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<title>03 February, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>CITY LEADERSHIP IN PARA-DIPLOMACY: DRIVERS OF JAKARTA’S INTERNATIONAL ENGAGEMENT IN ADDRESSING COVID-19 PANDEMIC</strong> -
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<div>
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The outbreak of COVID-19 pandemic has impacted all the world’s aspects, including the interactions among governments. While some either chose to be conflicting with others or overlooked the pandemic, the rest attempted to collaborate in addressing the new global threat. Mega-cities in many countries were the most suffering regions due to the enormous virus confirmed cases, deaths, and economic declines, intertwining with other urban issues. As the largest city in Southeast Asia and in Indonesia, Jakarta also experienced the unprecedented crisis. However, apart from the efforts to tackle the crisis at home, the city showed its international engagement in addressing the issue together with other world’s cities as its para-diplomacy. This research aimed to answer the driving factors encouraging the city for such engagement. This research employed the qualitive method with a descriptive analysis and the city leadership theory proposed by Rapoport, Acuto and Grcheva. This research found that the Jakarta’s international engagement in addressing the pandemic as the city leadership action was driven by the role of city leader, decentralization and global city networking, and the regional COVID-19 policies and internet representing three elements in the theory: actor, structures, and tools. This paper argues that cities within the global city networking have demonstrated their stronger role during the pandemic, providing opportunity for nation branding by regional initiatives in handling the pandemic in addition to state foreign policy. As cities have been more consolidated within the networks, seeing the city leadership in responding to global issues merits attentions among scholars.
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🖺 Full Text HTML: <a href="https://osf.io/6f3j5/" target="_blank">CITY LEADERSHIP IN PARA-DIPLOMACY: DRIVERS OF JAKARTA’S INTERNATIONAL ENGAGEMENT IN ADDRESSING COVID-19 PANDEMIC</a>
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</div></li>
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<li><strong>Development of a mobile laboratory system in hydrogen fuel cell buses and evaluation of the performance for COVID-19</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Introduction: We newly designed and developed two types of hydrogen fuel cell (HFC) buses (motorcoach type and minibus type) with a mobile laboratory system. Feasibility studies have been performed for mobile laboratory testing, especially for the laboratory performance of COVID-19 RT-PCR (PCR). Methods: We evaluated the driving range capability, PCR sample size capacity, turn-around time (TAT), and analytical performance for the detection of SARS-CoV-2. Saliva samples were used for the current research and the analytical performance was compared with reference PCR. Results: The estimated driving range and sample size capacity were 432 km and 3,258 samples, respectively for the HFC motorcoach and 313 km and 2,146 samples for the HFC minibus, respectively. For the TAT, the median time between the sample submission and the completion of PCR were 86 min for the motorcoach and 76 min for the minibus, and the median time between sample submission and the electronic reporting of the result to each visitor were 182 min for the motorcoach and 194 min for the minibus. A secondary analysis of 1,574 HFC mobile laboratory testing samples was conducted and all negative samples were negative by reference PCR. Furthermore, all positive samples were confirmed as positive by reference PCR or other molecular examinations. Conclusion: We confirmed the feasibility of HFC mobile laboratory systems for achieving the rapid reporting of highly accurate PCR results.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.30.23285220v1" target="_blank">Development of a mobile laboratory system in hydrogen fuel cell buses and evaluation of the performance for COVID-19</a>
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</div></li>
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<li><strong>Associations between reported healthcare disruption due to COVID-19 and avoidable hospitalisation: Evidence from seven linked longitudinal studies for England</strong> -
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Background: Health services across the UK struggled to cope during the COVID-19 pandemic. Many treatments were postponed or cancelled, although the impact was mitigated by new models of delivery. While the scale of disruption has been studied, much less is known about if this disruption impacted health outcomes. The aim of our paper is to examine whether there is an association between individuals experiencing disrupted access to healthcare during the pandemic and risk of an avoidable hospitalisation. Methods: We used individual-level data for England from seven longitudinal cohort studies linked to electronic health records from NHS Digital (n = 29 276) within the UK Longitudinal Linkage Collaboration trusted research environment. Avoidable hospitalisations were defined as emergency hospital admissions for ambulatory care sensitive and emergency urgent care sensitive conditions (1st March 2020 to 25th August 2022). Self-reported measures of whether people had experienced disruption during the pandemic to appointments (e.g., visiting their GP or an outpatient department), procedures (e.g., surgery, cancer treatment) or medications were used as our exposures. Logistic regression models examined associations. Results: 35% of people experienced some form of disrupted access to healthcare. Those whose access was disrupted were at increased risk of any (Odds Ratio (OR) = 1.80, 95% Confidence Intervals (CIs) = 1.34-2.41), acute (OR = 1.68, CIs = 1.13-2.53) and chronic (OR = 1.93, CIs = 1.40-2.64) ambulatory care sensitive hospital admissions. There were positive associations between disrupted access to appointments and procedures to measures of avoidable hospitalisations as well. Conclusions: Our study presents novel evidence from linked individual-level data showing that people whose access to healthcare was disrupted were more likely to have an avoidable or potentially preventable hospitalisation. Our findings highlight the need to increase healthcare investment to tackle the short- and long-term implications of the pandemic beyond directly dealing with SARS-CoV-2 infections.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.01.23285333v1" target="_blank">Associations between reported healthcare disruption due to COVID-19 and avoidable hospitalisation: Evidence from seven linked longitudinal studies for England</a>
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</div></li>
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<li><strong>Immunogenicity of the BA.1 and BA.4/5 Bivalent Boosts: A Brief Report of Preliminary Results from the COVAIL Randomized Clinical Trial</strong> -
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The emergence of Omicron subvariants and waning immunity to initial vaccine regimens led to the authorization of updated SARS-CoV-2 bivalent vaccines containing wildtype with either Omicron BA.1 or BA.4/5. Here, we compare early serologic responses from a randomized clinical trial of a second boost with either the Pfizer/BioNTech BNT162b2 (30 mcg dose) Wildtype/Omicron BA.1 or Wildtype/Omicron BA.4/5 vaccines against homologous and heterologous strains including contemporary Omicron subvariants BQ.1.1 and XBB.1.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.31.23285306v1" target="_blank">Immunogenicity of the BA.1 and BA.4/5 Bivalent Boosts: A Brief Report of Preliminary Results from the COVAIL Randomized Clinical Trial</a>
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</div></li>
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<li><strong>Discovering SARS-CoV-2 neoepitopes and the associated TCR-pMHC recognition mechanisms by combining single-cell sequencing, deep learning, and molecular dynamics simulation techniques</strong> -
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<div>
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The molecular mechanisms underlying the recognition of epitopes by T cell receptors (TCRs) are critical for activating T cell immune responses and rationally designing TCR-based therapeutics. Single-cell sequencing techniques vastly boost the accumulation of TCR sequences, while the limitation of available TCR-pMHC structures hampers further investigations. In this study, we proposed a comprehensive strategy that incorporates structural information and single-cell sequencing data to investigate the epitope-recognition mechanisms of TCRs. By antigen specificity clustering, we mapped the epitope sequences between epitope-known and epitope unknown TCRs from COVID-19 patients. One reported SARS-CoV-2 epitope, NQKLIANQF (S919-927), was identified for a TCR expressed by 614 T cells (TCR-614). Epitope screening also identified a potential cross-reactive epitope, KLKTLVATA (NSP31790-1798), for a TCR expressed by 204 T cells (TCR-204). According to the molecular dynamics (MD) simulations, we revealed the detailed epitope-recognition mechanisms for both TCRs. The structural motifs responsible for epitope recognition revealed by the MD simulations are consistent with the sequential features recognized by the sequence-based clustering method. This strategy will facilitate the discovery and optimization of TCR-based therapeutics. In addition, the comprehensive strategy can also promote the development of cancer vaccines in virtue of the ability to discover neoepitopes and epitope-recognition mechanisms.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.02.526761v1" target="_blank">Discovering SARS-CoV-2 neoepitopes and the associated TCR-pMHC recognition mechanisms by combining single-cell sequencing, deep learning, and molecular dynamics simulation techniques</a>
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</div></li>
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<li><strong>Effectiveness of a chatbot in improving the mental wellbeing of health workers in Malawi during the COVID-19 pandemic: A randomized, controlled trial</strong> -
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We conducted a randomized, controlled trial (RCT) to investigate our hypothesis that the interactive chatbot, Vitalk, is more effective in improving mental wellbeing and resilience outcomes of health workers in Malawi than the passive use of Internet resources. For our 2-arm, 8-week, parallel RCT (ISRCTN Registry: trial ID ISRCTN16378480), we recruited participants from 8 professional cadres from public and private healthcare facilities. The treatment arm used Vitalk; the control arm received links to Internet resources. The research team was blinded to the assignment. Of 1,584 participants randomly assigned to the treatment and control arms, 215 participants in the treatment and 296 in the control group completed baseline and endline anxiety assessments. Six assessments provided outcome measures for: anxiety (GAD-7); depression (PHQ-9); burnout (OLBI); loneliness (ULCA); resilience (RS-14); and resilience-building activities. We analyzed effectiveness using mixed-effects linear models, effect size estimates, and reliable change in risk levels. Results support our hypothesis. Difference-in-differences estimators showed that Vitalk reduced: depression (-0.68 [95% CI -1.15 to -0.21]); anxiety (-0.44 [95% CI -0.88 to 0.01]); and burnout (-0.58 [95% CI -1.32 to 0.15]). Changes in resilience (1.47 [95% CI 0.05 to 2.88]) and resilience-building activities (1.22 [95% CI 0.56 to 1.87]) were significantly greater in the treatment group. Our RCT produced a medium effect size for the treatment and a small effect size for the control group. This is the first RCT of a mental health app for healthcare workers during the COVID-19 pandemic in Southern Africa combining multiple mental wellbeing outcomes, and measuring resilience and resilience-building activities. A significant number of participants could have benefited from mental health support (1 in 8 reported anxiety and depression; 3 in 4 suffered burnout; and 1 in 4 had low resilience). Such help is not readily available in Malawi. Vitalk has the potential to fill this gap.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.24.23284959v2" target="_blank">Effectiveness of a chatbot in improving the mental wellbeing of health workers in Malawi during the COVID-19 pandemic: A randomized, controlled trial</a>
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</div></li>
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<li><strong>Effectiveness of a nation-wide COVID-19 vaccination program in Mexico against symptomatic COVID-19, hospitalizations, and death: a retrospective analysis of national surveillance data</strong> -
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BACKGROUND: Vaccination has been effective in ameliorating the impact of COVID-19. Here, we report vaccine effectiveness (VE) for nationally available COVID-19 vaccines in Mexico. METHODS: Retrospective analysis of a COVID-19 surveillance system to assess VE of the BNT162b2, mRNA-12732, Gam-COVID-Vac, Ad5-nCoV, Ad26.COV2.S, ChAdOx1 and CoronaVac vaccines, against SARS-CoV-2 infection, COVID-19 hospitalization, and death in Mexico. VE was estimated using time-varying Cox proportional hazard models in vaccinated and unvaccinated adults, adjusted for age, sex and comorbidities. VE was also estimated for adults with diabetes, ≥60 years, and comparing predominance of SARS-CoV-2 variants B.1.1.519 and B.1.617.2. RESULTS: We assessed 793,487 vaccinated and 4,792,338 unvaccinated adults between December 24th, 2020, and September 27th, 2021. VE against SARS-CoV-2 infection was highest for fully vaccinated individuals with mRNA-12732 (91.5%, 95%CI 90.3-92.4) and Ad26.COV2.S (82.2%, 95%CI 81.4-82.9), for COVID-19 hospitalization were BNT162b2 (84.3%, 95%CI 83.6-84.9) and Gam-COVID-Vac (81.4% 95%CI 79.5-83.1) and for mortality BNT162b2 (89.8%, 95%CI 89.2-90.2) and mRNA-12732 (93.5%, 95%CI 86.0-97.0). VE decreased for all vaccines in adults ≥60 years, people with diabetes, and periods of Delta variant predominance. CONCLUSIONS: All vaccines implemented in Mexico were effective against SARS-CoV-2 infection, COVID-19 hospitalization, and death. Mass vaccination with multiple vaccines is useful to maximize vaccination coverage.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.04.22273330v2" target="_blank">Effectiveness of a nation-wide COVID-19 vaccination program in Mexico against symptomatic COVID-19, hospitalizations, and death: a retrospective analysis of national surveillance data</a>
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</div></li>
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<li><strong>Bioinformatic investigation of discordant sequence data for SARS-CoV-2: insights for robust genomic analysis during pandemic surveillance</strong> -
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<div>
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The capacity to undertake whole genome sequencing (WGS) in public health laboratories (PHLs) has grown rapidly in response to COVID-19, and SARS-CoV-2 genomic data has been invaluable for managing the pandemic. The public health response has been further supported by the rapid upgrade and implementation of laboratory and bioinformatic resources. However, there remains a high degree of variability in methods and capabilities between laboratories. In addition to evolving methodology and improved understanding of SARS-CoV-2, public health laboratories have become strained during surges in case numbers, adding to the difficulty of ensuring the highest data accuracy. Here, we formed a national working group comprised of laboratory scientists and bioinformaticians from Australia and New Zealand to improve data concordance across PHLs. Through investigating discordant sequence data from Australia’s first external SARS-CoV-2 WGS proficiency testing program (PTP), we show that most discrepancies in genome assessment arose from intrahost variation. While others could be remedied using reasonable, parsimonious bioinformatic quality control. Furthermore, we demonstrate how multidisciplinary national working groups can inform guidelines in real time for bioinformatic quality acceptance criteria. Provision of technical feedback allows laboratory improvement during a pandemic in real time, enhancing public health responses.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.01.526694v1" target="_blank">Bioinformatic investigation of discordant sequence data for SARS-CoV-2: insights for robust genomic analysis during pandemic surveillance</a>
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</div></li>
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<li><strong>Crystal Structures of Inhibitor-Bound Main Protease from Delta- and Gamma-Coronaviruses</strong> -
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With the spread of SARS-CoV-2 throughout the globe to cause the COVID-19 pandemic, the threat of zoonotic transmissions of coronaviruses (CoV) has become even more evident. As human infections have been caused by alpha- and beta-CoVs, structural characterization and inhibitor design mostly focused on these two genera. However, viruses from the delta and gamma genera also infect mammals and pose potential zoonotic transmission threat. Here, we determined the inhibitor-bound crystal structures of the main protease (Mpro) from the delta-CoV porcine HKU15 and gamma-CoV SW1 from beluga whale. Comparison with the apo structure of SW1 Mpro, which we also present here, enabled identifying structural arrangements upon inhibitor binding at the active site. The binding modes and interactions of two covalent inhibitors, PF-00835231 (lufotrelvir) bound to HKU15 and GC376 bound to SW1 Mpro, reveal features that may be leveraged to target diverse coronaviruses and toward structure-based design of pan-CoV inhibitors.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.01.526623v1" target="_blank">Crystal Structures of Inhibitor-Bound Main Protease from Delta- and Gamma-Coronaviruses</a>
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<li><strong>Investigations on SARS-CoV-2 and other coronaviruses in mink farms in France at the end of the first year of COVID-19 pandemic</strong> -
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Soon after the beginning of the COVID-19 pandemic in early 2020, the Betacoronavirus SARS-CoV-2 infection of several mink farms breeding American minks (Neovison vison) for fur was detected in several countries of Europe. The risk of a new reservoir formation and of a reverse zoonosis from minks was then a major concern. The aim of this study was to investigate the four French mink farms for the circulation of SARS-CoV-2 at the end of 2020. The investigations took place during the slaughtering period thus facilitating different types of sampling (swabs and blood). In one of the four mink farms, 96.6% of serum samples were positive in SARS-CoV-2 ELISA coated with purified N protein recombinant antigen and 54 out of 162 (33%) pharyngo-tracheal swabs were positive by RT-qPCR. The genetic variability among 12 SARS-CoV-2 genomes sequenced in this farm indicated the co-circulation of several lineages at the time of sampling. All SARS-CoV-2 genomes detected were nested within the 20A clade (Nextclade), together with SARS-CoV-2 genomes from humans sampled at the same period. The percentage of SARS-CoV-2 seropositivity by ELISA varied between 0.5 and 1.2% in the three other farms. Interestingly, among these three farms, 11 pharyngo-tracheal swabs and 3 fecal pools from two farms were positive by end-point RT-PCR for an Alphacoronavirus highly similar to a mink coronavirus sequence observed in Danish farms in 2015. In addition, a mink Caliciviridae was identified in one of the two positive farms for Alphacoronavirus. The clinical impact of these unapparent viral infections is not known. The co-infection of SARS-CoV-2 with other viruses in mink farms could contribute to explain the diversity of clinical symptoms noted in different infected farms in Europe. In addition, the co-circulation of an Alphacoronavirus and SARS-CoV-2 within a mink farm would increase potentially the risk of viral recombination between alpha and betacoronaviruses already suggested in wild and domestic animals, as well as in humans.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.02.526749v1" target="_blank">Investigations on SARS-CoV-2 and other coronaviruses in mink farms in France at the end of the first year of COVID-19 pandemic</a>
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<li><strong>Antiviral activity of molnupiravir precursor NHC against SARS-CoV-2 Variants of Concern (VOCs) and implications for the therapeutic window and resistance</strong> -
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Several regulatory agencies have either licensed or given emergency use approval for treatment of patients at risk of developing severe COVID-19 with the anti-viral drug, Molnupiravir. Recent trials involving Molnupiravir suggested the drug was not as efficacious as earlier studies suggested. This study aimed to: (i) determine the effectiveness of the Molnupiravir active metabolite (NHC) against different SARS-CoV-2 Variants of Concern (VoCs), (ii) establish the therapeutic window of NHC in a human lung cell model, and (iii) and evaluate the genetic barrier to resistance. Dose response assays were performed in parallel to determine the IC50 (the concentration required to inhibit virus titre by 50%) of NHC against different variants. Human ACE-2 A549 cells were treated with NHC at different time points either before, during or after infection with SARS-CoV-2. Multiple passaging in the presence or absence of drug was used to evaluate whether resistance occurred. To obtain genomic information, virus was sequenced at regular intervals. After 20 passages in the presence of the drug, dose response assays and sequencing showed the virus did not appear to have developed resistance. The drug had equivalent activity against four VOCs ranging from 0.04 to 0.16M IC50. The efficacy of the drug diminished when applied after 24 hours post-infection. Our results suggest that earlier administration in patients, perhaps pre- or post-exposure rather than symptom onset, would be a more effective treatment option.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.11.23.469695v3" target="_blank">Antiviral activity of molnupiravir precursor NHC against SARS-CoV-2 Variants of Concern (VOCs) and implications for the therapeutic window and resistance</a>
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</div></li>
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<li><strong>Household Hardships during the COVID-19 Pandemic: Examining Household Vulnerability and Responses to Pandemic Related Shocks in Eastern Ethiopia</strong> -
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COVID-19 is associated with one of the largest disturbances to life in the 21st century. To quell disease spread, governments implemented lockdowns that likely created hardships for house-holds. To improve knowledge of consequences, we examine how the pandemic period was associ-ated with household hardships and assess factors associated with these hardships. We conducted a cross-sectional study using quasi-Poisson regression to examine factors associated with house-hold hardships. Data were collected between August and September of 2021 from a random sam-ple of 880 households living in a Health and Demographic Surveillance System (HDSS) located in the Harari Region and the District of Kersa, both in Ethiopia. Having a head of household with no education, residing in a rural area, larger household size, lower income and/or wealth, and community responses to COVID-19 including lockdowns and travel restrictions were inde-pendently associated with experiencing household hardships. Our results identify characteristics of groups at-risk for food insecurity during the pan-demic; households that were already strug-gling prior to the onset of the pandemic were at greatest risk of adverse consequences during the pandemic period. These findings may inform future efforts to mitigate the consequences of COVID-19 and future disease out-breaks.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.01.23285322v1" target="_blank">Household Hardships during the COVID-19 Pandemic: Examining Household Vulnerability and Responses to Pandemic Related Shocks in Eastern Ethiopia</a>
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<li><strong>Minimal mRNA uptake and inflammatory response to COVID-19 mRNA vaccine exposure in human placental explants</strong> -
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Despite universal recommendations for COVID-19 mRNA vaccination in pregnancy, uptake has been lower than desired. There have been limited studies of the direct impact of COVID-19 mRNA vaccine exposure in human placental tissue. Using a primary human villous explant model, we investigated the uptake of two common mRNA vaccines (BNT162b2 Pfizer-BioNTech or mRNA-1273 Moderna), and whether exposure altered villous cytokine responses. Explants derived from second or third trimester chorionic villi were incubated with vaccines at supraphysiologic concentrations and analyzed at two time points. We observed minimal uptake of mRNA vaccines in placental explants by in situ hybridization and quantitative RT-PCR. No specific or global cytokine response was elicited by either of the mRNA vaccines in multiplexed immunoassays. Our results suggest that the human placenta does not readily absorb the COVID-19 mRNA vaccines nor generate a significant inflammatory response after exposure.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.01.23285349v1" target="_blank">Minimal mRNA uptake and inflammatory response to COVID-19 mRNA vaccine exposure in human placental explants</a>
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<li><strong>Food Insecurity amid COVID-19 Lockdowns: Assessing Sociodemographic Indicators of Vulnerability in Harar and Kersa, Ethiopia</strong> -
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Objective The COVID-19 pandemic was associated with widespread social disruptions, as governments implemented lockdowns to quell disease spread. To advance knowledge of consequences for households in lower-income countries, we examine food insecurity during the pandemic period. Design Cross-sectional study using logistic regression to examine factors associated with food insecurity. Data were collected between August and September of 2021 through a Health and Demographic Surveillance System (HDSS) using a survey instrument focused on knowledge regarding the spread of COVID-19; food availability; COVID-19 related shocks/coping; under-five child healthcare services; and healthcare services for pregnant women. Setting The study is set in two communities in Eastern Ethiopia, one rural and one urban. Participants A random sample of 880 households residing in Kersa and Harar. Results Roughly 16% of households reported not having enough food to eat during the pandemic, an increase of 6% since before the pandemic. After adjusting for other variables, households were more likely to report food insecurity if they were living in an urban area, were a larger household, had a family member lose employment, reported an increase in food prices, or were food insecure before the pandemic. Households were less likely to report food insecurity if they were wealthier or had higher household income. Discussion After taking other characteristics into consideration, households in urban areas were at higher risk for food insecurity. These findings point to the need for expanding food assistance programs to more urban areas to help mitigate the impact of lockdowns on more vulnerable households.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.31.23284545v1" target="_blank">Food Insecurity amid COVID-19 Lockdowns: Assessing Sociodemographic Indicators of Vulnerability in Harar and Kersa, Ethiopia</a>
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<li><strong>Immunogenicity and safety of SARS-CoV-2 recombinant protein nanoparticle vaccine GBP510 adjuvanted with AS03: randomised, active-controlled, observer-blinded, phase 3 trial</strong> -
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<b> Background:</b> GBP510 vaccine contains self-assembling, recombinant nanoparticles displaying SARS-CoV-2 spike receptor-binding domains. We report interim phase 3 immunogenicity results for GBP510 adjuvanted with AS03 (GBP510/AS03) compared with ChAdOx1-S (Vaxzevria, AstraZeneca) up to 2 weeks after the second dose, and safety data up to a median of 2.5 months follow-up. <b>Methods:</b> Randomised, active-controlled, observer-blinded, multinational study: Cohort 1 (no history of SARS-CoV-2 infection/COVID-19 vaccination, n=1956) randomised 2:1 to receive two doses of GBP510/AS03 or ChAdOx1-S (immunogenicity and safety); Cohort 2 (regardless of baseline serostatus; n=2080) randomised 5:1 (safety). Primary objectives: demonstrate superiority in geometric mean titre (GMT) and non-inferiority in seroconversion rate (SCR; ≥4-fold rise from baseline) of GBP510/AS03 versus ChAdOx1-S for neutralising antibodies against the ancestral strain by live-virus neutralisation assay. Secondary objectives included assessment of safety and reactogenicity. <b>Findings:</b> At 2 weeks after the second vaccination, the GMT ratio (GBP510/AS03 / ChAdOx1-S) was 2.93 (95% CI 2.63 - 3.27), demonstrating superiority (95% CI lower limit >1). The between-group SCR difference of 10.76% (95% CI 7.68 - 14.32) satisfied the non-inferiority criterion (95% CI lower limit >5%).The proportion of subjects with adverse events (AEs) after any vaccination was higher with GBP510/AS03 versus ChAdOx1-S for solicited local AEs (56.69% vs 49.20%), but was similar for solicited systemic AEs (51.21% vs 53.51%) and unsolicited AEs (13.27% vs 14.56%). No safety concerns were identified during follow-up for a median 2.5-months after the second vaccination. <b>Interpretation:</b> GBP510/AS03 met the superiority criterion for neutralising antibodies and non-inferiority criterion for SCR compared with ChAdOx1-S, and showed a clinically acceptable safety profile. <b>Funding:</b> This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investments INV-010680 and INV-006462. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.31.23284895v1" target="_blank">Immunogenicity and safety of SARS-CoV-2 recombinant protein nanoparticle vaccine GBP510 adjuvanted with AS03: randomised, active-controlled, observer-blinded, phase 3 trial</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>Phase Ⅰ Clinical Trial of a Candidate COVID-19 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant COVID-19 Vaccine (chimpanzee adenovirus vector) for Inhalation<br/><b>Sponsors</b>: Wuhan BravoVax Co., Ltd.; National University Hospital, Singapore; Shanghai BravoBio 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>Plitidepsin Versus Control in Immunocompromised Adult Participants With Symptomatic COVID-19 Requiring Hospital Care</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Plitidepsin<br/><b>Sponsor</b>: PharmaMar<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 Corfluvec Vaccine for the Prevention of COVID-19 in Healthy Volunteers</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Corfluvec component 1 low dose; Biological: Corfluvec component 2 low dose; Biological: Corfluvec component 1 high dose; Biological: Corfluvec component 2 high dose; Biological: Corfluvec low dose; Biological: Corfluvec high dose; Biological: Placebo<br/><b>Sponsors</b>: Tatyana Zubkova; MDP-CRO, LLC; St. Petersburg State Pavlov Medical University<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Self-testing Study</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: SMARTest mobile app for COVID-19 self-testing<br/><b>Sponsor</b>: Columbia University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of Efficacy and Safety of Azvudine vs. Nirmatrelvir-Ritonavir in the Treatment of COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Azvudine; Drug: Nirmatrelvir-Ritonavir<br/><b>Sponsors</b>: Shandong Provincial Hospital; Central hospital Affiliated to Shandong First Medical University; The Second Affiliated Hospital of Shandong First Medical University; The Affiliated Hospital Of Southwest Medical University; Gansu Provincial Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Low-Dose Radiation Therapy for Severe COVID-19 Pneumonia</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Radiation: Low-Dose Radiation Therapy<br/><b>Sponsors</b>: Jiangsu Cancer Institute & Hospital; Nanjing Chest Hospital; The Affiliated BenQ Hospital of Nanjing Medical University; Central South University; Zhongda Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Tetrandrine Tablets Used in Hospitalized Adults With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Tetrandrine<br/><b>Sponsor</b>: Peking University Third Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>INFLUENCE OF HIGH FREQUENCY CHEST WALL OSCILLATION IN HOSPITALIZED PATIENTS WITH COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: HIGH FREQUENCY CHEST WALL OSCILLATION<br/><b>Sponsor</b>: Cairo University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of Megadose Vitamin C in Severe and Critical Ill COVID-19 Patients.</strong> - <b>Conditions</b>: Vitamin C; COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: Vitamin C; Drug: Placebo<br/><b>Sponsor</b>: Zhujiang Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Difference Between Non-invasive High-frequency Oscillatory Ventilation and Non-invasive Continuous Airway Pressure Ventilation in COVID-19 With Acute Hypoxemia</strong> - <b>Conditions</b>: COVID-19 Pneumonia; Non-invasive Ventilation<br/><b>Interventions</b>: Device: Non-invasive high-frequency oscillatory ventilation; Device: Non-invasive continuous positive airway pressure ventilation<br/><b>Sponsor</b>: Guangzhou Institute of Respiratory Disease<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>COVID-19 Molecular OTC At Home Test</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Diagnostic Test: Diagnostic Test: IN Vitro<br/><b>Sponsor</b>: 3EO Health<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>Randomized-controlled Trial of Immunoadsorption (IA) in Patients With Chronic Fatigue Syndrome (CFS) Including Patients With Post-COVID-19 CFS (PACS-CFS)</strong> - <b>Condition</b>: ME/CSF Including CFS Related to Post-acute COVID-19 Syndrome (PACS)<br/><b>Intervention</b>: Device: Immunoadsorption<br/><b>Sponsor</b>: Charite University, Berlin, Germany<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase II/III Immunogenicity and Safety Study of the AVX/COVID-12 Vaccine Against COVID-19 Applied as a Booster.</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: AVX-COVID/12; Biological: ChAdOx-1-S[recombinant]<br/><b>Sponsors</b>: Laboratorio Avi-Mex, S.A. de C.V.; National Council of Science and Technology, Mexico; Instituto Nacional de Enfermedades Respiratorias<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>Acupuncture as an Adjunctive Therapy for Covid-19 Omicron Randomised Controlled Trial in Patients With Moderate/Severe Pneumonia</strong> - <b>Conditions</b>: Acupuncture; Covid-19 Omicron; Pulmonary Function<br/><b>Intervention</b>: Other: Acupuncture<br/><b>Sponsor</b>: The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine<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>Brain-Training Treatment for Long COVID in Older Adults</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>: Other: NeuroFlex (computerized gamified tasks)<br/><b>Sponsor</b>: UConn Health<br/><b>Not yet recruiting</b></p></li>
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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>Dantrolene and ryanodine receptors in COVID-19:The daunting taskand neglected warden</strong> - Dantrolene (DTN) is a ryanodine receptor (RyR) antagonist that inhibits Ca^(2+) release from stores in the sarcoplasmic reticulum. DTN is mainly used in the management of malignant hyperthermia. RyRs are highly expressed in immune cells and are involved in different viral infections, including SARS-CoV-2, since Ca^(2+) is necessary for viral replication, maturation, and release. DTN can inhibit the proliferation of SARS-CoV-2, indicating its potential role in reducing entry and pathogenesis 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>Modular Metal-Quinone Networks with Tunable Architecture and Functionality</strong> - Nanostructured materials with tunable structures and functionality are of interest in diverse areas. Herein, metal ions are coordinated with quinones via metal-acetylacetone coordination bonds to generate a class of structurally tunable, universally adhesive, superhydrophilic, and pH-degradable materials. A library of metal-quinone networks (MQNs) is produced from five model quinone ligands paired with nine metal ions, leading to particles, tubes, capsules, and films. Importantly, MQNs show…</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>Weathering and degradation of polylactic acid masks in a simulated environment in the context of the COVID-19 pandemic and their effects on the growth of winter grazing ryegrass</strong> - The COVID-19 pandemic has led to explosive growth in the production and consumption of disposable medical masks, which has caused new global environmental problems due to the improper disposal of these masks and lack of effective mask recycling methods. To reduce the environmental load caused by the inability of synthetic plastics to degrade, polylactic acid (PLA) masks, as a biodegradable environmentally friendly plastic, may become a solution. This study simulated the actual degradation…</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>Family functioning of families experiencing intensive care and the specific impact of the COVID-19 pandemic: A grounded theory study</strong> - CONCLUSION: There is awareness about the love that exists within the family. A willing to supporting each other in the family even if the critical illness made the family anxious and afraid.</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>Inhibiting the Deubiquitinase UCHL1 Reduces SARS-CoV-2 Viral Uptake by ACE2</strong> - COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) remains a significant public health burden with limited treatment options. Many beta-coronaviruses, including SARS-CoV-2, gain entry to host cells through interaction of SARS-CoV-2 Spike (S) protein with membrane-bound angiotensin-converting enzyme 2 (ACE2). Given its necessity for SARS-CoV-2 infection, ACE2 represents a potential therapeutic target in COVID-19. However, early attempts…</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>Siglec-9 Restrains Antibody-Dependent Natural Killer Cell Cytotoxicity against SARS-CoV-2</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters the immunological profiles of natural killer (NK) cells. However, whether NK antiviral functions are impaired during severe coronavirus disease 2019 (COVID-19) and what host factors modulate these functions remain unclear. We found that NK cells from hospitalized COVID-19 patients degranulate less against SARS-CoV-2 antigen-expressing cells (in direct cytolytic and antibody-dependent cell cytotoxicity [ADCC] assays)…</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>Discovery of Isojacareubin as a covalent inhibitor of SARS-CoV-2 main protease using structural and experimental approaches</strong> - The ongoing pandemic with the emergence of immune evasion potential and particularly the current omicron sub variants intensified the situation further. Although vaccine are available but the immune evasion capabilities of the recent variants demand further efficient therapeutic choices to control the SARS-CoV-2 pandemic. Hence, considering the necessity of the small molecule inhibitor we target the main protease (3CLpro) which is an appealing target for the development of anti-viral 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>A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron <em>in vivo</em></strong> - The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron…</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>High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors</strong> - The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^(pro)) and papain like protease (PL^(pro)), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^(pro) inhibitors and 205 PL^(pro) inhibitors with low nmol/l activity of the best hits….</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>Kaempferol has potential anti-coronavirus disease 2019 (COVID-19) targets based on bioinformatics analyses and pharmacological effects on endotoxin-induced cytokine storm</strong> - COVID-19 has infected 272 million patients and caused 5.33 million deaths around the world, and it remains the main global threat. Previous studies revealed that Chinese traditional medicine is an effective treatment for COVID-19 infection. This study aims to reveal the pharmacological effects of kaempferol, which is the active component of Radix Bupleuri and Tripterygii Radix, and potential mechanisms for the treatment of COVID-19. Here, we employed the bioinformatics methods to filter 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>Use of Iontophoresis Technology for Transdermal Delivery of a Minimal mRNA Vaccine as a Potential Melanoma Therapeutic</strong> - mRNA vaccines have attracted considerable attention as a result of the 2019 coronavirus pandemic; however, challenges remain regarding use of mRNA vaccines, including insufficient delivery owing to the high molecular weights and high negative charges associated with mRNA. These characteristics of mRNA vaccines impair intracellular uptake and subsequent protein translation. In the current study, we prepared a minimal mRNA vaccine encoding a tumor associated antigen human gp100(25-33) peptide…</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>Development of indolealkylamine derivatives as potential multi-target agents for COVID-19 treatment</strong> - COVID-19 is a complex disease with short-term and long-term respiratory, inflammatory and neurological symptoms that are triggered by the infection with SARS-CoV-2. As many drugs targeting single targets showed only limited effectiveness against COVID-19, here, we aimed to explore a multi-target strategy. We synthesized a focused compound library based on C2-substituted indolealkylamines (tryptamines and 5-hydroxytryptamines) with activity for three potential COVID-19-related proteins, namely…</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>O</em>-GalNAc glycosylation affects the immunogenicity of the receptor-binding domain (RBD) of SARS-CoV-2 spike protein</strong> - The spike protein of SARS-CoV-2 has been widely used as an effective vaccine immunogen, although some limitations still remain. Herein, O-GalNAc glycosylated RBD (Tn-RBD) was synthesized as an antigen via in vitro glycosylation reactions. The inhibition ability against hACE2 binding of antibodies induced with Tn-RBD was 30-40% increased compared to that induced with RBD. This result implies that Tn-glycosylation might play important roles in the immunogenicity of the RBD protein, which should be…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of SARS-CoV-2 M<sup>pro</sup> with Vitamin C, L-Arginine and a Vitamin C/L-Arginine Combination</strong> - CONCLUSIONS: The findings of the current study are important because they help to identify COVID-19 treatments that are efficient, inexpensive, and have a favorable safety profile. The results of this study also suggest a possible adjuvant nutritional strategy for COVID-19 that could be used in conjunction with pharmacological agents.</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 Potential of Vouacapanes from <em>Pterodon emarginatus</em> Vogel Against COVID-19 Cytokine Storm</strong> - Purpose: The emergence of the COVID-19 pandemic has led to the search for potential therapeutic responses for various aspects of this disease. Fruits of Pterodon emarginatus Vogel (Fabaceae), sucupira, have been used in Brazilian traditional medicine because of their anti-inflammatory properties, which have been proven in vivo, in vitro, and in silico. Therefore, the aim of this work is to evaluate P. emarginatus oleoresin and isolated diterpenes by in vitro anti-inflammatory models. Methods: In…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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