiences: A Case of Mooc Utm-Porsec

In the wake of the current COVID-19 pandemic, most face-to-face activities have been restricted including the scientific program such as capacity building. This, in turn, requires rapid redesign of capacity building implementation during the pandemic period. Hence, this study aims at organizing a virtual capacity building for early-career scientists as an alternative to traditional setting which requires face-to-face interaction. This virtual capacity building focuses on the use of remote sensing for effective monitoring of ocean climate resilience. This program was developed using Massive Open Online Course (MOOC) under UTM Open Learning platform which is known as MOOC on Ocean Remote Sensing towards Climate Resilience. A total of 26 international participants successfully participated in this MOOC UTM-PORSEC. This virtual program contains 14 modules that were conducted by experienced instructors in the field of ocean remote sensing. The program evaluation has shown that the overall Programme Learning Outcomes have scored above 70%. Furthermore, 88% of the MOOC-PORSEC participants have completed all the course content, assignments and quizzes. The developed virtual capacity building has provided a new digital learning experience as well as it saves the cost of travelling and time at the expense of physical interaction.

Genomics, metagenomics, and pan-genomics approaches in COVID-19

The coronavirus outbreak, which initially started in Wuhan China, has rapidly led to numerous morbidities and mortalities worldwide. Although potential antiviral and antiinflammatory medicines are available, several individuals are dying daily. In order to thoroughly tackle this deadly virus, the knowledge of genomics, metagenomics, and pan genomics is required, not only to devise new treatment regimens but also to improve the present approaches. Understanding the genomic organization, diversity and structural complexity of this virus can help to figure out several previously unanswered questions. SARS-CoV-2 corona virus comprises of four major structural proteins, namely, the spike surface glycoprotein, tiny envelope protein, matrix protein, and nucleocapsid protein along with accessory proteins that contribute to pathogenesis and persistence of the virus in one way or the other. This chapter covers genomics, metagenomics, and pan-genomics-based strategies that can facilitate to figure the possible mutational recombination and trace the phylogenetic background of the species. Sequencing has been performed and the hence derived viral sequences have been deposited into exclusive repositories to speed up research and explore targeted treatment options. Moreover, immunoinformatics approaches and reverse vaccinology have been applied to speed up the process of formulating reliable, safe, and specific therapeutic options, rapidly. © 2023 Elsevier Inc. All rights reserved.

Did COVID-19 Make Me an Afro-Pessimist? A Conversation in Three Parts

As the COVID-19 pandemic continues to rage and disproportionately affect BIPOC, we keep count of the death toll around the world, in the U.S., in our own communities and in our own families. How can we have a "wish to live,” while so many around us die? Does a space exist between fateful (faithful) optimism present in Aretha Franklin's, "Mary Don't You Weep?” and the ever-present power structure, that as Reverend Al Sharpton noted, has always had its knee on our necks? More concretely, how do we reconcile what Aisha Durham discusses as "weathering and wounded,” as we sit in the space of being both and not wanting to endure much more. This piece articulates some of the conversations that we have stumbled upon, worked through and raged against from the space of our collective homes and fatigued spirits. It addresses notions of Afro-Pessimism and the intersection of Black Feminist Theory, the role that grief plays in Black Feminist praxis, the role of Diaspora in the historical imagination, and asks the question, "Did COVID and the state-sanctioned killings of Black people make us Afro-Pessimists?”

Are You with Us or Against Us? Studying Conflicts Over Conspiracy Theories and Overcoming the Great Conspiratorial Divide

When the COVID-19 pandemic hit, two contrasting images quickly became repre-sentative of the crisis. On the one hand, there were heroic doctors working day and night with the novel virus, risking their lives and making sacrifices to save others. On the other, there were ‘anti-maskers' and ‘anti-vaxxers': people doubting if the virus is real, questioning the ef-fectiveness of protective measures, suspicious that the crisis is nothing more than an elaborate plot, a scam aimed to redesign their world and to destroy the values they hold dear. Reflecting on research conducted in Ireland with people separated by the conspiratorial divide, this paper examines some methodological and analytical challenges of doing simultaneous research with opposing stakeholders. Analysing my own entanglements in the conflicts over vaccines and conspiracy theories in this paper I argue that the pandemic was not just a battle to secure the acceptability of specific medical technology (the COVID-19 vaccine) but was also about safeguarding respectability of science and maintaining the rule of experts. It was about pre-venting ontological turn, the end of the era of reason, a dawn of modernity. © The Author(s).

Pan-cancer landscape of CENPO and its underlying mechanism in LUAD.

BACKGROUND: Centromere protein O (CENPO) is a newly discovered constitutive centromeric protein, associated with cell death. However, little is known about how CENPO expression is associated with human cancers or immune infiltration. Here, we assessed the function of CENPO in pan-cancer and further verified the results in lung adenocarcinoma (LUAD) through in vitro and in vivo experiments. METHODS: Sangerbox and TCGA databases were used to evaluate the CENPO expression level in different human cancer types. A subsequent evaluation of the potential role of CENPO as a diagnostic and prognostic biomarker in pancancer was conducted. The CENPO mutations were analyzed using the cBioPortal database and its function was analyzed using the LinkedOmics and CancerSEA databases. The TIMER2 and TISIDB websites were used to find out how CENPO affects immune infiltration. The expression level of CENPO in LUAD was revealed by TCGA database and immunohistochemical (IHC) staining. Targetscan, miRWalk, miRDB, miRabel, LncBase databases, and Cytoscape tool were used to identify microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) that regulate expression and construct ceRNA network. Subsequently, loss-of-function assays were performed to identify the functions of CENPO on the malignant behavior and tumor growth of LUAD in vitro and in vivo experiments. RESULTS: In most cancers, CENPO was upregulated and mutated, which predicted a poorer prognosis. Furthermore, infiltration of CENPO and myeloid-derived suppressor cells (MDSC) showed a significant positive correlation, while T-cell NK infiltration showed a significant negative correlation in most cancers. CENPO was expressed at high levels in LUAD and was correlated with p-TNM stage. Furthermore, CENPO knockdown suppressed the malignant phenotypes of LUAD cells, manifested by slower proliferation, cycle in G2, increased apoptosis, decreased migration, and attenuated tumorigenesis. Furthermore, CENPO knockdown decreased CDK1/6, PIK3CA, and inhibited mTOR phosphorylation, suggesting that the mTOR signaling pathway may be involved in CENPO-mediated regulation of LUAD development. CONCLUSIONS: In pan-cancer, especially LUAD, CENPO may be a potential biomarker and oncogene. Furthermore, CENPO has been implicated in immune cell infiltration in pan-cancer and represents a potential immunotherapeutic target for tumor therapy.

CoVe-Tracker: An Interactive SARS-CoV-2 Pan Proteome Evolution Tracker.

SARS-CoV-2 has significantly mutated its genome during the past 3 years, leading to the periodic emergence of several variants. Some of the variants possess enhanced fitness advantage, transmissibility, and pathogenicity and can also reduce vaccine efficacy. Thus, it is important to track the viral evolution to prevent and protect the mankind from SARS-CoV-2 infection. To this end, an interactive web-GUI platform, namely, CoVe-tracker (SARS-CoV-2 evolution tracker), is developed to track its pan proteome evolutionary dynamics (https://project.iith.ac.in/cove-tracker/). CoVe-tracker provides an opportunity for the user to fetch the country-wise and protein-wise amino acid mutations (currently, 44139) of SARS-CoV-2 and their month-wise distribution. It also provides position-wise evolution observed in the SARS-CoV-2 proteome. Importantly, CoVe-tracker provides month- and country-wise distributions of 2065 phylogenetic assignment of named global outbreak (PANGO) lineages and their 177564 variants. It further provides periodic updates on SARS-CoV-2 variant(s) evolution. CoVe-tracker provides the results in a user-friendly interactive fashion by projecting the results onto the world map (for country-wise distribution) and protein 3D structure (for protein-wise mutation). The application of CoVe-tracker in tracking the closest cousin(s) of a variant is demonstrated by considering BA.4 and BA.5 PANGO lineages as test cases. Thus, CoVe-tracker would be useful in the quick surveillance of newly emerging mutations/variants/lineages to facilitate the understanding of viral evolution, transmission, and disease epidemiology.

Equity throughout the life course and the evolving role of the Pan American Health Organization.

The objective of this article is to summarize the evolution of the regional commitments of the Pan American Health Organization (PAHO) on health promotion and strategies to improve the health and well-being of women, children, adolescents, and older persons. PAHO regional strategies approved by Member States in the last 20 years are used as the main source of information. The article presents the challenges of making health promotion a public health strategy widely applied in the Region of the Americas and the efforts to renew Member States' collective actions. The article also describes current PAHO efforts to include the positive aspects of health (i.e., well-being, optimal development, and functional ability) and the life course approach as opportunities to advance equity. The article reflects on immunization as a public good and the urgency to address the current challenges as a core element of the regional efforts to transform health systems after more than two years of the COVID-19 pandemic.

El objetivo de este artículo es resumir la evolución de los compromisos regionales de la Organización Panamericana de la Salud (OPS) en materia de promoción de la salud y estrategias para mejorar la salud y el bienestar de mujeres, niños y niñas, adolescentes y personas mayores. Se han empleado como principal fuente de información las estrategias regionales de la OPS aprobadas por los Estados Miembros en los últimos 20 años. En el artículo se presentan los desafíos de convertir la promoción de la salud en una estrategia de salud pública de amplia ejecución en la Región de las Américas y los esfuerzos para renovar las medidas colectivas de los Estados Miembros. Asimismo, se describe la labor actual de la OPS para incluir los aspectos positivos de la salud (como el bienestar, el desarrollo óptimo y la capacidad funcional) y el enfoque del curso de vida como oportunidades para fomentar la equidad. Finalmente, se reflexiona sobre la inmunización como bien público y la urgencia de abordar los desafíos actuales como elemento central de los esfuerzos regionales para transformar los sistemas de salud tras más de dos años de pandemia de COVID-19.

O objetivo deste artigo é resumir a evolução dos compromissos regionais da Organização Pan-Americana da Saúde (OPAS) relativos à promoção da saúde e estratégias para melhorar a saúde e o bem-estar de mulheres, crianças, adolescentes e pessoas idosas. As estratégias regionais da OPAS aprovadas pelos Estados Membros nos últimos 20 anos são a principal fonte de informação. O artigo apresenta os desafios enfrentados para fazer da promoção da saúde uma estratégia de saúde pública amplamente aplicada na Região das Américas e os esforços para renovar as ações coletivas dos Estados Membros. O artigo também descreve os atuais esforços da OPAS para incluir os aspectos positivos da saúde (isto é, bem-estar, desenvolvimento ideal e habilidade funcional) e a abordagem de curso da vida como oportunidades para promover a equidade. O artigo faz reflexões sobre a imunização como um bem público e a urgência de abordar os desafios atuais como um elemento central dos esforços regionais para transformar os sistemas de saúde após mais de dois anos da pandemia de COVID-19.

Managerial Aspect of Private Health Care Institutions in the Republic of Croatia at the Time of COVID-19 Pandemic

Managerial economics, with its specificity, provides a special insight into the management of private health care institutions. According to the sources of the Financial Agency (FINA) and the national classification of activities (8622 and 8610), the observed industry in the Republic of Croatia in 2020 contains 675 entities, out of which 9 are in special private hospitals (8610), and others are in specialist medical practice (8622). The effectiveness of managers in conditions of uncertainty and increased risk is reflected in the availability of information and their experience in similar situations. Precisely the lack of information that was present at the time of the COVID-19 pandemic indicates the effective strategic thinking of managers (owners) of the observed institutions who responded in a timely manner to market needs in these conditions. In doing so, they acted as a substitute for specialist health care because it was not able to provide adequate service to the required extent. © 2022, University of Zagreb, Faculty of Mining, Geology and Petroleum Engineering. All rights reserved.

Crystal Structures of Inhibitor-Bound Main Protease from Delta- and Gamma-Coronaviruses.

With the spread of SARS-CoV-2 throughout the globe causing the COVID-19 pandemic, the threat of zoonotic transmissions of coronaviruses (CoV) has become even more evident. As human infections have been caused by alpha- and beta-CoVs, structural characterization and inhibitor design mostly focused on these two genera. However, viruses from the delta and gamma genera also infect mammals and pose a potential zoonotic transmission threat. Here, we determined the inhibitor-bound crystal structures of the main protease (Mpro) from the delta-CoV porcine HKU15 and gamma-CoV SW1 from the beluga whale. A comparison with the apo structure of SW1 Mpro, which is also presented here, enabled the identification of structural arrangements upon inhibitor binding at the active site. The cocrystal structures reveal binding modes and interactions of two covalent inhibitors, PF-00835231 (active form of lufotrelvir) bound to HKU15, and GC376 bound to SW1 Mpro. These structures may be leveraged to target diverse coronaviruses and toward the structure-based design of pan-CoV inhibitors.

Multi-omics analysis reveals genomic, clinical and immunological features of SARS-CoV-2 virus target genes in pan-cancer.

The SARS-CoV-2 virus, also known as the severe acute respiratory syndrome coronavirus 2, has raised great threats to humans. The connection between the SARS-CoV-2 virus and cancer is currently unclear. In this study, we thus evaluated the multi-omics data from the Cancer Genome Atlas (TCGA) database utilizing genomic and transcriptomic techniques to fully identify the SARS-CoV-2 target genes (STGs) in tumor samples from 33 types of cancers. The expression of STGs was substantially linked with the immune infiltration and may be used to predict survival in cancer patients. STGs were also substantially associated with immunological infiltration, immune cells, and associated immune pathways. At the molecular level, the genomic changes of STGs were frequently related with carcinogenesis and patient survival. In addition, pathway analysis revealed that STGs were involved in the control of signaling pathways associated with cancer. The prognostic features and nomogram of clinical factors of STGs in cancers have been developed. Lastly, by mining the cancer drug sensitivity genomics database, a list of potential STG-targeting medicines was compiled. Collectively, this work demonstrated comprehensively the genomic alterations and clinical characteristics of STGs, which may offer new clues to explore the mechanisms on a molecular level between SARS-CoV-2 virus and cancers as well as provide new clinical guidance for cancer patients who are threatened by the COVID-19 epidemic.

The Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs.

This Review initiates a wide-ranging discussion over 2023 by selecting and exploring core themes to be investigated more deeply in papers submitted to the Vaccines Special Issue on the "Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs". To tackle the SARS-CoV-2 pandemic, an acceleration of vaccine development across different technology platforms resulted in the emergency use authorization of multiple vaccines in less than a year. Despite this record speed, many limitations surfaced including unequal access to products and technologies, regulatory hurdles, restrictions on the flow of intellectual property needed to develop and manufacture vaccines, clinical trials challenges, development of vaccines that did not curtail or prevent transmission, unsustainable strategies for dealing with variants, and the distorted allocation of funding to favour dominant companies in affluent countries. Key to future epidemic and pandemic responses will be sustainable, global-public-health-driven vaccine development and manufacturing based on equitable access to platform technologies, decentralised and localised innovation, and multiple developers and manufacturers, especially in low- and middle-income countries (LMICs). There is talk of flexible, modular pandemic preparedness, of technology access pools based on non-exclusive global licensing agreements in exchange for fair compensation, of WHO-supported vaccine technology transfer hubs and spokes, and of the creation of vaccine prototypes ready for phase I/II trials, etc. However, all these concepts face extraordinary challenges shaped by current commercial incentives, the unwillingness of pharmaceutical companies and governments to share intellectual property and know-how, the precariousness of building capacity based solely on COVID-19 vaccines, the focus on large-scale manufacturing capacity rather than small-scale rapid-response innovation to stop outbreaks when and where they occur, and the inability of many resource-limited countries to afford next-generation vaccines for their national vaccine programmes. Once the current high subsidies are gone and interest has waned, sustaining vaccine innovation and manufacturing capability in interpandemic periods will require equitable access to vaccine innovation and manufacturing capabilities in all regions of the world based on many vaccines, not just "pandemic vaccines". Public and philanthropic investments will need to leverage enforceable commitments to share vaccines and critical technology so that countries everywhere can establish and scale up vaccine development and manufacturing capability. This will only happen if we question all prior assumptions and learn the lessons offered by the current pandemic. We invite submissions to the special issue, which we hope will help guide the world towards a global vaccine research, development, and manufacturing ecosystem that better balances and integrates scientific, clinical trial, regulatory, and commercial interests and puts global public health needs first.

The diversity of the glycan shield of sarbecoviruses related to SARS-CoV-2.

Animal reservoirs of sarbecoviruses represent a significant risk of emergent pandemics, as evidenced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Vaccines remain successful at limiting severe disease and death, but the potential for further coronavirus zoonosis motivates the search for pan-coronavirus vaccines. This necessitates a better understanding of the glycan shields of coronaviruses, which can occlude potential antibody epitopes on spike glycoproteins. Here, we compare the structure of 12 sarbecovirus glycan shields. Of the 22 N-linked glycan attachment sites present on SARS-CoV-2, 15 are shared by all 12 sarbecoviruses. However, there are significant differences in the processing state at glycan sites in the N-terminal domain, such as N165. Conversely, glycosylation sites in the S2 domain are highly conserved and contain a low abundance of oligomannose-type glycans, suggesting a low glycan shield density. The S2 domain may therefore provide a more attractive target for immunogen design efforts aiming to generate a pan-coronavirus antibody response.

Koronavírus-világjárvány - a COVID-19-kaleidoszkóp ma (2022. május).

The article attempts to review the principal epidemiological data of the coronavirus pandemic (COVID-19) based on the rapidly changing and expanding international and domestic literature. The review covers the so-called "long COVID-19" as well as the latest pharmacological and immunotherapeutic developments. The manuscript deals with the future of innovative vaccinology, the so-called 'pan-vaccines' developed through artificial intelligences and nanotechnology. Orv Hetil. 2022; 163(24): 935-942.

Fc-mediated pan-sarbecovirus protection after alphavirus vector vaccination.

Group 2B ß-coronaviruses (sarbecoviruses) have caused regional and global epidemics in modern history. Here, we evaluate the mechanisms of cross-sarbecovirus protective immunity, currently less clear yet important for pan-sarbecovirus vaccine development, using a panel of alphavirus-vectored vaccines covering bat to human strains. While vaccination does not prevent virus replication, it protects against lethal heterologous disease outcomes in both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and clade 2 bat sarbecovirus challenge models. The spike vaccines tested primarily elicit a highly S1-specific homologous neutralizing antibody response with no detectable cross-virus neutralization. Rather, non-neutralizing antibody functions, mechanistically linked to FcgR4 and spike S2, mediate cross-protection in wild-type mice. Protection is lost in FcR knockout mice, further supporting a model for non-neutralizing, protective antibodies. These data highlight the importance of FcR-mediated cross-protective immune responses in universal pan-sarbecovirus vaccine designs.

A pan-sarbecovirus vaccine based on RBD of SARS-CoV-2 original strain elicits potent neutralizing antibodies against XBB in non-human primates.

The recently emerged Omicron subvariants XBB and BQ.1.1 have presented striking immune evasion against most monoclonal neutralizing antibodies and convalescent plasma. Therefore, it is essential to develop broad-spectrum COVID-19 vaccines to combat current and future emerging variants. Here, we found that the human IgG Fc-conjugated RBD of the original SARS-CoV-2 strain (WA1) plus a novel STING agonist-based adjuvant CF501 (CF501/RBD-Fc) could induce highly potent and durable broad-neutralizing antibody (bnAb) responses against Omicron subvariants, including BQ.1.1 and XBB in rhesus macaques with NT50s ranging from 2,118 to 61,742 after three doses. A decline of 0.9- to 4.7-fold was observed in the neutralization activity of sera in the CF501/RBD-Fc group against BA.2.2, BA.2.9, BA.5, BA.2.75, and BF.7 relative to D614G after three doses, while a significant decline of NT50 against BQ.1.1 (26.9-fold) and XBB (22.5-fold) relative to D614G. However, the bnAbs were still effective in neutralizing BQ.1.1 and XBB infection. These results suggest that the conservative but nondominant epitopes in RBD could be stimulated by CF501 to generate bnAbs, providing a proof-of-concept for using "nonchangeable against changeables" strategy to develop pan-sarbecovirus vaccines against sarbecoviruses, including SARS-CoV-2 and its variants.