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174 lines
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<title>16 July, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Lasting alterations in monocyte and dendritic cell subsets in individuals after hospitalization for COVID-19</strong> -
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<div>
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After more than two years the COVID-19 pandemic continues to burden healthcare systems and economies worldwide, and it is evident that long-term effects of the disease can persist for months post-recovery in some individuals. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to SARS CoV-2 is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19. Here, we followed, for 6-7 months, a cohort of COVID-19 patients hospitalized during the early waves of the pandemic. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection. We found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in PD-L1 expression but increased CD86 expression across almost all cell types examined. Finally, viral load and CRP correlated to the appearance of circulating antibodies and levels of circulating DC and monocyte subsets, respectively. By elucidating some of the long-term effects that SARS-CoV-2 infection has on these key innate myeloid cells, we have shed more light on how the immune landscape remains affected in the months following severe COVID-19.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.15.500185v1" target="_blank">Lasting alterations in monocyte and dendritic cell subsets in individuals after hospitalization for COVID-19</a>
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</div></li>
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<li><strong>Understanding public support for COVID-19 pandemic mitigation measures over time: Does it wear out?</strong> -
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<div>
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COVID-19 mitigation measures intend to protect public health, but their adverse psychological, social, and economic effects weaken popular support. Less favorable trade-offs may especially weaken support for more restrictive measures. Support for mitigation measures may also differ between population subgroups who experience different benefits and costs, and decrease over time, a phenomenon termed ‘pandemic fatigue’. We examined self-reported support for COVID-19 mitigation measures in The Netherlands over 12 consecutives waves of data collection between April 2020 – May 2021 in an open population cohort study. Participants were recruited through community panels of the 25 regional public health services, and through links to the online surveys advertised on social media. The 54,010 unique participants in the cohort study on average participated in 4 waves of data collection. Most participants were female (65%), middle-aged (57% 40-69 years), highly educated (57%), not living alone (84%), residing in an urban area (60%), and born in the Netherlands (95%). COVID-19 mitigation measures implemented in the Netherlands remained generally well-supported over time (all scores >3 on 5-point scale ranging 1 (low) – 5 (high)). During the whole period studied, support was highest for personal hygiene measures, quarantine and wearing face masks, high but somewhat lower for not shaking hands, testing and self-isolation, and restricting social contacts, and lowest for limiting visitors at home, and not traveling abroad. Women and higher educated people were more supportive of some mitigation measures than men and lower educated people. Older people were more supportive of more restrictive measures than younger people, and support for more socially restrictive measures decreased most over time in higher educated people or in younger people. This study found no support for pandemic fatigue in terms of a gradual decline in support for all mitigation measures over time. Rather, findings suggest that support for mitigation measures reflects a balancing of benefits and cost, which may change over time, and differ between measures and population subgroups.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/yq2az/" target="_blank">Understanding public support for COVID-19 pandemic mitigation measures over time: Does it wear out?</a>
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</div></li>
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<li><strong>Teladentistry and distance learning :Access to oral health state : systematic Reviews</strong> -
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<div>
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:Covid19 pandemic has changed the vision on how to deal in emergency situations .Advanced technology and spreading growth of internet connection encourage people to use it to obtain helpful advice in critical climate of covid 19 crisis . The aim of this study to through the light on importance of teledentistry in critical emergency situations .
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/p794v/" target="_blank">Teladentistry and distance learning :Access to oral health state : systematic Reviews</a>
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</div></li>
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<li><strong>Genome-first detection of emerging resistance to novel therapeutic agents for SARS-CoV-2</strong> -
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<div>
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Some COVID-19 patients are unable to clear their infection or are at risk of severe disease, requiring treatment with neutralising monoclonal antibodies (nmAb) and/or antivirals. The rapid roll-out of novel therapeutics means there is limited understanding of the likely genetic barrier to drug resistance. Unprecedented genomic surveillance of SARS-CoV-2 in the UK has enabled a genome-first approach to the detection of emerging drug resistance. Here we report the accrual of mutations in Delta and Omicron cases treated with casirivimab+imdevimab and sotrovimab respectively. Mutations occur within the epitopes of the respective nmAbs. For casirivimab+imdevimab these are present on contiguous raw reads, simultaneously affecting both components. Using surface plasmon resonance and pseudoviral neutralisation assays we demonstrate these mutations reduce or completely abrogate antibody affinity and neutralising activity, suggesting they are driven by immune evasion. In addition, we show that some mutations also reduce the neutralising activity of vaccine-induced serum.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.14.500063v1" target="_blank">Genome-first detection of emerging resistance to novel therapeutic agents for SARS-CoV-2</a>
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</div></li>
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<li><strong>Pangenome analysis of SARS-CoV2 strains to Identify Potential vaccine targets by Reverse Vaccinology</strong> -
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<div>
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Background: Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) leads to respiratory failure and obstructive alveolar damage, which may be fatal in immunocompromised individuals. COVID-19 pandemic has badly affected every part of the world, and still, the situation in the world is getting worse with the emergence of novel variants. The aim of our study is to explore the genome of SARS-CoV2 followed by in silico reverse vaccinology analysis. This will help to identify the most putative vaccine candidate against the virus in a robust manner and enables cost-effective development of vaccines compared with traditional strategies. Methods: The genomic sequencing data is retrieved from NCBI (Reference Sequence Number NC_045512.2). The sequences are explored through comparative genomics approaches by GENOMICS to find out the core genome. A comprehensive set of proteins obtained was employed in computational vaccinology approaches (names of tools?) for the prediction of the best possible B and T cell epitopes through ABCpred and IEDB Analysis Resource, respectively. The multi-epitopes were further tested against human toll-like receptors and cloned in an E. coli plasmid vector. Findings: The designed Multiepitope Subunit Vaccine was non-allergenic, antigenic (0.6543), & non-toxic, with significant connections with the human leukocyte antigen (HLA) binding alleles, and collective global population coverage of 84.38%. It has 276 amino acids, consisting of an adjuvant with the aid of an EAAAK linker, AAY linkers used to join the 4 CTL epitopes, and GPGPG linkers used to join the 3 HTL epitopes and KK linkers used to join the 7 B-cell epitopes. MESV docking with human pathogenic toll-like receptors-3 (TLR3) exhibited a stable & high binding affinity. An in-silico codon optimization approach was used in the codon system of E. coli (strain K12) to obtain the GC-Content of Escherichia coli (strain K12): 50.7340272413779 and CAI-Value of the improved sequence: 0.9542834278823386. The multi-epitope vaccine’s optimized gene sequence was cloned in-silico in E. coli plasmid vector pET-30a (+), BamHI, and HindIII restriction sites were added to the N and C-terminals of the sequence, respectively. Conclusion: There is a pressing need to combat Covid-19 and we need quick and reliable approaches to Covid-19. By using In-silico approaches, we acquire an effective vaccine that could trigger adequate immune responses at the cellular and humoral levels. The suggested sequences can be further validated through in vivo and in vitro experimentation. Keywords: Covid-19, SARS Cov-2, Pangenome Analysis, Reverse Vaccinology
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.15.500170v1" target="_blank">Pangenome analysis of SARS-CoV2 strains to Identify Potential vaccine targets by Reverse Vaccinology</a>
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</div></li>
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<li><strong>Exploring the trajectory and correlates of social isolation for veterans across a 6-month period during COVID-19</strong> -
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<div>
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Social isolation is a relevant problem for veterans who are at risk for disengaging from others as a function of transition stress from military life to civilian life, and given high rates of exposure to trauma and psychological distress. Few researchers have examined social isolation in veterans over time, particularly during COVID-19 that led to significant barriers and restrictions on social interactions. The purpose of this longitudinal study was to assess veterans’ experience of social isolation and its mental health and social functioning correlates during a 6-month period of the COVID-19 pandemic. Participants were 188 United States veterans of the Iraq and Afghanistan wars, who completed a total of four assessments: one every two months for a total duration of six months. Surveys included measures of global mental health and social functioning as indicated by perceived emotional support, quality of marriage, and couple satisfaction. Multilevel modeling was used to assess 1) growth models to determine whether social isolation changed over time and the trajectory of that change (i.e., linear or quadratic); and 2) whether social isolation was related to both concurrent and prospective indicators of mental health and social functioning. All analyses included person mean centered and grand mean centered isolation to assess for within-and between-person effects. Veterans reported a quadratic trajectory in social isolation that decreased slightly and stabilized over time. Findings indicate that higher social isolation, at both the within- and between-person level, was negatively associated with concurrent emotional support, mental health, quality of marriage, and couple satisfaction. However, all prospective effects were nonsignificant at the within-person level. Results suggest although isolation may decrease over time, veterans report worse mental health and social functioning during times when they report higher levels of social isolation compared to themselves and others. Future work is needed to determine if interventions can be applied during those times to prevent or target those negative associations.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/xf3zb/" target="_blank">Exploring the trajectory and correlates of social isolation for veterans across a 6-month period during COVID-19</a>
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</div></li>
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<li><strong>Vitamin C is an efficient natural product for prevention of SARS-CoV-2 infection by targeting ACE2 in both cell and in vivo mouse models</strong> -
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<div>
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ACE2 is a major receptor for cell entry of SARS-CoV-2. Despite advances in targeting ACE2 to inhibit SARS-CoV-2’s binding, how to efficiently and flexibly control ACE2 levels for prevention of SARS-CoV-2 infection has not been explored. Here, we revealed Vitamin C (VitC) administration as an effective strategy to prevent SARS-CoV-2 infection. VitC reduced ACE2 protein levels in a dose-dependent manner, while partial reduction of ACE2 can greatly restrict SARS-CoV-2 infection. Further studies uncovered that USP50 is a crucial regulator of ACE2 protein levels, and VitC blocks the USP50-ACE2 interaction, thus promoting K48-linked polyubiquitination at Lys788 and degradation of ACE2, without disrupting ACE2 transcriptional expression. Importantly, VitC administration reduced host ACE2 and largely blocked SARS-CoV-2 infection in mice. This study identified an in vivo ACE2 balance controlled by both USP50 and an essential nutrient VitC, and revealed a critical role and application of VitC in daily protection from SARS-CoV-2 infection.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.14.499651v1" target="_blank">Vitamin C is an efficient natural product for prevention of SARS-CoV-2 infection by targeting ACE2 in both cell and in vivo mouse models</a>
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</div></li>
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<li><strong>Neutralization sensitivity of Omicron BA.2.75 to therapeutic monoclonal antibodies</strong> -
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<div>
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Since the end of 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant outcompeted other variants and took over the world. After the emergence of original Omicron BA.1, Omicron BA.2 subvariant emerged and outcompeted BA.1. As of July 2022, some BA.2 subvariants, including BA.2.12.1, BA.4 and BA.5, emerged in multiple countries and begun outcompeting original BA.2. Moreover, a novel BA.2 subvariant, BA.2.75, was detected in eight countries including India at the end of June 2022, and preliminary investigations suggest that BA.2.75 is more transmissible over the other BA.2 subvariants. On July 7, 2022, the WHO classified BA.2.75 as a variant-of-concern lineage under monitoring. We have recently demonstrated that BA.4/5 is highly resistant to a therapeutic monoclonal antibody, cilgavimab, than BA.2. The resistance of SARS-CoV-2 variants to therapeutic antibodies can be attributed to the mutations in the viral spike protein. Compared to the BA.2 spike, BA.2.12.1 and BA.4/5 respectively bear two and four mutations in their spike proteins. On the other hand, the majority of BA.2.75 spike bears nine substitutions. The fact that the mutation number in the BA.2.75 spike is larger than those in the BA.4/5 spike raises the possibility that the BA.2.75 spike significantly reduces sensitivity towards therapeutic monoclonal antibodies than BA.2 and BA.4/5. In this study, we generated pseudoviruses harboring the spike proteins of BA.2.75, BA.4/5 and BA.2 and evaluated the efficacy of ten therapeutic monoclonal antibodies and three antibody cocktails against BA.2.75.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.14.500041v1" target="_blank">Neutralization sensitivity of Omicron BA.2.75 to therapeutic monoclonal antibodies</a>
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</div></li>
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<li><strong>A zebrafish model of COVID-19-associated cytokine storm syndrome reveals that the Spike protein signals via TLR2</strong> -
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<div>
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Understanding the mechanism of virulence of SARS-CoV-2 and host innate immune responses are essential to develop novel therapies. One of the most studied defense mechanisms against invading pathogens, including viruses, are Toll-like receptors (TLRs). Among them, TLR3, TLR7, TLR8 and TLR9 detect different forms of viral nucleic acids in endosomal compartments, whereas TLR2 and TLR4 recognize viral structural and nonstructural proteins outside the cell. Although many different TLRs have been shown to be involved in SARS-CoV-2 infection and detection of different structural proteins, most studies have been performed in vitro and the results obtained are rather contradictory. In this study, we report using the unique advantages of the zebrafish model for in vivo imaging and gene editing that the S1 domain of the Spike protein from the Wuhan strain (S1WT) induced hyperinflammation in zebrafish larvae via a Tlr2/Myd88 signaling pathway and independently of interleukin-1{beta} production. In addition, S1WT also triggered emergency myelopoiesis, but in this case through a Tlr2/Myd88-independent signaling pathway. These results shed light on the mechanisms involved in the COVID-19-associated cytokine storm syndrome.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.14.500031v1" target="_blank">A zebrafish model of COVID-19-associated cytokine storm syndrome reveals that the Spike protein signals via TLR2</a>
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</div></li>
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<li><strong>SARS-CoV-2 BA.4 infection triggers more cross-reactive neutralizing antibodies than BA.1</strong> -
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<div>
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SARS-CoV-2 variants of concern (VOCs) differentially trigger neutralizing antibodies with variable cross-neutralizing capacity. Here we show that unlike SARS-CoV-2 Omicron BA.1, which triggered neutralizing antibodies with limited cross-reactivity, BA.4/5 infection triggers highly cross-reactive neutralizing antibodies. Cross-reactivity was observed both in the absence of prior vaccination and also in breakthrough infections following vaccination. This suggests that next-generation vaccines incorporating BA.4, which is spreading globally, might result in enhanced neutralization breadth.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.14.500039v1" target="_blank">SARS-CoV-2 BA.4 infection triggers more cross-reactive neutralizing antibodies than BA.1</a>
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</div></li>
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<li><strong>Fc effector activity and neutralization against SARS-CoV-2 BA.4 is compromised in convalescent sera, regardless of the infecting variant</strong> -
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<div>
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The SARS-CoV-2 Omicron BA.1 variant, which exhibits high level neutralization resistance, has since evolved into several sub-lineages including BA.4 and BA.5, which have dominated the fifth wave of infection in South Africa. Here we assessed the sensitivity of BA.4 to neutralization and antibody dependent cellular cytotoxicity (ADCC) in convalescent donors infected with four previous variants of SARS-CoV-2, as well as in post-vaccination breakthrough infections (BTIs) caused by Delta or BA.1. We confirm that BA.4 shows high level resistance to neutralization, regardless of the infecting variant. However, breakthrough infections, which trigger potent neutralization, retained activity against BA.4, albeit at reduced titers. Fold reduction of neutralization in BTIs was lower than that seen in unvaccinated convalescent donors, suggesting maturation of neutralizing responses to become more resilient against VOCs in hybrid immunity. BA.4 sensitivity to ADCC was reduced but remained detectable in both convalescent donors and in BTIs. Overall, the high neutralization resistance of BA.4, even to antibodies from BA.1 infections, provides an immunological mechanism for the rapid spread of BA.4 immediately after a BA.1-dominated wave. Furthermore, although ADCC activity against BA.4 was reduced, residual activity may nonetheless contribute to the protection from disease.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.14.500042v1" target="_blank">Fc effector activity and neutralization against SARS-CoV-2 BA.4 is compromised in convalescent sera, regardless of the infecting variant</a>
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</div></li>
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<li><strong>Ending transmission of SARS-CoV-2: sterilizing immunity using an intranasal subunit vaccine</strong> -
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<div>
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Immunization programs against SARS-CoV-2 with commercial intramuscular (IM) vaccines prevent disease but not infections. The continued evolution of variants of concern (VOC) like Delta and Omicron has increased infections even in countries with high vaccination coverage. This is due to commercial vaccines being unable to prevent viral infection in the upper airways and exclusively targeting the spike (S) protein that is subject to continuous evolution facilitating immune escape. Here we report a multi-antigen, intranasal vaccine, NanoSTING-NS that yields sterilizing immunity and leads to the rapid and complete elimination of viral loads in both the lungs and the nostrils upon viral challenge with SARS-CoV-2 VOC. We formulated vaccines with the S and nucleocapsid (N) proteins individually to demonstrate that immune responses against S are sufficient to prevent disease whereas combination immune responses against both proteins prevents viral replication in the nasal compartment. Studies with the highly infectious Omicron VOC showed that even in vaccine-naive animals, a single dose of NanoSTING-NS significantly reduced transmission. These observations have two implications: (1) mucosal multi-antigen vaccines present a pathway to preventing transmission and ending the pandemic, and (2) an explanation for why hybrid immunity in humans is superior to vaccine-mediated immunity by current IM vaccines.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.14.500068v1" target="_blank">Ending transmission of SARS-CoV-2: sterilizing immunity using an intranasal subunit vaccine</a>
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</div></li>
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<li><strong>Malinformation – an emergent problem for medical journals and scientific communication</strong> -
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<div>
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Background: Malinformation is the presentation of curated facts in manner that presents a false narrative and/or creates a misleading impression by leaving out important context. Unlike its better-known relatives, misinformation and disinformation, malinformation depends not on false information, but rather on employing cherry-picked facts and deliberate omissions to mislead. While medical journals are the vanguards of new biomedical research, results and commentary published in them can be misrepresented to produce insidious malinformation, with distortions introduced by third parties interpreting the research, authors themselves, or both. Objective: To investigate the proliferation and interpretation of medical malinformation. Design: An altmetric and sentiment analysis of an article on a COVID-19 vaccine with the highest engagement score ever published in a medical journal. Setting: Worldwide. Participants: Media outlets and social media users worldwide. Measurements: Quantification of the context, spread, adoption, and interpretation of a prominent recent case study of medical malinformation. Results: This analysis suggests the selective and leading presentation made this an especially powerful piece of malinformation, in large part because the imprimatur of a respected medical journal gave it a veneer of legitimacy. Sentiment analysis suggests it has been chiefly amplified by antivaccine activists and conspiracy theorists worldwide, with negative ramifications for vaccine acceptance. The appearance of malinformation in a medical journal can adversely affect public understanding of medical science. Conclusion: To maintain public trust in medical science, authors, editors, and reviewers need be aware of the potential for malinformation and decontextualized misappropriation of bona fide results.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/g4jwr/" target="_blank">Malinformation – an emergent problem for medical journals and scientific communication</a>
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<li><strong>Another doubling of excess mortality in the United States relative to its European peers between 2017 and 2021</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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A mortality gap has emerged between the United States and other high-income nations before the pandemic and was estimated to account for one in seven US deaths in 2017. International comparisons in Covid-19 mortality suggest both the number and proportion of US deaths that can be attributed to this gap should have increased during the pandemic. Publicly available data on deaths from all causes and 2020-2021 Covid-19 death counts in the United States and five European countries, were combined with population estimates by sex and age group in these European countries to produce sex- and age-specific mortality rates. These rates are averaged and applied to the US population by sex and age-group to compare the resulting and actual US death counts. This counterfactual reveals 892,491 excess deaths in the United States in 2021—deaths that would have been prevented had the United States achieved the average mortality rates of its main West European peers. Excess deaths doubled between 2017 and 2021, with most of the increase occurring during the pandemic (89.1% increase between 2019 and 2021). Population change contributed little to the 2017- 2021 increase in excess deaths (42,317 additional deaths, 9.4% of the increase). Covid-19 mortality alone continue contributed 230,672 excess deaths in 2021 (51.2%), more than 2020, whereas other causes of deaths contributed 177,235 more excess deaths in 2021 than in 2017 (39.4% of the increase). In 2021, excess mortality in the United States relative to its European peers accounted for 25.8% of all deaths (3,426,249), up from 15.7% in 2017. The increase was driven in part by the large share of Covid- 19 deaths that are excess deaths (relative to European Covid-19 mortality rates),a proportion that has hovered around 50% but increased to 63.3% in 2021 as US vaccination rates plateaued at lower levels than in European countries. The overall increase in mortality from other causes during the pandemic increasingly separates the United States from West European countries as well.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.03.21.22272722v2" target="_blank">Another doubling of excess mortality in the United States relative to its European peers between 2017 and 2021</a>
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<li><strong>Practical application of CO2 as an indicator regarding the risk of infection</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The air quality of enclosed spaces has attracted great attention due to the ongoing Covid-19 pandemic. The infection risk in these spaces can be estimated for various scenarios with different methods so the important parameters and effective infection prevention measures can be compared. Previous studies showed that indoor CO 2 concentration could be considered a surrogate for infection risk. In this regard, a generic relation can be established between the CO 2 levels and infection probability. Based on this consideration, some practical evaluations between CO 2 concentration and infection risk are conducted in this study. The effect of mask efficiency, viral emission rate, and duration of exposure are also included in the assessments. It is shown that continuous CO 2 monitoring can be helpful in the evaluation of possible preventive measures. Findings are expected to contribute to the understanding of the simple parameters related to the infection risk.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.14.22277631v1" target="_blank">Practical application of CO2 as an indicator regarding the risk of infection</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bank of Human Leukocytes From COVID-19 Convalescent Donors With an Anti-SARS-CoV-2 Cellular Immunity</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Generation of a biobank allowing the cryopreservation of leucocytes from COVID19 convalescent donors<br/><b>Sponsor</b>: Central Hospital, Nancy, France<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Generation of SARS-CoV-2-specific T Lymphocytes From Recovered Donors and Administration to High-risk COVID-19 Patients</strong> - <b>Condition</b>: Severe COVID-19<br/><b>Interventions</b>: Biological: Coronavirus-2-specific T cells; Other: standard of care (SOC)<br/><b>Sponsors</b>: George Papanicolaou Hospital; General Hospital Of Thessaloniki Ippokratio<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Randomised, Multi-centre, Double-blind, Phase 3 Study to Observe the Effectiveness, Safety and Tolerability of Molnupiravir Compared to Placebo Administered Orally to High-risk Adult Outpatients With Mild COVID-19 Receiving Local Standard of Care in South Africa</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Molnupiravir 200 mg<br/><b>Sponsors</b>: University of Witwatersrand, South Africa; Bill and Melinda Gates Foundation<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluate the Efficacy and Safety of FB2001 in Hospitalized Patients With Moderate to Severe COVID-19 (BRIGHT Study)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: FB2001; Drug: FB2001 placebo<br/><b>Sponsor</b>: Frontier Biotechnologies Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Engaging Staff to Improve COVID-19 Vaccination Response at Long-Term Care Facilities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Full Intervention; Other: Enhanced Usual Care<br/><b>Sponsors</b>: Kaiser Permanente; Patient-Centered Outcomes Research Institute; Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Efficacy of PanCytoVir™ for the Treatment of Non-Hospitalized Patients With COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: PanCytoVir™ (probenecid); Drug: Placebo<br/><b>Sponsor</b>: TrippBio, Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Value of Montelukast as a Potential Treatment of Post COVID-19 Persistent Cough</strong> - <b>Condition</b>: Post COVID-19<br/><b>Intervention</b>: Drug: Montelukast Sodium Tablets<br/><b>Sponsor</b>: Assiut University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Topical Antibacterial Agents for Prevention of COVID-19</strong> - <b>Conditions</b>: COVID-19; SARS-CoV2 Infection<br/><b>Interventions</b>: Drug: Neosporin; Other: Vaseline<br/><b>Sponsors</b>: Yale University; Bill and Melinda Gates Foundation<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">**NanoMn®_COVID-19 A Prospective, Multicenter, Randomized, Placebo-controlled, Parallel-group, Double-blind Trial to Evaluate the Clinical Efficacy of NanoManganese® on Top of Standard of Care, in Adult Patients With Moderate to Severe Coronavirus Disease 2019 (COVID-19)** - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Drug: Placebo; Drug: Experimental drug<br/><b>Sponsor</b>: Medesis Pharma SA<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study</strong> - <b>Condition</b>: Post-COVID19 Condition<br/><b>Interventions</b>: Combination Product: Plasma Exchange Procedure; Other: Sham Plasma Exchange Procedure<br/><b>Sponsors</b>: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; IrsiCaixa; Banc de Sang i Teixits<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of Effectiveness of Proprietary Rehabilitation Program in Patients After COVID-19 Infection</strong> - <b>Conditions</b>: COVID-19; Rehabilitation<br/><b>Interventions</b>: Other: Respiratory training with the use of resistance set on respiratory muscle trainer; Other: Respiratory training without resistance set on respiratory muscle trainer<br/><b>Sponsor</b>: Medical University of Bialystok<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Developing an Integrative, Recovery-Based, Post-Acute COVID-19 Syndrome (PACS) Psychotherapeutic Intervention</strong> - <b>Condition</b>: Post-acute COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: PACS Coping and Recovery (PACS-CR) Intervention<br/><b>Sponsor</b>: VA Office of Research and Development<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mineralocorticoid Use in COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; ARDS<br/><b>Intervention</b>: Drug: Fludrocortisone Acetate 0.1 MG<br/><b>Sponsor</b>: Ain Shams University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Dose Escalation Phase 1 Study Evaluating the Safety and Pharmacokinetics of an Inhaled COVID-19 Inhibitor Delcetravir in Healthy Subjects</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Combination Product: Delcetravir dry powder inhaler<br/><b>Sponsor</b>: Esfam Biotech Pty Ltd<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety and Immunogenicity of Ad5-vector Based Vaccine Against Coronavirus Variants in Adults (≥18 Years) Immunized With 2 Doses of mRNA Vaccines Plus One Dose of Booster AZD1222 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Bivalent Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector); Biological: Bivalent Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) for Inhalation; Biological: mRNA-based COVID-19 vaccine<br/><b>Sponsor</b>: CanSino Biologics Inc.<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of the lectin pathway of complement ameliorates hypocomplementemia and restores serum bactericidal activity in patients with severe COVID-19</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluating the Effects of Curcumin on the Cytokine Storm in COVID-19 Using a Chip-Based Multiplex Analysis</strong> - SARS-CoV-2 can stimulate the expression of various inflammatory cytokines and induce the cytokine storm in COVID-19 patients leading to multiple organ failure and death. Curcumin as a polyphenolic compound has been shown to have anti-inflammatory properties and inhibit the release of numerous pro-inflammatory cytokines. We present multiplex analysis using the Evidence Investigator biochip system to determine the effect of curcumin on serum level of cytokines which are typically elevated in…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immune dynamics in SARS-CoV-2 experienced immunosuppressed rheumatoid arthritis or multiple sclerosis patients vaccinated with mRNA-1273</strong> - Background: Patients affected by different types of autoimmune diseases, including common conditions such as Multiple Sclerosis (MS) and Rheumatoid Arthritis (RA), are often treated with immunosuppressants to suppress disease activity. It is not fully understood how the SARS-CoV-2 specific humoral and cellular immunity induced by infection and/or upon vaccination is affected by immunosuppressants.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Analysis of the molecular mechanism of Huangqi herb treating COVID-19 with myocardial injury by pharmacological tools, programming software and molecular docking</strong> - CONCLUSIONS: Huangqi may play a therapeutic role in treating COVID-19 with myocardial injury by the effects of resisting virus and protecting myocardium concurrently.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Prolonged NHE Activation may be Both Cause and Outcome of Cytokine Release Syndrome in COVID-19</strong> - The release of cytokines and chemokines such as IL-1β, IL-2, IL-6, IL-7, IL-10, TNF-α, IFN-γ, CCL2, CCL3, and CXCL10 is increased in critically ill patients with COVID-19. Excessive cytokine release during COVID-19 is related to increased morbidity and mortality. Several mechanisms are put forward for cytokine release syndrome during COVID-19. Here we would mention a novel pathways. SARS-CoV-2 increases angiotensin II levels by rendering ACE2 nonfunctional. Angiotensin II causes cytokine release…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Beneficial effect of polyphenols in COVID-19 and the ectopic F<sub>1</sub> F<sub>O</sub> -ATP synthase: Is there a link?</strong> - COVID-19 has been proposed to be an endothelial disease, as endothelial damage and oxidative stress contribute to its systemic inflammatory and thrombotic events. Polyphenols, natural antioxidant compounds appear as promising agents to prevent and treat COVID-19. Polyphenols bind and inhibit the F(1) F(o) -ATP synthase rotary catalysis. An early target of polyphenols may be the ectopic F(1) F(o) -ATP synthase expressed on the endothelial plasma membrane. Among the pleiotropic beneficial action…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Surface Display of Peptides Corresponding to the Heptad Repeat 2 Domain of the Feline Enteric Coronavirus Spike Protein on <em>Bacillus subtilis</em> Spores Elicits Protective Immune Responses Against Homologous Infection in a Feline Aminopeptidase-N-Transduced Mouse Model</strong> - Although feline coronavirus (FCoV) infection is extremely common in cats, there are currently few effective treatments. A peptide derived from the heptad repeat 2 (HR2) domain of the coronavirus (CoV) spike protein has shown effective for inhibition of various human and animal CoVs in vitro, but further use of FCoV-HR2 in vivo has been limited by lack of practical delivery vectors and small animal infection model. To overcome these technical challenges, we first constructed a recombinant…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Corona versus Dengue: Distinct Mechanisms for Inhibition of Polyprotein Processing by Antiviral Drugs</strong> - Inhibitors interfering with processing of the viral polyprotein are used successfully for the control of extremely important viral pathogens, such as HIV and most recently SARS-CoV-2. This Viewpoint provides a mechanistic evaluation of a promising antiviral lead compound against dengue virus, JNJ-A07, 4-(3-((1-(4-chlorophenyl)-2-oxo-2-(6-(trifluoromethoxy)indolin-1-yl)ethyl)amino)-5-methoxyphenoxy)butanoic acid. The antiviral effect of JNJ-A07 appears, in our opinion, to be connected to an…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Impact on COVID-19 by Intravenous Bevacizumab Used for Hereditary Hemorrhagic Telangiectasia: A Case Report</strong> - Coronavirus disease 2019 (COVID-19) continues as an infectious pandemic. With emphasis on mitigating its impact globally, strategies have been emphasized on prevention to treatment in severe cases. As for pharmacotherapies, many have been researched, with a few being recommended for patients with COVID-19 depending upon their severity. Bevacizumab, a recombinant monoclonal antibody often used for oncological disease and rare genetic disorders, has gained attention in combatting COVID-19 due to…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of Clove Phytochemicals as Potential Antiviral Drug Candidates Targeting SARS-CoV-2 Main Protease: Computational Docking, Molecular Dynamics Simulation, and Pharmacokinetic Profiling</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can cause a sudden respiratory disease spreading with a high mortality rate arising with unknown mechanisms. Still, there is no proper treatment available to overcome the disease, which urges the research community and pharmaceutical industries to screen a novel therapeutic intervention to combat the current pandemic. This current study exploits the natural phytochemicals obtained from clove, a traditional natural therapeutic…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Potential inhibitors for blocking the interaction of the coronavirus SARS-CoV-2 spike protein and its host cell receptor ACE2</strong> - CONCLUSION: This platform is a rapid, sensitive, specific, and high throughput system, and available for screening large compound libraries. TS-984 is a potent blocker of the interaction between the S-protein and ACE2, which might have the potential to be developed into an effective anti-coronavirus drug.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Early administration of remdesivir plus convalescent plasma therapy is effective to treat COVID-19 pneumonia in B-cell depleted patients with hematological malignancies</strong> - Patients with hematological malignancies (HMs) are at a higher risk of developing severe form and protracted course of COVID-19 disease. We investigated whether the combination of viral replication inhibition with remdesivir and administration of anti-SARS-CoV-2 immunoglobulins with convalescent plasma (CP) therapy might be sufficient to treat B-cell-depleted patients with COVID-19. We enrolled 20 consecutive patients with various HMs with profound B-cell lymphopenia and COVID-19 pneumonia…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Multi-target mechanisms against coronaviruses of constituents from Chinese Dagang Tea revealed by experimental and docking studies</strong> - CONCLUSION: This study proposes E. chinensis and its triterpenoids and flavonoids as promising potential treatments for coronaviruses.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Allosteric inhibitors of the main protease of SARS-CoV-2</strong> - SARS-CoV-2 has raised the alarm to search for effective therapy for this virus. To date several vaccines have been approved but few available drugs reported recently still need approval from FDA. Remdesivir was approved for emergency use only. In this report, the SARS-CoV-2 3CLpro was expressed and purified. By using a FRET-based enzymatic assay, we have screened a library consisting of more than 300 different niclosamide derivatives and identified three molecules JMX0286, JMX0301, and JMX0941…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Crystal structure of the Rubella virus protease reveals a unique papain-like protease fold</strong> - Rubella, a viral disease characterized by a red skin rash, is well-controlled due to an effective vaccine, but outbreaks are still occurring in the absence of available antiviral treatments. The rubella virus (RUBV) papain-like protease (RubPro) is crucial for RUBV replication, cleaving the non-structural polyprotein p200 into two multi-functional proteins, p150 and p90. This protease could represent a potential drug target, but structural and mechanistic details important for the inhibition of…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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