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196 lines
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<title>04 September, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>COVID-19 vaccines and autoimmune disorders: A scoping review protocol</strong> -
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<div>
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Background Two years into the global vaccination program, important questions about the association between COVID-19 vaccines and autoimmune diseases have arisen. A growing number of reports have documented associations between COVID-19 vaccination and autoimmunity, suggesting, for example, a causal link between vaccination and new-onset and/or relapsing autoimmune disorders such as type 1 diabetes mellitus, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, Graves disease, and Hashimoto’s thyroiditis. These autoimmune phenomena have occurred with various COVID-19 vaccines and research is required to elucidate the underlying mechanisms and causal directions, for example, whether persons with no history of autoimmune disorders may experience them upon vaccination or persons with autoimmune disorders may experience exacerbation or new adverse events post-vaccination. Methods and analysis Specific objectives of this scoping review will address the following questions: Can COVID-19 vaccination trigger and/or exacerbate autoimmune disorders? Are persons with autoimmune disorders at higher risk of experiencing additional autoimmune disorders? What are the mechanisms connecting autoimmune disorders with COVID-19 vaccination? Can COVID-19 vaccination interact with immunosuppressive therapy in persons with autoimmune disorders? Does the risk of autoimmune disorders following COVID-19 vaccination differ by vaccine type, age, gender, or other still unidentified characteristics (e.g., SES)? What is the consensus of care concerning COVID-19 vaccination in persons with autoimmune disorders and what evidence informs it? Our review will follow Arksey and O’Malley’s (2005) framework, enhanced by Levac et al.’s team-based approach (2010), and adhering to the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist. To capture the broadest range of perspectives on the phenomenon of interest, data will be synthesized through numerical summaries describing general characteristics of included studies and thematic analysis. Subgroup analysis of primary outcomes will be performed to compare findings according to 1) the previous existence of autoimmune disorder, 2) the presence of relevant co-morbidities, 3) vaccine type; and other relevant factors that we may encounter as the research proceeds. Significance COVID-19 has triggered the largest vaccination campaign in history, targeting literally the global human community. Drug safety is a crucial aspect of any medical intervention, critical to a proper assessment of the balance of risks and benefits. Our investigation should yield information useful to improve medical and public health practice in multiple ways, including assisting in clinical decision-making, policy development, and ethical medical practice.
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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/kc4be/" target="_blank">COVID-19 vaccines and autoimmune disorders: A scoping review protocol</a>
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</div></li>
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<li><strong>Live virus neutralizing antibodies against pre and post Omicron strains in food and retail workers in Quebec, Canada.</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Objectives. To assess the neutralization activity pre and post Omicron BA.1 emergence in a unique cohort of 280 vaccinated restaurant/bar, grocery and hardware store workers in Quebec, Canada. Methods. Participants were recruited during the emergence of Omicron BA.1 variant. The neutralizing activity of participant sera was assessed by microneutralization assay. Results. Serum neutralizing antibody (NtAb) titers of all participants against the ancestral SARS-CoV-2 strain was comparable with the response against Delta variant, however, their response was significantly reduced against Omicron BA.1, BA2, BA.2.12.1, BA.4 and BA.5. The neutralizing response of each group of workers was similar. Individuals who received 2 doses of vaccine had significantly reduced NtAb titers against all SARS-CoV-2 strains compared to those infected and then vaccinated (≥ 1 dose), vaccinated (≥ 2 doses) and then infected, or those who received 3 doses of vaccine. Participants vaccinated with 2 or 3 doses of vaccine and then infected had the highest NtAb titers against all SARS-CoV-2 strains tested. Conclusion. We assessed for the first time the NtAb response in food and retail workers. Individuals infected after ≥ 2 doses of vaccine had the highest levels of NtAbs against Omicron BA.1, BA.2 and BA.5 variants and might be better protected against reinfection.
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</p>
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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.medrxiv.org/content/10.1101/2023.09.03.23294976v1" target="_blank">Live virus neutralizing antibodies against pre and post Omicron strains in food and retail workers in Quebec, Canada.</a>
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</div></li>
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<li><strong>Integrated antigenic and nucleic acid detection in single virions and virion-infected host-derived extracellular vesicles</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The coronavirus disease of 2019 (COVID-19) led to the rapid development of novel assays to improve sensitivities for detecting the virion responsible for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite that, there have been over 767 million reported cases and over 6.9 million deaths worldwide. Therefore, tunable, sensitive, and high-throughput assays are warranted to control future outbreaks. Herein, we developed a tunable in situ assay to selectively sort virions and infected host-derived extracellular vesicles (IHD-EVs) and simultaneously detect their antigens and nucleic acid cargo at a single-particle resolution. The Biochip Antigen and RNA Assay (BARA<sup>TM</sup>) integrates positive immunoselection and infection dynamics to sort particles, immunofluorescence to detect antigens, and fluorescence in situ hybridization to detect nucleic acids. BARATM enhanced sensitivities by detecting biomolecular signatures at the single-particle level, enabling the detection of virions in asymptomatic patients, and genetic mutations in single SARS-CoV-2 virions. Furthermore, BARA<sup>TM</sup> revealed the continued long-term expression of virion-RNA in the IHD-EVs of post-acute sequelae SARS-CoV-2 infection (PASC) patients. BARATM was validated on saliva (30 healthy donors and 33 symptomatic and 20 asymptomatic patients) and nasopharyngeal swabs (19 healthy donors and 40 patients), revealing a highly accurate diagnosis by simultaneously detecting the spike glycoprotein and nucleocapsid-encoding RNA on single SARS-CoV-2 virions with sensitivities of 100 % and 95 %, respectively, and specificities of 100 % for both biofluids. Altogether, the single-particle detection of antigens and virion-RNA provides a tunable framework for the diagnosis, monitoring, and mutation screening of current and future outbreaks.
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</p>
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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.medrxiv.org/content/10.1101/2023.08.31.23292825v1" target="_blank">Integrated antigenic and nucleic acid detection in single virions and virion-infected host-derived extracellular vesicles</a>
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</div></li>
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<li><strong>Pulmonary function and survival one year after dupilumab treatment of acute moderate to severe COVID-19: A follow up study from a Phase IIa trial</strong> -
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<div>
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Background: We previously conducted a Phase IIa randomized placebo-controlled trial of 40 subjects to assess the efficacy and safety of dupilumab use in those hospitalized with COVID-19 (NCT04920916). Based on our pre-clinical data suggesting downstream pulmonary dysfunction with COVID-19 induced type 2 inflammation, we contacted patients from our Phase IIa study at 1 year for assessment of Post Covid-19 Conditions (PCC). Methods: Subjects at 1 year after treatment underwent pulmonary function testing (PFTs), high resolution computed tomography (HRCT) imaging, symptom questionnaires, neurocognitive assessments, and serum immune biomarker analysis, with subject survival also monitored. The primary outcome was the proportion of abnormal PFTs, defined as an abnormal diffusion capacity for carbon monoxide (DLCO) or 6-minute walk testing (6MWT) at the 1-year visit. Results: Sixteen of the 29 one-year survivors consented to the follow up visit. We found that subjects who had originally received dupilumab were less likely to have abnormal PFTs compared to those who received placebo (Fishers exact p=0.011, adjusted p=0.058). We additionally found that 3 out of 19 subjects (16%) in the dupilumab group died by 1 year compared to 8 out of 21 subjects (38%) in the placebo group (log rank p=0.12). We did not find significant differences in neurocognitive testing, symptoms or CT chest imaging between treatment groups but observed evidence of reduced type 2 inflammation in those who received dupilumab. Conclusions: We observed evidence of reduced long-term morbidity and mortality from COVID-19 with dupilumab treatment during acute hospitalization when added to standard of care regimens.
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</p>
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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.medrxiv.org/content/10.1101/2023.09.01.23293947v1" target="_blank">Pulmonary function and survival one year after dupilumab treatment of acute moderate to severe COVID-19: A follow up study from a Phase IIa trial</a>
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</div></li>
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<li><strong>Toward an Online System to Generate Tailored Infographics: Supporting the Health Information Sharing Needs of Community-Based Organizations</strong> -
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<div>
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Infographics are an engaging way to share health information with the public, but their relevance and appeal can be improved if they can be tailored to the language, culture, and information needs of their target audience. Digital tools are needed to make such tailoring feasible at scale, and to meet the needs of the community-based organizations (CBOs) that are well-situated to share health information with the public. Here, we describe our progress toward the development of the TailorVis Toolbox, an online system that facilitates infographic tailoring at the level of the CBO and the individual viewer. Incorporated within this project was the participatory design of infographics related to COVID-19 testing and vaccination. The system will be extended to numerous health topics in the future.
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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/8r2cm/" target="_blank">Toward an Online System to Generate Tailored Infographics: Supporting the Health Information Sharing Needs of Community-Based Organizations</a>
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</div></li>
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<li><strong>Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets</strong> -
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<div>
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After years of the COVID-19 pandemic, over 40 million children worldwide are at risk of measles due to delayed vaccination and temporary SARS-CoV-2 viral dominance. Acute measles has a case-fatality rate of ~1%, but most morbidity and mortality arise post-measles due to destruction of pre-existing immune memory by lymphotropic measles virus (MeV), a paramyxovirus of the Morbillivirus genus. MeV-induced immune amnesia is not mitigated by post-exposure vaccination and the impact of unrelated respiratory virus disease history on measles severity has not been defined. We used a lethal canine distemper virus (CDV)-ferret model as surrogate for human morbillivirus disease and employed the orally efficacious broad-spectrum paramyxovirus polymerase inhibitor GHP-88309 to establish measles treatment paradigms. Applying a receptor tropism-intact recombinant CDV with low lethality, we provide in vivo confirmation of the morbillivirus immune amnesia hypothesis and reveal an 8-day advantage of antiviral treatment versus therapeutic vaccination in preserving immune memory. Infection of ferrets with non-lethal influenza A virus (IAV) A/CA/07/2009 (H1N1) or respiratory syncytial virus (RSV) four weeks prior to CDV caused exacerbated CDV disease that rapidly advanced to fatal hemorrhagic pneumonia associated with lung onslaught by commensal bacteria. RNAseq of BAL samples and lung tissue identified CDV-induced expression of trefoil factor (TFF) peptides, which was absent in animals pre-infected with IAV, thus highlighting that immune priming by unrelated respiratory viruses influences morbillivirus infection outcome. Non-invasive pulmonary ferret MRI revealed that severe outcomes of consecutive IAV/CDV infections were prevented by oral GHP-88309 treatment even when initiated after peak clinical signs of CDV. These findings validate the morbillivirus immune amnesia hypothesis, define treatment paradigms for measles, identify prior disease history as risk factor for exacerbated morbillivirus disease, and demonstrate that treating morbillivirus infection with direct-acting oral antivirals provides therapeutic benefit regardless of whether the time window to mitigate primary clinical signs of infection has closed.
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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/10.1101/2023.09.01.555992v1" target="_blank">Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets</a>
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</div></li>
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<li><strong>A response playbook for early detection and population surveillance of new SARS-CoV-2 variants in a regional public health laboratory</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: Timely genomic surveillance is required to inform public health responses to new SARS-CoV-2 variants. However, the processes involved in local genomic surveillance introduce inherent time constraints. The Regional Innovative Public Health Laboratory in Chicago developed and employed a genomic surveillance response playbook for the early detection and surveillance of emerging SARS-CoV-2 variants. Methods: The playbook outlines modifications to sampling strategies, laboratory workflows, and communication processes based on the emerging variant9s predicted viral characteristics, observed public health impact in other jurisdictions and local community risk level. The playbook outlines procedures for implementing and reporting enhanced and accelerated genomic surveillance, including supplementing whole genome sequencing (WGS) with variant screening by quantitative PCR (qPCR). Results: The ability of the playbook to improve the response to an emerging variant was tested for SARS-CoV-2 Omicron BA.1. Increased submission of clinical remnant samples from local hospital laboratories enabled detection of a new variant at 1% prevalence with 95% confidence rather than 2% at baseline. Genotyping qPCR concurred with WGS lineage assignments in 99.9% of 1541 samples with results by both methods, and was more sensitive, providing lineage results in 90.4% of 1833 samples rather than 85.1% for WGS, while reducing the time to lineage result from 27 to 7 days. Conclusions: The genomic surveillance response playbook provides a structured, stepwise, and data-driven approach to responding to emerging SARS-CoV-2 variants. These pre-defined processes can streamline workflows and expedite the detection and public health response to emerging variants. Based on the processes piloted during the Omicron BA.1 response, this method has been applied to subsequent Omicron subvariants and can be readily applied to future SARS-CoV-2 emerging variants and other public health surveillance activities.
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</p>
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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.medrxiv.org/content/10.1101/2023.09.01.23293209v1" target="_blank">A response playbook for early detection and population surveillance of new SARS-CoV-2 variants in a regional public health laboratory</a>
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</div></li>
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<li><strong>Application of MALDI-MS and Machine Learning to Detection of SARS-CoV-2 and non-SARS-CoV-2 Respiratory Infections.</strong> -
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Background: Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) could aid the diagnosis of acute respiratory infections (ARI) owing to its affordability and high-throughput capacity. MALDI-MS has been proposed for use on commonly available respiratory samples, without specialized sample preparation, making this technology especially attractive for implementation in low-resource regions. Here, we assessed the utility of MALDI-MS in differentiating SARS-CoV-2 versus non-COVID acute respiratory infections (NCARI) in a clinical lab setting of Kazakhstan. Methods: Nasopharyngeal swabs were collected from in- and outpatients with respiratory symptoms and from asymptomatic controls (AC) in 2020-2022. PCR was used to differentiate SARS-CoV-2+ and NCARI cases. MALDI-MS spectra were obtained for a total of 252 samples (115 SARS-CoV-2+, 98 NCARI and 39 AC) without specialized sample preparation. In our first sub-analysis, we followed a published protocol for peak preprocessing and Machine Learning (ML), trained on publicly available spectra from South American SARS-CoV-2+ and NCARI samples. In our second sub-analysis, we trained ML models on a peak intensity matrix representative of both South American (SA) and Kazakhstan (Kaz) samples. Results: Applying the established MALDI-MS pipeline “as is” resulted in a high detection rate for SARS-CoV-2+ samples (91.0%), but low accuracy for NCARI (48.0%) and AC (67.0%) by the top-performing random forest model. After re-training of the ML algorithms on the SA-Kaz peak intensity matrix, the accuracy of detection by the top-performing Support Vector Machine with radial basis function kernel model was at 88.0, 95.0 and 78% for the Kazakhstan SARS-CoV-2+, NCARI, and AC subjects, respectively with a SARS-CoV-2 vs. rest ROC AUC of 0.983 [0.958, 0.987]; a high differentiation accuracy was maintained for the South American SARS-CoV-2 and NCARI. Conclusions: MALDI-MS/ML is a feasible approach for the differentiation of ARI without a specialized sample preparation. The implementation of MALDI-MS/ML in a real clinical lab setting will necessitate continuous optimization to keep up with the rapidly evolving landscape of ARI.
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</p>
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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.medrxiv.org/content/10.1101/2023.08.31.23294891v1" target="_blank">Application of MALDI-MS and Machine Learning to Detection of SARS-CoV-2 and non-SARS-CoV-2 Respiratory Infections.</a>
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</div></li>
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<li><strong>A mathematical model for multiple COVID-19 waves applied to Kenya</strong> -
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The COVID-19 pandemic, which began in December 2019, prompted governments to implement non-pharmaceutical interventions (NPIs) to curb its spread. Despite these efforts and the discovery of vaccines and treatments, the disease continued to circulate globally, evolving into multiple waves, largely driven by emerging COVID-19 variants. Mathematical models have been very useful in understanding the dynamics of the pandemic. Mainly, their focus has been limited to individual waves without easy adaptability to multiple waves. In this study, we propose a compartmental model that can accommodate multiple waves, built on three fundamental concepts. Firstly, we consider the collective impact of all factors affecting COVID-19 and express their influence on the transmission rate through piecewise exponential-cum-constant functions of time. Secondly, we introduce techniques to model the fore sections of observed waves, that change infection curves with negative gradients to those with positive gradients, hence, generating new waves. Lastly, we implement a jump mechanism in the susceptible fraction, enabling further adjustments to align the model with observed infection curve. By applying this model to the Kenyan context, we successfully replicate all COVID-19 waves from March 2020 to January 2023. The identified change points align closely with the emergence of dominant COVID-19 variants, affirming their pivotal role in driving the waves. Furthermore, this adaptable approach can be extended to investigate any new COVID-19 variant or any other periodic infectious diseases, including influenza. Keywords: Mathematical model, COVID-19 pandemic, non-pharmaceutical interventions, delay functions, multiple waves
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.09.01.23294943v1" target="_blank">A mathematical model for multiple COVID-19 waves applied to Kenya</a>
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<li><strong>Characteristics of the sexual networks of gay, bisexual, and other men who have sex with men in Montréal, Toronto, and Vancouver: implications for the transmission and control of mpox in Canada</strong> -
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Background: The 2022-2023 global mpox outbreak disproportionately affected gay, bisexual, and other men who have sex with men (GBM). In Canada, >70% of cases thus far have been among GBM in Montréal, Toronto, and Vancouver. We examined how the distributions of sexual partners 1) varied by city and over time related to the COVID-19 pandemic and 2) were associated with mpox transmission. Methods: The <i>Engage Cohort Study</i> (2017-2023) recruited GBM via respondent-driven sampling in Montréal, Toronto, and Vancouver (n=2,449). We compared numbers of sexual partners in the past 6 months across cities and three time periods: pre-COVID-19 pandemic (2017-2019), pandemic (2020-2021), and post-restrictions (2021-2023). We modeled the distribution of sexual partner numbers using Bayesian negative binomial regressions and post-stratification, adjusting for sampling design and attrition. We estimated the basic reproduction number (<i>R<sub>0</sub></i>), secondary attack rate (SAR), and cumulative incidence proportion of mpox using the fitted distributions and case timeseries. Results: The pre-COVID-19 pandemic distribution of sexual partner numbers was similar across cities: participants9 mean number of partners was 10.3 (95%CrI: 9.3-11.3) in Montréal, 12.8 (11.1-14.7) in Toronto, and 10.6 (9.41-11.9) in Vancouver. Partner numbers decreased during the pandemic in all cities. Post-restrictions, sexual activity increased but remained well below pre-pandemic levels. Based on reported cases and post-restrictions distributions, the estimated <i>R<sub>0</sub></i> (2.4-2.6) and cumulative incidences (0.6-0.9%) were similar across cities. The estimated average SAR across cities was 79%. Conclusion: GBM sexual activity after restrictions were lifted remained below pre-pandemic levels. Comparable sexual partner distributions across cities may explain similarities in mpox <i>R<sub>0</sub></i> and cumulative incidence across cities. Public health authorities should consider the risk of mpox resurgence for future vaccination and surveillance strategies as sexual activity is expected to recover.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.31.23294912v1" target="_blank">Characteristics of the sexual networks of gay, bisexual, and other men who have sex with men in Montréal, Toronto, and Vancouver: implications for the transmission and control of mpox in Canada</a>
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</div></li>
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<li><strong>Symptom experience before vs. after confirmed SARS-CoV-2 infection: a population and case control study using prospectively recorded symptom data.</strong> -
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Background: Some individuals experience prolonged illness after acute COVID-19. We assessed whether pre-infection symptoms affected post-COVID illness duration. Methods Survival analysis was performed in adults (n=23,452) with community-managed SARC-CoV-2 infection prospectively self-logging data through the ZOE COVID Symptom Study app, at least weekly, from 8 weeks before to 12 weeks after COVID-19 onset, conditioned on presence vs. absence of baseline symptoms (4-8 weeks before COVID-19). A case-control study was performed in 1350 individuals with long illness (≥8 weeks, 906 [67.1%] with illness ≥12 weeks), matched 1:1 (for age, sex, body mass index, testing week, prior infection, vaccination, smoking, index of multiple deprivation) with 1350 individuals with short illness (<4 weeks). Baseline symptoms were compared between the two groups; and against post-COVID symptoms. Findings: Individuals reporting baseline symptoms had longer post-COVID symptom duration (from 10 to 15 days) with baseline fatigue nearly doubling duration. Two-thirds (910 of 1350 [67.4%]) of individuals with long illness were asymptomatic beforehand. However, 440 (32.6%) had baseline symptoms, vs. 255 (18.9%) of 1350 individuals with short illness (p<0.0001). Baseline symptoms increased the odds ratio for long illness (2.14 [CI: 1.78; 2.57]). Prior comorbidities were more common in individuals with long vs. short illness. In individuals with long illness, baseline symptomatic (vs. asymptomatic) individuals were more likely to be female, younger, and have prior comorbidities; and baseline and post-acute symptoms and symptom burden correlated strongly. Interpretation: Individuals experiencing symptoms before COVID-19 have longer illness duration and increased odds of long illness. However, many individuals with long illness are well before SARS-CoV-2 infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.30.23294821v1" target="_blank">Symptom experience before vs. after confirmed SARS-CoV-2 infection: a population and case control study using prospectively recorded symptom data.</a>
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<li><strong>Observational Study of Repeat Immunoadsorption (RIA) in Post-COVID ME/CFS Patients with Elevated Beta-2-Adrenergic Receptor Autoantibodies</strong> -
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There is increasing evidence for an autoimmune aetiology in post-infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). SARS-CoV-2 has now become the main trigger for ME/CFS. We have already conducted two small proof-of-concept studies of IgG depletion by immunoadsorption (IA) in post-infectious ME/CFS, which showed efficacy in most patients. This observational study aims to evaluate the efficacy of IA in patients with post-COVID-19 ME/CFS. The primary objective is to assess the improvement in functional ability. Due to the urgency of finding therapies for post-Covid-Syndrome (PCS), we report here the interim results of the first ten patients with seven responders defined by an increase of between 10 and 35 points in the Short-Form 36 Physical Function (SF36-PF) at week four after IA. The results of this observational study will provide the basis for patient selection for a randomised controlled trial (RTC) including sham apheresis and for a RTC combining IA with B-cell depletion therapy.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.31.23294813v1" target="_blank">Observational Study of Repeat Immunoadsorption (RIA) in Post-COVID ME/CFS Patients with Elevated Beta-2-Adrenergic Receptor Autoantibodies</a>
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<li><strong>Changes in child and adolescent mental health across the COVID-19 pandemic (2018-2023): Insights from general population and clinical samples in the Netherlands</strong> -
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Background The COVID-19 pandemic negatively affected child and adolescent mental health and at the end of the pandemic (April 2022) child mental health had not returned to pre‐pandemic levels. We investigated whether this observed increase in mental health problems has continued, halted, or reversed after the end of the pandemic in children from the general population and in children in psychiatric care. Methods We collected parent-reported and child-reported data at two additional post-pandemic time points (November/December 2022 and March/April 2023) in children (8-18 years) from two general population samples (N=818-1056 per measurement) and one clinical sample receiving psychiatric care (N=320-370) and compared these with data from before the pandemic. We collected parent‐reported data on internalizing and externalizing problems with the Brief Problem Monitor (BPM) and self‐reported data on Anxiety, Depressive symptoms, Sleep‐related impairments, Anger, Global health, and Peer relations with the Patient‐Reported Outcomes Measurement Information System (PROMIS). Results In the general population, parents reported no changes in externalizing problems but did report higher internalizing problems post-pandemic than pre-pandemic. Children also reported increased mental health problems post-pandemic, especially in anxiety and depression, to a lesser extent in sleep-related impairment and global health, and least in anger. In the clinical sample, parents reported higher internalizing, but not externalizing problems post-pandemic compared to the start of the pandemic. Children reported greatest increases in problems in anxiety, depression, and global health, to a lesser extent on sleep-related impairment, and least on anger. Conclusions Child mental health problems in the general population are substantially higher post-pandemic compared to pre-pandemic measurements. In children in psychiatric care mental health problems have increased during the pandemic and are substantially higher post-pandemic than at the start of the pandemic. Longitudinal and comparative studies are needed to assess what the most important drivers of these changes are.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.29.23294764v1" target="_blank">Changes in child and adolescent mental health across the COVID-19 pandemic (2018-2023): Insights from general population and clinical samples in the Netherlands</a>
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<li><strong>ISARIC COVID-19 Clinical Data Report: 10 January 2023</strong> -
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ISARIC (International Severe Acute Respiratory and emerging Infections Consortium) partnerships and outbreak preparedness initiatives enabled the rapid launch of standardised clinical data collection on COVID-19 in Jan 2020. Extensive global participation has resulted in a large, standardised collection of comprehensive clinical data from hundreds of sites across dozens of countries. Data are analysed regularly and reported publicly to inform patient care and public health response. This report, our 18th and final report, is a part of a series published over 3 years. Data have been entered for 945,317 individuals from 1807 partner institutions and networks across 76 countries. The comprehensive analyses detailed in this report includes hospitalised individuals of all ages for whom data collection occurred between 30 January 2020 and up to and including 10 January 2023, AND who have laboratory-confirmed SARS-COV-2 infection or clinically diagnosed COVID-19. For the 845,291 cases who meet eligibility criteria for this report, selected findings include: o Median age of 57 years, with an approximately equal (50/50) male:female sex distribution o 29% of the cohort are at least 70 years of age, whereas 6% are 0-19 years of age o The most common symptom combination in this hospitalised cohort is shortness of breath, cough, and history of fever, which has remained constant over time o The five most common symptoms at admission were shortness of breath, cough, history of fever, fatigue/malaise, and altered consciousness/confusion, which is unchanged from the previous reports o Age-associated differences in symptoms are evident, including the frequency of altered consciousness increasing with age, and fever, respiratory and constitutional symptoms being present mostly in those 40 years and above o 15% of patients with relevant data available (845,291) were admitted at some point during their illness into an intensive care unit (ICU), which has decreased from 19% during the 3 years of ISARIC reporting o Antibiotic agents were used in 37% of patients for whom relevant data are available (802,241), a significant reduction from our previous reports (80%) which reflects a shifting proportion of data contributed by different institutions; in ICU/HDU admitted patients with data available (64,669), 90% received antibiotics o Use of corticosteroids was reported in 25% of all patients for whom data were available (809,043); in ICU/HDU admitted patients with data available (64,713), 71% received corticosteroids o Outcomes are known for 762,728 patients and the overall estimated case fatality ratio (CFR) is 22% (95%CI 21.9-22), rising to 36% (95%CI 35.6-36.1) for patients who were admitted to ICU/HDU, demonstrating worse outcomes in those with the most severe disease We thank all the data contributors for their ongoing support.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2020.07.17.20155218v16" target="_blank">ISARIC COVID-19 Clinical Data Report: 10 January 2023</a>
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<li><strong>Can long-term COVID-19 vaccination be improved by serological surveillance?: a modeling study for Mozambique</strong> -
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Seroprevalence provides an estimate of the population-level susceptibility to infection. In this study, we used a transmission model to examine the potential of using serological surveillance to inform the timing of COVID-19 boosters in Mozambique. We simulated using population-level seroprevalence thresholds as an estimate of the risk of outbreaks to trigger the timing of re-vaccination campaigns among older adults. We compare this approach to a strategy of re-vaccination at fixed time intervals. Vaccinating older adults each time the seroprevalence among older adults falls below 50% and 80% resulted in medians of 20% and 71% reduction in deaths, respectively, and number-needed-to-vaccinate to avert one death (NNT) of 1,499 (2.5th-97.5th centile:1,252-1,905) and 3,151 (2,943-3,429), respectively. In comparison, biennial and annual re-vaccination of older adults resulted in medians of 35% and 52% deaths averted, respectively, and NNTs of 1,443 (1,223-1,733) and 1,941 (1,805-2,112), respectively. We conducted sensitivity analysis over a range of antibody waning rates and epidemic scenarios and found that re-vaccination trigger thresholds of 50-60% seroprevalence are most likely to be efficient compared to fixed-time strategies. However, given marginal gains in efficiency even in the best-case scenarios, our results favor the use of simpler fixed-time strategies for long-term control of SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.29.23294793v1" target="_blank">Can long-term COVID-19 vaccination be improved by serological surveillance?: a modeling study for Mozambique</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>THE EFFECT OF ARGININE AND GLUTAMINE ON COVID-19 PATIENTS OUTCOME: A RANDOMIZED CLINICAL TRIAL</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Dietary Supplement: Neomune<br/><b>Sponsors</b>: Universitas Sriwijaya; M. Djamil General Hospital<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>KAND567 Versus Placebo in Subjects Hospitalized With COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: KAND567; Drug: Microcrystalline cellulose<br/><b>Sponsor</b>: Kancera AB<br/><b>Terminated</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 2/3 2nd Generation E1/E2B/E3-Deleted Adenoviral COVID-19 Vaccine: The TCELLVACCINE TRIAL</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: hAd5-S-Fusion+N-ETSD; Biological: Placebo (0.9% (w/v) saline)<br/><b>Sponsor</b>: ImmunityBio, Inc.<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Aerobic Training for Rehabilitation of Patients With Post Covid-19 Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Long-COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: Aerobic Exercise Training<br/><b>Sponsors</b>: University of Witten/Herdecke; Institut für Rehabilitationsforschung Norderney<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Digital Health Literacy on COVID-19 for All: Co-creation and Evaluation of Interventions for Ethnic Minorities and Chinese People With Chronic Illnesses in Hong Kong</strong> - <b>Conditions</b>: Digital Health Literacy; COVID-19<br/><b>Intervention</b>: Behavioral: Digital health literacy intervention<br/><b>Sponsor</b>: The Hong Kong Polytechnic University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Pilot Clinical Evaluation of Astepro® Nasal Spray for Management of Early SARS-CoV-2 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Experimental: Primary Cohort; Other: Placebo Comparator: Primary Cohort - Placebo<br/><b>Sponsor</b>: University of Chicago<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>COVID-19 Vaccination Hesitancy in Adults With Sickle Cell Disease</strong> - <b>Conditions</b>: Sickle Cell Disease; COVID-19 Vaccine; Vaccine Hesitancy<br/><b>Intervention</b>: Behavioral: SCD-specific COVID-19 vaccination information (SCVI) video<br/><b>Sponsors</b>: Duke University; American Society of Hematology<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Comparative Immunogenicity of Concomitant vs Sequential mRNA COVID-19 and Influenza Vaccinations</strong> - <b>Conditions</b>: Influenza; COVID-19; Influenza Immunogencity; COVID-19 Immunogenicity<br/><b>Interventions</b>: Biological: Simultaneous Vaccination (Influenza Vaccine and mRNA COVID booster); Biological: Sequential Vaccination (Influenza vaccine then mRNA COVID booster); Biological: Sequential Vaccination (mRNA COVID booster then Influenza vaccine)<br/><b>Sponsors</b>: Duke University; Centers for Disease Control and Prevention; Arizona State University; University Hospitals Cleveland Medical Center; University of Pittsburgh; Washington University School of Medicine; Valleywise Health; VA Northeast Ohio Health Care; Senders Pediatrics<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Pulmonary Rehabilitation Among Post-COVID-19 Patients in a Tertiary Care Hospital in Bangladesh</strong> - <b>Condition</b>: Pulmonary Pathology<br/><b>Intervention</b>: Behavioral: Pulmonary Rehabilitation<br/><b>Sponsor</b>: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh<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>Bronchoalveolar Lavage in Recovered From COVID-19 Pneumonia</strong> - <b>Condition</b>: Bronchoalveolar Lavage<br/><b>Intervention</b>: Procedure: Bronchoalveolar Lavage<br/><b>Sponsors</b>: Mohamed Abd Elmoniem Mohamed; Marwa Salah Abdelrazek Ghanem; Mohammad Khairy El-Badrawy; Tamer Ali Elhadidy; Dalia Abdellateif Abdelghany<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Randomized, Double-blind, Placebo-controlled Trial of the Efficacy and Safety of Tianeptine in the Treatment of Covid Fog Symptoms in Patients After COVID-19.</strong> - <b>Condition</b>: Nervous System Diseases<br/><b>Interventions</b>: Drug: Tianeptine; Drug: Placebo<br/><b>Sponsors</b>: Military Institute od Medicine National Research Institute; ABM Industries<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of Cognitive-behavioral Therapy for Insomnia in Nurses With Post Covid-19 Condition</strong> - <b>Condition</b>: Cognitive Behavioral Therapy<br/><b>Intervention</b>: Behavioral: cognitive behavioral therapy<br/><b>Sponsor</b>: Tri-Service General Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effectiveness of Natural Resources for Reducing Stress</strong> - <b>Conditions</b>: Distress, Emotional; COVID-19<br/><b>Interventions</b>: Combination Product: Balneotherapy plus complex; Combination Product: Combined nature resources treatment; Other: Nature therapy procedure<br/><b>Sponsors</b>: Klaipėda University; Research Council of Lithuania<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of LAU-7b for the Treatment of Long COVID in Adults</strong> - <b>Condition</b>: Long COVID<br/><b>Interventions</b>: Drug: LAU-7b for 3 cycles; Drug: LAU-7b for 1 cycle, then placebo; Other: Placebo for 3 cycles<br/><b>Sponsor</b>: Laurent Pharmaceuticals 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>Complementary and Integrative Medicine as an Online Intervention in Patients With Post-covid Syndrome After COVID-19</strong> - <b>Condition</b>: Post-COVID Syndrome<br/><b>Interventions</b>: Behavioral: Complementary and Integrative Medicine online intervention, routine care and book; Behavioral: Routine care and book<br/><b>Sponsor</b>: Charite University, Berlin, Germany<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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>High-CBD cannabis extracts inhibit the expression of proinflammatory factors via miRNA-mediated silencing in human small intestinal epithelial cells</strong> - The incidence of chronic inflammatory disorders and autoimmune diseases is rapidly growing. To date, the COVID-19 pandemic caused by SARS-CoV-2 has killed over 6,209,000 people globally, while no drug has been proven effective for the disease. Screening natural anti-inflammatory compounds for clinical application has drawn much attention. In this study, we showed that high-CBD cannabis extracts #1, #5, #7, #169, and #317 suppressed the levels of expression of proinflammatory cyclooxygenase 2…</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>Plant flavonoid inhibition of SARS-CoV-2 main protease and viral replication</strong> - Plant-based flavonoids have been evaluated as inhibitors of β-coronavirus replication and as therapies for COVID-19 on the basis of their safety profile and widespread availability. The SARS-CoV-2 main protease (Mpro) has been implicated as a target for flavonoids in silico. Yet no comprehensive in vitro testing of flavonoid activity against SARS-CoV-2 Mpro has heretofore been performed. We screened 1,019 diverse flavonoids for their ability to inhibit SARS-CoV-2 Mpro. Multiple…</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>Combating pan-coronavirus infection by indomethacin through simultaneously inhibiting viral replication and inflammatory response</strong> - Severe infections with coronaviruses are often accompanied with hyperinflammation, requiring therapeutic strategies to simultaneously tackle the virus and inflammation. By screening a safe-in-human broad-spectrum antiviral agents library, we identified that indomethacin can inhibit pan-coronavirus infection in human cell and airway organoids models. Combining indomethacin with oral antiviral drugs authorized for treating COVID-19 results in synergistic anti-coronavirus activity. Coincidentally,…</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>Assessing the outcomes of prescribing angiotensin converting enzyme inhibitors and angiotensin receptor blockers for COVID-19 patients</strong> - CONCLUSION: Inhibition of the renin-angiotensin-aldosterone-system had no effect on the mortality of patients with COVID-19 and on their overall disease progression. However, it may be beneficial not to stop these medications as they decrease inflammation in the body and the levels of troponin, which are related to increased stress on the heart.</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>Deadly interactions: synergistic manipulations of concurrent pathogen infections potentially enabling future pandemics</strong> - Certain monoinfections of influenza viruses and novel coronaviruses, including severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) are significant threats to human health. Concurrent infections by influenza viruses and coronaviruses increases their threat. Influenza viruses have eight manipulations capable of assisting SARS-CoV-2 and other coronaviruses, and several of these manipulations, which are not specific to viruses, can also directly or indirectly boost dangerous secondary…</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>An evolutionarily conserved strategy for ribosome binding and host translation inhibition by β-coronavirus non-structural protein 1</strong> - An important pathogenicity factor of SARS-CoV-2 and related coronaviruses is Non-structural protein 1 (Nsp1), which suppresses host gene expression and stunts antiviral signaling. SARS-CoV-2 Nsp1 binds the ribosome to inhibit translation through mRNA displacement and induces degradation of host mRNAs. Here we show that Nsp1-dependent host shutoff is conserved in diverse coronaviruses, but only Nsp1 from β-Coronaviruses (β-CoV) inhibits translation through ribosome binding. The C-terminal domain…</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 envelope protein induces necroptosis and mediates inflammatory response in lung and colon cells through receptor interacting protein kinase 1</strong> - SARS-CoV-2 Envelope protein (E) is one of the crucial components in virus assembly and pathogenesis. The current study investigated its role in the SARS-CoV-2-mediated cell death and inflammation in lung and gastrointestinal epithelium and its effect on the gastrointestinal-lung axis. We observed that transfection of E protein increases the lysosomal pH and induces inflammation in the cell. The study utilizing Ethidium bromide/Acridine orange and Hoechst/Propidium iodide staining demonstrated…</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>Structure and function of SARS-CoV and SARS-CoV-2 main proteases and their inhibition: A comprehensive review</strong> - Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) identified in 2003 infected ∼8000 people in 26 countries with 800 deaths, which was soon contained and eradicated by syndromic surveillance and enhanced quarantine. A closely related coronavirus SARS-CoV-2, the causative agent of COVID-19 identified in 2019, has been dramatically more contagious and catastrophic. It has infected and caused various flu-like symptoms of billions of people in >200 countries, including >6 million…</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>Antimicrobial effect of oral care gel containing hinokitiol and 4-isopropyl-3-methylphenol against intraoral pathogenic microorganisms</strong> - CONCLUSIONS: These data suggest that oral care gel-containing hinokitiol and IPMP has strong biofilm formation inhibitory activity, as well as antifungal and antimicrobial effects against Candida fungi and multiple intraoral pathogenic microorganisms. Therefore, it may be a promising treatment option for oral infections.</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>Inhibition of the Cellular Deubiquitinase UCHL1 Suppresses SARS-CoV-2 Replication</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Hybrid molecules based on an emodin scaffold. Synthesis and activity against SARS-CoV-2 and <em>Plasmodium</em></strong> - Since the Covid-19 epidemic, it has been clear that the availability of small and affordable drugs that are able to efficiently control viral infections in humans is still a challenge in medicinal chemistry. The synthesis and biological activities of a series of hybrid molecules that combine an emodin moiety and other structural moieties expected to act as possible synergistic pharmacophores in a single molecule were studied. Emodin has been reported to block the entry of the SARS-CoV-2 virus…</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 molecular mechanism of non-covalent inhibitor WU-04 targeting SARS-CoV-2 3CLpro and computational evaluation of its effectiveness against mainstream coronaviruses</strong> - There is an urgent need for highly effective therapeutic agents to interrupt the continued spread of SARS-CoV-2. As a pivotal protease in the replication process of coronaviruses, the 3CLpro protein is considered as a potential target of drug development to stop the spread and infection of the virus. In this work, molecular dynamics (MD) simulations were used to elucidate the molecular mechanism of a novel and highly effective non-covalent inhibitor, WU-04, targeting the SARS-CoV-2 3CLpro…</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 use of <em>Ephedra</em> herbs in the treatment of COVID-19</strong> - CONCLUSION: Some plants used in traditional medicine, including the Ephedra herbs, with their active compounds, can be considered a candidate with high potential for the control and prevention of COVID-19.</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 network pharmacology analysis and in vitro validation revealed the underlying mechanism of Xiyanping injection in treating coronavirus disease 2019</strong> - CONCLUSION: Through effective network pharmacology analysis and molecular docking, this study suggests that XYP contains many effective compounds that may target COVID-19 related signaling pathways. Moreover, the in vitro experiment confirmed that XYP could inhibit the cytokine storm by regulating genes or proteins related to immune and inflammatory responses.</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>Engineered clinical-grade mesenchymal stromal cells combating SARS-CoV-2 omicron variants by secreting effective neutralizing antibodies</strong> - CONCLUSIONS: Our data suggested that engineered clinical-grade MSCs secreting effective neutralizing antibodies as cellular production machines had the potential to combat SARS-CoV-2 infection, which provided a new avenue for effectively treating the older and immunocompromised COVID-19 patients.</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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