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188 lines
52 KiB
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>03 September, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<ul>
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<li><strong>TikTok Tourette’s: are we witnessing a rise in neurological conditions driven by adolescent social media use?</strong> -
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<div>
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Perceptions of Tourette Syndrome (TS) and tic disorders are often driven by social media. During the COVID-19 pandemic, social media consumption greatly increased, particularly in the adolescent population. In parallel with increased social media consumption, there has also been an increase in tic severity and functional tic-like behavior (FTLB). Given that many of the tic videos posted on social media are misleading, perpetuate false beliefs about TS, or reinforce tic-like behaviors, there is increasing concern that these videos are driving the rapid increase in FTLBs. Several studies have reviewed newly presenting cases of FTLB and have found shared characteristics, including that a higher proportion of affected individuals are female, there is a low proportion with a history of childhood or family tics, and symptom onset is typically acute and develops in the teenage years. In addition, the quality of the tics seen in association with FTLB mirror many of the tics seen on popular social media channels, with higher rates of coprophenomena, tic attacks, and involvement of the trunk and extremities than is seen with typical tics. FTLBs are likely a specific subgroup of functional tics largely influenced by the portrayal of and growing popularity of functional tics posted on social media during the COVID-19 pandemic. However, several factors, including increased anxiety, social isolation, and social media use in general during the pandemic are likely also contributing factors to the surge of FTLBs seen recently. In this era of increased social media consumption, it will become increasingly important for clinicians to educate patients about where and how medical information is spread, to ensure the best possible diagnosis, treatment, and outcomes for patients.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/vs3tm/" target="_blank">TikTok Tourette’s: are we witnessing a rise in neurological conditions driven by adolescent social media use?</a>
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</div></li>
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<li><strong>COVID-19-associated AKI in hospitalized US patients: incidence, temporal trends, geographical distribution, risk factors and mortality</strong> -
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Background: Acute kidney injury (AKI) is associated with mortality in patients hospitalized with COVID-19, however, its incidence, geographic distribution, and temporal trends since the start of the pandemic are understudied. Methods: Electronic health record data were obtained from 53 health systems in the United States (US) in the National COVID Cohort Collaborative (N3C). We selected hospitalized adults diagnosed with COVID-19 between March 6th, 2020, and January 6th, 2022. AKI was determined with serum creatinine (SCr) and diagnosis codes. Time were divided into 16-weeks (P1-6) periods and geographical regions into Northeast, Midwest, South, and West. Multivariable models were used to analyze the risk factors for AKI or mortality. Results: Out of a total cohort of 306,061, 126,478 (41.0 %) patients had AKI. Among these, 17.9% lacked a diagnosis code but had AKI based on the change in SCr. Similar to patients coded for AKI, these patients had higher mortality compared to those without AKI. The incidence of AKI was highest in P1 (49.3%), reduced in P2 (40.6%), and relatively stable thereafter. Compared to the Midwest, the Northeast, South, and West had higher adjusted AKI incidence in P1, subsequently, the South and West regions continued to have the highest relative incidence. In multivariable models, AKI defined by either SCr or diagnostic code, and the severity of AKI was associated with mortality. Conclusions: Uncoded cases of COVID-19-associated AKI are common and associated with mortality. The incidence and distribution of COVID-19-associated AKI have changed since the first wave of the pandemic in the US.
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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/10.1101/2022.09.02.22279398v1" target="_blank">COVID-19-associated AKI in hospitalized US patients: incidence, temporal trends, geographical distribution, risk factors and mortality</a>
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</div></li>
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<li><strong>Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK)</strong> -
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Background: The imposition of restrictions on social mixing early in the COVID-19 pandemic was followed by a reduction in asthma exacerbations in multiple settings internationally. Temporal trends in social mixing, incident acute respiratory infections (ARI) and asthma exacerbations following relaxation of COVID-19 restrictions have not yet been described. Methods: We conducted a population-based longitudinal study in 2,312 UK adults with asthma between November 2020 and April 2022. Details of face covering use, social mixing, incident ARI and moderate/severe asthma exacerbations were collected via monthly on-line questionnaires. Temporal changes in these parameters were visualised using Poisson generalised additive models. Multilevel logistic regression was used to test for associations between incident ARI and risk of asthma exacerbations, adjusting for potential confounders. Results: Relaxation of COVID-19 restrictions from April 2021 coincided with reduced face covering use (p<0.001), increased frequency of indoor visits to public places and other households (p<0.001) and rising incidence of COVID-19 (p<0.001), non-COVID-19 ARI (p<0.001) and moderate/severe asthma exacerbations (p=0.007). Incident non-COVID-19 ARI associated independently with increased risk of asthma exacerbation (adjusted odds ratio 5.75, 95% CI 4.75 to 6.97) as did incident COVID-19, both prior to emergence of the omicron variant of SARS-CoV-2 (5.89, 3.45 to 10.04) and subsequently (5.69, 3.89 to 8.31). Conclusions: Relaxation of COVID-19 restrictions coincided with decreased face covering use, increased social mixing and a rebound in ARI and asthma exacerbations. Associations between incident ARI and risk of moderate/severe asthma exacerbation were similar for non-COVID-19 ARI and COVID-19, both before and after emergence of the SARS-CoV-2 omicron variant.
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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/10.1101/2022.09.01.22279473v1" target="_blank">Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK)</a>
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</div></li>
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<li><strong>Neutrophil extracellular traps have auto-catabolic activity and produce mononucleosome-associated circulating DNA</strong> -
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<div>
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Background: Because circulating DNA (cirDNA) are mainly detected as mononucleosome-associated circulating DNA (mono-N cirDNA) in blood apoptosis has until now been considered as the main source of cirDNA. The mechanism of cirDNA release into the circulation, however, is still not fully understood. This work addresses that knowledge gap, working from the postulate that neutrophil extracellular traps (NET) may be a source of cirDNA, and by investigating whether NET may directly produce mono-N cirDNA Methods: We used the synergistic analytical information provided by specifically quantifying DNA by qPCR, and analyzing fragment size analysis by shallow WGS, and capillary electrophoresis to unequivocally study the following: the in vitro kinetics of cell derived genomic high molecular weight (gHMW) DNA degradation in serum; the production of extracellular DNA and NET markers such as neutrophil elastase (NE) and myeloperoxidase (MPO) by ex vivo activated neutrophils; in vitro NET degradation in serum. We also performed an in vivo study in knockout mice, and an in vitro study of gHMW DNA degradation, to elucidate the role of NE and MPO in effecting DNA degradation and fragmentation. We then compared the NET associated markers and fragmentation size profiles of cirDNA in plasma obtained from patients with inflammatory diseases found to be associated with NET formation and high levels of cirDNA (COVID-19, N= 28; systemic lupus erythematosus, N= 10; metastatic colorectal cancer, N= 10; and from healthy individuals, N= 114). Results: Our studies reveal that: gHMW DNA degradation in serum results in the accumulation of mono-N DNA (81.3% of the remaining DNA following 24H incubation in serum corresponded to mono-N DNA); ex vivo NET formation, as demonstrated by a concurrent 5-, 5- and 35-fold increase of NE, MPO, and cell-free DNA (cfDNA) concentration in PMA-activated neutrophil culture supernatant, leads to the release of high molecular weight DNA that degrades down to mono-N in serum; NET mainly in the form of gHMW DNA generate mono-N cirDNA (2% and 41% of the remaining DNA after 2 hours in serum corresponded to 1-10 kbp fragments and mono-N, respectively) independent of any cellular process when degraded in serum; NE and MPO may contribute synergistically to NET autocatabolism, resulting in a 25-fold decrease in total DNA concentration and a DNA fragment size profile similar to that observed from cirDNA following 8h incubation with both NE and MPO; the cirDNA size profile of NE KO mice significantly differed from that of the WT, suggesting NE involvement in DNA degradation; and a significant increase in the levels of NE, MPO and cirDNA was detected in plasma samples from lupus, COVID-19 and mCRC, showing a high correlation with these inflammatory diseases, while no correlation of NE and MPO with cirDNA was found in HI. Conclusions: Our work thus describes the mechanisms by which NET and cirDNA are linked, by demonstrating that NET are a major source of mono-N cirDNA independent of apoptosis, and thus establishing a new paradigm of the mechanisms of cirDNA release in normal and pathological conditions, as well as demonstrating a link between immune response and cirDNA.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.01.506266v1" target="_blank">Neutrophil extracellular traps have auto-catabolic activity and produce mononucleosome-associated circulating DNA</a>
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</div></li>
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<li><strong>Novel monoclonal antibodies showing broad neutralizing activity for SARS-CoV-2 variants including Omicrons BA.5 and BA.2.75</strong> -
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We identified novel neutralizing monoclonal antibodies against SARS-CoV-2 variants (including Omicron) from individuals received two doses of mRNA vaccination after they had been infected with wildtype. We named them MO1, MO2 and MO3. MO1 shows high neutralizing activity against authentic variants: D614G, Delta, BA.1, BA.1.1, BA.2, and BA.2.75 and BA.5. Our findings confirm that the wildtype-derived vaccination can induce neutralizing antibodies that recognize the epitopes conserved among the SARS-CoV-2 variants (including BA.5 and BA.2.75). The monoclonal antibodies obtained herein could serve as novel prophylaxis and therapeutics against not only current SARS-CoV-2 viruses but also future variants that may arise.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.02.506305v1" target="_blank">Novel monoclonal antibodies showing broad neutralizing activity for SARS-CoV-2 variants including Omicrons BA.5 and BA.2.75</a>
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<li><strong>SARS-CoV-2 nucleocapsid protein inhibits the stress response through RNA-binding domain N2b</strong> -
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The nucleocapsid protein N of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enwraps and condenses the viral genome for packaging but is also an antagonist of the innate antiviral defense. It suppresses the integrated stress response (ISR), purportedly by interacting with stress granule (SG) assembly factors G3BP1 and 2, and inhibits type I interferon responses. To elucidate its mode of action, we systematically deleted and over-expressed distinct regions and domains. We show that N via domain N2b blocks PKR-mediated ISR activation, as measured by suppression of ISR-induced translational arrest and SG formation. N2b mutations that prevent dsRNA binding abrogate these activities also when introduced in the intact N protein. Substitutions reported to block post-translation modifications of N or its interaction with G3BP1/2 did not have a detectable additive effect. In an encephalomyocarditis virus-based infection model, N2b - but not a derivative defective in RNA binding - prevented PKR activation, inhibited {beta}-interferon expression and promoted virus replication. Apparently, SARS-CoV-2 N inhibits innate immunity by sequestering dsRNA to prevent activation of PKR and RIG-I-like receptors. Observations made for the N protein of human coronavirus 229E suggests that this may be a general trait conserved among members of other orthocoronavirus (sub)genera.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.02.506332v1" target="_blank">SARS-CoV-2 nucleocapsid protein inhibits the stress response through RNA-binding domain N2b</a>
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<li><strong>White-tailed deer (Odocoileus virginianus) may serve as a wildlife reservoir for nearly extinct SARS-CoV-2 variants of concern</strong> -
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The spillover of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from humans into white-tailed deer (WTD) and its ability to transmit from deer-to-deer raised concerns about the role of WTD in the epidemiology and ecology of the virus. In the present study, we conducted a comprehensive investigation to assess the prevalence, genetic diversity, and evolution of SARS-CoV-2 in WTD in the State of New York (NY). A total of 5,462 retropharyngeal lymph node (RPLN) samples collected from free-ranging hunter-harvested WTD during the hunting seasons of 2020 (Season 1, September-December 2020, n=2,700) and 2021 (Season 2, September-December 2021, n=2,762) were tested by SARS-CoV-2 real-time RT-PCR. SARS-CoV-2 RNA was detected in 17 samples (0.6%) from Season 1 and in 583 (21.1%) samples from Season 2. Hotspots of infection were identified in multiple confined geographic areas of NY. Sequence analysis of SARS-CoV-2 genomes from 164 samples demonstrated the presence multipls SARS-CoV-2 lineages as well as the co-circulation of three major variants of concern (VOCs) (Alpha, Gamma, and Delta) in WTD. Our analysis suggests the occurrence of multiple spillover events (human-to-deer) of the Alpha and Delta lineages with subsequent deer-to-deer transmission of the viruses. Detection of Alpha and Gamma variants in WTD long after their broad circulation in humans in NY suggests that WTD may serve as a wildlife reservoir for VOCs no longer circulating in humans. Thus, implementation of continuous surveillance programs to monitor SARS-CoV-2 dynamics in WTD are warranted, and measures to minimize virus transmission between humans and animals are urgently needed.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.02.506368v1" target="_blank">White-tailed deer (Odocoileus virginianus) may serve as a wildlife reservoir for nearly extinct SARS-CoV-2 variants of concern</a>
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<li><strong>COVID-19 disruptions of food systems and nutrition services in Ethiopia: Evidence of the impacts and policy responses</strong> -
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Background: Since its first case of COVID-19 on March 13, 2020 and Ethiopia has exerted efforts to curb the spread of the Coronavirus disease 2019 (COVID-19) without imposing a nationwide lockdown. Globally, COVID-19 related disruptions and mitigation measures have impacted livelihoods and food systems, nutrition, as well as access and use of health services. Objective: To develop a comprehensive understanding of the impacts of the COVID-19 pandemic on food security and maternal and child nutrition and health services and to synthesize lessons from policy responses to the COVID-19 pandemic in Ethiopia. Methods: We conducted a review of literature and 8 key informant interviews across government agencies, donors, and non-governmental organizations (NGOs), to map the impacts of the COVID-19 pandemic on the food and health systems in Ethiopia. We summarized policy responses and identified recommendations for future actions related to the COVID-19 pandemic and other future emergencies. Results: The impacts of the COVID-19 pandemic were felt across the food system. Disruptions were noted in inputs supply due to travel restrictions and closed borders restricting trade, reduced in-person support by agriculture extension workers, income losses, increases in food prices, and the reduction in food security and consumption of less diverse diets. Maternal and child health services were disrupted due to fear of contacting COVID-19, diversion of resources, and lack of personal protective equipment. Disruptions eased over time due to the expansion of social protection, through the Productive Safety Net Program, and the increased outreach and home service provision by the health extension workers. Conclusion: Ethiopia experienced disruptions to food systems and expanded existing social protection and public health infrastructure and leveraged partnerships with non-state actors. Nevertheless, vulnerabilities and gaps remain and there is a need for a long-term strategy that considers the cyclical nature of COVID-19 cases.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.31.22279432v1" target="_blank">COVID-19 disruptions of food systems and nutrition services in Ethiopia: Evidence of the impacts and policy responses</a>
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<li><strong>Spatial analysis of COVID-19 booster vaccine uptake in Scotland, and projection of future distributions</strong> -
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Vaccine hesitancy is one of the critical challenges for the implementation of a successful vaccination strategy. Rates of vaccine hesitancy and refusal vary substantially across different socioeconomic groups, and can result in those considered most vulnerable to disease having the lowest levels of uptake. Widespread coverage of COVID-19 vaccination is of particular importance as prevalence remains high, in effort to reduce overall burden from serious disease. Scotland9s COVID-19 vaccination programme has progressed to booster vaccinations, however uptake is falling across successive doses, and there is concern that some vulnerable individuals will not have sustained protection. To this end we analyse uptake in Scotland9s first (starting September 2021) booster dose round, as a benchmark for future rounds. We fit a machine learning model to explain variation in uptake across Scotland at fine population scales. The model is able to estimate a neighbourhood9s booster uptake with high precision using its population structure and relative deprivation alone, without any knowledge of geographic location. This is indicative of a strong relationship between increasing local deprivation and falling uptake, and specifically in those failing to return for a booster, despite getting a first dose. Geographically, this manifests as clusters of lower uptake, coinciding with communities with higher deprivation. With an upcoming booster rollout in Autumn 2022, we use first booster uptake as a baseline, to generate a set of plausible distributions for future uptake, if nationwide uptake were to fall. We make the core assumption that as uptake falls, trends with respect to deprivation will persist. Projected uptake declines more rapidly in clusters of more deprived neighbourhoods. If these projected distributions were to manifest, gaps in immunity would emerge in more deprived communities, which have historically had the highest rates of COVID-19 hospitalisation and mortality.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.30.22279415v1" target="_blank">Spatial analysis of COVID-19 booster vaccine uptake in Scotland, and projection of future distributions</a>
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<li><strong>The impact and progression of the COVID-19 pandemic in Bulgaria in its first two years</strong> -
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After initially having low levels of SARS-CoV-2 infections for much of the year, at the end of 2020 Bulgaria experienced a major epidemic surge, which caused the highest recorded excess mortality in Europe and among the highest in the word (Excess Mortality Rate, or EMR ~0.25%). Two more major waves followed in 2021, followed by another one in early 2022. In this study we analyze the temporal and spatial patterns of excess mortality at the national and local levels and across different demographic groups in Bulgaria, and compare those at the European level. The country has continued to exhibit the previous pattern of extremely high excess mortality as measured both by crude mortality metrics (EMR ~1.05% up to the end of March 2022) and by standardized ones – Potential Years of Life Lost (PYLL) and Aged-Standardized Years of life lost Rate (ASYR). Unlike Western Europe, the bulk of excess mortality in Bulgaria, as well as in several other countries in Eastern Europe, occurred in the second year of the pandemic, likely related to the differences in the levels of vaccination coverage between these regions. We also observe even more extreme levels of excess mortality at the regional level and in some subpopulations (e.g. total EMR values for males ~2% and EMR values for males aged 40-64 ~1% in certain areas). We discuss these observations in light of the estimates of infection fatality rate (IFR) and eventual population fatality rate (PFR) made early in the course of the pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.01.22279496v1" target="_blank">The impact and progression of the COVID-19 pandemic in Bulgaria in its first two years</a>
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<li><strong>Cardiac Magnetic Resonance Findings of COVID-19 Vaccine Associated Myocarditis at Intermediate Follow Up: a Comparison to Classic Myocarditis and MIS-C Related Myocarditis</strong> -
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Objective: To report intermediate cardiac magnetic resonance (CMR) findings of COVID-19 vaccine associated myocarditis (C-VAM) and compare to classic myocarditis (CM) and multisystem inflammatory syndrome in children (MIS-C). Study Design: Retrospective cohort study including children diagnosed with C-VAM from 5/2021 through 12/2021 with early and intermediate CMR. Patients with CM and MIS-C with intermediate CMR were included for comparison. Results: There were 8 patients with C-VAM, 20 with CM, and 61 with MIS-C. Among those with C-VAM, CMR performed at median 3 days (IQR 3, 7) revealed 2/8 patients with left ventricular ejection fraction (LVEF)<55%, 7/7 patients with late gadolinium enhancement (LGE), and 5/8 patients with elevated native T1 values. Borderline T2 values suggestive of myocardial edema were present in 6/8. Follow-up CMRs performed at median 107 days (IQR 97, 177) showed normal ventricular systolic function, T1, and T2 values; 3/7 patients had LGE. At intermediate follow up the C-VAM group had a lower percentage of LVEF<55% compared to CM and MIS-C (0.0 vs 30.0 vs 6.6%, respectively, p=0.018) and an intermediate degree of LGE (42.9 vs 75.0 vs 3.3%, respectively, p<0.001). Pairwise comparisons showed fewer myocardial segments with LGE in the C-VAM group versus CM (4/119 vs 42/340, p=0.004) and more segments with LGE than MIS-C (4/119 vs 2/1020, p=0.0014). Conclusion: Patients with C-VAM had no evidence of active inflammation or ventricular dysfunction on intermediate CMR although a minority had persistent LGE. Intermediate findings in C-VAM may be favorable compared to CM though LGE is more common compared to MIS-C.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.01.22279517v1" target="_blank">Cardiac Magnetic Resonance Findings of COVID-19 Vaccine Associated Myocarditis at Intermediate Follow Up: a Comparison to Classic Myocarditis and MIS-C Related Myocarditis</a>
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<li><strong>Deep immune profiling uncovers novel associations with clinical phenotypes of Multisystem Inflammatory Syndrome in Children (MIS-C)</strong> -
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Multisystem Inflammatory Syndrome in Children (MIS-C) is a systemic inflammatory condition that follows SARS-CoV2 infection or exposure in children. Clinical presentations are highly variable and include fever, gastrointestinal (GI) disease, shock, and Kawasaki Disease-like illness (MIS-C/KD). Compared to patients with acute COVID, patients with MIS-C have a distinct immune signature and expansion of TRVB11 expressing T cells. However, the relationship between immunological and clinical phenotypes of MIS-C is unknown. Here, we measured serum biomarkers, TCR repertoire, and SARS-CoV2-specific T cell responses in a cohort of 76 MIS-C patients. Serum biomarkers associated with macrophage and Th1 activation were elevated in patients with shock, consistent with previous reports. Significantly increased SARS-CoV-2-induced IFN-g; IL-2, and TNF-a; production were seen in CD4+ T cells from patients with neurologic involvement and respiratory failure. Diarrhea was associated with a significant reduction in shock-associated serum biomarkers, suggesting a protective effect. TRVB11 usage was highly associated with MIS-C/KD and coronary aneurysms, suggesting a potential biomarker for these manifestations in MIS-C patients. By identifying novel immunologic associations with the different clinical phenotypes of MIS-C, this study provides insights into the clinical heterogeneity of MIS-C. These unique immunophenotypic associations could provide biomarkers to identify patients at risk for severe complications of MIS-C, including shock and MIS-C/KD.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.31.22279265v1" target="_blank">Deep immune profiling uncovers novel associations with clinical phenotypes of Multisystem Inflammatory Syndrome in Children (MIS-C)</a>
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<li><strong>Vaccine Effectiveness Against Hospitalization Among Adolescent and Pediatric SARS-CoV-2 Cases in Ontario, Canada</strong> -
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Background: Vaccines against SARS-CoV-2 have been shown to reduce risk of infection, as well as severe disease among those with breakthrough infection, in adults. The latter effect is particularly important as Immune evasion by Omicron variants appears to have made vaccines less effective for prevention of infection. There is currently little available information on the protection conferred by vaccination against severe illness due to SARS-CoV-2 in children. Methods: To minimize confounding by changing vaccination practices and dominant circulating viral variants, we performed an age- and time-matched nested case-control design. Reported SARS-CoV-2 case records in Ontario children and adolescents aged 4 to 17 were linked to vaccination records. We used multivariable logistic regression to estimate the effectiveness of one and two vaccine doses against hospitalization. Results: We identified 130 hospitalized SARS-CoV-2 cases and 1,300 non-hospitalized, age- and time-matched controls, with disease onset between May 28, 2021 and January 9, 2022. One vaccine dose was shown to be 34% effective against hospitalization among SARS-CoV-2 cases (aOR = 0.66 [95% CI: 0.34, 1.21]). In contrast, two doses were 56% (aOR = 0.44 [95% CI: 0.23, 0.83]) effective at preventing hospitalization among SARS-CoV-2 cases. Exploratory instrumental variable analyses, and calculation of E-values, suggested that these effects are unlikely to be explained by unmeasured confounding. Conclusions: Even with immune evasion by SARS-CoV-2 variants, two vaccine doses continue to provide protection against hospitalization among adolescent and pediatric SARS-CoV-2 cases, even when the vaccines do not prevent infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.03.24.22272919v2" target="_blank">Vaccine Effectiveness Against Hospitalization Among Adolescent and Pediatric SARS-CoV-2 Cases in Ontario, Canada</a>
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<li><strong>Evaluation of Secondary Chemistry due to Disinfection of Indoor Air with Germicidal Ultraviolet Lamps</strong> -
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The disinfection of air using Germicidal Ultraviolet light (GUV) is a long-standing technique, which has received intense attention during the COVID-19 pandemic. GUV generally uses UVC lamps as its light source, which are known to initiate photochemistry in air. However, the impact of GUV on indoor air quality and chemistry has not been investigated in detail, to our knowledge. In this study, we model the chemistry initiated by GUV at 254 or 222 nm (“GUV254” or “GUV222”) in a typical room with typical indoor pollutant levels, and for different ventilation levels. GUV254 is irritating for skin and eyes, has an occupational exposure limit, and thus these fixtures typically irradiate a smaller volume near the ceiling, or inside ventilation ducts. In contrast, GUV222 is described by some as harmless to skin or eyes due to rapid absorption in a very thin external layer. Our analysis showed that GUV254 is able to significantly photolyze O3, generating OH radicals, which initiates the oxidation of all indoor volatile organic compounds (VOCs). While secondary organic aerosol (SOA) can be formed as a product of VOC oxidation, most of SOA in our case studies is produced through GUV-independent terpene ozonolysis. GUV254-induced SOA formation is of the order of 0.1-1 μg m-3. GUV222 with the same effective virus removal rate makes a smaller impact on indoor air quality at mid to high ventilation rates, mainly because of the significantly lower UV irradiance needed and substantially less efficient O3 photolysis (for primary OH generation) than at 254 nm, while it has a higher impact than GUV254 when ventilation is poor due to a small but significant photochemical production of O3 at 222 nm.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.25.22279238v2" target="_blank">Evaluation of Secondary Chemistry due to Disinfection of Indoor Air with Germicidal Ultraviolet Lamps</a>
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<li><strong>Rush hour-and-a-half: traffic is spreading out post-lockdown</strong> -
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Urban roadways are used inefficiently, with capacity scaled to meet peak demands and underutilization at off-peak hours. The COVID-19 pandemic has significantly disrupted the transportation system, and one possible outcome is a spreading of rush hour. We use six years of highway sensor data from the California state highway system to evaluate that possibility, and find that peaks are spreading in the post-lockdown period, the spreading is statistically significant, and has been relatively stable since summer 2021. Spreading of peak travel periods calls into question highway expansion plans based on pre-pandemic travel forecasts.
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🖺 Full Text HTML: <a href="https://osf.io/6khsj/" target="_blank">Rush hour-and-a-half: traffic is spreading out post-lockdown</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>Booster Study of COVID-19 Protein Subunit Recombinant Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: SARS-CoV-2 subunit protein recombinant vaccine; Biological: Active Comparator<br/><b>Sponsors</b>: PT Bio Farma; Faculty of Medicine Universitas Padjadjaran; Faculty of Medicine Universitas Udayana<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 Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine SCTV01E-1 in Population Aged Above 18 Years</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: SCTV01E-1 on D0; Biological: SCTV01E-1 on D28; Biological: SCTV01E-1 on D150; Biological: SCTV01E on D0; Biological: SCTV01E on D28; Biological: SCTV01E on D150; Biological: SCTV01E-1 on D120; Biological: SCTV01E on D120<br/><b>Sponsor</b>: Sinocelltech 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 Novel Parameter LIT/N That Predicts Survival in COVID-19 ICU Patients</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Diagnostic Test: the LIT test<br/><b>Sponsors</b>: Gazi University; Oxford MediStress<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>Efficacy and Safety of ES16001 in Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: ES16001 40 mg; Drug: ES16001 80 mg; Drug: ES16001 160 mg; Drug: Placebo<br/><b>Sponsor</b>: Genencell 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>Phase 2a Trial to Evaluate Safety and Immunogenicity of COVID-19 Vaccine Strategies in HIV-infected/Uninfected Adults.</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Ad26.COV2.S (VAC31518, JNJ-78436735) Vaccine, SARS-CoV-2 rS (CovovaxTM), BNT162b2 (Pfizer)<br/><b>Sponsors</b>: The Aurum Institute NPC; Coalition for Epidemic Preparedness Innovations<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>COVID Protection After Transplant - Sanofi GSK (CPAT-SG) Study</strong> - <b>Conditions</b>: COVID-19; Kidney Transplant<br/><b>Intervention</b>: Biological: Sanofi-GSK monovalent (B.1.351) CoV2 preS dTM-AS03 COVID-19 vaccine<br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID); PPD; Johns Hopkins University; Sanofi Pasteur, a Sanofi Company<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Immunogenicity of COVID-19 Vaccine, AdCLD-CoV19-1</strong> - <b>Conditions</b>: COVID-19; Vaccines<br/><b>Intervention</b>: Biological: AdCLD-CoV19-1<br/><b>Sponsors</b>: International Vaccine Institute; Cellid 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>Smartphone Intervention for Overdose and COVID-19</strong> - <b>Conditions</b>: Substance Use Disorders; Overdose; COVID-19<br/><b>Intervention</b>: Device: iThrive WI Intervention<br/><b>Sponsors</b>: University of Wisconsin, Madison; National Institute on Drug Abuse (NIDA)<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety and Immunogenicity of COVID-19 and Influenza Combination Vaccine</strong> - <b>Conditions</b>: COVID-19; Influenza<br/><b>Interventions</b>: Drug: CIC Vaccine; Drug: qNIV Vaccine; Drug: SARS-CoV-2 rS Vaccine; Drug: Influenza Vaccine<br/><b>Sponsor</b>: Novavax<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Assess Efficacy and Safety of Treamid for Patients With Reduced Exercise Tolerance After COVID-19</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; Lung Fibrosis<br/><b>Interventions</b>: Drug: Treamid; Drug: Treamid twice a day; Drug: Treamid once a day; Drug: Placebo<br/><b>Sponsor</b>: PHARMENTERPRISES LLC<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>Self-proning and Repositioning in COVID-19 Outpatients at Risk of Complicated Illness</strong> - <b>Conditions</b>: COVID-19; COVID-19 Pneumonia; Proning; Hospitalization; Death; Outpatient; Complication<br/><b>Intervention</b>: Other: Self-proning<br/><b>Sponsors</b>: Unity Health Toronto; Applied Health Research Centre<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 Immulina TM Supplements With PASC Patients</strong> - <b>Condition</b>: Post Acute COVID-19 Syndrome<br/><b>Interventions</b>: Dietary Supplement: Immulina TM; Dietary Supplement: Placebo<br/><b>Sponsors</b>: University of Mississippi Medical Center; National Institute of General Medical Sciences (NIGMS)<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>Evaluation of Clinical Performance and Usability of iStatis COVID-19 Ag Rapid Test at POC</strong> - <b>Conditions</b>: COVID-19 Virus Infection; COVID-19; Coronavirus Disease-19; COVID-19 Pandemic; SARS-CoV-2 Infection<br/><b>Interventions</b>: Diagnostic Test: iStatis COVID-19 Ag Rapid Test; Diagnostic Test: “COVID-19 RT-PCR Test EUA Number: EUA200011, Company: Laboratory Corporation of America (”Labcorp")<br/><b>Sponsor</b>: bioLytical Laboratories<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>Resilience Intervention for Health Professionals COVID-19</strong> - <b>Condition</b>: Mental Health Wellness 1<br/><b>Intervention</b>: Other: Mindfulness-based Intervention<br/><b>Sponsor</b>: Universidad de Monterrey<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>Addressing Post-COVID-19 Musculoskeletal Symptoms</strong> - <b>Conditions</b>: Telemedicine; Musculoskeletal Disease; SARS-CoV-2; Pain; COVID-19; Exercise<br/><b>Interventions</b>: Other: Multicomponent exercise program; Other: Tele-health primary care rehabilitation program<br/><b>Sponsor</b>: Universidad Europea de Madrid<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>Dipeptidylpeptidase (DPP)-4 inhibitor therapy increases circulating levels of anti-inflammatory soluble frizzle receptor protein (sFRP)-5 which is decreased in severe COVID-19 disease</strong> - Obesity and type 2 diabetes (T2D) show an increased risk for a severe COVID-19 disease. Treatment with DPP4 inhibitor (DPP4i) results in reduced mortality and better clinical outcome. Here, we aimed to identify potential mechanisms for the observed DPP4i effect in COVID-19. Comparing T2D subjects with and without DPP4i treatment, we identified a significant increase of the anti-inflammatory adipokine sFRP5 in relation to DPP4 inhibition. sFRP5 is a specific antagonist to Wnt5a, a glycopeptide…</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>Retro-2 alters Golgi structure</strong> - Retro-2 directly interacts with an ER exit site protein, Sec16A, inhibiting ER exit of a Golgi tSNARE, Syntaxin5, which results in rapid re-distribution of Syntaxin5 to the ER. Recently, it was shown that SARS-CoV-2 infection disrupts the Golgi apparatus within 6-12 h, while its replication was effectively inhibited by Retro-2 in cultured human lung cells. Yet, exactly how Retro-2 may influence ultrastructure of the Golgi apparatus have not been thoroughly investigated. In this study, we…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Pathogenesis of African Trypanosomiasis</strong> - African trypanosomes are bloodstream protozoan parasites that infect mammals including humans, where they cause sleeping sickness. Long-lasting infection is required to favor parasite transmission between hosts. Therefore, trypanosomes have developed strategies to continuously escape innate and adaptive responses of the immune system, while also preventing premature death of the host. The pathology linked to infection mainly results from inflammation and includes anemia and brain dysfunction 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>Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion</strong> - Hundreds of millions of SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding of the immune effects of this platform. The mRNA-LNP-based SARS-CoV-2 vaccine is highly inflammatory, and its synthetic ionizable lipid component responsible for the induction of inflammation has a long in vivo half-life. Since chronic inflammation can lead to immune exhaustion and non-responsiveness, we sought to determine the effects of pre-exposure…</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>Cotton flower metabolites inhibit SARS-CoV-2 main protease</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading globally for over two years, causing serious contagious disease and incalculable damage. The introduction of vaccines has slowed the spread of SARS-CoV-2 to some extent, but there remains a need for specific and effective treatment. The high chemical diversity and safety profiles of natural products make them a potential source of effective anti-SARS-CoV-2 drugs. Cotton plant is one of the most important economic and…</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>Lipocalin-2 is an essential component of the innate immune response to Acinetobacter baumannii infection</strong> - Acinetobacter baumannii is an opportunistic pathogen and an emerging global health threat. Within healthcare settings, major presentations of A. baumannii include bloodstream infections and ventilator-associated pneumonia. The increased prevalence of ventilated patients during the COVID-19 pandemic has led to a rise in secondary bacterial pneumonia caused by multidrug resistant (MDR) A. baumannii. Additionally, due to its MDR status and the lack of antimicrobial drugs in the development…</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>Middle East respiratory syndrome coronavirus ORF4b protein inhibits TLR7- and TLR9-dependent alpha interferon induction</strong> - The Toll-like receptor (TLR)7- and TLR9-dependent signaling cascade is responsible for production of a large amount of alpha interferon by plasmacytoid dendritic cells upon viral infection. Here, we show that Middle East respiratory syndrome coronavirus (MERS-CoV) accessory protein ORF4b has the most potential among the MERS-CoV accessory proteins to inhibit the TLR7/9-signaling-dependent alpha interferon production. ORF4b protein, which has a bipartite nuclear localization signal, was found to…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Human ACE2 Peptide-Attached Plasmonic-Magnetic Heterostructure for Magnetic Separation, Surface Enhanced Raman Spectroscopy Identification, and Inhibition of Different Variants of SARS-CoV-2 Infections</strong> - The emergence of Alpha, Beta, Gamma, Delta, and Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for several million deaths up to now. Because of the huge amount of vaccine escape mutations in the spike (S) protein for different variants, the design of material for combating SARS-CoV-2 is very important for our society. Herein, we report on the design of a human angiotensin converting enzyme 2 (ACE2) peptide-conjugated plasmonic-magnetic…</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>Eugenol alleviates transmissible gastroenteritis virus-induced intestinal epithelial injury by regulating NF-κB signaling pathway</strong> - Increasing evidence supports the ability of eugenol to maintain intestinal barrier integrity and anti-inflammatory in vitro and in vivo; however, whether eugenol alleviates virus-mediated intestinal barrier damage and inflammation remains a mystery. Transmissible gastroenteritis virus (TGEV), a coronavirus, is one of the main causative agents of diarrhea in piglets and significantly impacts the global swine industry. Here, we found that eugenol could alleviate TGEV-induced intestinal functional…</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>Blood-brain Barrier Damage is Pivotal for SARS-CoV-2 Infection to the Central Nervous System</strong> - Transsynaptic transport is the most accepted proposal to explain the SARS-CoV-2 infection of the CNS. Nevertheless, emerging evidence shows that neurons do not express the SARS-CoV-2 receptor ACE2, which highlights the importance of the blood-brain barrier (BBB) in preventing virus entry to the brain. In this study, we examine the presence of SARS-CoV-2 messenger ribonucleic acid (mRNA) and the cytokine profile in cerebrospinal fluids (CSF) from two patients with a brain tumor and COVID-19. To…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Insights into functional connectivity in mammalian signal transduction pathways by pairwise comparison of protein interaction partners of critical signaling hubs</strong> - Growth factors and cytokines activate signal transduction pathways and regulate gene expression in eukaryotes. Intracellular domains of activated receptors recruit several protein kinases as well as transcription factors that serve as platforms or hubs for the assembly of multi-protein complexes. The signaling hubs involved in a related biologic function often share common interaction proteins and target genes. This functional connectivity suggests that a pairwise comparison of protein…</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>Molecular Docking Study of Several Seconder Metabolites from Medicinal Plants as Potential Inhibitors of COVID-19 Main Protease</strong> - CONCLUSION: Our results obtained from docking studies suggest that pycnamine should be examined in vitro to combat 2019-CoV. Moreover, pycnamine might be a promising lead compound for anti-CoV drugs.</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><em>Withania somnifera</em> (L.) Dunal (Ashwagandha) for the possible therapeutics and clinical management of SARS-CoV-2 infection: Plant-based drug discovery and targeted therapy</strong> - Coronavirus disease 2019 (COVID-19) pandemic has killed huge populations throughout the world and acts as a high-risk factor for elderly and young immune-suppressed patients. There is a critical need to build up secure, reliable, and efficient drugs against to the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Bioactive compounds of Ashwagandha [Withania somnifera (L.) Dunal] may implicate as herbal medicine for the management and treatment of patients infected…</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>Antibodies against the SARS-CoV-2 S1-RBD cross-react with dengue virus and hinder dengue pathogenesis</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally since December 2019. Several studies reported that SARS-CoV-2 infections may produce false-positive reactions in dengue virus (DENV) serology tests and vice versa. However, it remains unclear whether SARS-CoV-2 and DENV cross-reactive antibodies provide cross-protection against each disease or promote disease severity. In this study, we confirmed that antibodies against the SARS-CoV-2 spike protein and its…</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>Promising Marine Natural Products for Tackling Viral Outbreaks: A Focus on Possible Targets and Structure-Activity Relationship</strong> - Recently, people worldwide have experienced several outbreaks caused by viruses that have attracted much interest globally, such as HIV, Zika, Ebola, and the one being faced, SARSCoV-2 viruses. Unfortunately, the availability of drugs giving satisfying outcomes in curing those diseases is limited. Therefore, it is necessary to dig deeper to provide compounds that can tackle the causative viruses. Meanwhile, the efforts to explore marine natural products have been gaining great interest as the…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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