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196 lines
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<title>29 June, 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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<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>A human primary airway microphysiological system infected with SARS-CoV-2 distinguishes the treatment efficacy between nirmatrelvir and repurposed compounds fluvoxamine and amodiaquine</strong> -
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The COVID-19 pandemic necessitated a rapid mobilization of resources toward the development of safe and efficacious vaccines and therapeutics. Finding effective treatments to stem the wave of infected individuals needing hospitalization and reduce the risk of adverse events was paramount. For scientists and healthcare professionals addressing this challenge, the need to rapidly identify medical countermeasures became urgent, and many compounds in clinical use for other indications were repurposed for COVID-19 clinical trials after preliminary preclinical data demonstrated antiviral activity against SARS-CoV-2. Two repurposed compounds, fluvoxamine and amodiaquine, showed efficacy in reducing SARS-CoV-2 viral loads in preclinical experiments, but ultimately failed in clinical trials, highlighting the need for improved predictive preclinical tools that can be rapidly deployed for events such as pandemic emerging infectious diseases. The PREDICT96-ALI platform is a high-throughput, high-fidelity microphysiological system (MPS) that recapitulates primary human tracheobronchial tissue and supports highly robust and reproducible viral titers of SARS-CoV-2 variants Delta and Omicron. When amodiaquine and fluvoxamine were tested in PREDICT96-ALI, neither compound demonstrated an antiviral response, consistent with clinical outcomes and in contrast with prior reports assessing the efficacy of these compounds in other human cell-based in vitro platforms. These results highlight the unique prognostic capability of the PREDICT96-ALI proximal airway MPS to assess the potential antiviral response of lead compounds.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.27.546790v1" target="_blank">A human primary airway microphysiological system infected with SARS-CoV-2 distinguishes the treatment efficacy between nirmatrelvir and repurposed compounds fluvoxamine and amodiaquine</a>
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</div></li>
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<li><strong>Efficacy of the oral nucleoside prodrug GS-5245 (Obeldesivir) against SARS-CoV-2 and coronaviruses with pandemic potential</strong> -
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Despite the wide availability of several safe and effective vaccines that can prevent severe COVID-19 disease, the emergence of SARS-CoV-2 variants of concern (VOC) that can partially evade vaccine immunity remains a global health concern. In addition, the emergence of highly mutated and neutralization-resistant SARS-CoV-2 VOCs such as BA.1 and BA.5 that can partially or fully evade (1) many therapeutic monoclonal antibodies in clinical use underlines the need for additional effective treatment strategies. Here, we characterize the antiviral activity of GS-5245, Obeldesivir (ODV), an oral prodrug of the parent nucleoside GS-441524, which targets the highly conserved RNA-dependent viral RNA polymerase (RdRp). Importantly, we show that GS-5245 is broadly potent in vitro against alphacoronavirus HCoV-NL63, severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-related Bat-CoV RsSHC014, Middle East Respiratory Syndrome coronavirus (MERS-CoV), SARS-CoV-2 WA/1, and the highly transmissible SARS-CoV-2 BA.1 Omicron variant in vitro and highly effective as antiviral therapy in mouse models of SARS-CoV, SARS-CoV-2 (WA/1), MERS-CoV and Bat-CoV RsSHC014 pathogenesis. In all these models of divergent coronaviruses, we observed protection and/or significant reduction of disease metrics such as weight loss, lung viral replication, acute lung injury, and degradation in pulmonary function in GS-5245-treated mice compared to vehicle controls. Finally, we demonstrate that GS-5245 in combination with the main protease (Mpro) inhibitor nirmatrelvir had increased efficacy in vivo against SARS-CoV-2 compared to each single agent. Altogether, our data supports the continuing clinical evaluation of GS-5245 in humans infected with COVID-19, including as part of a combination antiviral therapy, especially in populations with the most urgent need for more efficacious and durable interventions.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.06.27.546784v1" target="_blank">Efficacy of the oral nucleoside prodrug GS-5245 (Obeldesivir) against SARS-CoV-2 and coronaviruses with pandemic potential</a>
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<li><strong>Targeting Multiple Conserved T-Cell Epitopes for Protection against COVID-19 Moderate-Severe Disease by a Pan-Sarbecovirus Vaccine</strong> -
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Background Most of current approved vaccines, based on a Spike-only as single immunogen, fall short of producing a full-blown T-cell immunity. SARS-CoV-2 continues to evolve with ever-emergent higher-contagious mutants that may take a turn going beyond Omicron to bring about a new pandemic outbreak. New recombinant SARS-CoV-2 species could be man-made through genetic manipulation to infect systemically. Development of composition-innovated, pan-variant COVID-19 vaccines to prevent from hospitalization and severe disease, and to forestall the next pandemic catastrophe, is an urgent global objective. Methods and findings In a retrospective, e-questionnaire Observational Study, extended from a clinical Phase-2 trial conducted in Taiwan, during the prime time of Omicron outbreak dominated by BA.2 and BA.5 variants, we investigated the preventive effects against COVID-19 moderate-severe disease (hospitalization and ICU admission) by a pan-Sarbecovirus vaccine UB-612 that targets monomeric S1-RBD-focused subunit protein and five designer peptides comprising sequence-conserved, non-mutable helper and cytotoxic T lymphocyte (Th/CTL) epitopes derived from Spike (S2), Membrane (M) and Nucleocapsid (N) proteins. Per UB-612 vaccination, there were no hospitalization and ICU admission cases (0% rate, 6 months after Omicron outbreak) reported ≥14 months post-2nd dose of primary series, and ≥10 months post-booster (3rd dose), to which the potent memory cytotoxic CD8 T cell immunity may be the pivotal in control of the infection disease severity. Six months post-booster, the infection rate (asymptomatic and symptomatic mild) was only 1.2%, which increased to 27.8% observed ≥10 months post-booster. The notable protection effects are in good alignment with a preliminary Phase-3 heterologous booster trial report showing that UB-612 can serve as a competent booster substitute for other EUA-approved vaccine platforms to enhance their seroconversion rate and viral-neutralizing titer against Omicron BA.5. Conclusions UB-612, a universal multitope vaccine promoting full-blown T cell immunity, may work as a competent primer and booster for persons vulnerable to Sarbecovirus infection. Trial Registration. Clinical Trials.gov ID: NCT04773067.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.28.23291948v1" target="_blank">Targeting Multiple Conserved T-Cell Epitopes for Protection against COVID-19 Moderate-Severe Disease by a Pan-Sarbecovirus Vaccine</a>
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<li><strong>Bayesian nowcasting with Laplacian-P-splines</strong> -
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During an epidemic, the daily number of reported infected cases, deaths or hospitalizations is often lower than the actual number due to reporting delays. Nowcasting aims to estimate the cases that have not yet been reported and combine it with the already reported cases to obtain an estimate of the daily cases. In this paper, we present a fast and flexible Bayesian approach to do nowcasting by combining P-splines and Laplace approximations. The main benefit of Laplacian-P-splines (LPS) is the flexibility and faster computation time compared to Markov chain Monte Carlo (MCMC) algorithms that are often used for Bayesian inference. In addition, it is natural to quantify the prediction uncertainty with LPS in the Bayesian framework, and hence prediction intervals are easily obtained. Model performance is assessed through simulations and the method is applied to COVID-19 mortality and incidence cases in Belgium.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.26.22279249v2" target="_blank">Bayesian nowcasting with Laplacian-P-splines</a>
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<li><strong>COVID-19 Impact in Crohn Disease Patients Underwent Autologous Hematopoietic Stem Cell Transplantation</strong> -
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SARS COV 2 is the virus responsible for COVID-19, a disease that has been blamed for inducing or exacerbating symptoms in patients with autoimmune diseases. Crohn9s disease (CD) is an inflammatory bowel disease that affects genetically susceptible patients who develop an abnormal mucosal immune response to the intestinal microbiota. Patients who underwent Hematopoietic Stem cell Transplantation are considered at risk for COVID-19. The objective of this report was to describe for the first time the impact of COVID-19 in a group of 50 patients with Crohn9s Disease (CD, 28 females, and 22 male) with a mean age of 38 years, previously submitted to Autologous, non-myeloablative, Hematopoietic Stem Cell Transplantation (Auto HSCT) between 2013 and 2021. In this series, 19 patients were diagnosed with positive COVID-19. In two (2) patients there was a report of the occurrence of two infectious episodes. Parameters related to HSCT, such as time elapsed since the procedure, vaccination status, CD status before and after infection, and clinical manifestations resulting from COVID-19, were evaluated. Among the patients with COVID-19, in three, submitted to Auto HSCT less than six (6) months ago, there was a change in the CD status, and one of them, in addition to the CD symptoms, started to present thyroid impairment with positive anti-TPO. Only one of the patients required hospitalization for five days to treat COVID-19 and remained in CD clinical remission. Nine patients reported late symptoms that may be related to COVID-19. There were no deaths, and the statistical evaluation of the series of COVID-19 patients after HSCT and those who did not present an infectious episode did not present significant data regarding the analyzed parameters. Despite the change in CD status in three patients and the presence of nine patients with late symptoms, we can conclude that there was no significant adverse impact concerning COVID-19 in the evaluated patients who underwent HSCT to treat CD. Key Words: Inflammatory bowel disease, Crohn Disease, SARs COV 2, COVID - 19, Autologous Hematopoietic Stem Cell Transplantation, Stem Cell Therapy.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.22.23291610v1" target="_blank">COVID-19 Impact in Crohn Disease Patients Underwent Autologous Hematopoietic Stem Cell Transplantation</a>
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<li><strong>SARS-CoV-2 testing in the Slovak Republic from March 2020 to September 2022 - summary of the pandemic trends</strong> -
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The COVID-19 pandemic has been part of Slovakia since March 2020. Intensive laboratory testing ended in October 2022, when the number of tests dropped significantly, but the state of the pandemic continues to this day. For the management of COVID-19, it is important to find an indicator that can predict pandemic changes in the community. The average daily/weekly Ct value with a certain time delay can predict changes in the number of cases of SARS-CoV-2 infection, which can be a useful indicator for the healthcare system. The study analyzed the results of 1,420,572 RT-qPCR tests provided by one accredited laboratory during the ongoing pandemic in Slovakia from March 2020 to September 2022. The total positivity of the analyzed tests was 24.64%. The average Ct values found were the highest in the age group of 3-5 years, equal to the number 30.75; the lowest were in the age group > 65 years, equal to the number 27. The average weekly Ct values ranged from 22.33 (pandemic wave week) to 30.12 (summer week). We have summarized the results of SARS-CoV-2 diagnostic testing in Slovakia with the scope defined by the rate and positivity of tests carried out at Medirex a.s. laboratories.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.26.23291891v1" target="_blank">SARS-CoV-2 testing in the Slovak Republic from March 2020 to September 2022 - summary of the pandemic trends</a>
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<li><strong>Design and Analysis Heterogeneity in Observational Studies of COVID-19 Booster Effectiveness: A Review and Case Study</strong> -
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Background Observational vaccine effectiveness (VE) studies based on real-world data are a crucial supplement to initial randomized clinical trials of Coronavirus Disease 2019 (COVID-19) vaccines. However, there exists substantial heterogeneity in study designs and statistical methods for estimating VE. The impact of such heterogeneity on VE estimates is not clear. Methods We conducted a two-step literature review of booster VE: a literature search for first or second monovalent boosters on January 1, 2023, and a rapid search for bivalent boosters on March 28, 2023. For each study identified, study design, methods, and VE estimates for infection, hospitalization, and/or death were extracted and summarized via forest plots. We then applied methods identified in the literature to a single dataset from Michigan Medicine (MM), providing a comparison of the impact of different statistical methodologies on the same dataset. Results We identified 53 studies estimating VE of the first booster, 16 for the second booster. Of these studies, 2 were case-control, 17 were test-negative, and 50 were cohort studies. Together, they included nearly 130 million people worldwide. VE for all outcomes was very high (around 90%) in earlier studies (i.e., in 2021), but became attenuated and more heterogeneous over time (around 40%-50% for infection, 60%-90% for hospitalization, and 50%-90% for death). VE compared to the previous dose was lower for the second booster (10-30% for infection, 30-60% against hospitalization, and 50-90% against death). We also identified 11 bivalent booster studies including over 20 million people. Early studies of the bivalent booster showed increased effectiveness compared to the monovalent booster (VE around 50-80% for hospitalization and death). Our primary analysis with MM data using a cohort design included 186,495 individuals overall (including 153,811 boosted and 32,684 with only a primary series vaccination), and a secondary test-negative design included 65,992 individuals tested for SARS-CoV-2. When different statistical designs and methods were applied to MM data, VE estimates for hospitalization and death were robust to analytic choices, with test-negative designs leading to narrower confidence intervals. Adjusting either for the propensity of getting boosted or directly adjusting for covariates reduced the heterogeneity across VE estimates for the infection outcome. Conclusion While the advantage of the second monovalent booster is not obvious from the literature review, the first monovalent booster and the bivalent booster appear to offer strong protection against severe COVID-19. Based on both the literature view and data analysis, VE analyses with a severe disease outcome (hospitalization, ICU admission, or death) appear to be more robust to design and analytic choices than an infection endpoint. Test-negative designs can extend to severe disease outcomes and may offer advantages in statistical efficiency when used properly.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.22.23291692v1" target="_blank">Design and Analysis Heterogeneity in Observational Studies of COVID-19 Booster Effectiveness: A Review and Case Study</a>
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<li><strong>The effect of residential aged care facility COVID-19 lockdowns on resident mortality</strong> -
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Aims This perspective is exploring the effect of residential aged care facility COVID-19 lockdowns on resident mortality. Relevance People living in residential aged care facilities (RACFs) are at increased risk of COVID-19 infection and death. In Australia, COVID-19 infections in RACF residents represented seven percent of recorded infections and the case fatality rate (CFR) was 33%. RACFs were categorised as high-risk settings for COVID-19 and a number of measures to reduce the risk of acquiring COVID-19 were implemented at the National and State and Territory levels, such as strict infection control, monitoring, testing, vaccination and increased clinical capacity. Methods All COVID-19 infections and deaths in the 12-months from 15 October 2021 to 14 October 2022 for the cohort of residents living in an Australian RACF (except Western Australia) at the beginning of this period were analysed. Key points Lockdowns of RACFs were successful in substantially reducing the number of COVID-19 infections and deaths in RACF residents. This was largely because the infection and mortality rates of COVID-19 were high in 2020 and 2021. The findings of this study could be used to evaluate and inform national and local states and territory guidelines on the management of COVID-19 in RACFs.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.26.23291907v1" target="_blank">The effect of residential aged care facility COVID-19 lockdowns on resident mortality</a>
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<li><strong>Identification of a molnupiravir-associated mutational signature in SARS-CoV-2 sequencing databases</strong> -
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Molnupiravir, an antiviral medication that has been widely used against SARS-CoV-2, acts by inducing mutations in the virus genome during replication. Most random mutations are likely to be deleterious to the virus, and many will be lethal, and so molnupiravir-induced elevated mutation rates reduce viral load. However, if some patients treated with molnupiravir do not fully clear SARS-CoV-2 infections, there could be the potential for onward transmission of molnupiravir-mutated viruses. Here we show that SARS-CoV-2 sequencing databases contain extensive evidence of molnupiravir mutagenesis. Using a systematic approach, we find that a specific class of long phylogenetic branches, distinguished by a high proportion of G-to-A and C-to-T mutations, appear almost exclusively in sequences from 2022, after the introduction of molnupiravir treatment, and in countries and age-groups with widespread usage of the drug. We identify a mutational spectrum, with preferred nucleotide contexts, from viruses in patients known to have been treated with molnupiravir and show that its signature matches that seen in these long branches, in some cases with onwards transmission of molnupiravir-derived lineages. Finally, we analyse treatment records to confirm the association between these high G-to-A branches and the use of molnupiravir.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.26.23284998v3" target="_blank">Identification of a molnupiravir-associated mutational signature in SARS-CoV-2 sequencing databases</a>
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<li><strong>Prevalence, knowledge, causes, and practices of self-medication during the COVID-19 pandemic in Bangladesh: A cross-sectional survey</strong> -
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Background: During the COVID-19 pandemic, self-medication (SM) has become a critical element in the healthcare system. SM can ease the burden on hospitals and medical resources by treating minor illnesses. However, inappropriate SM practices can lead to adverse drug reactions, drug resistance, and incorrect diagnoses, resulting in poor health outcomes. Methods: To evaluate the prevalence, knowledge, causes, and practices of SM among the Bangladeshi population during the COVID-19 outbreak, a cross-sectional survey with structured questionnaires was conducted in Chittagong from March to May 2022. The survey included 265 participants, with an average age of 35.09 years, and a multiple-choice questionnaire was used to gather information. Results: The study found that 64.15% of respondents had sufficient knowledge of SM, while 35.8% had insufficient knowledge. The primary reasons for SM during the pandemic were the influence of friends/family (90.74%), fear of infection or contact with COVID-19 cases (73.15%), and fear of quarantine or self-isolation (72.22%). Analgesics/pain relievers (84%) were the most commonly used drugs for SM for COVID-19 prevention and treatment. Antiulcerants/anti acid (42%), Vitamin C and Multivitamin (42%), and Antibiotics (32%) were also frequently used. Conclusion: This study suggests that SM is prevalent among Chittagong City residents, particularly those with less than a tertiary education. The study highlights the importance of building awareness about SM practices and taking necessary steps to control them.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.27.23291974v1" target="_blank">Prevalence, knowledge, causes, and practices of self-medication during the COVID-19 pandemic in Bangladesh: A cross-sectional survey</a>
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<li><strong>What works and for whom in treating depression in older adults in deprived communities in Brazil: Findings from a causal mediation analyses of the PROACTIVE trial that overlapped with the COVID-19 pandemic</strong> -
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Background: The PROACTIVE trial was a task-shared, collaborative care, psychosocial intervention that was highly effective at improving recovery from depression in older adults in Brazil that overlapped with the COVID-19 pandemic. Here we investigate mediators of the interventions effectiveness. Methods: Causal mediation analysis using interventional indirect effects, decomposed the total effect of PROACTIVE on recovery from depression (PHQ-9 less than 10), into multiple indirect effects including: dose of intervention (number of sessions and number of activities completed); social support measured through Luben Social Network Scale; perceived loneliness through the three-item UCLA questionnaire; conditions associated with frailty; and extra sessions offered to participants who did not respond to the intervention. Findings: Of the interventions total effect (difference in probability of recovery from depression between the intervention and control arms 0.211 [bias-corrected 95% CI: 0.139, 0.274]): 14% was mediated through improved conditions associated with frailty 0.030 [0.003, 0.065]); 6% through reduced loneliness (0.013 [0.001, 0.028]); and 20% through attending extra sessions for participants who did not respond to the intervention (0.042 [0.007, 0.105]). Interpretation: Our findings emphasise the importance of a home-based intervention to improve depression outcomes where participants are encouraged to self-select activities to mitigate against loneliness and are referred to primary care to manage health issues relating to frailty. Importantly, our findings suggest that offering extra sessions to participants who did not respond to the intervention shows promise in ensuring a sustained recovery from depression.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.26.23291868v1" target="_blank">What works and for whom in treating depression in older adults in deprived communities in Brazil: Findings from a causal mediation analyses of the PROACTIVE trial that overlapped with the COVID-19 pandemic</a>
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<li><strong>The Role of VSL#3 in the Treatment of Fatigue and Other Symptoms in Long Covid-19 Syndrome: a Randomized, Double-blind, Placebo-controlled Pilot Study (DELong#3)</strong> -
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Long COVID, also known as Post-acute COVID-19 Syndrome (PACS), is a chronic condition affecting individuals who have recovered from acute COVID-19. It is currently estimated that around 65 million people worldwide suffer from Long COVID. It is characterized by a range of symptoms, including fatigue, exertion intolerance, neurocognitive and sensory impairment, sleep disturbance, myalgia/arthralgia, and dysautonomia. Among them fatigue has emerged as a burdensome and pervasive issue, significantly impacting the quality of life and daily functioning of Long COVID patients. Alterations in the composition of the intestinal microbiota has been reported in COVID-19 patients. Dysbiosis persists even after several months of recovery from acute SARS-CoV-2 infection. Based on this evidence, we carried out a phase 3, randomized, double-blind, placebo-controlled trial aimed at evaluating the efficacy of VSL#3, a consortium of probiotic bacterial strains, in reducing fatigue and improving various aspects of patients9 well-being in patients with Long COVID syndrome.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.28.23291986v1" target="_blank">The Role of VSL#3 in the Treatment of Fatigue and Other Symptoms in Long Covid-19 Syndrome: a Randomized, Double-blind, Placebo-controlled Pilot Study (DELong#3)</a>
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<li><strong>Examining the inter-relationships between social isolation and loneliness and their correlates among older British adults before and during the COVID-19 lockdown: evidence from four British longitudinal studies</strong> -
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Background and Objectives: Unprecedented social restrictions during the COVID-19 pandemic have provided a new lens for considering the inter-relationship between social isolation and loneliness in later life. We present these inter-relationships before and during the COVID-19 restrictions and investigate to what extent demographic, socio-economic, and health factors associated with such experiences differed during the pandemic. Research Design and Method: We used data from four British longitudinal population-based studies (1946 MRC NSHD, 1958 NCDS, 1970 BCS, and ELSA). Rates, co-occurrences, and correlates of social isolation and loneliness are presented prior to and during the early stage of the COVID-19 pandemic and the inter-relationships between these experiences are elucidated in both periods. Results: Across the four studies, pre-pandemic proportions reporting social isolation ranged from 15 to 54%, with higher rates in older ages (e.g., 32% of 70-79 and 54% of those over 80). During the pandemic, the percentage of older people reporting both social isolation and loneliness and isolation only slightly increased. The inter-relationship between social isolation and loneliness did not change. Associations between socio-demographic and health characteristics and social isolation and loneliness also remained consistent, with greater burden among those with greater economic precarity (females, non-homeowners, unemployed, illness and greater financial stress). Discussion and Implications: There were already large inequalities in experiences of social isolation and loneliness and the pandemic had a small impact on worsening these inequalities. The concepts of loneliness and social isolation are not transferable and clarity is needed in how they are conceptualised, operationalised, and interpreted.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.27.23291947v1" target="_blank">Examining the inter-relationships between social isolation and loneliness and their correlates among older British adults before and during the COVID-19 lockdown: evidence from four British longitudinal studies</a>
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<li><strong>Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq</strong> -
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Genomic and proteomic screens have identified numerous host factors of SARS-CoV-2, but efficient delineation of their molecular roles during infection remains a challenge. Here we use Perturb-seq, combining genetic perturbations with a single-cell readout, to investigate how inactivation of host factors changes the course of SARS-CoV-2 infection and the host response in human lung epithelial cells. Our high-dimensional data resolve complex phenotypes such as shifts in the stages of infection and modulations of the interferon response. However, only a small percentage of host factors showed such phenotypes upon perturbation. We further identified the NF-{kappa}B inhibitor I{kappa}B (NFKBIA), as well as the translation factors EIF4E2 and EIF4H as strong host dependency factors acting early in infection. Overall, our study provides massively parallel functional characterization of host factors of SARS-CoV-2 and quantitatively defines their roles both in virus-infected and bystander cells.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.15.500120v2" target="_blank">Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq</a>
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<li><strong>mRNA-1273 vaccine effectiveness against symptomatic SARS-CoV-2 infection and COVID-19-related hospitalization in children aged 6 months to 5 years</strong> -
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Importance: Data on mRNA-1273 (Moderna) vaccine effectiveness in children aged 6 months to 5 years are limited. Objective: To assess mRNA-1273 vaccine effectiveness against symptomatic SARS-CoV-2 infection and COVID-19-related hospitalization among children aged 6 months to 5 years. Design, Setting, and Participants: A test-negative study using linked health administrative data in Ontario, Canada. Participants included symptomatic children aged 6 months to 5 years who were tested by RT-PCR. Exposures: mRNA-1273 vaccination. Main Outcomes and Measures: Symptomatic SARS-CoV-2 infection and COVID-19-related hospitalization. Results: We included 3467 test-negative controls and 572 test-positive cases. Receipt of mRNA-1273 was associated with reduced symptomatic SARS-CoV-2 infection (VE=90%; 95%CI: 53, 99%) and COVID-19-related hospitalization (VE=82%; 95%CI: 4, 99%) ≥7 days after the second dose. Conclusions and Relevance: Our findings suggest mRNA-1273 vaccine effectiveness is initially strong against symptomatic SARS-CoV-2 infection and hospitalization in children aged 6 months to 5 years. Further research is needed to understand long-term effectiveness and the need for booster doses.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.27.23291933v1" target="_blank">mRNA-1273 vaccine effectiveness against symptomatic SARS-CoV-2 infection and COVID-19-related hospitalization in children aged 6 months to 5 years</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>Probiotic and Colchicine in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Colchicine 0.5 MG; Dietary Supplement: Probiotic Formula; Other: Standard protocol<br/><b>Sponsor</b>: Ain Shams University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Influence of Manual Diaphragm Release on Pulmonary Functions in Women With COVID-19</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Other: manual therapy; Other: breathing exercise and prone position alone<br/><b>Sponsor</b>: Cairo University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study Evaluating SHEN26 Capsule in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SHEN26 capsule; Drug: SHEN26 placebo<br/><b>Sponsor</b>: Shenzhen Kexing Pharmaceutical 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>A Clinical Trial of Recombinant COVID-19 Bivalent (XBB+Prototype) Protein Vaccine (Sf9 Cell) in Booster Vaccination</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant COVID-19 Bivalent (XBB+Prototype) Protein Vaccine (Sf9 Cell) (WSK-V101C); Biological: Recombinant COVID-19 vaccine(Sf9 Cell) (WSK-V101)<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase Ⅲ Clinical Trial of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell) in Booster Vaccination</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: High dose of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell); Biological: Low dose of Recombinant COVID-19 Trivalent (XBB+BA.5+Delta) Protein Vaccine (Sf9 Cell); Biological: control group; Biological: Placebo group<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Impact Of Sensory Re-Education Paradigm On Sensation And Quality Of Life In Patients Post-Covid 19 Polyneuropathy</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Other: sensory re-education training; Other: traditional treatment<br/><b>Sponsor</b>: Cairo 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>Comprehensive Imaging Exam of Convalesced COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; COVID Long-Haul<br/><b>Interventions</b>: Other: Magnetic Resonance Imaging; Other: Ultra-High Resolution Computed Tomography (CT) Scan<br/><b>Sponsors</b>: Johns Hopkins University; Canon Medical Systems, USA<br/><b>Enrolling by invitation</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>UNAIR Inactivated COVID-19 Vaccine as Heterologue Booster (Immunobridging Study)</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines<br/><b>Interventions</b>: Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg; Biological: CoronaVac Biofarma COVID-1 9 Vaccine 3 µg<br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Investigate the Safety, Immunogenicity of Bivalent mRNA Vaccine RQ3027 and RQ3025 as a Booster Dose in Healthy Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: RQ3013; Biological: RQ3025; Biological: RQ3027<br/><b>Sponsors</b>: Affiliated Hospital of Yunnan University; Yunnan University; Kunming Medical 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>A Study to Evaluate the Safety and Efficacy of COVID-19 Convalescent Plasma (CCP) Transfusion to Prevent COVID-19 in Adult Recipients Following Hematopoietic Stem Cell Transplantation</strong> - <b>Conditions</b>: COVID-19; Hematopoietic Stem Cell Transplantation<br/><b>Intervention</b>: Biological: COVID Convalescent Plasma<br/><b>Sponsor</b>: Institute of Hematology & Blood Diseases Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluating the Efficacy of Remdesivir for Long COVID Following a Confirmed COVID-19 Infection.</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19<br/><b>Intervention</b>: Drug: Remdesivir<br/><b>Sponsors</b>: University of Derby; University of Exeter; Peninsula Clinical Trials Unit; University Hospitals of Derby and Burton NHS Foundation Trust<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety Study of SARS-CoV-2 DNA Vaccine (ICCOV)</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: SARS-CoV-2 DNA Vaccine (ICCOV)<br/><b>Sponsors</b>: Immuno Cure 3 Limited; The University of Hong Kong<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>The Effect of Smart Sensor Combined With APP for Individualized Precise Exercise Training in Long Covid-19</strong> - <b>Conditions</b>: Coronavirus Disease; COVID-19; Long Covid-19; Telerehabilitation<br/><b>Interventions</b>: Device: KNEESUP smart knee assistive device + KNEESUP care APP; Device: KNEESUP care APP; Behavioral: Healthy consulation<br/><b>Sponsor</b>: Shang-Lin Chiang<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>Open Label Extension of Efgartigimod in Adults With Post-COVID-19 POTS</strong> - <b>Condition</b>: Post-COVID Postural Orthostatic Tachycardia Syndrome Postural Orthostatic Tachycardia Syndrome<br/><b>Intervention</b>: Drug: Efgartigimod<br/><b>Sponsors</b>: argenx; Iqvia Pty 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>Digital Interventions to Understand and Mitigate Stress Response</strong> - <b>Conditions</b>: Distress, Emotional; Stress Response Among Nursing Professionals During the COVID-19; Stress Reaction; Acute<br/><b>Intervention</b>: Behavioral: Digital Intervention Group<br/><b>Sponsors</b>: Unity Health Toronto; Toronto Metropolitan University; University of Toronto; University of Ontario Institute of Technology; Boston University; University of Ottawa; Western University, Canada; Centre for Addiction and Mental Health<br/><b>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>Novel Tissue Factor Inhibition for Thromboprophylaxis in COVID-19: Primary Results of the ASPEN-COVID-19 Trial</strong> - CONCLUSIONS: rNAPc2 treatment in hospitalized patients with COVID-19 was well tolerated without excess bleeding or serious adverse events but did not significantly reduce D-dimer more than heparin at day 8.</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>Endotyping of IgE-mediated polyethylene glycol and/or polysorbate 80 allergy</strong> - CONCLUSION: PEG and PS80 cross-reactivity is determined by IgE recognizing short PEG motifs, whilst PS80 mono-allergy is PEG-independent. PS80 skin test positivity in PEG allergics was associated with a severe and persistent phenotype, higher serum PEG-specific IgE levels and enhanced BAT reactivity. Spherical PEG-exposure via LNP enhances BAT sensitivity through increased avidity. All PEG and/or PS80 excipient allergic patients can safely receive SARS-CoV-2 vaccines.</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>Hindered visibility improvement despite marked reduction in anthropogenic emissions in a megacity of southwestern China: An interplay between enhanced secondary inorganics formation and hygroscopic growth at prevailing high RH conditions</strong> - The PM(2.5)-bound visibility improvement remains challenging in China despite vigorous control on anthropogenic emissions in recent years. One critical issue could exist in the distinct physicochemical properties especially of secondary aerosol components. Taken the COVID-19 lockdown as an extreme case, we focus on the relationship between visibility, emission cuts, and secondary formation of inorganics with changing optical and hygroscopic behaviors in Chongqing, a representative city…</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>Anthracyclines inhibit SARS-CoV-2 infection</strong> - Vaccines and drugs are two effective medical interventions to mitigate SARS-CoV-2 infection. Three SARS-CoV-2 inhibitors, remdesivir, paxlovid, and molnupiravir, have been approved for treating COVID-19 patients, but more are needed, because each drug has its limitation of usage and SARS-CoV-2 constantly develops drug resistance mutations. In addition, SARS-CoV-2 drugs have the potential to be repurposed to inhibit new human coronaviruses, thus help to prepare for future coronavirus outbreaks….</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>Statins: Beneficial Effects in Treatment of COVID-19</strong> - The recent viral disease COVID-19 has attracted much attention. The disease is caused by SARS-CoV-19 virus which has different variants and mutations. The mortality rate of SARS-CoV-19 is high and efforts to establish proper therapeutic solutions are still ongoing. Inflammation plays a substantial part in the pathogenesis of this disease causing mainly lung tissue destruction and eventually death. Therefore, anti-inflammatory drugs or treatments that can inhibit inflammation are important…</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>mLST8 is essential for coronavirus replication and regulates its replication through the mTORC1 pathway</strong> - Coronaviruses (CoVs), which pose a serious threat to human and animal health worldwide, need to hijack host factors to complete their replicative cycles. However, the current study of host factors involved in CoV replication remains unknown. Here, we identified a novel host factor, mammalian lethal with sec-13 protein 8 (mLST8), which is a common subunit of mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), and is critical for CoV replication. Inhibitor and knockout (KO) experiments revealed…</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>Validity of Rapid Antibody Testing for COVID-19 Vaccine in Homeless People</strong> - (1) Background: There is a paucity of data regarding the validity of rapid antibody testing for SARS-CoV-2 vaccine response in homeless people worldwide. The objective of this study was to evaluate a rapid SARS-CoV-2 IgM/IgG antibody detection kit as a qualitative screen for vaccination in homeless people. (2) Methods: This study included 430 homeless people and 120 facility workers who had received one of BNT162b2, mRNA-1273, AZD1222/ChAdOx1, or JNJ-78436735/AD26.COV2.5 vaccines. They were…</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>Correlation between Clinical Characteristics and Antibody Levels in COVID-19 Convalescent Plasma Donor Candidates</strong> - COVID-19 convalescent plasma (CCP) with high neutralizing antibodies has been suggested in preventing disease progression in COVID-19. In this study, we investigated the relationship between clinical donor characteristics and neutralizing anti-SARS-CoV-2 antibodies in CCP donors. COVID-19 convalescent plasma donors were included into the study. Clinical parameters were recorded and anti-SARS-CoV-2 antibody levels (Spike Trimer, Receptor Binding Domain (RBD), S1, S2 and nucleocapsid protein) as…</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>Anticoronavirus Evaluation of Antimicrobial Diterpenoids: Application of New Ferruginol Analogues</strong> - The abietane diterpene (+)-ferruginol (1), like other natural and semisynthetic abietanes, is distinguished for its interesting pharmacological properties such as antimicrobial activity, including antiviral. In this study, selected C18-functionalized semisynthetic abietanes prepared from the commercially available (+)-dehydroabietylamine or methyl dehydroabietate were tested in vitro against human coronavirus 229E (HCoV-229E). As a result, a new ferruginol analogue caused a relevant reduction in…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Molnupiravir Inhibits Porcine Epidemic Diarrhea Virus Infection In Vitro</strong> - Porcine epidemic diarrhea virus (PEDV) is a swine coronavirus that is highly infectious and prone to variation. Vaccines derived from traditional PEDV strains provide less protection against PEDV-variant strains. Furthermore; there is a complex diversity of sequences among various PEDV-variant strains. Therefore; there is an urgent need to develop alternative antiviral strategies to defend against PEDV. Molnupiravir is a nucleotide analogue that could replace natural nucleosides to restrain…</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 Structural Proteins Modulated Blood-Testis Barrier-Related Proteins through Autophagy in the Primary Sertoli Cells</strong> - The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disrupts the blood-testis barrier (BTB), resulting in alterations in spermatogenesis. However, whether BTB-related proteins (such as ZO-1, claudin11, N-cadherin, and CX43) are targeted by SARS-CoV-2 remains to be clarified. BTB is a physical barrier between the blood vessels and the seminiferous tubules of the animal testis, and it is one of the tightest blood-tissue barriers in the mammalian body. In this study, we investigated…</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>Complement Activation-Independent Attenuation of SARS-CoV-2 Infection by C1q and C4b-Binding Protein</strong> - The complement system is a key component of the innate immune response to viruses and proinflammatory events. Exaggerated complement activation has been attributed to the induction of a cytokine storm in severe SARS-CoV-2 infection. However, there is also an argument for the protective role of complement proteins, given their local synthesis or activation at the site of viral infection. This study investigated the complement activation-independent role of C1q and C4b-binding protein (C4BP)…</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>BNT162b2 Vaccination after SARS-CoV-2 Infection Changes the Dynamics of Total and Neutralizing Antibodies against SARS-CoV-2: A 6-Month Prospective Cohort Study</strong> - This study aimed to analyze the dynamics, duration, and production of total and neutralizing antibodies induced by the BNT162b2 vaccine and the possible effect of gender and prior SARS-CoV-2 infection on the generation of these antibodies. Total antibodies were quantified via chemiluminescent microparticle immunoassay (CMIA), and neutralizing antibodies were quantified using the cPass SARS-CoV-2 kit. Individuals with a history of COVID-19 produced twice as many antibodies than vaccinated…</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>Intranasal Single-Replication Influenza Vector Induces Cross-Reactive Serum and Mucosal Antibodies against SARS-CoV-2 Variants</strong> - Current SARS-CoV-2 vaccines provide protection for COVID-19-associated hospitalization and death, but remain inefficient at inhibiting initial infection and transmission. Despite updated booster formulations, breakthrough infections and reinfections from emerging SARS-CoV-2 variants are common. Intranasal vaccination to elicit mucosal immunity at the site of infection can improve the performance of respiratory virus vaccines. We developed SARS-CoV-2 M2SR, a dual SARS-CoV-2 and influenza vaccine…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting Spike Glycoprotein S1 Mediated by NLRP3 Inflammasome Machinery and the Cytokine Releases in A549 Lung Epithelial Cells by Nanocurcumin</strong> - Chronic inflammation and tissue damage can result from uncontrolled inflammation during SARS-CoV-2 or COVID-19 infections, leading to post-acute COVID conditions or long COVID. Curcumin, found in turmeric, has potent anti-inflammatory properties but limited effectiveness. This study developed nanocurcumin, a curcumin nanoparticle, to enhance its physical and chemical stability and investigate its in vitro anti-inflammatory properties upon CoV2-SP induction in lung epithelial cells. Nanocurcumin…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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