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186 lines
53 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 May, 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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<li><strong>Specific Treatment exists for SARS-CoV-2 ARDS</strong> -
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The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), seems to be difficult to overcome. A pandemic of such a scale has not been seen since the 1918 influenza pandemic. Although the predominant clinical presentation is respiratory disease, neurological manifestations and sequelae are increasingly being recognized. We observed a case series of rapid recovery of ARDS within 24 h in the preliminary clinical features of COVID-19 ARDS-associated neurological disease. It was also noted that by 15 April, 2021, there was no SARS-CoV-2 ARDS on Sorok Island in South Korea, where lepers had been living together. We compared each of dapsone’s effects on humans and considered those of SARS-CoV-2. Dapsone showed different effects in the brain. The Sorokdo National Hospital reported a relationship between dapsone and the neuroinflammasome of Alzheimer’s disease (AD) in Sorok Island from January 2005 to June 2020. AD prevalence was low in the leprosy patient group who took dapsone regularly. The preliminary cross-sectional study of the trial group (22 subjects) and the control group (22 subjects) in the Hunt Regional Hospital reported the following results: The chi-square statistic is 5.1836. The p-value is 0.022801. The result is considered significant at p < 0.05. The results from the medical treatment from 21 December to 29 December 2020 were considered. The mortality rates at the ARDS onset stage were 0% with dapsone administered as a standard COVID-19 treatment and 40% without dapsone administered as a standard COVID-19 treatment, respectively. Based on the respiratory failure and sudden high death rate originating from the involvement of the brainstem, especially the pre- Bötzinger complex, dapsone can be used to significantly reduce the incidence of the cases of acute respiratory distress syndrome and other illnesses caused by SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://osf.io/jq5tc/" target="_blank">Specific Treatment exists for SARS-CoV-2 ARDS</a>
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<li><strong>The COVID-19 Rapid Survey of Adherence to Interventions and Responses (CORSAIR) study: errata</strong> -
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Since February 2020, we have been working with the Department of Health and Social Care on a series of surveys, the COVID-19 Rapid Survey of Adherence to Interventions and Responses (CORSAIR) study. This entails a series of cross- sectional national (UK) surveys of approximately 2000 participants per wave, recruited via two survey panels. Surveys have been conducted weekly or fortnightly since the end of January 2020, with 73 waves of data collection to date (correct at time of writing: 20 April 2022). There have been some errors with the datasets delivered to us. We have re- analysed those of our previously reported results that are affected by these corrections. The changes make very little difference to any of our conclusions.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/8jcbq/" target="_blank">The COVID-19 Rapid Survey of Adherence to Interventions and Responses (CORSAIR) study: errata</a>
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<li><strong>COVID-19 Pandemic vs. Pre-Pandemic Period: Changes in Hospital Admission Rates, Length of Stay, and In-Hospital Mortality of Common Neurologic Conditions</strong> -
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Background and Objective: COVID-19 pandemic caused massive adjustments to healthcare systems in the country. This study determined the change in hospital admission rates, length of hospital stay and in-hospital mortality of common (non-COVID related) neurologic conditions during the COVID-19 pandemic and pre-pandemic period. Methods: The study utilized a retrospective cross-sectional study of patients admitted under the Department of Neurology at Jose R. Reyes Memorial Medical Center from the period of March 2019 to March 2020 (pre-pandemic group), and April 2020 to April 2021 (COVID-19 pandemic). Admission rates, length of stay and in-hospital mortality were calculated for cerebrovascular diseases, CNS infections, CNS neoplasms and Seizure disorders. Results: There were 1090 admissions from April 2019 to March 2020 and 393 admissions from April 2020 to March 2021 with an over-all decline of 63%. During the pandemic, the duration of hospital stay was longer for CNS neoplasms. Duration of hospital stay for cerebrovascular disease, CNS infection, and seizure disorders were not significantly different. There was an increase in over-all in hospital mortality from 22.75% to 26.46% with significant increase in the case fatality rate of cerebrovascular diseases. Conclusion: We observed a large decline in the over-all admission rate and longer hospital stays. The over-all in- hospital mortality rate also increased during the pandemic period.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/z2dpn/" target="_blank">COVID-19 Pandemic vs. Pre-Pandemic Period: Changes in Hospital Admission Rates, Length of Stay, and In-Hospital Mortality of Common Neurologic Conditions</a>
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<li><strong>What Goes Down Must Come Up? Misinformation Search Behavior During an Unplanned Facebook Outage</strong> -
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<div>
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Pundits and public health experts alike suspect that Facebook plays a role in not only exposing Americans to public health misinformation, but potentially encouraging them to seek out misinformation from other sources. Whether or not Facebook is responsible for stimulating misinformation consumption beyond the social networking site, however, is an open question. If Facebook indeed stimulates pandemic misinformation search behavior, we might expect search volume on other websites to simultaneously decrease when web traffic to Facebook is comparatively low. Here, we exploit a naturally occurring and exogenous interruption to Facebook’s service to study the site’s impact on misinformation search. Difference-in-difference analyses reveal that minute-by-minute Google searches for pandemic misinformation (e.g., unproven COVID-19 remedies, vaccine conspiracy theories) tended to increase during the outage period, in comparison to a typical day (and vs. a placebo). These findings are less consistent with views that the site stimulates misinformation search, and more consistent with a steady and transferrable demand for pandemic misinformation. We conclude by discussing the implications of Americans’ demand for health misinformation – and Facebook’s potential role in shaping it – for health communication efforts to encourage evidence-based health behavior.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/pm9gy/" target="_blank">What Goes Down Must Come Up? Misinformation Search Behavior During an Unplanned Facebook Outage</a>
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<li><strong>Fear of COVID-19 predicts vaccination willingness 14 months later</strong> -
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<div>
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Vaccines are an important tool for governments and health agencies to contain and curb the Coronavirus Disease-19 (COVID-19) pandemic. However, despite their effectiveness and safeness, a substantial portion of the population worldwide is hesitant to get vaccinated. In the current study, we examined whether fear of COVID-19 predicts vaccination willingness. In a longitudinal study (N = 938), fear for COVID-19 was assessed in April 2020 and vaccination willingness was measured in June 2021. Approximately 11% of our sample indicated that they were not willing to get vaccinated. Results of a logistic regression showed that increased fear of COVID-19 predicts vaccination willingness 14 months later, even when controlling for several anxious personality traits, infection control perceptions, risks for loved ones, self-rated health, previous infection, media use, and demographic variables. These results show that fear of COVID-19 is a relevant construct to consider for predicting and possibly influencing vaccination willingness. Nonetheless, sensitivity and specificity of fear of COVID-19 to predict vaccination willingness were quite low and only became slightly better when fear of COVID-19 was measured concurrently. This indicates that other potential factors, such as perceived risks of the vaccines, probably also play a role in explaining vaccination willingness.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/rt7u4/" target="_blank">Fear of COVID-19 predicts vaccination willingness 14 months later</a>
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<li><strong>Continued Emergence and Evolution of Omicron in South Africa: New BA.4 and BA.5 lineages</strong> -
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South Africa9s fourth COVID-19 wave was driven predominantly by three lineages (BA.1, BA.2 and BA.3) of the SARS-CoV-2 Omicron variant of concern. We have now identified two new lineages, BA.4 and BA.5. The spike proteins of BA.4 and BA.5 are identical, and comparable to BA.2 except for the addition of 69-70del, L452R, F486V and the wild type amino acid at Q493. The 69-70 deletion in spike allows these lineages to be identified by the proxy marker of S-gene target failure with the TaqPath COVID-19 qPCR assay. BA.4 and BA.5 have rapidly replaced BA.2, reaching more than 50% of sequenced cases in South Africa from the first week of April 2022 onwards. Using a multinomial logistic regression model, we estimate growth advantages for BA.4 and BA.5 of 0.08 (95% CI: 0.07 - 0.09) and 0.12 (95% CI: 0.09 - 0.15) per day respectively over BA.2 in South Africa.
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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/10.1101/2022.05.01.22274406v1" target="_blank">Continued Emergence and Evolution of Omicron in South Africa: New BA.4 and BA.5 lineages</a>
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<li><strong>Omicron infection induces low-level, narrow-range SARS-CoV-2 neutralizing activity</strong> -
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Background: The rapid worldwide spread of the mildly pathogenic SARS-CoV-2 Omicron variant has led to the suggestion that it will induce levels of collective immunity that will help putting an end to the COVID19 pandemics. Methods: Convalescent serums from non-hospitalized individuals previously infected with Alpha, Delta or Omicron BA.1 SARS-CoV-2 or subjected to a full mRNA vaccine regimen were evaluated for their ability to neutralize a broad panel of SARS-CoV-2 variants. Findings: Prior vaccination or infection with the Alpha or to a lesser extent Delta strains conferred robust neutralizing titers against most variants, albeit more weakly against Beta and even more Omicron. In contrast, Omicron convalescent serums only displayed low level of neutralization activity against the cognate virus and were unable to neutralize other SARS-CoV-2 variants. Interpretation: Moderately symptomatic Omicron infection is only poorly immunogenic and does not represent a substitute for vaccination.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.02.22274436v1" target="_blank">Omicron infection induces low-level, narrow-range SARS-CoV-2 neutralizing activity</a>
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<li><strong>The highly conserved stem-loop II motif is important for the lifecycle of astroviruses but dispensable for SARS- CoV-2</strong> -
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<div>
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The stem-loop II motif (s2m) is an RNA element present in viruses from divergent viral families, including astroviruses and coronaviruses, but its functional significance is unknown. We created deletions or substitutions of the s2m in astrovirus VA1 (VA1), classic human astrovirus 1 (HAstV1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For VA1, recombinant virus could not be rescued upon partial deletion of the s2m or substitutions of G-C base pairs. Compensatory substitutions that restored the G-C base-pair enabled recovery of VA1. For HAstV1, a partial deletion of the s2m resulted in decreased viral titers compared to wild-type virus, and reduced activity in a replicon system. In contrast, deletion or mutation of the SARS-CoV-2 s2m had no effect on the ability to rescue the virus, growth in vitro, or growth in Syrian hamsters. Our study demonstrates the importance of the s2m is virus-dependent.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.04.30.486882v1" target="_blank">The highly conserved stem-loop II motif is important for the lifecycle of astroviruses but dispensable for SARS-CoV-2</a>
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<li><strong>Nsp1 proteins of human coronaviruses HCoV-OC43 and SARS-CoV2 inhibit stress granule formation</strong> -
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Stress granules (SGs) are cytoplasmic condensates that often form as part of the cellular antiviral response. Despite the growing interest in understanding the interplay between SGs and other biological condensates and viral replication, the role of SG formation during coronavirus infection remains poorly understood. Several proteins from different coronaviruses have been shown to suppress SG formation upon overexpression, but there are only a handful of studies analyzing SG formation in coronavirus-infected cells. To better understand SG inhibition by coronaviruses, we analyzed SG formation during infection with the human common cold coronavirus OC43 (HCoV-OC43) and the highly pathogenic SARS-CoV2. We did not observe SG induction in infected cells and both viruses inhibited eukaryotic translation initiation factor 2 (eIF2) phosphorylation and SG formation induced by exogenous stress (e.g. sodium arsenite treatment). Furthermore, in SARS-CoV2 infected cells we observed a sharp decrease in the levels of SG-nucleating protein G3BP1. Ectopic overexpression of nucleocapsid (N) and non-structural protein 1 (Nsp1) from both HCoV-OC43 and SARS- CoV-2 inhibited SG formation. The Nsp1 proteins of both viruses inhibited arsenite-induced eIF2 phosphorylation, and the Nsp1 of SARS-CoV2 alone was sufficient to cause decrease in G3BP1 levels. This phenotype was dependent on the depletion of cytoplasmic mRNA mediated by Nsp1 and associated with nuclear retention of the SG-nucleating protein TIAR. To test the role of G3BP1 in coronavirus replication, we infected cells overexpressing EGFP-tagged G3BP1 with HCoV-OC43 and observed a significant decrease in infection compared to control cells expressing EGFP. The antiviral role of G3BP1 and the existence of multiple SG suppression mechanisms that are conserved between HCoV-OC43 and SARS-CoV2 suggest that SG formation may represent an important antiviral host defense that coronaviruses target to ensure efficient replication.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.02.490272v1" target="_blank">Nsp1 proteins of human coronaviruses HCoV-OC43 and SARS-CoV2 inhibit stress granule formation</a>
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<li><strong>BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection</strong> -
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Recent emergence of SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.2.13, BA.4 and BA.5 all contain L452 mutations and show potential higher transmissibility over BA.2. The new variants’ receptor binding and immune evasion capability require immediate investigation, especially on the role of L452 substitutions. Herein, coupled with structural comparisons, we showed that BA.2 sublineages, including BA.2.12.1 and BA.2.13, exhibit increased ACE2-binding affinities compared to BA.1; while BA.4/BA.5 shows the weakest receptor-binding activity due to F486V and R493Q reversion. Importantly, compared to BA.2, BA.2.12.1 and BA.4/BA.5 exhibit stronger neutralization escape from the plasma of 3-dose vaccinees and, most strikingly, from vaccinated BA.1 convalescents. To delineate the underlying evasion mechanism, we determined the escaping mutation profiles, epitope distribution and Omicron sublineage neutralization efficacy of 1640 RBD-directed neutralizing antibodies (NAbs), including 614 isolated from BA.1 convalescents. Interestingly, post- vaccination BA.1 infection mainly recalls wildtype (WT) induced humoral memory and elicits antibodies that neutralize both WT and BA.1. These cross-reactive NAbs are significantly enriched on non-ACE2-competing epitopes; and surprisingly, the majority are undermined by R346 and L452 substitutions, namely R346K (BA.1.1), L452M (BA.2.13), L452Q (BA.2.12.1) and L452R (BA.4/BA.5), suggesting that R346K and L452 mutations appeared under the immune pressure of Omicron convalescents. Nevertheless, BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1 but do not respond to WT SARS-CoV-2, due to the high susceptibility to N501, N440, K417 and E484. However, these NAbs are largely escaped by BA.2 sublineages and BA.4/BA.5 due to D405N and F486V, exhibiting poor neutralization breadths. As for therapeutic NAbs, LY-CoV1404 (Bebtelovimab) and COV2-2130 (Cilgavimab) can still effectively neutralize BA.2.12.1 and BA.4/BA.5, while the S371F, D405N and R408S mutations carried by BA.2/BA.4/BA.5 sublineages would undermine most broad sarbecovirus NAbs. Together, our results indicate that Omicron can evolve mutations to specifically evade humoral immunity elicited by BA.1 infection. The continuous evolution of Omicron poses great challenges to SARS-CoV-2 herd immunity and suggests that BA.1-derived vaccine boosters may not be ideal for achieving broad-spectrum protection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.04.30.489997v1" target="_blank">BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection</a>
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<li><strong>SARS-CoV-2 Main Protease: a Kinetic Approach</strong> -
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In this article, I present a new model of the interaction of the main protease (Mpro) from SARS-CoV-2 virus with its substrate. The reaction scheme used to describe this mechanism is an extension of the well-known Michaelis Menten model proposed in 1913 by Leonor Michaelis and Maud Menten [1]. The model I present here takes into account that one Mpro enzyme monomer interacts with another Mpro monomer in the presence of the substrate, leading to the formation of an enzyme dimer bound to one substrate molecule. Indeed, this dimer is formed by the sequentially binding of one Mpro enzyme monomer to one molecule of substrate, followed by another Mpro enzyme monomer binding to this Mpro-substrate complex. This reaction mechanism is also known in the literature as substrate-induced dimerization [3]. Starting from this new reaction scheme established for this catalytic mechanism, I derived a mathematical expression describing the catalytic rate of the active Mpro enzyme dimer as a function of the substrate concentration [S]. The plot corresponding to this substrate-induced dimerization reaction shows a function f([S]) that is not monotonic, i.e. not strictly increasing or decreasing, but with a second derivative initially negative and then becoming positive after having passed the Vmax point. This is typically a type of curve showing a phenomenon like the one of substrate inhibition (for instance, inhibition by excess-substrate [7]). The graphical representation of this process shows an interesting behaviour: from zero micro M/s, the reaction rate increases progressively, similar to the kind of curve described by the Michaelis-Menten model. However, after having reached its maximum catalytic rate, Vmax, the reaction rate decreases progressively as we continue to increase the substrate concentration. I propose an explanation to this interesting behavior. At the moment where Vcat is maximum, we can assume that, in theory, every single substrate molecule in solution is bound to two enzyme monomers (i.e. to one active dimer). The catalytic rate is thus theoretically maximized. At the time where the reaction rate begins to decrease, we observe a new phenomenon that appears: the enzyme monomers begin to be “diluted” in the solution containing the excess substrate. The dimers begin to dissociate and to bind increasingly to the substrate as inactive monomers instead of active dimers. Hence, it is more and more unlikely for the enzyme monomers to sequentially bind twice to the same substrate molecule (here, [E] << [S]). Thus, at this stage, the substrate-induced dimerization occurs less often. At the limit, when the substrate is in high excess, there is virtually no more dimerization which occurs. This is one example of excess-substrate inhibition. Furthermore, after having established this fact, I wanted to see if this catalytic behavior was also observed in vitro. Therefore, I conducted an experiment where I measured the catalytic rate of the Mpro dimer for different substrate concentrations. The properties of my substrate construct were such, that I could determine the catalytic rate of the enzyme dimer by directly measuring the spectrophotometric absorbance of the cleaved substrate at lambda = 405 nm. The results show explicitly - within a margin of error - that the overall shape of the experimental curve looks like the one of the theoretical curve. I thus conclude that the biochemical behavior of the Mpro in vitro follows a new path when it is in contact with its substrate: an excess substrate concentration decreases the activity of the enzyme by the phenomenon of a type of excess-substrate inhibition. This finding could open a new door in the discovery of drugs directed against the Mpro enzyme of the SARS-CoV-2 virus, acting on the inhibition by excess-substrate of the Mpro enzyme, this protein being a key component in the metabolism of the virus. Furthermore, I have established that the maximum of the fitted curve, Vmax, depends only on [E]T and not on [S]. [S]_Vmax exhibits the same dependence pattern. Therefore, if
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.01.490203v1" target="_blank">SARS-CoV-2 Main Protease: a Kinetic Approach</a>
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<li><strong>Time-varying death risk after SARS-CoV-2-infection in Swedish long-term care facilities</strong> -
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Background: The case fatality rate of SARS-CoV-2 has been high among residents of long-term care (LTC) facilities. It is unknown whether there is also higher mortality after the first month from documented infection. Methods: We extended the follow-up period to 8 months of a previous, retrospective cohort study based on the Swedish Senior Alert register. 3731 LTC residents infected with SARS-CoV-2 were matched to 3731 uninfected controls using time- dependent propensity scores on age, sex, body mass index, health status, comorbidities, and prescription medication use. In a sensitivity analysis, residents were also matched on geographical region and time of Senior Alert registration. Results: Median age was 87 years (65% women). Excess mortality was highest 5 days after documented infection (hazard ratio 19.1; 95% confidence interval [CI], 14.6-24.8); subsequently excess mortality decreased rapidly. After the second month, mortality rate became lower in infected residents than in controls. Median survival of uninfected controls was 577 days (1.6 years), much lower than national life expectancy in Sweden at age 87 (5.05 years in men, 6.07 years in women). During days 61-210 of follow-up, hazard ratio for death was 0.41 (95% CI, 0.34-0.50) (0.76 (95% CI, 0.62-0.93) in the sensitivity analysis). Conclusions: No excess mortality was observed in LTC residents who survived acute SARS- CoV-2 infection (the first month). Life expectancy of uninfected residents was much lower than that of the general population of same age and sex. This difference should be taken into account in calculations of years of life lost among LTC residents.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.03.10.22272097v2" target="_blank">Time-varying death risk after SARS- CoV-2-infection in Swedish long-term care facilities</a>
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<li><strong>COVID-19 vaccines effectiveness against symptomatic SARS-CoV-2 during Delta variant surge: a population-based case- control study in St. Petersburg, Russia</strong> -
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Background: Studies of mRNA and vector-based vaccines used in different countries report acceptable levels of effectiveness against SARS-CoV-2 infection caused by the Delta variants of SARS-CoV-2. No studies estimated vaccine effectiveness (VE) of Gam-COVID-Vac and other vaccines used in Russia against symptomatic infection with Delta variant. In this population-based case-control study, we aimed to estimate the effectiveness of the Russian COVID-19 vaccines against symptomatic SARS-CoV-2 during the recent outbreak caused by the Delta VOC in October 2021 in St. Petersburg, Russia. Methods: In a population-based case-control study with density sampling of controls, we acquired information on cases and controls from two independent studies conducted in St. Petersburg. Cases were symptomatic patients with confirmed SARS-CoV-2 (using polymerase chain reaction (PCR) test) referred to low-dose computed tomography (LDCT) triage in two outpatient centres between October 6 and 14, 2021 during the Delta variant outbreak. We recruited the controls during the representative survey of the seroprevalence study conducted during the same period in St. Petersburg using random digit dialling. In the primary analysis, we used logistic regression models to estimate the adjusted (age, gender, and history of confirmed COVID-19) VE against symptomatic SARS-CoV-2 resulted in a referral to triage centre for three vaccines used in Russia: Gam-COVID-Vac, EpiVacCorona, and CoviVac. Findings: We included 1,254 cases and 2,747 controls recruited between the 6th and 14th of October in the final analysis. VE was 56% (95% CI: 48 to 63) for Gam- COVID-Vac (Sputnik V), 49% (95% CI: 29 to 63) for 1-dose Gam-COVID-Vac (Sputnik V) or Sputnik Light, -58% (95% CI: -225 to 23) for EpiVacCorona and 40% (95% CI: 3 to 63) for CoviVac. Without adjustment for the history of confirmed COVID-19 VE for all vaccines was lower, except for one-dose Gam-COVID-Vac (Sputnik Light). The adjusted VE was slightly lower in women - 51% (95% CI: 39 to 60) than men - 65% (95% CI: 5 to 73). It was also higher in younger age. However, in the analysis restricted to participants without a history of confirmed COVID-19, the differences in VE by age group were smaller Interpretation: In contrast to other Russian vaccines, Gam-COVID-Vac is effective against symptomatic SARS-CoV-2 infection caused by Delta VOC. Effectiveness is likely higher than the estimated 56% due to bias arising from high prevalence of the past COVID-19 in St. Petersburg. Funding: Population-based survey in St. Petersburg was funded by Polymetal International, plc.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.24.22269714v2" target="_blank">COVID-19 vaccines effectiveness against symptomatic SARS-CoV-2 during Delta variant surge: a population-based case-control study in St. Petersburg, Russia</a>
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<li><strong>Effectiveness of Covid-19 vaccines against SARS-CoV-2 Omicron variant (B.1.1.529): A systematic review with meta- analysis and meta-regression</strong> -
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Background: There is a need for evaluation regarding vaccine effectiveness (VE) and the urgency of booster vaccination against Covid-19 B.1.1.529 (Omicron) variant. Methods: Systematic search was conducted on April 6th, 2022, on databases (PubMed, ScienceDirect, CENTRAL, Web of Science, Scopus). VE difference (VED) estimates were assessed using random-effects model and DerSimonian-Laird tau estimators. Two models result, i.e., within 3 months and within 3 months or more, are compared. VE versus time meta-regression analysis was evaluated using mixed-effects model with Restricted- Maximum Likelihood tau estimators and Hartung-Knapp adjustments. Results: Ad26.COV2.S, BNT162b2, ChAdOx1 nCov-19, and mRNA-1273 vaccines were included in the analyses. Compared to full dose, booster dose of overall vaccines provided better protection against any (VED=22% (95%CI 15%-29%), p<0.001), severe (VED=20% (95%CI 8%-32%), p=0.001) and symptomatic (VED=22% (95%CI 11%-34%), p<0.001) Omicron infections within 3 months, as well as within 3 months or more (VED=30% (95%CI 24%-37%), p<0.001 for any, VED=18% (95%CI 13%-23%), p<0.001 for severe and VED=37% (95%CI 29%-46%), p<0.001 for symptomatic infections). The meta-regression analysis of overall vaccines revealed that the full dose VE against any and symptomatic Omicron infections were significantly reduced each month by 3.0% (95%CI 0.9%-4.8%, p=0.004) and 5.2% (95%CI 3.3%-7.1%, p=0.006), respectively; whereas booster dose effectiveness against severe and symptomatic Omicron infections were decreased by 3.7% (95%CI 5.1%-12.6%, p=0.030) and 3.9% (95%CI 1.2%-6.5%, p=0.006), respectively. Conclusion: Compared to full dose only, a booster dose addition provides better protection against B.1.1.529 infection. Although the VE estimates of Ad26.COV2.S, BNT162b2, ChAdOx1 nCov-19, and mRNA-1273 vaccines against B.1.1.529 infection after both full and booster doses are generally moderate, and the booster dose provides excellent protection against severe infection, it is important to note that the VE estimates decline over time, suggesting the need for a regular Covid-19 booster injection after certain period of time to maintain VE.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.29.22274454v1" target="_blank">Effectiveness of Covid-19 vaccines against SARS-CoV-2 Omicron variant (B.1.1.529): A systematic review with meta-analysis and meta-regression</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Keeping it close: The role of a Campus COVID Support Team (CCST) in sustaining a safe and healthy university campus during COVID-19</strong> -
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It has been over 24 months since the start of the COVID-19 pandemic forced university campuses to shut down and then reopen under new safety guidelines. Now as we move into subsequent years of the pandemic, we can look back and evaluate what has worked, improvements to be made, and plans for providing a sustained response for a campus community. In this article we detail one campus response to the COVID-19 pandemic and directions being taken to ensure a sustained campus COVID support team (CCST) is in hand to ensure the health and safety of the university community. The CCST was created to serve as a one-stop-shop to help the university community navigate COVID-19 policies and procedures. The responsibilities of the CCST include conducting case investigations for any positive COVID-19 tests within the university community, contact tracing for authorized university affiliates, epidemiological surveillance and mitigation efforts, and communication through real-time analysis and dashboards. Continuous monitoring procedures demonstrated the CCST conducted all case investigations within the post-testing 24-hour window, thus keeping the university test- positivity rate below 3%. Quality improvement surveys demonstrated a high level of satisfaction with the CCST efforts and provided areas for improvement and sustainability. Having a public health faculty led CCST enabled the university to act swiftly when COVID-19 positive cases were emerging and deter widespread campus COVID-19 outbreaks. The CCST timeliness and connectivity to the campus has demonstrated benefits to the health and safety of the campus.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.01.22274540v1" target="_blank">Keeping it close: The role of a Campus COVID Support Team (CCST) in sustaining a safe and healthy university campus during COVID-19</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>Clinical Performance Evaluation of the Bio-Self™ COVID-19 Antigen Home Test</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Device: Bio-Self COVID-19 Antigen Home Test; Device: Standard of Care COVID-19 Test; Diagnostic Test: RT-PCR Test<br/><b>Sponsors</b>: BioTeke USA, LLC; CSSi Life Sciences<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety of Fractional Booster Dose of COVID-19 Vaccines Available for Use in Pakistan/Brazil: A Phase 4 Dose-optimizing Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Sinovac; Biological: AZD1222; Biological: BNT162b2<br/><b>Sponsors</b>: Albert B. Sabin Vaccine Institute; Aga Khan University; Oswaldo Cruz Foundation; Stanford University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine as a Booster Dose in Population Aged 12-17 Years</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: SCTV01E; Biological: mRNA-1273<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 First-In-Human Phase 1b Study of AmnioPul-02 in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: AmnioPul-02<br/><b>Sponsor</b>: Amniotics AB<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 of COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Older Adults.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: 20 μg dose of SYS6006; Biological: 30 μg dose of SYS6006; Biological: 50 μg dose of SYS6006; Drug: Placebo<br/><b>Sponsor</b>: <br/>
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CSPC ZhongQi Pharmaceutical Technology 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>Safety, Reactogenicity, and Immunogenicity Study of a Lyophilized COVID-19 mRNA Vaccine</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: A Lyophilized COVID-19 mRNA Vaccine; Biological: Placebo<br/><b>Sponsor</b>: Jiangsu Rec-Biotechnology 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 Study of COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Adults Aged 18 -59 Years.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: 20 μg dose of SYS6006; Biological: 30 μg dose of SYS6006; Biological: 50 μg dose of SYS6006; Drug: Placebo<br/><b>Sponsor</b>: <br/>
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CSPC ZhongQi Pharmaceutical Technology 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 2b/3 Trial of NuSepin® in COVID-19 Pneumonia Patients</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: NuSepin® 0.2 mg/kg; Drug: NuSepin® 0.4 mg/kg; Drug: Placebo<br/><b>Sponsor</b>: Shaperon<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>Aerobic Exercise and Covid-19 Survivors With Post-Intensive Care Syndrome (Pics)</strong> - <b>Conditions</b>: COVID-19; Post Intensive Care Syndrome<br/><b>Interventions</b>: <br/>
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Other: Aerobic Exercise Training; Other: Home Plan<br/><b>Sponsor</b>: Riphah International 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>Efficacy and Safety of JT001 (VV116) Compared With Paxlovid</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: JT001; Drug: Paxlovid<br/><b>Sponsor</b>: <br/>
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Vigonvita Life Sciences<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>Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles as Early Goal Directed Therapy for COVID-19 Moderate-to-Severe Acute Respiratory Distress Syndrome (ARDS): A Phase III Clinical Trial</strong> - <b>Condition</b>: COVID-19 Acute Respiratory Distress Syndrome<br/><b>Intervention</b>: Drug: EXOFLO<br/><b>Sponsor</b>: Direct Biologics, 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>Use of Continuous Glucose Monitors in Coronavirus Disease 2019 ICU and Potential Inpatient Settings</strong> - <b>Conditions</b>: Covid19; Diabetes Mellitus<br/><b>Intervention</b>: Device: continuous glucose monitoring<br/><b>Sponsor</b>: Tanureet K Arora<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>Phase Ⅱ Clinical Trial of SARS-CoV-2 mRNA Vaccine</strong> - <b>Condition</b>: SARS-CoV-2<br/><b>Interventions</b>: Biological: SARS-CoV-2 (LVRNA009) 50μg group; Biological: SARS-CoV-2 (LVRNA009) 100μg group; Other: Placebo<br/><b>Sponsors</b>: AIM Vaccine Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Sample Collection for Evaluation of the Panbio™ COVID-19/ Flu A&B Rapid Panel.</strong> - <b>Conditions</b>: COVID-19; Influenza A; Influenza Type B<br/><b>Intervention</b>: Diagnostic Test: Nasal and Nasopharyngeal Sampling of the Panbio™ COVID-19/ Flu A&B Rapid Panel<br/><b>Sponsor</b>: Abbott Rapid Dx<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>Pilot Trial on Immunosuppression Modulation to Increase SARS-CoV-2 Vaccine Response in Kidney Transplant Recipients</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Immunosuppression reduction; Other: No immunosuppression reduction<br/><b>Sponsor</b>: Medical University of Vienna<br/><b>Active, not 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>Identifying SARS-CoV-2 main protease inhibitors by applying the computer screening of a large database of molecules</strong> - The outbreak of coronavirus disease 2019 (COVID-19) at the end of 2019 affected global health. Its infection agent was called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Wearing a mask, maintaining social distance, and vaccination are effective ways to prevent infection of SARS-CoV-2, but none of them help infected people. Targeting the enzymes of SARS-CoV-2 is an effective way to stop the replication of the virus in infected people and treat COVID-19 patients. SARS-CoV-2 main…</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>Synthetic lethality-based prediction of anti-SARS-CoV-2 targets</strong> - Novel strategies are needed to identify drug targets and treatments for the COVID-19 pandemic. The altered gene expression of virus-infected host cells provides an opportunity to specifically inhibit viral propagation via targeting the synthetic lethal and synthetic dosage lethal (SL/SDL) partners of such altered host genes. Pursuing this disparate antiviral strategy, here we comprehensively analyzed multiple in vitro and in vivo bulk and single-cell RNA-sequencing datasets of SARS-CoV-2…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Prediction of COVID-19 manipulation by selective ACE inhibitory compounds of <em>Potentilla reptant</em> root: <em>In silico</em> study and ADMET profile</strong> - In the novel SARS-CoV-2 (COVID-19) as a global emergency event, the main reason of the cardiac injury from COVID-19 is angiotensin-converting enzyme 2 (ACE2) targeting in SARS-CoV-2 infection. The inhibition of ACE2 induces an increase in the angiotensin II (Ang II) and the angiotensin II receptor type 1 (AT1R) leading to impaired cardiac function or cardiac inflammatory responses. The ethyl acetate fraction of Potentilla reptans L. root can rescue heart dysfunction, oxidative stress, cardiac…</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>In silico evidence of antiviral activity against SARS-CoV-2 main protease of oligosaccharides from Porphyridium sp</strong> - The coronavirus pandemic (COVID-19) has created an urgent need to develop effective strategies for prevention and treatment. In this context, therapies against protease M^(pro), a conserved viral target, would be essential to contain the spread of the virus and reduce mortality. Using combined techniques of structure modelling, in silico docking and pharmacokinetics prediction, many compounds from algae were tested for their ability to inhibit the SARS-CoV-2 main protease and compared to the…</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>TARDBP Inhibits Porcine Epidemic Diarrhea Virus Replication through Degrading Viral Nucleocapsid Protein and Activating Type I Interferon Signaling</strong> - In global infection and serious morbidity and mortality, porcine epidemic diarrhea virus (PEDV) has been regarded as a dreadful porcine pathogen, but the existing commercial vaccines are not enough to fully protect against the epidemic strains. Therefore, it is of great necessity to feature the PEDV-host interaction and develop efficient countermeasures against viral infection. As an RNA/DNA protein, the trans-active response DNA binding protein (TARDBP) plays a variety of functions 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>Journey of remdesivir from the inhibition of hepatitis C virus to the treatment of COVID-19</strong> - If a planned path reaches a dead-end, one can simply stop. Or one can turn around, walk back to the last intersection and take another path, or one can consider taking few paths in parallel. The last scenario is reflective of the journey of remdesivir, the first antiviral for the treatment of COVID-19, that was approved by FDA less than 10 months after the isolation of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. As of January 2022, 10 million COVID-19 patients have been treated…</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>Oral hymecromone decreases hyaluronan in human study participants</strong> - BACKGROUNDHyaluronan (HA), an extracellular matrix glycosaminoglycan, has been implicated in the pathophysiology of COVID-19 infection, pulmonary hypertension, pulmonary fibrosis, and other diseases, but is not targeted by any approved drugs. We asked whether hymecromone (4-methylumbelliferone [4-MU]), an oral drug approved in Europe for biliary spasm treatment that also inhibits HA in vitro and in animal models, could be repurposed as an inhibitor of HA synthesis in humans.METHODSWe conducted…</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>Bis-indolylation of aldehydes and ketones using silica-supported FeCl<sub>3</sub>: molecular docking studies of bisindoles by targeting SARS-CoV-2 main protease binding sites</strong> - We report herein an operationally simple, efficient and versatile procedure for the synthesis of bis-indolylmethanes via the reaction of indoles with aldehydes or ketones in the presence of silica-supported ferric chloride under grindstone conditions. The prepared supported catalyst was characterized by SEM and EDX spectroscopy. The present protocol has several advantages such as shorter reaction time, high yield, avoidance of using harmful organic solvents during the reaction and tolerance of a…</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>Role of T Regulatory Cells and Myeloid-Derived Suppressor Cells in COVID-19</strong> - Coronavirus disease 2019 (COVID-19) has been raised as a pandemic disease since December 2019. Immunosuppressive cells including T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs) are key players in immunological tolerance and immunoregulation; however, they contribute to the pathogenesis of different diseases including infections. Tregs have been shown to impair the protective role of CD8^(+) T lymphocytes against viral infections. In COVID-19 patients, most studies…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>What goes around comes around: artificial circular RNAs bypass cellular antiviral responses</strong> - Natural circular RNAs have been found to sequester microRNAs and suppress their function. We have used this principle as a molecular tool, and produced artificial circular RNA sponges in a cell-free system by in vitro transcription and ligation. Formerly, we were able to inhibit hepatitis C virus propagation by applying a circular RNA decoy strategy against microRNA-122, which is essential for the viral life cycle. In another proof-of-principle study, we used circular RNAs to sequester…</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 Lithium Treatment in SARS-CoV-2 Infected Patients</strong> - At the beginning of the pandemic, we observed that lithium carbonate had a positive effect on the recovery of severely ill patients with COVID-19. Lithium is able to inhibit the replication of several types of viruses, some of which are similar to the SARS-CoV-2 virus, increase the immune response and reduce inflammation by preventing or reducing the cytokine storm. Previously, we published an article with data from six patients with severe COVID-19 infection, where we proposed that lithium…</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>Learning in Adverse Circumstances: Impaired by Learning With Anxiety, Maladaptive Cognitions, and Emotions, but Supported by Self-Concept and Motivation</strong> - The COVID-19 summer semester 2020 posed many challenges and uncertainties, quite unexpectedly and suddenly. In a sample of 314 psychology students, it was investigated how they experienced learning and preparing for an end-of-semester exam, which emotions and strain they experienced, how academic performance was affected, and how personal antecedents of learning as important facets of a learner’s identity could support or prevent overcoming adverse circumstances of learning. The participants of…</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>Potential Application of Tea Polyphenols to the Prevention of COVID-19 Infection: Based on the Gut-Lung Axis</strong> - Coronavirus disease 2019 (COVID-19) disrupts the intestinal micro-ecological balance, and patients often develop the intestinal disease. The gut is the largest immune organ in the human body; intestinal microbes can affect the immune function of the lungs through the gut-lung axis. It has been reported that tea polyphenols (TPs) have antiviral and prebiotic activity. In this review, we discussed TPs reduced lung-related diseases through gut-lung axis by inhibiting dysbiosis. In addition, we also…</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>Performance of Severe Acute Respiratory Syndrome Coronavirus 2 Serological Diagnostic Tests and Antibody Kinetics in Coronavirus Disease 2019 Patients</strong> - Serological testing is recommended to support the detection of undiagnosed coronavirus disease 2019 (COVID-19) cases. However, the performance of serological assays has not been sufficiently evaluated. Hence, the performance of six severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binding antibody assays [three chemiluminescence (CLIAs) and three lateral flow immunoassays (LFIAs)] and a surrogate virus neutralization test (sVNT) was analyzed in a total of 988 serum samples comprising…</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 pan-variant inhibitory peptides deter S1-ACE2 interaction and neutralize delta and omicron pseudoviruses</strong> - Approved neutralizing antibodies that target the prototype Spike are losing their potency against the emerging variants of concern (VOCs) of SARS-CoV-2, particularly Omicron. Although SARS-CoV-2 is continuously adapting the host environment, emerging variants recognize the same ACE2 receptor for cell entry. Protein and peptide decoys derived from ACE2 or Spike proteins may hold the pan-variant inhibitory potential. Here, we deployed interactive structure- and pharmacophore-based approaches to…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<script>AOS.init();</script></body></html>
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