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<title>05 January, 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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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>COVID-19 Deaths are Not Consequences of Infection and the Chinese are Not their Harbinger</strong> -
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<div>
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The fears of the world’s people ought to be immediately allayed with the results obtained by visualizing the reality in which COVID-19 deaths occur in the process of constructing immunological concepts which have eluded us since the birth of the repeatedly proven germ theory. These results reveal that the event from which COVID-19 deaths emerge is not one in which a COVID-19 alone is brought about by the coronavirus but rather one in which pathological mechanisms bring about different diseases that co-manifest to bring about the severe outcomes that cause such deaths ONLY when the causes of such diseases are ALL present at a time of the occurrence of the COVID-19 event. They also reveal that the immunological mechanisms that protect us from the severe outcomes of COVID-19 events that cause such deaths, are not those of coronavirus elimination as we have assumed but rather of as uneventful exposure to all the causes of such different diseases that co-manifest for the emergence of such outcomes. These results constitute the “Spectral theory of COVID-19 events” in which the germ theory’s description of the coronavirus as the cause of the outcomes of this event lives on as a limiting case. After all, this coronavirus is the cause of uneventful outcomes that do not call attention to the presence of this coronavirus which occur in the absence of the causes of other disease in the COVID-19 spectrum which must co-manifest with COVID-19 for the emergence of such severe outcomes that called our attention to the presence of this pathogen in Wuhan where it appeared new to us because humanity’s attention had never been called to it since viruses became detectable. The path to the solution to the problem constituted by COVID-19 deaths therefore lies does not lie in branding the variants of the coronavirus in China as the source of such deaths but rather in recognizing the following consequence of these results of reality visualization which has found representation in reality. This consequence is that the severe outcomes of the COVID-19 event did not cause deaths in some of those who were exposed to all of such causes of the diseases in the COVID-19 spectrum which include even those that co-manifest for the emergence of outcomes that include hematological malignancies even in the uninfected, when those conditions that permit immunological mechanisms to bring about uneventful exposure to such causes appeared and remission was observed in such COVID-19 patients in spite of the absence of treatments that are capable of bringing about the same result. The solution to the problem constituted by COVID-19 deaths therefore lies in answering the question that this consequence of the empirical results we have obtained with the Einsteinian method of reality visualization begs. What brings about uneventful exposure to the causes of such different diseases in the COVID-19 spectrum that co-manifested for the appearance of hematological malignancies even before our attention was called to the coronavirus by the severe outcomes of this event at the end of 2019? The answer to this question ought to be our topmost priority now.
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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/36vnm/" target="_blank">COVID-19 Deaths are Not Consequences of Infection and the Chinese are Not their Harbinger</a>
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</div></li>
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<li><strong>Decoding the fundamental drivers of phylodynamic inference</strong> -
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<div>
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Despite its increasing role in the understanding of infectious disease transmission at the applied and theoretical levels, phylodynamics lacks a well-defined notion of ideal data and optimal sampling. We introduce a formal method to visualise and quantify the relative impact of pathogen genome sequence and sampling times—two fundamental sources of data for phylodynamics under birth-death-sampling models—to understand how each drive phylodynamic inference. Applying our method to simulations and outbreaks of SARS-CoV-2 and H1N1 Influenza data, we use this insight to elucidate fundamental trade-offs and guidelines for phylodynamic analyses to draw the most from sequence data. Phylodynamics promises to be a staple of future responses to infectious disease threats globally. Continuing research into the inherent requirements and trade-offs of phylodynamic data and inference will help ensure phylodynamic tools are wielded in ever more targeted and efficient ways.
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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/10.1101/2022.06.07.495205v2" target="_blank">Decoding the fundamental drivers of phylodynamic inference</a>
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</div></li>
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<li><strong>In vivo activity of Sotrovimab against BQ.1.1 Omicron sublineage</strong> -
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<div>
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The successive emergence of SARS-CoV-2 Omicron variants has completely changed the modalities of use of therapeutic monoclonal antibodies. Recent in vitro studies indicated that only Sotrovimab has maintained partial activity against BQ.1.1, a sub-variant of BA.5 that is spreading in the USA and Europe. In the present study, we used the hamster model to determine whether Sotrovimab retains antiviral activity against BQ.1.1 in vivo. Our results show that at exposures consistent with those observed in humans, Sotrovimab remains active against BQ.1.1 variant, although at a lower level than that observed against the first globally dominant BA.1 and BA.2 Omicron sublineages.
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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/10.1101/2023.01.04.522629v1" target="_blank">In vivo activity of Sotrovimab against BQ.1.1 Omicron sublineage</a>
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</div></li>
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<li><strong>HPC-Atlas: Computationally Constructing A Comprehensive Atlas of Human Protein Complexes</strong> -
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<div>
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A fundamental principle of biology is that proteins tend to form complexes to play significant roles in the core functions of cells. For a complete understanding of human cellular functions, we require a comprehensive atlas of human protein complexes. Unfortunately, we still lack such a comprehensive atlas of experimentally validated protein complexes, which prevents us from gaining a complete understanding of the compositions and functions of human protein complexes and biological mechanisms. To fill this gap, we built HPC-Atlas, as far as we know, the most accurate and comprehensive atlas of human protein complexes available to date. We integrated two latest protein interaction networks, and developed a novel computational method to identify nearly 9000 protein complexes, including many previously uncharacterized complexes. Compared with the existing works, our method achieves outstanding performance on both test and independent sets. Furthermore, with HPC-Atlas we also identified 751 SARS-CoV-2 affected human protein complexes, and 456 multifunctional proteins that contain many potential moonlighting proteins. These results suggest that HPC-Atlas can serve as not only a computing framework to effectively integrate new protein data sources for identifying biologically meaningful protein complexes, but also a valuable resource for exploring new biological findings. The HPC-Atlas webserver is freely available at http://www.yulpan.top/HPC-Atlas.
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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/10.1101/2023.01.03.522554v1" target="_blank">HPC-Atlas: Computationally Constructing A Comprehensive Atlas of Human Protein Complexes</a>
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</div></li>
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<li><strong>Bioinformatics Approaches to Determine the Effect of SARS-CoV-2 Infection on Patients with Intrahepatic Cholangiocarcinoma</strong> -
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<div>
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19), has infected millions of individuals throughout the world, which poses a serious threat to human health. COVID-19 is a systemic disease that affects tissues and organs, including the lung and liver. Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common liver cancer, and cancer patients are particularly at high risk of SARS-CoV-2 infection. The relationship between HCC and COVID-19 has been reported in previous studies, but ICC has been rare. With the methods of systems biology and bioinformatics, this study explored the link between COVID-19 and ICC. Transcriptional profiling of COVID-19 and ICC were obtained from the GEO database. A total of 70 common differentially expressed gene (DEGs) of both diseases were identified to investigate shared pathways. Then top-ranked 10 key DEGs (SCD, ACSL5, ACAT2, HSD17B4, ALDOA, ACSS1, ACADSB, CYP51A1, PSAT1, and HKDC1) were identified as hub genes by protein-protein interaction (PPI) network analysis. In addition, transcriptional regulatory networks regulating hub genes were revealed by hub Gene- transcription factor (TF) interaction analysis and hub gene-microRNA (miRNAs) interaction analysis. This study is expected to provide new references for future research and treatment of COVID-19 and ICC.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.04.522709v1" target="_blank">Bioinformatics Approaches to Determine the Effect of SARS-CoV-2 Infection on Patients with Intrahepatic Cholangiocarcinoma</a>
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</div></li>
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<li><strong>The prospect of universal coronavirus immunity: a characterization of reciprocal and non-reciprocal T cell responses against SARS-CoV2 and common human coronaviruses</strong> -
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<div>
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T cell immunity plays a central role in clinical outcomes of Coronavirus Infectious Disease 2019 (COVID-19). Therefore, T cell-focused vaccination or cellular immunotherapy might provide enhanced protection for immunocompromised patients. Pre-existing T cell memory recognizing SARS-CoV2 antigens antedating COVID-19 infection or vaccination, may have developed as an imprint of prior infections with endemic non-SARS human coronaviruses (hCoVs) OC43, HKU1, 229E, NL63, pathogens of common cold. In turn, SARS-CoV2-primed T cells may recognize emerging variants or other hCoV viruses and modulate the course of subsequent hCoV infections. Cross-immunity between hCoVs and SARS-CoV2 has not been well characterized. Here, we systematically investigated T cell responses against the immunodominant SARS-CoV2 spike, nucleocapsid and membrane proteins and corresponding antigens from alpha and beta hCoVs among vaccinated, convalescent, and unexposed subjects. Broad T cell immunity against all tested SARS-CoV2 antigens emerged in COVID-19 survivors. In convalescent and in vaccinated individuals, SARS-CoV2 spike-specific T cells reliably recognized most SARS-CoV2 variants, however cross-reactivity against the omicron variant was reduced by approximately 50%. Responses against spike, nucleocapsid and membrane antigens from endemic hCoVs were more extensive in COVID-19 survivors than in unexposed subjects and displayed cross-reactivity between alpha and beta hCoVs. In some, non-SARS hCoV-specific T cells demonstrated a prominent non-reciprocal cross-reactivity with SARS-CoV2 antigens, whereas a distinct anti-SARS-CoV2 immunological repertoire emerged post-COVID-19, with relatively limited cross-recognition of non-SARS hCoVs. Based on this cross-reactivity pattern, we established a strategy for in-vitro expansion of universal anti-hCoV T cells for adoptive immunotherapy. Overall, these results have implications for the future design of universal vaccines and cell-based immune therapies against SARS- and non-SARS-CoVs.
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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/10.1101/2023.01.03.519511v1" target="_blank">The prospect of universal coronavirus immunity: a characterization of reciprocal and non-reciprocal T cell responses against SARS-CoV2 and common human coronaviruses</a>
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<li><strong>Assessment of Immunogenicity and Efficacy of CV0501 mRNA-based Omicron COVID-19 Vaccination in Small Animal Models</strong> -
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<div>
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron and its subvariants (BA.2, BA.4, BA.5) represent the most commonly circulating variants of concern (VOC) in the coronavirus disease 2019 (COVID-19) pandemic in 2022. Despite high vaccination rates with approved SARS-CoV-2 vaccines encoding the ancestral spike (S) protein, these Omicron subvariants have collectively resulted in increased viral transmission and disease incidence. This necessitates the development and characterization of vaccines incorporating later emerging S proteins to enhance protection against VOC. In this context, bivalent vaccine formulations may induce broad protection against VOC and potential future SARS CoV 2 variants. Here, we report preclinical data for a lipid nanoparticle (LNP) formulated RNActive N1-methylpseudouridine (N1m{Psi}) modified mRNA vaccine (CV0501) based on our second-generation SARS-CoV-2 vaccine CV2CoV, encoding the S protein of Omicron BA.1. The immunogenicity of CV0501, alone or in combination with a corresponding vaccine encoding the ancestral S protein (ancestral N1m{Psi}), was first measured in dose-response and booster immunization studies performed in Wistar rats. Both monovalent CV0501 and bivalent CV0501/ancestral N1m{Psi} immunization induced robust neutralizing antibody titers against the BA.1, BA.2 and BA.5 Omicron subvariants, in addition to other SARS-CoV-2 variants in a booster immunization study. The protective efficacy of monovalent CV0501 against live SARS-CoV-2 BA.2 infection was then assessed in hamsters. Monovalent CV0501 significantly reduced SARS CoV 2 BA.2 viral loads in the airways, demonstrating protection induced by CV0501 vaccination. CV0501 has now advanced into human Phase 1 clinical trials (ClinicalTrials.gov Identifier: NCT05477186).
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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/10.1101/2023.01.04.521629v1" target="_blank">Assessment of Immunogenicity and Efficacy of CV0501 mRNA-based Omicron COVID-19 Vaccination in Small Animal Models</a>
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<li><strong>Safety and Effectiveness of SA58 Nasal Spray against COVID-19 Infection in Medical Personnel： An Open-label, Blank-controlled Study</strong> -
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Approved COVID-19 vaccines to date have limited effectiveness in protecting infection and blocking transmission. A nasal spray of broad-spectrum antibody against COVID-19 (SA58 Nasal Spray) has recently been developed by Sinovac Life Sciences Co., Ltd.. From October 31 to November 30, 2022, an open-label, blank controlled study on the SA58 Nasal Spray against COVID-19 infection was conducted with the medical personnel working in the designated COVID-19 hospitals and Fangcang shelter hospitals (alternate care sites) of COVID-19 cases in Hohhot city, the Inner Mongolia Autonomous Region. A total of 6662 medical personnel were involved in this study: 3368 used SA58 Nasal Spray from the drug group, and 3294 not used from blank control group. The medication was self-administered intranasally 1~2 times per day with an interval of 6 hours for 30 days.. The safety results indicated that the SA58 Nasal Spray was well tolerant. The incidence of adverse events (AEs) was 28.6% (497/1736), and the majority of the AEs were mild and from administrative site. 135 COVID-19 cases were identified for SARS-CoV-2 by RT-PCR during the 30-day observation. The cumulative incidence of COVID-19 in the drug group and the control group were 0.026% and 0.116%, respectively. The effectiveness of the SA58 Nasal Spray for preventing COVID-19 infection among medical personnel was evaluated as 77.7% (95% CI: 52.2% - 89.6%). In conclusion, the SA58 Nasal Spray is well-tolerant and highly effective against COVID-19 infection.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.27.22283698v2" target="_blank">Safety and Effectiveness of SA58 Nasal Spray against COVID-19 Infection in Medical Personnel： An Open-label, Blank-controlled Study</a>
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<li><strong>Spatiotemporal trends in self-reported mask-wearing behavior in the United States: Analysis of a large cross-sectional survey</strong> -
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Background: Face mask-wearing has been identified as an effective strategy to prevent transmission of SARS-CoV-2, yet mask mandates were never imposed nationally in the United States. This decision resulted in a patchwork of local policies and varying compliance potentially generating heterogeneities in the local trajectories of COVID-19 in the U.S. While numerous studies have investigated patterns and predictors of masking behavior nationally, most suffer from survey biases and none have been able to characterize mask-wearing at fine spatial scales across the U.S. through different phases of the pandemic. Objective: Urgently needed is a debiased spatiotemporal characterization of mask-wearing behavior in the U.S. This information is critical to further assess the effectiveness of masking, evaluate drivers of transmission at different time points during the pandemic, and guide future public health decisions through, for example, forecasting disease surges. Methods: We analyze spatiotemporal masking patterns in over eight million behavioral survey responses from across the United States starting in September 2020 through May 2021. We adjust for sample size and representation using binomial regression models and survey raking, respectively, to produce county-level monthly estimates of masking behavior. We additionally debias self-reported masking estimates using bias measures derived by comparing vaccination data from the same survey to official records at the county-level. Lastly, we evaluate whether individuals9 perceptions of their social environment can serve as a less biased form of behavioral surveillance than self-reported data. Results: We find that county-level masking behavior is spatially heterogeneous along an urban-rural gradient, with mask-wearing peaking in winter 2021 and declining sharply through May 2021. Our results identify regions where targeted public health efforts could have been most effective and suggest that individuals9 frequency of mask-wearing may be influenced by national guidance and disease prevalence. We validate our bias-correction approach by comparing debiased self-reported mask-wearing estimates with community-reported estimates, after addressing issues of small sample size and representation. Self-reported behavior estimates are especially prone to social desirability and non-response biases and our findings demonstrate that these biases can be reduced if individuals are asked to report on community rather than self behaviors. Conclusions: Our work highlights the importance of characterizing public health behaviors at fine spatiotemporal scales to capture heterogeneities that may drive outbreak trajectories. Our findings also emphasize the need for a standardized approach to incorporating behavioral big data into public health response efforts. Even large surveys are prone to bias; thus, we advocate for a social sensing approach to behavioral surveillance to enable more accurate estimates of health behaviors. Finally, we invite the public health and behavioral research communities to use our publicly available estimates to consider how bias-corrected behavioral estimates may improve our understanding of protective behaviors during crises and their impact on disease dynamics.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.19.22277821v2" target="_blank">Spatiotemporal trends in self-reported mask-wearing behavior in the United States: Analysis of a large cross-sectional survey</a>
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<li><strong>Correcting the Reproduction Number for Time-Varying Tests: a Proposal and an Application to COVID-19 in France</strong> -
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We provide a novel way to correct the effective reproduction number for the time-varying amount of tests, using the acceleration index (Baunez et al., 2021) as a simple measure of viral spread dynamics. Not correcting results in the reproduction number being a biased estimate of viral acceleration and we provide a formal decomposition of the resulting bias, involving the useful notions of test and infectivity intensities. When applied to French data for the COVID-19 pandemic (May 13, 2020 - October 26, 2022), our decomposition shows that the reproduction number, when considered alone, characteristically underestimates the resurgence of the pandemic, compared to the acceleration index which accounts for the time-varying volume of tests. Because the acceleration index aggregates all relevant information and captures in real time the sizable time variation featured by viral circulation, it is a more parsimonious indicator to track the dynamics of an infectious disease outbreak in real time, compared to the equivalent alternative which would combine the reproduction number with the test and infectivity intensities.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.12.01.20241570v5" target="_blank">Correcting the Reproduction Number for Time-Varying Tests: a Proposal and an Application to COVID-19 in France</a>
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<li><strong>Psychological distress during the coronavirus pandemic: A population-representative study</strong> -
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The COVID-19 pandemic is major stressor for the general population. Little is known on the sociodemographic predictors of psychological distress during this crisis. Using the CoRonavIruSHealth Impact Survey (CRISIS), psychological distress (PD) was analyzed in a population-representative cohort of 29,986 participants across Germany comparing June 2020 with three months before the pandemic. Responses of participants demonstrated an overall stark increase of PD. PD was independently predicted by young age, female gender/motherhood, higher education and residency in West-Germany with highest risk in the two largest cities of the country. Findings are discussed in the context of stress burden and stress resilience.
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🖺 Full Text HTML: <a href="https://osf.io/rvgcs/" target="_blank">Psychological distress during the coronavirus pandemic: A population-representative study</a>
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<li><strong>Early risk-assessment of pathogen genomic variants emergence</strong> -
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Accurate, reliable, and timely estimates of pathogen variant risk are essential for informing effective public health responses to infectious diseases. Despite decades of use for influenza vaccine strain selection and PCR-based molecular diagnostics, data on pathogen variant prevalence and growth advantage has only risen to its current prominence during the SARS-CoV-2 pandemic. However, such data are still often sparse: novel variants are initially rare or a region has limited sequencing. To ensure real-time estimates of risk are available in these types of data-sparse conditions, we develop a hierarchical modeling approach that estimates variant fitness advantage and prevalence by pooling data across geographic regions. We apply this method to estimate SARS-CoV-2 variant dynamics at the country-level and assess its stability with retrospective validation. Our results show that more stable and robust estimates can be obtained even when sequencing data are sparse, as compared to established, single-country estimation approaches. We discuss how this method can inform risk assessment of novel emerging variants and provide situational awareness on currently circulating variants, for a range of pathogens and use-cases.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.02.23284123v1" target="_blank">Early risk-assessment of pathogen genomic variants emergence</a>
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<li><strong>The impact of the COVID-19 pandemic on health related quality of life in head and neck cancer survivors: an observational cohort study</strong> -
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<b>Background:</b> Physical, psychological, and social aspects of health-related quality of life (HRQOL) among head and neck cancer (HNC) survivors may be more affected during the COVID-19 pandemic than before the pandemic. However, the impact is not yet understood well.<br /><b>Methods:</b> Prospectively collected data from the NETherlands QUality of life and BIomedical Cohort study in HNC were used. All patients were diagnosed and treated before the COVID-19 pandemic. Patient reported outcome measures (PROMs) collected 24 and 36 months after treatment (M24 and M36) were compared between survivors who completed both assessments before the COVID-19 pandemic and those who completed M24 before but M36 during the pandemic. Personal, clinical, physical, psychological, social, and lifestyle characteristics of the survivors assessed at baseline or M24 were investigated as potential effect modifiers.<br /><b>Results:</b> In total, 318 HNC survivors were included, of which 199 completed both M24 and M36 before the COVID-19 pandemic and 119 completed M24 before but M36 during the pandemic. Changes in HRQOL between 24 and 36 months follow-up did not differ between the two groups for any of the PROMs. However, in some subgroups of HNC survivors the COVID-19 pandemic negatively affected the course of HRQOL for several PROMs while it positively affected the course of HRQOL for other PROMs.<br /><b>Conclusions:</b> The COVID-19 pandemic did not affect HRQOL in HNC survivors in general, but some subgroups were affected in a positive and others in a negative way.<br /><b>Funding:</b> This work was supported by the Dutch Cancer Society [grant number VU 2013–5930] and the Dutch Cancer Society, Alpe Young Investigator Grant [grant number 12820].
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.03.23284145v1" target="_blank">The impact of the COVID-19 pandemic on health related quality of life in head and neck cancer survivors: an observational cohort study</a>
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<li><strong>A CLOSER LOOK AT INDIRECT CAUSES OF DEATH AFTER HURRICANE MARIA USING A SEMIPARAMETRIC MODEL</strong> -
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The Covid-19 pandemic as well as other recent natural emergencies have put the spotlight on emergency planning. One important aspect is that natural disasters or emergencies often lead to indirect deaths and studying the behavior of indirect deaths during emergencies can guide emergency planning. While many studies have implied a large number of indirect deaths in Puerto Rico due to Hurricane Maria; the specific causes of these deaths have not being carefully studied. In this paper, we use a semiparametric model and mortality data to evaluate cause of death trends. Our model adjusts for cause of death effect potentially varying over time while also inferring on how long excess deaths occurred. From September 2017 to March 2018, after adjusting for intra-annual variability and population displacement, we find evidence of significant excess deaths due to Alzheimer9s/Parkinson, heart disease, sepsis, diabetes, renal failure, and pneumonia & influenza. In contrast, for the same time period we find no evidence of significant excess deaths due to cancer, hypertension, respiratory diseases, cerebrovascular disease, suicide, homicide, falling accidents and traffic accidents.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.03.23284158v1" target="_blank">A CLOSER LOOK AT INDIRECT CAUSES OF DEATH AFTER HURRICANE MARIA USING A SEMIPARAMETRIC MODEL</a>
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<li><strong>The time between vaccination and infection impacts immunity against SARS-CoV-2 variants</strong> -
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As the COVID-19 pandemic continues, long-term immunity against SARS-CoV-2 will be globally important. Official weekly cases have not dropped below 2 million since September of 2020, and continued emergence of novel variants have created a moving target for our immune systems and public health alike. The temporal aspects of COVID-19 immunity, particularly from repeated vaccination and infection, are less well understood than short-term vaccine efficacy. In this study, we explore the impact of combined vaccination and infection, also known as hybrid immunity, and the timing thereof on the quality and quantity of antibodies produced by a cohort of 96 health care workers. We find robust neutralizing antibody responses among those with hybrid immunity against all variants, including Omicron BA.2, and we further found significantly improved neutralizing titers with longer vaccine-infection intervals up to 400 days. These results indicate that anti-SARS-CoV-2 antibody responses undergo continual maturation following primary exposure by either vaccination or infection for at least 400 days after last antigen exposure. We show that neutralizing antibody responses improved upon secondary boosting with greater impact seen after extended intervals. Our findings may also extend to booster vaccine doses, a critical consideration in future vaccine campaign strategies.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.02.23284120v1" target="_blank">The time between vaccination and infection impacts immunity against SARS-CoV-2 variants</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>Efficacy and Safety of SA58 Nasal Spray in Close Contact With COVID-19 People</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SA58 Nasal Spray; Drug: Placebo<br/><b>Sponsors</b>: Sinovac Life Sciences Co., Ltd.; Beijing Ditan Hospital<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>Efficacy and Safety of Anti-COVID-19 Antibody SA58 Nasal Spray to Prevent Infection in High-risk Populations</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: SA58 Nasal Spray<br/><b>Sponsor</b>: Sinovac Life Sciences Co., Ltd.<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>Immunogenicity and Safety of COVID-19 Vaccine in Population Aged 18 Years and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: One dose group; Biological: Two doses group; Biological: Aged 18-59 years; Biological: Aged 60 years old and above<br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., 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>Immunogenicity and Safety of COVID-19 Vaccine as a Booster Vaccination in Population Aged 18 Years and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant SARS-CoV-2 Vaccine (CHO Cell) LYB001; Biological: ZF2001<br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., 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>Immunogenicity of Heterologous Versus Homologous Prime Boost Schedule With mRNA and Inactivated COVID-19 Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: CoronaVac/CoronaVac; Biological: CoronaVac/BNT162b2<br/><b>Sponsor</b>: Institut Pasteur de Tunis<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>Sars-COV-2 Immunity in immunoCOmpromised Populations</strong> - <b>Conditions</b>: SARS CoV 2 Infection; COVID-19<br/><b>Intervention</b>: Diagnostic Test: Humoral immunity<br/><b>Sponsors</b>: Maria Goossens; Université Libre de Bruxelles; Institute of Tropical Medicine, Belgium; Mensura EDPB; Erasme 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>Safety, Tolerability and Pharmacokinetic Characteristics Evaluation on GST-HG171 Tablets</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: GST-HG171; Drug: placebo of GST-HG171<br/><b>Sponsor</b>: Fujian Akeylink Biotechnology Co., Ltd.<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>Benefits of an Aerobic and Strength Rehabilitation Program With Post- SARS-CoV-2 Patients Moderate-severe</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Aerobic plus strength group; Other: Aerobic group<br/><b>Sponsor</b>: Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz<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 Effect of Amantadine on Post-COVD-19 Fatigue</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Drug: Amantadine<br/><b>Sponsor</b>: Shahid Beheshti University of Medical Sciences<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>Effectiveness of Rapid Antigen Testing of Students for COVID-19 in Reducing Absences From Schools in Bangladesh</strong> - <b>Condition</b>: School Absenteeism<br/><b>Intervention</b>: Diagnostic Test: Rapid Antigen Testing (RAT) for COVID-19<br/><b>Sponsors</b>: International Centre for Diarrhoeal Disease Research, Bangladesh; Columbia 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>Enhanced External Counterpulsation to Treat Long COVID Fatigue</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>: Procedure: Enhanced external counterpulsation<br/><b>Sponsor</b>: Sheba Medical Center<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>Melatonin, Vitamins and Minerals Supplements for the Treatment of Covid-19 and Covid-like Illness</strong> - <b>Condition</b>: Influenza -Like Illness<br/><b>Intervention</b>: Drug: kelavit<br/><b>Sponsor</b>: Hôpital Universitaire Sahloul<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>Jing Si Herbal Tea for Long-Coronavirus Disease(COVID) Gut-brain Interaction</strong> - <b>Conditions</b>: Healthy Subjects; COVID-19 Pneumonia; Irritable Bowel Syndrome; Functional Gastrointestinal Disorders<br/><b>Interventions</b>: Dietary Supplement: Jing Si Herbal Tea Liquid Packet; Dietary Supplement: Jing Si Herbal Tea Liquid Packet Placebo<br/><b>Sponsor</b>: Buddhist Tzu Chi General Hospital<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>Treatment of Long COVID Utilizing Autologous Stem Cells</strong> - <b>Condition</b>: Long COVID<br/><b>Interventions</b>: Procedure: Adipose Tissue Harvest; Biological: ATCell<br/><b>Sponsor</b>: American CryoStem Corporation<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>Identification and semisynthesis of (-)-anisomelic acid as oral agent against SARS-CoV-2 in mice</strong> - (-)-Anisomelic acid, isolated from Anisomeles indica (L.) Kuntze (Labiatae) leaves, is a macrocyclic cembranolide with a trans-fused α-methylene-γ-lactone motif. Anisomelic acid effectively inhibits SARS-CoV-2 replication and viral-induced cytopathic effects with an EC(50) of 1.1 and 4.3 μM, respectively. Challenge studies of SARS-CoV-2-infected K18-hACE2 mice showed that oral administration of anisomelic acid and subcutaneous dosing of remdesivir can both reduce the viral titers in the lung…</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>Rapid Resolution of Post-COVID-19 Inflammatory Syndrome in an Adult With Targeted Inhibition of Interleukin-1B</strong> - Multisystem inflammatory syndrome (MIS) is a severe inflammatory response that occurs days to weeks following the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). Initially known in children and named MIS-C, recently several cases of MIS in adults have been reported to the Centers for Disease Control and Prevention (CDC), leading to the recognition of a new disease MIS in adults (MIS-A). The current…</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>Anti-CD73 antibody activates human B cells, enhances humoral responses and induces redistribution of B cells in patients with cancer</strong> - CONCLUSIONS: Mupadolimab activates B cells and stimulates the production of antigen specific antibodies. The effects in patients with cancer suggest that activated, CD69^(POS) B cells redistribute to lymphoid tissues. Minor tumor regression was observed in several patients. These results support further investigation of mupadolimab as an immunotherapy for cancer and its potential use as a vaccine adjuvant.</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>Spleen tyrosine kinase inhibition restores myeloid homeostasis in COVID-19</strong> - Spleen tyrosine kinase (SYK) is a previously unidentified therapeutic target that inhibits neutrophil and macrophage activation in coronavirus disease 2019 (COVID-19). Fostamatinib, a SYK inhibitor, was studied in a phase 2 placebo-controlled randomized clinical trial and was associated with improvements in many secondary end points related to efficacy. Here, we used a multiomic approach to evaluate cellular and soluble immune mediator responses of patients enrolled in this trial. We…</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>Targeting Spike Glycans to Inhibit SARS-CoV2 Viral Entry</strong> - SARS-CoV-2 Spike harbors glycans which function as ligands for lectins. Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the Spike protein. Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. Here, we show that BOA binds to the Spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. Using a variety…</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>Data-driven drug discovery for drug repurposing</strong> - To improve the decreased efficiency of drug discovery and development, drug repurposing (also called drug repositioning) has been expected, that it is a strategy for identifying new medical indications for approved, investigational or suspended drugs. Particularly, according to the rapid expansion of medical and life science data and the remarkable technological progress of AI technology in recent years, the approach of computational drug repurposing has been attracted as one of the applications…</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>Endogenous G-quadruplex-forming RNAs inhibit the activity of SARS-CoV-2 RNA polymerase</strong> - Replication of RNA viruses is catalysed by virus-specific polymerases, which can be targets of therapeutic strategies. In this study, we used a selection strategy to identify endogenous RNAs from a transcriptome library derived from lung cells that interact with the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. Some of the selected RNAs weakened the activity of RdRp by forming G-quadruplexes. These results suggest that certain endogenous RNAs, which potentially form G-quadruplexes, can…</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>Prospective mode of action of Ivermectin: SARS-CoV-2</strong> - The well-known anti-helminthic drug ivermectin (IVM) has been established as an example of drug repurposing for the management of SARS-CoV-2 infection. Various study has been done to understand the inhibitory mechanism of IVM against SARS-CoV-2 targets. Broadly, IVM has been categorized as a host-directed agent and the proposed mechanism involves inhibition of the IMPα/ß1-mediated nuclear import of viral proteins. In addition, in vitro/in vivo and molecular docking/dynamic simulation studies…</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>Circulating microRNAs as emerging regulators of COVID-19</strong> - Coronavirus disease 2019 (COVID-19), an infectious disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that has high incidence rates, spreads rapidly, and has caused more than 6.5 million deaths globally to date. Currently, several drugs have been used in the clinical treatment of COVID-19, including antivirals (e.g., molnupiravir, baricitinib, and remdesivir), monoclonal antibodies (e.g., etesevimab and tocilizumab), protease inhibitors…</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 ability of low- and High-SES schools to inhibit learning losses during the COVID-19 pandemic</strong> - The study examined whether the pandemic-induced digital distance learning affected the ability of educational units to inhibit learning losses and whether their SES compositions modified those effects. By applying random-intercept multinomial regression models to educational units’ average test scores comparing the 2019-2021 period to the 2017-2019 period based on data from the National Assessment of Basic Competencies in Hungary, the results indicated that educational units were less likely 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 a series of nucleoside analogs as effective anticoronaviral-2 drugs against the Omicron-B.1.1.529/BA.2 subvariant: A repurposing research study</strong> - Mysterious evolution of a new strain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the Omicron variant, led to a new challenge in the persistent coronavirus disease 2019 (COVID-19) battle. Objecting the conserved SARS-CoV-2 enzymes RNA-dependent RNA polymerase (RdRp) and 3’-to-5’ exoribonuclease (ExoN) together using one ligand is a successful new tactic to stop SARS-CoV-2 multiplication and COVID-19 progression. The current comprehensive study investigated most nucleoside…</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 snake venom-analog peptide that inhibits SARS-CoV-2 and papain-like protease displays antithrombotic activity in mice arterial thrombosis model, without interfering with bleeding time</strong> - CONCLUSION: These results demonstrate the antithrombotic activity of the peptide (p-BthTX-I)(2) K possibly by kallikrein inhibition, suggesting its strong biotechnological potential.</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>Diagnostic performance between in-house and commercial SARS-CoV-2 serological immunoassays including binding-specific antibody and surrogate virus neutralization test (sVNT)</strong> - This study aimed to evaluate the correlation between in-house and commercial binding-specific IgG antibodies and between in-house and commercial SARS-CoV-2 surrogate virus neutralization tests (sVNT). Samples from healthcare workers who received vaccines against SARS-CoV-2 were tested for RBD-specific antibody, S-specific antibody, and in-house ELISA, commercial sVNT, and in-house sVNT, against wild-type SARS-CoV-2. Three hundred and five samples were included in the analysis. The correlation…</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 humoral immunogenicity in solid organ transplant recipients after third-dose mRNA vaccine with homologous or heterologous schedules: An observational study</strong> - CONCLUSIONS: Regardless of the schedule, the neutralization inhibition rate against the Omicron variant was poor; therefore, additional preventive measures are required in such high-risk populations.</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>New insights into the mucosal immune pathogenesis of IgA nephropathy from the perspective of COVID-19 vaccination</strong> - Large-scale SARS-CoV-2 vaccination is one of the key strategies to curb the COVID-19 pandemic, however, there are increasing reports of IgA nephropathy following COVID-19 vaccination. The clinical manifestation, treatment and prognostic effects are different in IgAN patients who have had an onset after the first and second dose of vaccination, as well as new and recurrent IgAN patients. These conditions bring about a relatively important window for understanding the pathogenesis of IgAN. Gd-IgA1…</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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