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157 lines
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<title>17 January, 2024</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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<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>Impact of SARS-CoV-2 spike efficacy on tolerability of spike-based Covid-19 Vaccinations</strong> -
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Abstract: Knowledge about the efficacy of vaccine spikes has multiplied in recent years. The purpose of this review is to update the key findings from the scientific literature that provide explanations for many of the reported and analysed adverse effects associated with the spike-based Covid-19 vaccination. Principle results: An overwhelming body of evidence supports the main mode of action of spike-based Covid-19 vaccines, namely the downregulation of ACE2 by spikes. Direct spike effects, synergisms and RAAS-independent responses complement and multiply the already deleterious effects on tolerability. It has been repeatedly confirmed that the SARS-CoV spike protein alone is not only able to downregulate ACE2, but also to induce cell fusion, activation of TLR4, of co-receptors and gastrointestinal responses. The systemic and long-lasting detection of spikes after vaccination disproves the claimed regionally limited and short-lasting spike production and efficacy. The production volume of spikes, their dependencies and the non-neutralised spike proportion have so far remained unknown for unknown reasons. Conclusions: The exceptionally broad spectrum, frequency and severity of the reported side effects associated with spike-based Covid-19 vaccination exceed the known level of conventional vaccinations. According to my side effect analyses, the spike-based vaccines possess an unacceptable class-specific, unique side effect profile. From a pharmacological point of view, spikes are highly active substances, but not tolerable simple antigens. For this reason, they are not suitable for preventive immunisation to avoid comparatively harmless infections.
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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/pw8zr/" target="_blank">Impact of SARS-CoV-2 spike efficacy on tolerability of spike-based Covid-19 Vaccinations</a>
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</div></li>
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<li><strong>Discovery and Characterization of a Pan-betacoronavirus S2-binding antibody</strong> -
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Three coronaviruses have spilled over from animal reservoirs into the human population and caused deadly epidemics or pandemics. The continued emergence of coronaviruses highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using LIBRA-seq, we report a panel of 50 coronavirus antibodies isolated from human B cells. Of these antibodies, 54043-5 was shown to bind the S2 subunit of spike proteins from alpha-, beta-, and deltacoronaviruses. A cryo-EM structure of 54043-5 bound to the pre-fusion S2 subunit of the SARS-CoV-2 spike defined an epitope at the apex of S2 that is highly conserved among betacoronaviruses. Although non-neutralizing, 54043-5 induced Fc-dependent antiviral responses, including ADCC and ADCP. In murine SARS-CoV-2 challenge studies, protection against disease was observed after introduction of Leu234Ala, Leu235Ala, and Pro329Gly (LALA-PG) substitutions in the Fc region of 54043-5. Together, these data provide new insights into the protective mechanisms of non-neutralizing antibodies and define a broadly conserved epitope within the S2 subunit.
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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/10.1101/2024.01.15.575741v1" target="_blank">Discovery and Characterization of a Pan-betacoronavirus S2-binding antibody</a>
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<li><strong>Adsorption-driven deformation and landing-footprints of the RBD proteins in SARS-CoV-2 variants onto biological and inanimate surfaces</strong> -
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<div>
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Respiratory viruses, carried through airborne microdroplets, frequently adhere to surfaces, including plastics and metals. However, our understanding of the interactions between viruses and materials remains limited, particularly in scenarios involving polarizable surfaces. Here, we investigate the role of receptor-binding domain (RBD) mutations on the adsorption of SARS-CoV-2 to hydrophobic and hydrophilic surfaces employing molecular simulations. To contextualize our findings, we contrast the interactions on inanimate surfaces with those on native-biological interfaces, specifically the ACE2 receptor. Notably, we identify a twofold increase in structural deformations for the protein's receptor binding motif onto the inanimate surfaces, indicative of enhanced shock-absorbing mechanisms. Furthermore, the distribution of amino acids (landing-footprints) on the inanimate surface reveals a distinct regional asymmetry relative to the biological interface. In spite of the H-bonds formed at the hydrophilic substrate, the simulations consistently show a higher number of contacts and interfacial area with the hydrophobic surface, with the WT RBD adsorbed more strongly to than the delta or omicron RBDs. In contrast, the adsorption of delta and omicron to hydrophilic surfaces was characterized by a distinctive hopping-pattern. The novel shock-absorbing mechanisms identified in the virus adsorption on inanimate surfaces could lead current experimental efforts in the design of virucidal surfaces.
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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/10.1101/2024.01.15.575706v1" target="_blank">Adsorption-driven deformation and landing-footprints of the RBD proteins in SARS-CoV-2 variants onto biological and inanimate surfaces</a>
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<li><strong>Reference materials for SARS-CoV-2 molecular diagnostic quality control: validation of encapsulated synthetic RNAs for room temperature storage and shipping</strong> -
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<div>
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The Coronavirus pandemic unveiled the unprecedented need for diagnostic tests to rapidly detect the presence of pathogens in the population. Real-time RT-PCR and other nucleic acid amplification techniques are accurate and sensitive molecular techniques that necessitate positive controls. To meet this need, Twist Bioscience has developed and released synthetic RNA controls. However, RNA is an inherently unstable molecule needing cold storage, costly shipping, and resource-intensive logistics. Imagene provides a solution to this problem by encapsulating dehydrated RNA inside metallic capsules filled with anhydrous argon, allowing room temperature and eco-friendly storage and shipping. Here, RNA controls produced by Twist were encapsulated (RNAshells) and distributed to several laboratories that used them for COVID-19 detection tests by amplification. One RT-LAMP procedure, four different RT-PCR devices and 6 different PCR kits were used. The amplification targets were genes E, N; RdRp, Sarbeco-E and Orf1a/b. RNA retrieval was satisfactory, and the detection was reproducible. RNA stability was checked by accelerated aging. The results for a 10-year equivalent storage time at 25 {degrees}C were not significantly different from those for unaged samples. This room temperature RNA stability allows the preparation and distribution of large strategic batches which can be stored for a long time and used for standardization processes between detection sites. Moreover, it makes it also possible to use these controls for single use and in the field where large temperature differences can occur. Consequently, this type of encapsulated RNA controls, processed at room temperature, can be used as reference materials for the SARS-Cov-2 virus as well as for other pathogens detection.
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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/10.1101/2023.08.28.555008v3" target="_blank">Reference materials for SARS-CoV-2 molecular diagnostic quality control: validation of encapsulated synthetic RNAs for room temperature storage and shipping</a>
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</div></li>
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<li><strong>Lineage frequency time series reveal elevated levels of genetic drift in SARS-CoV-2 transmission in England</strong> -
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<div>
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Genetic drift in infectious disease transmission results from randomness of transmission and host recovery or death. The strength of genetic drift for SARS-CoV-2 transmission is expected to be high due to high levels of superspreading, and this is expected to substantially impact disease epidemiology and evolution. However, we don’t yet have an understanding of how genetic drift changes over time or across locations. Furthermore, noise that results from data collection can potentially confound estimates of genetic drift. To address this challenge, we develop and validate a method to jointly infer genetic drift and measurement noise from time-series lineage frequency data. Our method is highly scalable to increasingly large genomic datasets, which overcomes a limitation in commonly used phylogenetic methods. We apply this method to over 490,000 SARS-CoV-2 genomic sequences from England collected between March 2020 and December 2021 by the COVID-19 Genomics UK (COG-UK) consortium and separately infer the strength of genetic drift for pre-B.1.177, B.1.177, Alpha, and Delta. We find that even after correcting for measurement noise, the strength of genetic drift is consistently, throughout time, higher than that expected from the observed number of COVID-19 positive individuals in England by 1 to 3 orders of magnitude, which cannot be explained by literature values of superspreading. Our estimates of genetic drift will be informative for parameterizing evolutionary models and studying potential mechanisms for increased drift.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.11.21.517390v3" target="_blank">Lineage frequency time series reveal elevated levels of genetic drift in SARS-CoV-2 transmission in England</a>
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<li><strong>De novo-designed minibinders expand the synthetic biology sensing repertoire</strong> -
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<div>
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Synthetic and chimeric receptors capable of recognizing and responding to user-defined antigens have enabled "smart" therapeutics based on engineered cells. These cell engineering tools depend on antigen sensors which are most often derived from antibodies. Advances in the de novo design of proteins have enabled the design of protein binders with the potential to target epitopes with unique properties and faster production timelines compared to antibodies. Building upon our previous work combining a de novo-designed minibinder of the Spike protein of SARS-CoV-2 with the synthetic receptor synNotch (SARSNotch), we investigated whether minibinders can be readily adapted to a diversity of cell engineering tools. We show that the Spike minibinder LCB1 easily generalizes to a next-generation proteolytic receptor SNIPR that performs similarly to our previously reported SARSNotch. LCB1-SNIPR successfully enables the detection of live SARS-CoV-2, an improvement over SARSNotch which can only detect cell-expressed Spike. To test the generalizability of minibinders to diverse applications, we tested LCB1 as an antigen sensor for a chimeric antigen receptor (CAR). LCB1-CAR enabled CD8+ T cells to cytotoxically target Spike-expressing cells. Our findings suggest that minibinders represent a novel class of antigen sensors that have the potential to dramatically expand the sensing repertoire of cell engineering tools.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.12.575267v1" target="_blank">De novo-designed minibinders expand the synthetic biology sensing repertoire</a>
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<li><strong>mRNA-LNP COVID-19 vaccine lipids induce low level complement activation and production of proinflammatory cytokines: Mechanisms, effects of complement inhibitors, and relevance to adverse reactions</strong> -
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<div>
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Messenger RNA-containing lipid nanoparticles (mRNA-LNPs) enabled widespread COVID-19 vaccination with a small fraction of vaccine recipients displaying acute or sub-acute inflammatory symptoms. The molecular mechanism of these adverse events (AEs) remains undetermined. Here we report that the mRNA-LNP vaccine, Comirnaty, triggers low-level complement (C) activation and production of inflammatory cytokines, which may be key underlying processes of inflammatory AEs. In serum, Comirnaty and the control PEGylated liposome (Doxebo) caused different rises of C split products, C5a, sC5b-9, Bb and C4d, indicating stimulation of the classical pathway of C activation mainly by the liposomes, while a stronger stimulation of the alternative pathway was equal with the vaccine and the liposomes. Spikevax had similar C activation as Comirnaty, but viral or synthetic mRNAs had no such effect. In autologous serum-supplemented peripheral blood mononuclear cell (PBMC) cultures, Comirnaty caused increases in the levels of sC5b-9 and proinflammatory cytokines in the following order: IL-1 < IFN-{gamma} < IL-1{beta} < TNF- < IL-6 < IL-8, whereas heat-inactivation of serum prevented the rises of IL-1, IL-1{beta}, and TNF-. Clinical C inhibitors, Soliris and Berinert, suppressed vaccine-induced C activation in serum but did not affect cytokine production when applied individually. These findings suggest that the PEGylated lipid coating of mRNA-LNP nanoparticles can trigger C activation mainly via the alternative pathway, which may be causally related to the induction of some, but not all inflammatory cytokines. While innate immune stimulation is essential for the vaccine's efficacy, concurrent production of C- and PBMC-derived inflammatory mediators may contribute to some of the AEs. Pharmacological attenuation of harmful cytokine production using C inhibitors likely requires blocking the C cascade at multiple points.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.12.575122v1" target="_blank">mRNA-LNP COVID-19 vaccine lipids induce low level complement activation and production of proinflammatory cytokines: Mechanisms, effects of complement inhibitors, and relevance to adverse reactions</a>
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<li><strong>Primate-specific BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2</strong> -
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<div>
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Coronavirus disease 2019 (COVID-19) is an immune-related disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 invades cells via the entry receptor angiotensin-converting enzyme 2 (ACE2). While several attachment factors and co-receptors for SARS-CoV-2 have been identified, the complete pathogenesis of the virus remains to be determined. Unraveling the molecular mechanisms governing SARS-CoV-2 interactions with host cells is crucial for the formulation of effective prophylactic measures and the advancement of COVID-19 therapeutics. Here, we identified butyrophilin subfamily 3 member A2 (BTN3A2) as a potent inhibitor of SARS-CoV-2 infection. The mRNA level of BTN3A2 was correlated with COVID-19 severity. Upon re-analysis of a human lung single-cell RNA sequencing dataset, BTN3A2 expression was predominantly identified in epithelial cells. Moreover, this expression was elevated in pathological epithelial cells from COVID-19 patients and co-occurred with ACE2 expression in the same cellular subtypes in the lung. Additionally, BTN3A2 primarily targeted the early stage of the viral life cycle by inhibiting SARS-CoV-2 attachment through direct interactions with the receptor-binding domain (RBD) of the Spike protein and ACE2. Furthermore, BTN3A2 inhibited ACE2-mediated SARS-CoV-2 infection by reducing ACE2 in vitro and in a BTN3A2 transgenic mouse model. These results reveal a key role of BTN3A2 in the fight against COVID-19 and broaden our understanding of the pathobiology of SARS-CoV-2 infection. Identifying potential monoclonal antibodies that target BTN3A2 may facilitate disruption of SARS-CoV-2 infection, providing a therapeutic avenue for COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.13.575537v1" target="_blank">Primate-specific BTN3A2 protects against SARS-CoV-2 infection by interacting with and reducing ACE2</a>
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<li><strong>Intestinal helminth infection impairs vaccine-induced T cell responses and protection against SARS-CoV-2</strong> -
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<div>
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Although vaccines have reduced COVID-19 disease burden, their efficacy in helminth infection endemic areas is not well characterized. We evaluated the impact of infection by Heligmosomoides polygyrus bakeri (Hpb), a murine intestinal hookworm, on the efficacy of an mRNA vaccine targeting the Wuhan-1 spike protein of SARS-CoV-2. Although immunization generated similar B cell responses in Hpb-infected and uninfected mice, polyfunctional CD4+ and CD8+ T cell responses were markedly reduced in Hpb-infected mice. Hpb-infected and mRNA vaccinated mice were protected against the ancestral SARS-CoV-2 strain WA1/2020, but control of lung infection was diminished against an Omicron variant compared to animals immunized without Hpb infection. Helminth mediated suppression of spike-specific CD8+ T cell responses occurred independently of STAT6 signaling, whereas blockade of IL-10 rescued vaccine-induced CD8+ T cell responses. In mice, intestinal helminth infection impairs vaccine induced T cell responses via an IL-10 pathway and compromises protection against antigenically shifted SARS-CoV-2 variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.14.575588v1" target="_blank">Intestinal helminth infection impairs vaccine-induced T cell responses and protection against SARS-CoV-2</a>
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<li><strong>Different vaccine platforms result in distinct antibody responses to the same antigen in haemodialysis patients</strong> -
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Generalised immune dysfunction in chronic kidney disease, especially in patients requiring haemodialysis (HD), significantly enhances the risk of severe infections. Moreover, vaccine-induced immunity is typically reduced in HD populations, but the full mechanisms behind this remain unclear. The SARS-CoV-2 pandemic provided an opportunity to examine the magnitude and functionality of antibody responses in HD patients to a previously unencountered antigen, Spike (S)-glycoprotein, after vaccination with different vaccine platforms (viral vector (VV); mRNA (mRV)). Here, we compared total and functional anti-S antibody responses (cross-variant neutralisation and complement binding) in 187 HD patients and 43 healthy controls 21-28 days after serial immunisation. After 2 doses of the same vaccine, HD patients had anti-S antibody levels and complement binding capacity comparable to controls. However, 2 doses of mRV induced greater polyfunctional antibody responses than VV, yet previous SARS-CoV-2 infection or an mRV boost after 2 doses of VV significantly enhanced antibody functionality in HD patients. Therefore, HD patients can generate near-normal, functional antigen-specific antibody responses following serial vaccination to a novel antigen, suggesting largely intact B cell memory. Encouragingly, exploiting immunological memory by using mRNA vaccines and boosting may improve the success of vaccination strategies in this vulnerable patient population.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.14.575569v1" target="_blank">Different vaccine platforms result in distinct antibody responses to the same antigen in haemodialysis patients</a>
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<li><strong>Lipid nanoparticle composition for adjuvant formulation modulates disease after influenza virus infection in QIV vaccinated mice.</strong> -
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Adjuvants can enhance vaccine effectiveness of currently licensed influenza vaccines. We tested influenza vaccination in a mouse model with two adjuvants: Sendai virus derived defective interfering (SDI) RNA, a RIG-I agonist, and an amphiphilic imidazoquinoline (IMDQ-PEG-Chol), TLR7/8 adjuvant. The negatively charged SDI RNA was formulated into lipid nanoparticles (LNPs) facilitating the direct delivery of a RIG-I agonist to the cytosol. We have previously tested SDI and IMDQ-PEG-Chol as standalone and combination adjuvants for influenza and SARS-CoV-2 vaccines. Here we tested two different ionizable lipids, K-Ac7-Dsa and S-Ac7-Dog, for LNP formulations. The adjuvanticity of IMDQ-PEG-Chol with and without empty or SDI-loaded LNPs was validated in a licensed vaccine setting (quadrivalent influenza vaccine or QIV) against H1N1 influenza virus, showing robust induction of antibody titres and T cell responses. Depending on the adjuvant combination and LNP lipid composition (K-Ac7-Dsa or S-Ac7-Dog lipids), humoral and cellular vaccine responses could be tailored towards type 1 or type 2 host responses with specific cytokine profiles that correlated with protection during viral infection. The extent of protection conferred by different vaccine/LNP/adjuvant combinations was examined against challenge with the vaccine-matching strain of H1N1 influenza A virus. Groups that received either LNP formulated with SDI, IMDQ-PEG-Chol or both showed very low levels of viral replication in their lungs at five days post virus infection. LNP ionizable lipid composition as well as loading (empty versus SDI) also skewed host responses to infection, as reflected in the cytokine and chemokine levels in lungs of vaccinated animals upon infection. These studies show the potential of LNPs as adjuvant delivery vehicles for licensed vaccines and illustrate the importance of LNP composition for subsequent host responses to infection, an important point of consideration for vaccine safety.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.14.575599v1" target="_blank">Lipid nanoparticle composition for adjuvant formulation modulates disease after influenza virus infection in QIV vaccinated mice.</a>
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<li><strong>Eliminating the missing cone challenge through innovative approaches</strong> -
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Microcrystal electron diffraction (MicroED) has emerged as a powerful technique for unraveling molecular structures from microcrystals too small for X-ray diffraction. However, a significant hurdle arises with plate-like crystals that consistently orient themselves flat on the electron microscopy grid. If, as is typically the case, the normal of the plate correlates with the axes of the crystal lattice, the crystal orientations accessible for measurement are restricted because the grid cannot be arbitrarily rotated. This limits the information that can be acquired, resulting in a missing cone of information. We recently introduced a novel crystallization strategy called suspended drop crystallization and proposed that this method could effectively address the challenge of preferred crystal orientation. Here we demonstrate the success of the suspended drop crystallization approach in eliminating the missing cone in two samples that crystallize as thin plates: bovine liver catalase and the COVID-19 main protease (Mpro). This innovative solution proves indispensable for crystals exhibiting preferred orientations, unlocking new possibilities for structure determination by MicroED.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.11.575283v1" target="_blank">Eliminating the missing cone challenge through innovative approaches</a>
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<li><strong>Human mobility patterns to inform sampling sites for early pathogen detection and routes of spread: a network modeling and validation study</strong> -
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Background: Detecting and foreseeing pathogen dispersion is crucial in preventing widespread disease transmission. Human mobility is a critical issue in human transmission of infectious agents. Through a mobility data-driven approach, we determined municipalities in Brazil that could make up an advanced sentinel network, allowing for early detection of circulating pathogens and their associated transmission routes. Methods: We compiled a comprehensive dataset on intercity mobility spanning air, road, and waterway transport, and constructed a graph-based representation of Brazil9s mobility network. The Ford-Fulkerson algorithm, coupled with centrality measures, were employed to rank cities according to their suitability as sentinel hubs. Findings: Our results disentangle the complex transportation network of Brazil, with flights alone transporting 79.9 million (CI 58.3 to 10.1 million) passengers annually during 2017-22, seasonal peaks occurring in late spring and summer, and roadways with a maximum capacity of 78.3 million passengers weekly. We ranked the 5,570 Brazilian cities to offer flexibility in prioritizing locations for early pathogen detection through clinical sample collection. Our findings are validated by epidemiological and genetic data independently collected during the SARS-CoV-2 pandemic period. The mobility-based spread model defined here was able to recapitulate the actual dissemination patterns observed during the pandemic. By providing essential clues for effective pathogen surveillance, our results have the potential to inform public health policy and improve future pandemic response efforts. Interpretation: Our results unlock the potential of designing country-wide clinical sample collection networks using data-informed approaches, an innovative practice that can improve current surveillance systems.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.01.12.24301207v1" target="_blank">Human mobility patterns to inform sampling sites for early pathogen detection and routes of spread: a network modeling and validation study</a>
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<li><strong>Critically-ill COVID-19 susceptibility gene CCR3 shows natural selection in sub-Saharan Africans</strong> -
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The prevalence of COVID-19 critical illness varies across ethnicities, with recent studies suggesting that genetic factors may contribute to this variation. The aim of this study was to investigate natural selection signals of genes associated with critically-ill COVID-19 in sub-Saharan Africans. Severe COVID-19 SNPs were obtained from the HGI website. Selection signals were assessed in 661 sub-Sahara Africans from 1000 Genomes Project using integrated haplotype score (iHS), cross-population extended haplotype homozygosity (xpEHH), and fixation index (Fst). Allele frequency trajectory analysis of ancient DNA samples were used to validate the existing of selection in sub-Sahara Africans. We also used Mendelian randomization to decipher the correlation between natural selection and critically-ill COVID-19. We identified that CCR3 exhibited significant natural selection signals in sub-Sahara Africans. Within the CCR3 gene, rs17217831-A showed both high iHS (Standardized iHS = 2) and high XP-EHH (Standardized XP-EHH = 2.5) in sub-Sahara Africans. Allele frequency trajectory of CCR3 rs17217831-A revealed natural selection occurring in the recent 1,500 years. Natural selection resulted in increased CCR3 expression in sub-Sahara Africans. Mendelian Randomization provided evidence that increased blood CCR3 expression and eosinophil counts lowered the risk of critically ill COVID-19. Our findings suggest that sub-Saharan Africans are less vulnerable to critically ill COVID-19 due to natural selection and identify CCR3 as a potential novel therapeutic target.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.01.12.24301202v1" target="_blank">Critically-ill COVID-19 susceptibility gene CCR3 shows natural selection in sub-Saharan Africans</a>
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<li><strong>Risk factors for experiencing Long-COVID symptoms: Insights from two nationally representative surveys</strong> -
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Background: Long COVID (LC) is a complex and multisystemic condition marked by a diverse range of symptoms, yet its associated risk factors remain poorly defined. Methods: Leveraging data from the 2022 Behavioral Risk Factor Surveillance System (BRFSS) and National Health Interview Survey (NHIS), both representative of the United States population, this study aimed to identify demographic characteristics associated with LC. The sample was restricted to individuals aged 18 years and older who reported a positive COVID-19 test or doctor9s diagnosis. We performed a descriptive analysis comparing characteristics between participants with and without LC. Furthermore, we developed multivariate logistic regression models on demographic covariates that would have been valid at the time of the COVID-19 infection. Results: Among the 124,313 individuals in BRFSS and 10,131 in the NHIS reporting either a positive test or doctor9s diagnosis for COVID-19 (Table), 26,783 (21.5%) in BRFSS and 1,797 (17.1%) in NHIS reported LC. In the multivariate logistic regression model, we found middle age, female gender, Hispanic ethnicity, lack of a college degree, and residence in non-metropolitan areas associated with higher risk of LC. Notably, the initial severity of acute COVID-19 was strongly associated with LC risk. In contrast, significantly lower ORs were reported for Non-Hispanic Asian and Black Americans compared to Non-Hispanic White. Conclusions: In the United States, there is marked variation in the risk of LC by demographic factors and initial infection severity. Further research is needed to understand the underlying cause of these observations.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2024.01.12.24301170v1" target="_blank">Risk factors for experiencing Long-COVID symptoms: Insights from two nationally representative surveys</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 Study to Evealuate Safety, Reactogenicity, and Immunogenicity of TI-0010 Vaccine in Healthy Adults</strong> - <b>Conditions</b>: COVID-19; COVID-19 Immunisation <br/><b>Interventions</b>: Biological: TI-0010; Biological: Placebo <br/><b>Sponsors</b>: National Drug Clinical Trial Institute of the Second Affiliated Hospital of Bengbu Medical College; Therorna <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>Sodium Citrate in Smell Retraining for People With Post-COVID-19 Olfactory Dysfunction</strong> - <b>Conditions</b>: Long Haul COVID-19; Post-Acute COVID-19 Syndrome; Anosmia; Olfaction Disorders <br/><b>Interventions</b>: Drug: Sodium Citrate; Drug: Normal Saline; Other: Olfactory Training Kit - “The Olfactory Kit, by AdvancedRx” <br/><b>Sponsors</b>: University of North Carolina, Chapel Hill <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>Phase II, Double Blind, Randomized Trial of CX-4945 in Viral Community Acquired Pneumonia</strong> - <b>Conditions</b>: Community-acquired Pneumonia; SARS-CoV-2 -Associated Pneumonia; Influenza With Pneumonia <br/><b>Interventions</b>: Drug: CX-4945 (SARS-CoV-2 domain); Drug: Placebo (SARS-CoV-2 domain); Drug: CX-4945 (Influenza virus domain); Drug: Placebo (Influenza virus domain) <br/><b>Sponsors</b>: Senhwa Biosciences, Inc. <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Edge AI-deployed DIGItal Twins for PREDICTing Disease Progression and Need for Early Intervention in Infectious and Cardiovascular Diseases Beyond COVID-19 - Investigation of Biomarkers in Dermal Interstitial Fluid</strong> - <b>Conditions</b>: Heart Failure <br/><b>Interventions</b>: Device: Use of the PELSA System for dISF extraction <br/><b>Sponsors</b>: Charite University, Berlin, Germany <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>Phase III Clinical Study Evaluating the Efficacy and Safety of WPV01 in Patients With Mild/Moderate COVID-19</strong> - <b>Conditions</b>: Mild to Moderate COVID-19 <br/><b>Interventions</b>: Drug: WPV01; Drug: Placebo <br/><b>Sponsors</b>: Westlake Pharmaceuticals (Hangzhou) 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>Integrated Mindfulness-based Health Qigong Intervention for COVID-19 Survivors and Caregivers</strong> - <b>Conditions</b>: COVID-19 Infection <br/><b>Interventions</b>: Other: Mindfulness-based Health Qigong Intervention <br/><b>Sponsors</b>: The Hong Kong Polytechnic University <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>Effect of Aerobic Exercises Versus Incentive Spirometer Device on Post-covid Pulmonary Fibrosis Patients</strong> - <b>Conditions</b>: Lung Fibrosis Interstitial; Post-COVID-19 Syndrome <br/><b>Interventions</b>: Other: Aerobic Exercises; Device: Incentive Spirometer Device; Other: Traditional Chest Physiotherapy <br/><b>Sponsors</b>: McCarious Nahad Aziz Abdelshaheed Stephens; Cairo University <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>SARS-CoV-2 and Influenza A/B in Point-of-Care and Non-Laboratory Settings</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; Influenza A; Influenza B <br/><b>Interventions</b>: Diagnostic Test: Aptitude Medical Systems Metrix COVID/Flu Test <br/><b>Sponsors</b>: Aptitude Medical Systems; Biomedical Advanced Research and Development Authority <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>Can Doctors Reduce COVID-19 Misinformation and Increase Vaccine Uptake in Ghana? A Cluster-randomised Controlled Trial</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Motivational Interviewing, AIMS; Behavioral: Facility engagement <br/><b>Sponsors</b>: London School of Economics and Political Science; Innovations for Poverty Action; Ghana Health Services <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>Long COVID Ultrasound Trial</strong> - <b>Conditions</b>: Long Covid <br/><b>Interventions</b>: Device: Splenic Ultrasound <br/><b>Sponsors</b>: SecondWave Systems Inc.; University of Minnesota; MCDC (United States Department of Defense) <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 After COVID-19 Vaccines in Adapted Schedules</strong> - <b>Conditions</b>: Coronavirus Disease 2019; COVID-19 <br/><b>Interventions</b>: Drug: BNT162b2 30µg; Drug: BNT162b2 20µg; Drug: BNT162b2 6µg; Drug: mRNA-1273 100µg; Drug: mRNA-1273 50µg; Drug: ChAdOx1-S [Recombinant] <br/><b>Sponsors</b>: Universiteit Antwerpen <br/><b>Completed</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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