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190 lines
51 KiB
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>11 September, 2023</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>High fusion and cytopathy of SARS-CoV-2 variant B.1.640.1</strong> -
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SARS-CoV-2 variants with undetermined properties have emerged intermittently throughout the COVID-19 pandemic. Some variants possess unique phenotypes and mutations which allow further characterization of viral evolution and spike functions. Around 1100 cases of the B.1.640.1 variant were reported in Africa and Europe between 2021 and 2022, before the expansion of Omicron. Here, we analyzed the biological properties of a B.1.640.1 isolate and its spike. Compared to the ancestral spike, B.1.640.1 carried 14 amino acid substitutions and deletions. B.1.640.1 escaped binding by some anti-NTD and -RBD monoclonal antibodies, and neutralization by sera from convalescent and vaccinated individuals. In cell lines, infection generated large syncytia and a high cytopathic effect. In primary airway cells, B.1.640.1 replicated less than Omicron BA.1 and triggered more syncytia and cell death than other variants. The B.1.640.1 spike was highly fusogenic when expressed alone. This was mediated by two poorly characterized and infrequent mutations located in the spike S2 domain, T859N and D936H. Altogether, our results highlight the cytopathy of a hyper-fusogenic SARS-CoV-2 variant, supplanted upon the emergence of Omicron BA.1.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.06.556548v1" target="_blank">High fusion and cytopathy of SARS-CoV-2 variant B.1.640.1</a>
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</div></li>
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<li><strong>Pre-dominance of dengue non-cross-reacting SARS-CoV-2 spike antibodies during the Omicron era and their role in the ADE-mediated surge of Dengue virus serotype 3</strong> -
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In India, the SARS-CoV-2 Delta wave (2020-21) gradually faded away with the advent of the Omicron variants (2021-present). Dengue incidences were observably less in Southeast Asia during the active years of the pandemic (2020-21). However, Dengue virus type 3 (DV3) cases were increasingly reported in India and many other dengue-endemic countries concurrent with the progression of the Omicron wave since 2022. This observation prompted us to investigate the current state of cross-reactivity between prevalent SARS-CoV-2 variants and different DV serotypes. Fifty-five COVID-19 serum samples (collected between January-September, 2022) and three pre-pandemic healthy serum samples were tested for DV or SARS-CoV-2 Immunoglobulin G/Immunoglobulin M (IgG/IgM) using the lateral flow immunoassays (LFIAs). The SARS-CoV-2 antibody (Ab)-positive samples were further tested for their ability to cross-neutralize DV types 1-4 (DV1-4) in Huh7 cell lines. Cross-reactivity between SARS-CoV-2 and DV diminished with the shift from Delta to Omicron prevalence. COVID-19 serum samples that were DV cross-reactive neutralized all DV serotypes, including DV3. However, Omicron wave serum samples were predominantly DV non-cross-reactive (about 70%) in LFIAs and coincided with the prevalence of BA.2 Omicron variant. They also cross-neutralized DV1, 2 and 4 but enhanced DV3 infectivity as evident from increased DV3 titres in virus neutralization test (VNT) compared to control serum samples. In conclusion, DV non-cross-reactive COVID-19 serum samples are becoming increasingly prominent in the present times. These non-cross-reactive serums could neutralize DV1, 2 and 4 but they are contributing to the surge in DV3 cases worldwide by means of ADE.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.08.23295136v1" target="_blank">Pre-dominance of dengue non-cross-reacting SARS-CoV-2 spike antibodies during the Omicron era and their role in the ADE-mediated surge of Dengue virus serotype 3</a>
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</div></li>
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<li><strong>Change in body weight of older adults before and during the COVID-19 pandemic: Longitudinal results from the Berlin Aging Study II</strong> -
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Background: Change in body weight during the COVID-19 pandemic as an unintended side effect of lockdown measures has been predominantly reported for younger and middle-aged adults. However, information on older adults for which weight loss is known to result in adverse outcomes, is scarce. Aims: Describe body weight change in older adults before, during, and after the COVID-19 lockdown measures and explore putative associated factors with a focus on the period that includes the first six months of the COVID-19 containment measures. Methods: In this study, we analyzed the longitudinal weight change of 472 participants of the Berlin Aging Study II (mean age of 67.5 years at baseline, average follow-up time 10 years). Additionally, differences between subgroups characterized by socio-economic, cognitive, and psychosocial variables as well as morbidity burden, biological age markers (epigenetic clocks, telomere length), and frailty were compared. Results: On average, women and men lost 0.87% (n=227) and 0.5% (n=245) of their body weight per year in the study period covering the first six months of the COVID-19 pandemic. Weight loss among men was particularly pronounced among groups characterized by change in physical activity due to COVID-19 lockdown, low positive affect, premature epigenetic age (7-CpG clock), diagnosed metabolic syndrome, and a more masculine gender score (all variables: p<0.05, n=245). Conclusions: Older participants lost weight with a 2.5-times (women) and 2-times (men) higher rate than what is expected in this age.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.08.23295246v1" target="_blank">Change in body weight of older adults before and during the COVID-19 pandemic: Longitudinal results from the Berlin Aging Study II</a>
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</div></li>
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<li><strong>Recognition and Cleavage of Human tRNA Methyltransferase TRMT1 by the SARS-CoV-2 Main Protease</strong> -
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The SARS-CoV-2 main protease (Mpro) plays a crucial role in the production of functional viral proteins during infection and, like many viral proteases, can also target and cleave host proteins to subvert their cellular functions. Here, we show that the human tRNA methyltransferase TRMT1 can be recognized and cleaved by SARS-CoV-2 Mpro. TRMT1 installs the N2,N2-dimethylguanosine (m2,2G) modification at the G26 position of mammalian tRNA, which promotes global protein synthesis, cellular redox homeostasis, and has links to neurological disability. We find that Mpro can cleave endogenous TRMT1 in human cell lysate, resulting in removal of the TRMT1 zinc finger domain that is required for tRNA modification activity in cells. Evolutionary analysis shows that the TRMT1 cleavage site is highly conserved in mammals, except in Muroidea, where TRMT1 may be resistant to cleavage. In primates, regions outside of the cleavage site with rapid evolution could indicate possible adaptation to ancient viral pathogens. To visualize how Mpro recognizes the TRMT1 cleavage sequence, we determined the structure of a TRMT1 peptide in complex with Mpro, which reveals a substrate binding conformation distinct from the majority of available SARS-CoV-2 Mpro-peptide complexes. Kinetic parameters for peptide cleavage showed that while TRMT1(526-536) is cleaved much slower than the Mpro nsp4/5 autoprocessing sequence, it is proteolyzed with comparable efficiency to the Mpro-targeted nsp8/9 viral cleavage site. Mutagenesis studies and molecular dynamics simulations together indicate that kinetic discrimination occurs during a later step of Mpro-mediated proteolysis that follows substrate binding. Our results provide new information about the structural basis for Mpro substrate recognition and cleavage that could help inform future therapeutic design and raise the possibility that proteolysis of human TRMT1 during SARS-CoV-2 infection may impact protein translation or oxidative stress response and contribute to viral pathogenesis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.20.529306v3" target="_blank">Recognition and Cleavage of Human tRNA Methyltransferase TRMT1 by the SARS-CoV-2 Main Protease</a>
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<li><strong>Partial Face Visibility and Facial Cognition: An Electroencephalography and Eye-Tracking Investigation</strong> -
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Face masks became a part of everyday life in the SARS-CoV-2 pandemic. Previous studies showed that the face cognition mechanism involves holistic face processing, and the absence of face features could lower cognition ability. This is opposed to the experience during the pandemic, when people were able to correctly recognize faces, although the mask covered a part of the face. This paper shows a strong correlation in face cognition based on the EEG and eye-tracking data between the full and partial faces. We observed two event-related potentials, P3a in the frontal lobe and P3b in the parietal lobe, as subcomponents of P300. Both P3a and P3b were lowered when the eyes were invisible, and P3a evoked by the nose covered was larger than the full face. The eye-tracking data showed that 16 out of 18 participants focused on the eyes associated with the EEG results. Our results demonstrate that the eyes are the most crucial feature of facial cognition. Moreover, the face with the nose covered might enhance cognition ability due to the visual working memory capacity. Our experiment shows the possibility of people recognizing faces using both holistic face processing and structural face processing. Furthermore, people can recognize the masked face as well as the full face in similar cognition patterns due to the high correlation in the cognition mechanism.
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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/10.1101/2023.09.07.556282v1" target="_blank">Partial Face Visibility and Facial Cognition: An Electroencephalography and Eye-Tracking Investigation</a>
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<li><strong>Prevalence and predictors of self-medication for COVID-19 among slum dwellers in Jinja City, Uganda</strong> -
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Introduction: Self-medication is a serious public health concern globally and is more prevalent in underserved populations, especially in resource limited settings. The lack of effective treatment for COVID-19 and poor access to healthcare were drivers of self-medication. We investigated the prevalence and associated factors with self-medication for COVID-19 among slum dwellers in a Ugandan slum. Methods and materials: We conducted a cross-sectional study using randomly selected respondents from slums in Jinja city, Uganda. Households were proportionately selected from the slums and one participant with confirmed or self-reported COVID-19 during 2021 was recruited. Poisson regression with robust standard errors was used to determine the crude (CPR) and adjusted prevalence ratios (APR) (95% CI) of factors associated with self-medication. Variables were selected apriori and backward elimination approach used to fit the final multivariate model in which variables with a P≤ 0.05 were included. Results: Overall, 517 respondents were recruited, median age (years) was 31 (26-40), and 59% were male. The prevalence of self-medication for COVID-19 was 87.23% (451/517), 95% CI: [84.00%-90.00%] and 56% knew that self-medication was dangerous. Age≥50 years, compared to 20-29 years [APR: 1.12, 95% CI:1.05, 1.20], being female [APR: 1.07, 95% CI: 1.02, 1.13], minor [APR: 1.62, 95% CI: 1.25, 2.11], and severe symptoms [APR: 1.51, 95% CI: 1.16, 1.96], access to internet [APR: 1.13, 95% CI: 1.07, 1.20]. Having medical insurance [APR: 0.63, 95% CI: 0.46, 0.87] and awareness about laws against self-medication [APR: 0.89, 95% CI: 0.81, 0.97] were associated with a lower risk of self-medication. Conclusion: The prevalence of self-medication in slum dwellers in Uganda was high despite high awareness about its dangers. Self-medication was common in those with severe symptoms and those access to internet. There is need to control infodemia and improve health insurance cover in informal settlements within Uganda.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.08.23295267v1" target="_blank">Prevalence and predictors of self-medication for COVID-19 among slum dwellers in Jinja City, Uganda</a>
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<li><strong>Evolution and neutralization escape of the SARS-CoV-2 BA.2.86 subvariant</strong> -
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Omicron BA.2.86 subvariant differs from Omicron BA.2 as well as recently circulating variants by over 30 mutations in the spike protein alone. Here we report on the first isolation of the live BA.2.86 subvariant from a diagnostic swab collected in South Africa which we tested for escape from neutralizing antibodies and viral replication properties in cell culture. BA.2.86 did not have significantly more escape than Omicron XBB.1.5 from neutralizing immunity elicited by infection of Omicron subvariants ranging from BA.1 to XBB, either by infection alone or as breakthrough infection in vaccinated individuals. Neutralization escape was present relative to earlier strains: BA.2.86 showed extensive escape both relative to ancestral virus in sera from pre-Omicron vaccinated individuals and relative to Omicron BA.1 in sera from Omicron BA.1 infected individuals. We did not observe substantial differences in viral properties in cell culture relative to XBB.1.5. Both BA.2.86 and XBB.1.5 produced infection foci of similar size, had similar cytopathic effect (both lower than ancestral SARS-CoV-2), and had similar replication dynamics. We also investigated the relationship of BA.2.86 to BA.2 sequences and found that the closest were BA.2 samples from Southern Africa circulating in early 2022. These observations suggest that BA.2.86 is more closely related to sequences from Southern Africa than other regions and so may have evolved there, and that evolution led to escape from neutralizing antibodies similar in scale to recently circulating strains of SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.08.23295250v1" target="_blank">Evolution and neutralization escape of the SARS-CoV-2 BA.2.86 subvariant</a>
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<li><strong>How immunity shapes the long-term dynamics of seasonal influenza</strong> -
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Since its emergence in 1968, influenza A H3N2 has caused yearly epidemics in temperate regions. While infection confers immunity against antigenically similar strains, new antigenically distinct strains that evade existing immunity regularly emerge (9antigenic drift9). Immunity at the individual level is complex, depending on an individual9s lifetime infection history. An individual9s first infection with influenza typically elicits the greatest response with subsequent infections eliciting progressively reduced responses (9antigenic seniority9). The combined effect of individual-level immune responses and antigenic drift on the epidemiological dynamics of influenza are not well understood. Here we develop an integrated modelling framework of influenza transmission, immunity, and antigenic drift to show how individual-level exposure, and the build-up of population level immunity, shape the long-term epidemiological dynamics of H3N2. Including antigenic seniority in the model, we observe that following an initial decline after the pandemic year, the average annual attack rate increases over the next 80 years, before reaching an equilibrium, with greater increases in older age-groups. Our analyses suggest that the average attack rate of H3N2 is still in a growth phase. Further increases, particularly in the elderly, may be expected in coming decades, driving an increase in healthcare demand due to H3N2 infections. We anticipate our findings and methodological developments will be applicable to other antigenically variable pathogens. This includes the recent pandemic pathogens influenza A H1N1pdm09, circulating since 2009, and SARS-CoV-2, circulating since 2019. Our findings highlight that following the short-term reduction in attack rates after a pandemic, if there is any degree of antigenic seniority then a resurgence in attack rates should be expected over the longer-term. Designing and implementing studies to assess the dynamics of immunity for H1N1pdm09, SARS-CoV-2, and other antigenically variable pathogens may help anticipate any long-term rises in infection and health burden.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.08.23295244v1" target="_blank">How immunity shapes the long-term dynamics of seasonal influenza</a>
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<li><strong>Disease trajectories in hospitalized COVID-19 patients are predicted by clinical and peripheral blood signatures representing distinct lung pathologies.</strong> -
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Linking clinical biomarkers and lung pathology still is necessary to understand COVID-19 pathogenesis and the basis of progression to lethal outcomes. Resolving these knowledge gaps enables optimal treatment approaches of severe COVID-19. We present an integrated analysis of longitudinal clinical parameters, blood biomarkers and lung pathology in COVID-19 patients from the Brazilian Amazon. We identified core signatures differentiating severe recovered patients and fatal cases with distinct disease trajectories. Progression to early death was characterized by rapid and intense endothelial and myeloid activation, presence of thrombi, mostly driven by SARS-CoV-2 + macrophages. Progression to late death was associated with systemic cytotoxicity, interferon and Th17 signatures and fibrosis, apoptosis, and abundant SARS-CoV-2 + epithelial cells in the lung. Progression to recovery was associated with pro-lymphogenic and Th2-mediated responses. Integration of antemortem clinical and blood biomarkers with post-mortem lung-specific signatures defined predictors of disease progression, identifying potential targets for more precise and effective treatments.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.08.23295024v1" target="_blank">Disease trajectories in hospitalized COVID-19 patients are predicted by clinical and peripheral blood signatures representing distinct lung pathologies.</a>
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<li><strong>SARS-CoV-2 ORF8 modulates lung inflammation and clinical disease progression</strong> -
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The virus severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, is the causative agent of the current COVID-19 pandemic. It possesses a large 30 kilobase (kb) genome that encodes structural, non-structural, and accessory proteins. Although not necessary to cause disease, these accessory proteins are known to influence viral replication and pathogenesis. Through the synthesis of novel infectious clones of SARS-CoV-2 that lack one or more of the accessory proteins of the virus, we have found that one of these accessory proteins, ORF8, is critical for the modulation of the host inflammatory response. Mice infected with a SARS-CoV-2 virus lacking ORF8 exhibit increased weight loss and exacerbated macrophage infiltration into the lungs. Additionally, infection of mice with recombinant SARS-CoV-2 viruses encoding ORF8 mutations found in variants of concern reveal that naturally occurring mutations in this protein influence disease severity. Our studies with a virus lacking this ORF8 protein and viruses possessing naturally occurring point mutations in this protein demonstrate that this protein impacts pathogenesis.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.09.08.556788v1" target="_blank">SARS-CoV-2 ORF8 modulates lung inflammation and clinical disease progression</a>
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<li><strong>Early combination with remdesivir, nirmatrelvir/ritonavir and sotrovimab for the treatment of COVID-19 in immunocompromised hosts</strong> -
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Background: Immunocompromised patients with COVID-19 have higher morbidity and mortality than general population. Some authors have successfully used antiviral combination, but never in the early phase of the infection. Methods: Retrospective cohort study to describe efficacy and safety of the combination of 2 antivirals, with or without a mAb, both in early (within 10 days from symptoms) and in later phase (after 10 days) of SARS-CoV-2 infection in immunocompromised patients admitted to our facility. Results: We treated 11 patients (7 in early phase and 4 in later phase of COVID-19) with 10 days of intravenous remdesivir plus 5 days of oral nirmatelvir/ritonavir, also combined with sotrovimab in 10/11 cases. Notably, 100% of the <early> patients reached virological clearance at day 30 from the end of the therapy and were alive and well at follow-up, whereas corresponding figures in the <late> patients were 50% and 75%. Patients in late group more frequently needed oxygen supplementation (p=0.015) and steroid therapy (p=0.045) during admission and reached higher a COVID-19 severity (p=0.017). Discussion: The combination of antiviral and sotrovimab in early phase of COVID-19 in immunocompromised patients is well tolerated and associated with 100% of virological clearance. Patients treated later have lower response rate and higher disease severity, but a causative role of the therapy in such finding is yet to be demonstrated.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.07.23295202v1" target="_blank">Early combination with remdesivir, nirmatrelvir/ritonavir and sotrovimab for the treatment of COVID-19 in immunocompromised hosts</a>
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<li><strong>Uncovering the implications of IFN-I in severe COVID-19 neutrophil inflammasome</strong> -
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Excessive inflammation defines COVID-19 pathophysiology. Neutrophils represent a critical arm of the innate immune response and are major mediators of inflammation. We conducted transcriptomic profiling of polymorphonuclear cells (PMNs), consisting mainly of mature neutrophils, which revealed a pronounced type I interferon (IFN-I) gene signature in severe COVID-19, compared to mild COVID-19 and healthy controls. Notably, low-density granulocytes (LDGs) from severe COVID-19 did not exhibit this signature and displayed a distinct immature neutrophil phenotype. PMNs from severe COVID-19 patients showed heightened nigericin-induced caspase1 activation but reduced responsiveness to exogenous inflammasome priming. Interestingly, while mature neutrophils efficiently released IL-1? upon inflammasome activation, they were poor producers of IL-18. Furthermore, IFN-I emerged as a priming stimulus for neutrophil inflammasomes, which was confirmed in a COVID-19 mouse model. Overall, these findings underscore the crucial role of neutrophil inflammasomes in driving inflammation during severe COVID-19 and opens promising avenues for targeted therapeutic interventions to mitigate the pathological processes associated with the disease.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.07.23295190v1" target="_blank">Uncovering the implications of IFN-I in severe COVID-19 neutrophil inflammasome</a>
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<li><strong>Comparison of Different PCR Methods for the Detection of SARS-CoV-2 RNA in Wastewater Based on the Reported Incidence of COVID-19 in Finland</strong> -
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The spatial and temporal changes of the COVID–19 pandemic have been monitored with wastewater–based surveillance, which many countries have applied to their national public health monitoring measures. The most commonly used methods for the detection of SARS–CoV–2 in wastewater are RT–qPCR and RT–ddPCR. Previous comparisons of the two methods have produced conflicting results; some found RT–ddPCR to be more sensitive, one found RT–qPCR to be more sensitive, and others found them to be equal in sensitivity. This research was conducted to further study these two methods as well as two different RNA extraction methodologies and gene assays for the detection of SARS–CoV–2 in wastewater. We compared two RT–qPCR kits and RT–ddPCR based on sensitivity, variability, and the correlation of SARS–CoV–2 gene copy numbers in wastewater with the incidence of COVID–19. Our results indicate that the most sensitive and low–variance method to detect SARS–CoV–2 in wastewater was RT–ddPCR. However, we obtained the best correlation between COVID-19 incidence and SARS–CoV–2 gene copy number in wastewater using RT–qPCR (CC = 0.697, p < 0.001). We found a significant difference in sensitivity between the two RT–qPCR kits, one having a significantly lower limit of detection and a higher percentage of positive samples than the other. Furthermore, the CDC N1 primers and probe were the most sensitive for both RT–qPCR kits, while there was no significant difference between the tested gene targets using RT–ddPCR. For the most sensitive RT–qPCR, the use of different RNA extraction kits affected the result. All methods showed a trend between COVID–19 incidence and SARS–CoV–2 gene copy numbers in wastewater. In addition, we tested an isothermal amplification method for the detection of SARS–CoV–2 RNA in wastewater. It proved to be a viable option if results are expected quickly, resources are limited, and presence–absence information is sufficient.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.07.23295183v1" target="_blank">Comparison of Different PCR Methods for the Detection of SARS-CoV-2 RNA in Wastewater Based on the Reported Incidence of COVID-19 in Finland</a>
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<li><strong>Effectiveness of BNT162b2 COVID-19 Vaccination in Children Aged 5–17 Years in the United States</strong> -
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Importance: COVID–19 vaccines are authorized for use in children in the United States; real–world assessment of vaccine effectiveness in children is needed. Objective: To estimate the effectiveness of receiving a complete primary series of monovalent BNT162b2 (Pfizer–BioNTech) COVID-19 vaccine in US children. Design: A cohort study of children aged 5—17 years vaccinated with BNT162b2 matched with unvaccinated children. Setting: Participants identified in Optum and CVS Health insurance administrative claims databases were linked with Immunization Information System (IIS) COVID-19 vaccination records from 16 US jurisdictions between December 11, 2020, and May 31, 2022 (end date varied by database and IIS). Participants: Vaccinated children were followed from their first BNT162b2 dose and matched to unvaccinated children on calendar date, US county of residence, and demographic and clinical factors. Censoring occurred if vaccinated children failed to receive a timely dose 2 or if unvaccinated children received any dose. Exposure: BNT162b2 vaccinations were identified using IIS vaccination records and insurance claims. Main Outcomes and Measures: Two COVID–19 outcome definitions were evaluated: COVID–19 diagnosis in any medical setting and COVID–19 diagnosis in hospitals/emergency departments (EDs). Propensity score–weighted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models, and vaccine effectiveness (VE) was estimated as 1 minus HR. VE was estimated overall, within age subgroups, and within variant–specific eras. Sensitivity, negative control, and quantitative bias analyses evaluated various potential biases. Results: There were 453,655 eligible vaccinated children one–to–one matched to unvaccinated comparators (mean age 12 years; 50% female). COVID-19 hospitalizations/ED visits were rare in children, regardless of vaccination status (Optum, 41.2 per 10,000 person– years; CVS Health, 44.1 per 10,000 person– years). Overall, vaccination was associated with reduced incidence of any medically diagnosed COVID–19 (meta–analyzed VE = 38% [95% CI, 36%–40%]) and hospital/ED–diagnosed COVID-19 (meta–analyzed VE = 61% [95% CI, 56%–65%]). VE estimates were lowest among children 5—11 years and during the omicron variant era. Conclusions and Relevance: Receipt of a complete BNT162b2 vaccine primary series was associated with overall reduced medically diagnosed COVID–19 and hospital/ED–diagnosed COVID–19 in children; observed VE estimates differed by age group and variant era.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.06.23294426v1" target="_blank">Effectiveness of BNT162b2 COVID-19 Vaccination in Children Aged 5–17 Years in the United States</a>
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<li><strong>Effect of the 2022 COVID-19 booster vaccination campaign in 50 year olds in England: regression discontinuity analysis in OpenSAFELY</strong> -
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Background: SARS-CoV-2 vaccines are highly effective in preventing severe COVID-19 but require boosting to maintain protection. Changes to circulating variants and prevalent natural immunity may impact on real-world effectiveness of boosters in different time periods and in different populations. Methods: With NHS England approval, we used linked routine clinical data from >24 million patients to evaluate the effectiveness of the 2022 combined COVID-19 autumn booster and influenza vaccine campaign in non-clinically vulnerable 50-year-olds in England using a regression discontinuity design. Our primary outcome was a composite of 6-week COVID-19 emergency attendance, COVID-19 unplanned hospitalisation, or death. The secondary outcomes were: respiratory hospitalisations or death; any unplanned hospitalisation; and any death. Results: Our study included 1,917,375 people aged 45-54 years with no evidence of being in a high-risk group prioritised for vaccination. By 26 November 2022, booster vaccine coverage was 11.1% at age 49.75 years increasing to 39.7% at age 50.25 years. The estimated effect of the campaign on the risk of the primary outcome in 50-year-olds during weeks 7-12 after the campaign start was -0.4 per 100,000 (95% CI -7.8, 7.1). For the secondary outcomes the estimated effects were: -0.6 per 100,000 (95%CI -13.5, 12.3) for respiratory outcomes; 5.0 per 100,000 (95%CI -40.7, 50.8) for unplanned hospitalisations; and 3.0 per 100,000 (95%CI -2.7, 8.6) for any death. The results were similar when using different follow-up start dates, different bandwidths, or when estimating the effect of vaccination (rather than the campaign). Conclusion: This study found little evidence that the autumn 2022 vaccination campaign in England was associated with a reduction in severe COVID-19-related outcomes among non-clinically vulnerable 50-year-olds. Possible explanations include the low risk of severe outcomes due to substantial pre-existing vaccine- and infection-induced immunity. Modest booster coverage reduced the precision with which we could estimate effectiveness. The booster campaign may have had effects beyond those estimated, including reducing virus transmission and incidence of mild or moderate COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.07.23295194v1" target="_blank">Effect of the 2022 COVID-19 booster vaccination campaign in 50 year olds in England: regression discontinuity analysis in OpenSAFELY</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>A 2nd Generation E1/E2B/E3-Deleted Adenoviral COVID-19 Vaccine: The TCELLVACCINE TRIAL</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: hAd5-S-Fusion+N-ETSD; Biological: Placebo (0.9% (w/v) saline)<br/><b>Sponsor</b>: ImmunityBio, Inc.<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>Aerobic Training for Rehabilitation of Patients With Post Covid-19 Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Long-COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: Aerobic Exercise Training<br/><b>Sponsors</b>: University of Witten/Herdecke; Institut für Rehabilitationsforschung Norderney<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>Additional Recombinant COVID-19 Humoral and Cell-Mediated Immunogenicity in Immunosuppressed Populations</strong> - <b>Conditions</b>: Immunosuppression; COVID-19<br/><b>Intervention</b>: Biological: NVX-CoV2372<br/><b>Sponsors</b>: University of Wisconsin, Madison; Novavax<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>Comparative Immunogenicity of Concomitant vs Sequential mRNA COVID-19 and Influenza Vaccinations</strong> - <b>Conditions</b>: Influenza; COVID-19; Influenza Immunogencity; COVID-19 Immunogenicity<br/><b>Interventions</b>: Biological: Simultaneous Vaccination (Influenza Vaccine and mRNA COVID booster); Biological: Sequential Vaccination (Influenza vaccine then mRNA COVID booster); Biological: Sequential Vaccination (mRNA COVID booster then Influenza vaccine)<br/><b>Sponsors</b>: Duke University; Centers for Disease Control and Prevention; Arizona State University; University Hospitals Cleveland Medical Center; University of Pittsburgh; Washington University School of Medicine; Valleywise Health; VA Northeast Ohio Health Care; Senders Pediatrics<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>Bronchoalveolar Lavage in Recovered From COVID-19 Pneumonia</strong> - <b>Condition</b>: Bronchoalveolar Lavage<br/><b>Intervention</b>: Procedure: Bronchoalveolar Lavage<br/><b>Sponsors</b>: Mohamed Abd Elmoniem Mohamed; Marwa Salah Abdelrazek Ghanem; Mohammad Khairy El-Badrawy; Tamer Ali Elhadidy; Dalia Abdellateif Abdelghany<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>Phase I Safety Study of B/HPIV3/S-6P Vaccine Via Nasal Spray in Adults</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Intervention</b>: Biological: B/HPIV3/S-6P<br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID); Johns Hopkins Bloomberg School of Public Health; National Institutes of Health (NIH)<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>Effects of Cognitive-behavioral Therapy for Insomnia in Nurses With Post Covid-19 Condition</strong> - <b>Condition</b>: Cognitive Behavioral Therapy<br/><b>Intervention</b>: Behavioral: cognitive behavioral therapy<br/><b>Sponsor</b>: Tri-Service General Hospital<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>The Effectiveness of Natural Resources for Reducing Stress</strong> - <b>Conditions</b>: Distress, Emotional; COVID-19<br/><b>Interventions</b>: Combination Product: Balneotherapy plus complex; Combination Product: Combined nature resources treatment; Other: Nature therapy procedure<br/><b>Sponsors</b>: Klaipėda University; Research Council of Lithuania<br/><b>Active, not 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>Pre-probiotic Supplementation for Post-covid Fatigue Syndrome</strong> - <b>Condition</b>: Long COVID<br/><b>Interventions</b>: Dietary Supplement: Dietary Supplement: Experimental; Dietary Supplement: Dietary Supplement: Placebo<br/><b>Sponsor</b>: University of Novi Sad, Faculty of Sport and Physical Education<br/><b>Active, not 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>Long COVID Immune Profiling</strong> - <b>Conditions</b>: Long COVID; POTS - Postural Orthostatic Tachycardia Syndrome; Autonomic Dysfunction<br/><b>Interventions</b>: Diagnostic Test: IL-6; Diagnostic Test: cytokines (IL-17, and IFN-ɣ); Behavioral: Compass 31<br/><b>Sponsors</b>: Vanderbilt University Medical Center; American Heart Association<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 of Healthy Microbiome, Healthy Mind</strong> - <b>Conditions</b>: Critical Illness; COVID-19; PICS; Cognitive Impairment; Mental Health Impairment; Weakness, Muscle; Dysbiosis<br/><b>Intervention</b>: Behavioral: Fermented Food Diet<br/><b>Sponsor</b>: Mayo Clinic<br/><b>Not yet recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</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>Efficacy and safety evaluation of Azvudine in the prospective treatment of COVID-19 based on four phase III clinical trials</strong> - Azvudine (FNC) is a synthetic nucleoside analog used to treat adult patients living with human immunodeficiency virus-1 (HIV-1) infection with high viral load. After phosphorylation, Azvudine inhibits RNA-dependent RNA polymerase, leading to the discontinuation of RNA chain synthesis in viruses. In addition, Azvudine is the first dual-target nucleoside oral drug worldwide to simultaneously target reverse transcriptase and viral infectivity factors in the treatment of HIV infection. On 9 August…</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>Altered DNA methylation underlies monocyte dysregulation and innate exhaustion memory in sepsis</strong> - Innate immune memory is the process by which pathogen exposure elicits cell-intrinsic states to alter the strength of future immune challenges. Such altered memory states drive monocyte dysregulation during sepsis, promoting pathogenic behavior characterized by pro-inflammatory, immunosuppressive gene expression in concert with emergency hematopoiesis. Epigenetic changes, notably in the form of histone modifications, have been shown to underlie innate immune memory, but the contribution of DNA…</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>In Vivo Antiviral Efficacy of LCTG-002, a Pooled, Purified Human Milk Secretory IgA product, Against SARS-CoV-2 in a Murine Model of COVID-19</strong> - Immunoglobulin A (IgA) is the most abundant antibody (Ab) in human mucosal compartments including the respiratory tract, with the secretory form of IgA (sIgA) being dominant and uniquely stable in these environments. sIgA is naturally found in human milk, which could be considered a global resource for this biologic, justifying the development of human milk sIgA as a dedicated airway therapeutic for respiratory infections such as SARS-CoV-2. In the present study, methods were therefore developed…</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>Cationic Chitosan Derivatives for the Inactivation of HIV-1 and SARS-CoV-2 Enveloped Viruses</strong> - Cationic chitosan derivatives have been widely studied as potential antimicrobial agents. However, very little is known about their antiviral activity and mode of action against enveloped viruses. We investigated the ability of hydroxypropanoic acid-grafted chitosan (HPA-CS) and N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) to inactivate enveloped viruses like the human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The…</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>Preventive treatment of coronavirus disease-2019 virus using coronavirus disease-2019-receptor-binding domain 1C aptamer by suppress the expression of angiotensin-converting enzyme 2 receptor</strong> - The cause of the worldwide coronavirus disease-2019 (COVID-19) pandemic is the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is known to employ the same entry portal as SARS-CoV, which is the type 1 transmembrane angiotensin-converting enzyme 2 (ACE2) receptor. The receptor-binding domain (RBD) is located on the spike S-protein’s S1 subunit of the spike glycoprotein. The most important and effective therapy method is inhibiting the interaction between the ACE2 receptor and the…</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>Natural PAK1 inhibitors: potent anti-inflammatory effectors for prevention of pulmonary fibrosis in COVID-19 therapy</strong> - One of the main efforts of scientists to study drug development is the discovery of novel antiviral agents that could be beneficial in the struggle against viruses that cause diseases in humans. Natural products are complex metabolites that are designed and synthesised by different sources in an attempt to optimise nature. Recently, natural products are still a source of biologically active molecules, facilitating drug discovery. A p21-activating kinase PAK1 is a key regulator of cytoskeletal…</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>Nirmatrelvir/ritonavir-induced elevation of blood tacrolimus levels in a patient in the maintenance phase post liver transplantation</strong> - Nirmatrelvir is an orally administered anti-SARS-CoV-2 drug used in combination with ritonavir, the drug-metabolizing cytochrome P450 (CYP) 3A inhibitor, to evade metabolism and extend bioavailability. Meanwhile, the immunosuppressant tacrolimus is a CYP3A4/5 substrate, and CYP3A inhibition results in drug-drug interactions. Herein, we report the case of a coronavirus disease 19 (COVID-19) patient in the maintenance phase post liver transplantation, receiving tacrolimus treatment, with a marked…</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>Comparison of Zinc Oxide Nanoparticle Integration into Non-Woven Fabrics Using Different Functionalisation Methods for Prospective Application as Active Facemasks</strong> - The development of advanced facemasks stands out as a paramount priority in enhancing healthcare preparedness. In this work, different polypropylene non-woven fabrics (NWF) were characterised regarding their structural, physicochemical and comfort-related properties. The selected NWF for the intermediate layer was functionalised with zinc oxide nanoparticles (ZnO NPs) 0.3 and 1.2wt% using three different methods: electrospinning, dip-pad-dry and exhaustion. After the confirmation of ZnO NP…</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>Membrane-Targeting Perylenylethynylphenols Inactivate Medically Important Coronaviruses via the Singlet Oxygen Photogeneration Mechanism</strong> - Perylenylethynyl derivatives have been recognized as broad-spectrum antivirals that target the lipid envelope of enveloped viruses. In this study, we present novel perylenylethynylphenols that exhibit nanomolar or submicromolar antiviral activity against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and feline infectious peritonitis virus (FIPV) in vitro. Perylenylethynylphenols incorporate into viral and cellular membranes and block the entry of the virus into the host cell….</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>Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients?</strong> - Human neutrophil elastase (HNE) is involved in SARS-CoV-2 virulence and plays a pivotal role in lung infection of patients infected by COVID-19. In healthy individuals, HNE activity is balanced by α1-antitrypsin (AAT). This is a 52 kDa glycoprotein, mainly produced and secreted by hepatocytes, that specifically inhibits HNE by blocking its activity through the formation of a stable complex (HNE-AAT) in which the two proteins are covalently bound. The lack of this complex, together with the…</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>Small Molecules Targeting Viral RNA</strong> - The majority of antivirals available target viral proteins; however, RNA is emerging as a new and promising antiviral target due to the presence of highly structured RNA in viral genomes fundamental for their replication cycle. Here, we discuss methods for the identification of RNA-targeting compounds, starting from the determination of RNA structures either from purified RNA or in living cells, followed by in silico screening on RNA and phenotypic assays to evaluate viral inhibition. Moreover,…</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>Screening, Synthesis and Biochemical Characterization of SARS-CoV-2 Protease Inhibitors</strong> - The severe acute respiratory syndrome-causing coronavirus 2 (SARS-CoV-2) papain-like protease (PL^(pro)) and main protease (M^(pro)) play an important role in viral replication events and are important targets for anti-coronavirus drug discovery. In search of these protease inhibitors, we screened a library of 1300 compounds using a fluorescence thermal shift assay (FTSA) and identified 53 hits that thermally stabilized or destabilized PL^(pro). The hit compounds structurally belonged to two…</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 Influence of KE and EW Dipeptides in the Composition of the Thymalin Drug on Gene Expression and Protein Synthesis Involved in the Pathogenesis of COVID-19</strong> - Thymalin is an immunomodulatory drug containing a polypeptide extract of thymus that has demonstrated efficacy in the therapy of acute respiratory distress syndrome and chronic obstructive pulmonary disease, as well as in complex therapy related to severe COVID-19 in middle-aged and elderly patients.. KE and EW dipeptides are active substances of Thymalin. There is evidence that KE stimulates cellular immunity and nonspecific resistance in organisms, exerting an activating effect on macrophages,…</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>Differential Type-I Interferon Response in Buffy Coat Transcriptome of Individuals Infected with SARS-CoV-2 Gamma and Delta Variants</strong> - The innate immune system is the first line of defense against pathogens such as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The type I-interferon (IFN) response activation during the initial steps of infection is essential to prevent viral replication and tissue damage. SARS-CoV and SARS-CoV-2 can inhibit this activation, and individuals with a dysregulated IFN-I response are more likely to develop severe disease. Several mutations in different variants of SARS-CoV-2 have shown…</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>Nano-Enabled Antivirals for Overcoming Antibody Escaped Mutations Based SARS-CoV-2 Waves</strong> - This review discusses receptor-binding domain (RBD) mutations related to the emergence of various SARS-CoV-2 variants, which have been highlighted as a major cause of repetitive clinical waves of COVID-19. Our perusal of the literature reveals that most variants were able to escape neutralizing antibodies developed after immunization or natural exposure, pointing to the need for a sustainable technological solution to overcome this crisis. This review, therefore, focuses on nanotechnology and…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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