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<title>05 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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<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>Pre-existing autoimmunity is associated with increased severity of COVID-19: A retrospective cohort study using data from the National COVID Cohort Collaborative (N3C)</strong> -
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Importance: Identifying individuals with a higher risk of developing severe COVID-19 outcomes will inform targeted or more intensive clinical monitoring and management. Objective: To examine, using data from the National COVID Cohort Collaborative (N3C), whether patients with pre-existing autoimmune disease (AID) diagnosis and/or immunosuppressant (IS) exposure are at a higher risk of developing severe COVID-19 outcomes. Design, setting and participants: A retrospective cohort of 2,453,799 individuals diagnosed with COVID-19 between January 1st, 2020, and June 30th, 2022, was created from the N3C data enclave, which comprises data of 15,231,849 patients from 75 USA data partners. Patients were stratified as those with/without a pre-existing diagnosis of AID and/or those with/without exposure to IS prior to COVID-19. Main outcomes and measures: Two outcomes of COVID-19 severity, derived from the World Health Organization severity score, were defined, namely life-threatening disease and hospitalization. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression models with and without adjustment for demographics (age, BMI, gender, race, ethnicity, smoking status), and comorbidities (cardiovascular disease, dementia, pulmonary disease, liver disease, type 2 diabetes mellitus, kidney disease, cancer, and HIV infection). Results: In total, 2,453,799 (16.11% of the N3C cohort) adults (age> 18 years) were diagnosed with COVID-19, of which 191,520 (7.81%) had a prior AID diagnosis, and 278,095 (11.33%) had a prior IS exposure. Logistic regression models adjusted for demographic factors and comorbidities demonstrated that individuals with a prior AID (OR = 1.13, 95% CI 1.09 - 1.17; p=2.43E-13), prior exposure to IS (OR= 1.27, 95% CI 1.24 - 1.30; p=3.66E-74), or both (OR= 1.35, 95% CI 1.29 - 1.40; p=7.50E-49) were more likely to have a life-threatening COVID-19 disease. These results were confirmed after adjusting for exposure to antivirals and vaccination in a cohort subset with COVID-19 diagnosis dates after December 2021 (AID OR = 1.18, 95% CI 1.02 - 1.36; p=2.46E-02; IS OR= 1.60, 95% CI 1.41 - 1.80; p=5.11E-14; AID+IS OR= 1.93, 95% CI 1.62 - 2.30; p=1.68E-13). These results were consistent when evaluating hospitalization as the outcome and also when stratifying by race and sex. Finally, a sensitivity analysis evaluating specific IS revealed that TNF inhibitors were protective against life-threatening disease (OR = 0.80, 95% CI 0.66- 0.96; p=1.66E-2) and hospitalization (OR = 0.80, 95% CI 0.73 - 0.89; p=1.06E-05). Conclusions and Relevance: Patients with pre-existing AID, exposure to IS, or both are more likely to have a life-threatening disease or hospitalization. These patients may thus require tailored monitoring and preventative measures to minimize negative consequences of COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.02.23285353v1" target="_blank">Pre-existing autoimmunity is associated with increased severity of COVID-19: A retrospective cohort study using data from the National COVID Cohort Collaborative (N3C)</a>
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</div></li>
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<li><strong>Epidemic patterns of emerging variants with dynamical social distancing</strong> -
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Motivated by the emergence of new variants during the COVID-19 pandemic, we consider an epidemiological model of disease transmission dynamics, where novel strains appear by mutations of the virus. In the considered scenarios, disease prevalence in the population is modulated by social distancing. We study the various patterns that are generated under different assumptions of cross-immunity. If recovery from a given strain provides immunity against all previous strains, but not against more novel strains, then we observe a very regular sequential pattern of strain replacement where newer strains predominate over older strains. However, if protection upon recovery holds only against that particular strain and none of the others, we find much more complicated dynamics with potential recurrence of earlier strains, and co-circulation of various strains. We compare the observed patterns with genomic analysis we have seen during the COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.03.526970v1" target="_blank">Epidemic patterns of emerging variants with dynamical social distancing</a>
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<li><strong>Omicron’s Intrinsic Gene-Gene Interactions Jumped Away from Earlier SARS-CoV-2 Variants and Gene Homologs between Humans and Animals</strong> -
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Omicron and its subvariants have become the predominant SARS-CoV-2 variants worldwide. The Omicron’s basic reproduction number (R0) has been close to 20 or higher. However, it is not known what caused such an extremely high R0. This work aims to find an explanation for such high R0 Omicron infection. We found that Omicron’s intrinsic gene-gene interactions jumped away from earlier SARS-CoV-2 variants which can be fully described by a miniature set of genes reported in our earlier work. We found that the gene PTAFR (Platelet Activating Factor Receptor) is highly correlated with Omicron variants, and so is the gene CCNI (Cyclin I), which is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog. The combination of PTAFR and CCNI can lead to a 100% accuracy of differentiating Omicron COVID-19 infection and COVID-19 negative. We hypothesize that Omicron variants were potentially jumped from COVID-19-infected animals back to humans. In addition, there are also several other two-gene interactions that lead to 100% accuracy. Such observations can explain Omicron’s fast-spread reproduction capability as either of those two-gene interactions can lead to COVID-19 infection, i.e., multiplication of R0s leads to a much higher R0. At the genomic level, PTAFR, CCNI, and several other genes identified in this work rise to Omicron druggable targets and antiviral drugs besides the existing antiviral drugs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.01.526736v1" target="_blank">Omicron’s Intrinsic Gene-Gene Interactions Jumped Away from Earlier SARS-CoV-2 Variants and Gene Homologs between Humans and Animals</a>
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</div></li>
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<li><strong>Data-driven User Model Development of a Conversational AI Chatbot to provide Assistance to Unemployed People during the COVID-19 Pandemic</strong> -
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The COVID-19 pandemic triggered lockdowns all over the world, leading to unprecedented job losses. In the US, this resulted in many first time unemployment benefits filers struggled to navigate the benefits information provided by federal and state websites. We developed BEBO (Benefits Bot) to address these pain points and to provide appropriate and timely information. This paper explains the data-driven user model that was developed to create a user-centric conversational AI chatbot.
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🖺 Full Text HTML: <a href="https://osf.io/thqf5/" target="_blank">Data-driven User Model Development of a Conversational AI Chatbot to provide Assistance to Unemployed People during the COVID-19 Pandemic</a>
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<li><strong>Molecular Epidemiology and Diversity of SARS-CoV-2 in Ethiopia, 2020-2022</strong> -
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Ethiopia is the second most populous country in Africa and the sixth most affected by COVID-19 on the continent. Despite having experienced five infection waves, >499 000 cases, and ~7 500 COVID-19-related deaths as of January 2023, there is still no detailed genomic epidemiological report on the introduction and spread of SARS-CoV-2 in Ethiopia. In this study, we reconstructed and elucidated the COVID-19 epidemic dynamics. Specifically, we investigated the introduction, local transmission, ongoing evolution, and spread of SARS-CoV-2 during the first four infection waves using 353 high-quality near-whole genomes sampled in Ethiopia. Our results show that whereas viral introductions seeded the first wave, subsequent waves were seeded by local transmission. The B.1.480 lineage emerged in the first wave and notably remained in circulation even after the emergence of the Alpha variant. The B.1.480 was out-competed by the Delta variant. Notably, Ethiopia lack of local sequencing capacity was further limited by sporadic, uneven, and insufficient sampling that limited the incorporation of genomic epidemiology in the epidemic public health response in Ethiopia. These results highlight Ethiopia role in SARS-CoV-2 dissemination and the urgent need for balanced, near-real-time genomic sequencing.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.30.23285174v2" target="_blank">Molecular Epidemiology and Diversity of SARS-CoV-2 in Ethiopia, 2020-2022</a>
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<li><strong>Mechanisms of SARS-CoV-2 Inactivation using UVC Laser Radiation</strong> -
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Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has had a tremendous impact on humanity. Prevention of transmission by disinfection of surfaces and aerosols through a chemical-free method is highly desirable. Ultraviolet C (UVC) light is uniquely positioned to achieve inactivation of pathogens. We report the inactivation of SARS-CoV-2 virus by UVC radiation and explore its mechanisms. A dose of 50mJ/cm2 using a UVC laser at 266nm achieved an inactivation efficiency of 99.89%, whilst infectious virions were undetectable at 75mJ/cm2 indicating >99.99% inactivation. Infection by SARS-CoV-2 involves viral entry mediated by the spike glycoprotein (S), and viral reproduction, reliant on translation of its genome. We demonstrate that UVC radiation damages ribonucleic acid (RNA) and provide in-depth characterisation of UVC-induced damage of the S protein. We find that UVC severely impacts the ability of the SARS-CoV- 2 spike protein to bind human angiotensin-converting enzyme 2 (hACE2) and this correlates with loss of native protein conformation and aromatic amino acid integrity. This report has important implications for the design and development of rapid and effective disinfection systems against the SARS-CoV-2 virus and other pathogens.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.03.526944v1" target="_blank">Mechanisms of SARS-CoV-2 Inactivation using UVC Laser Radiation</a>
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<li><strong>Impact of the COVID-19 restrictions on the epidemiology of Cryptosporidium spp. in England and Wales, 2015-2021. A time-series analysis</strong> -
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<b>Background</b> In England and Wales, cryptosporidiosis cases peak in spring and autumn, usually associated with zoonotic and environmental exposures (<i>Cryptosporidium parvum</i>, spring/autumn) and with overseas travel and water-based activities (<i>Cryptosporidium hominis</i>, autumn). Restrictions to control the COVID-19 pandemic prevented social mixing and access to swimming pools and restaurants for many months. Foreign travel from the UK also reduced by 74% in 2020. However, these restrictions potentially increased environmental exposures as people sought alternative countryside activities locally. To inform and strengthen surveillance programmes, we investigated the impact of COVID-19 restrictions on the epidemiology of <i>C. hominis</i> and <i>C. parvum cases</i>. <b>Methods</b><i>Cryptosporidium</i>-positive stools, with case demographic data, are referred routinely for genotyping to the national Cryptosporidium Reference Unit (CRU). Cases were extracted from the CRU database (01 January 2015 to 31 December 2021). We defined two periods for pre- and post-COVID-19 restrictions implementation corresponding to the first UK-wide lockdown on 23 March 2020: pre-restrictions between week 1, 2015 and week 12, 2020, and post restrictions-implementation between week 13, 2020 and week 52, 2021. We conducted an interrupted time-series analysis, assessing differences in <i>C. parvum</i> and <i>C. hominis</i> incidence, trends and periodicity between these periods using negative binomial regression with linear-splines and interactions. <b>Results</b> There were 21,304 cases between 01 January 2015 and 31 December 2021 (<i>C. parvum</i> = 12,246; <i>C. hominis</i> = 9,058). Post restrictions-implementation incidence of <i>C. hominis</i> dropped by 97.5% (95%CI: 95.4%-98.6%; p<0.001). The decreasing incidence-trend observed pre-restrictions (IRR=0.9976; 95%CI: 0.9969-0.9982; p<0.001) was not observed post restrictions-implementation (IRR=1.0081; 95%CI: 0.9978-1.0186; p=0.128) due to lack of cases. No periodicity change was observed post restrictions-implementation. Where recorded, 22% of <i>C. hominis</i> cases had travelled abroad. There was also a strong social gradient, with those who lived in deprived areas experiencing a higher proportion of cases. This gradient did not exist post restrictions-implementation, but the effect was exacerbated for the most deprived: 27.2% of cases from the most deprived decile compared to 12.7% in the pre-restrictions period. For <i>C. parvum</i>, post restrictions-implementation incidence fell by 49.0% (95%CI: 38.4%-58.3%; p<0.001). There was no pre-restrictions incidence-trend (IRR=1.0003; 95%CI: 0.9997-1.0009; p=0.322) but a slight increasing incidence-trend existed post restrictions-implementation (IRR=1.0071; 95%CI: 1.0038-1.0104; p<0.001). A periodicity change was observed for <i>C. parvum</i> post restrictions-implementation, peaking one week earlier in spring and two weeks later in autumn. Where recorded, 8% of <i>C. parvum</i> cases had travelled abroad. The social gradient observed for <i>C. parvum</i> was inverse to that for <i>C. hominis</i>, and was stable pre-restrictions and post restrictions-implementation. <b>Conclusion</b><i>C. hominis</i> cases were almost entirely arrested post restrictions-implementation, reinforcing that foreign travel is a major driver of seeding infections. Increased hand-hygiene, reduced social mixing, limited access to swimming pools and limited foreign travel affected incidence of most gastrointestinal (GI) pathogens, including <i>Cryptosporidium</i>, in the same period. <i>C. parvum</i> incidence fell sharply but recovered throughout the post restrictions-implementation period, back to pre-restrictions levels by the end of 2021; this is consistent with relaxation of restrictions, reduced compliance and increased countryside use. The effect on our results of changes in health-seeking behaviours, healthcare access and diagnostic laboratory practices post restrictions-implementation is uncertain, but it is likely that access to GPs and
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.26.22280357v3" target="_blank">Impact of the COVID-19 restrictions on the epidemiology of Cryptosporidium spp. in England and Wales, 2015-2021. A time-series analysis</a>
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<li><strong>A pattern shift in SARS-CoV-2 Omicron variant transmission after the city lockdown–observational study based upon daily reported addresses of infected cases</strong> -
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Background Varied degrees of lockdown have been imposed for dozens of jurisdictions upon facing the SARS-CoV-2 epidemics during the past two years. Areal lockdown has been demonstrated effective to reduce the morbility and mortality of COVID-19. Even after the strict lockdown the peak of infection will appear around 9-25 days (median 18 days) thereafter. A wave of Omicron variant (BA.2 and BA.2.2) outbreak was seen from March to May 2022, in Shanghai, a megacity in China mainland. Aim To understand the sources of infection cases from outside or inside the isolated locations before and after the strict city lockdown. Methods The attributable addresses of SARS-CoV-2 infection were reported daily as well as the infected cases from March 18th, 2022 on through government website, which was publicly accessible. The address data and infected cases were collected until May 29th, 2022. The location (longitude and latitude) of these addresses were retrieved and the pattern of repeatedly reported addresses were analyzed. A tool of simple and meso-scale point-based (location-based) chronological graph was used to visualize and analyze the interactions of these locations. Results From March 18th to May 29th 2022, 173,350 items representing 35,743 unique addresses and 636,279 infected cases were released. The infection cases peaked 16 days after the city lockdown and were highly clustered in much crowded districts. The proportion of repeatedly reported locations of the previous day increased from around 20% before lockdown to greater than 40% in the plateau and remained at this level for up to one third (20/62) of the lockdown phase. This significantly increased proportion of intra-address infection indicated a pattern shift from inter-addresses to intra-address (D=0.2954, p<0.0001), which might perpetuate to the growth of infection cases. Based upon the day-to-day nearest neighbour transmission assumption the connections between some frequently repeated locations might be complex and heterogeneous. Interpretation During the strict areal isolation the intra-address infection may contribute significantly to infected cases of SARS-CoV-2 Omicron variant, the infection might have easily spilled over the boundary of family(with averaged family size of 2.3-3.1 people and family were required stay-at-home compulsively). This significant inter-addresses to intra-address pattern shift necessitated the understanding of intra-location transmission routes and corresponding interventions. Areal isolation and close off with homogeneous assumption inside and outside the isolated areas should be modified and the quantifing of the elevated risk for previously less exposed but much vulnerable sub-population was in pressing need.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.02.22279556v2" target="_blank">A pattern shift in SARS-CoV-2 Omicron variant transmission after the city lockdown–observational study based upon daily reported addresses of infected cases</a>
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<li><strong>Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial.</strong> -
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Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. Methods: The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine - either heterologous (PHH-1V group) or homologous (BNT162b2 group) - in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with ClinicalTrials.gov, NCT05142553. Findings: From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n=522) or BNT162b2 (n=260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p<0.0001), 1.31 (p=0.0007) and 0.86 (p=0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p<0.0001), 0.65 (p<0.0001) and 0.56 (p=0.003) for the Beta variant; 1.01 (p=0.92), 0.88 (p=0.11) and 0.52 (p=0.0003) for the Delta variant; and 0.59 (p=<0.0001), 0.66 (p<0.0001) and 0.57 (p=0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4+ and CD8+ T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p=0.45), and none of the subjects developed severe COVID-19. Interpretation: Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. Funding: HIPRA SCIENTIFIC, S.L.U.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.05.22277210v4" target="_blank">Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial.</a>
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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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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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<li><strong>Lung viral infection modelling in a bioengineered whole-organ</strong> -
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Lung infections are one of the leading causes of death worldwide, and this situation has been exacerbated by the emergence of COVID-19. Pre-clinical modelling of viral infections has relied on cell cultures that lack 3D structure and the context of lung extracellular matrices. Here, we propose a bioreactor-based, whole-organ lung model of viral infection. The bioreactor takes advantage of an automated system to achieve efficient decellularization of a whole rat lung, and recellularization of the scaffold using primary human bronchial cells. Automatization allowed for the dynamic culture of airway epithelial cells in a breathing-mimicking setup that led to an even distribution of lung epithelial cells throughout the distal regions. In the sealed bioreactor system, we demonstrate proof-of-concept for viral infection with the engineered lung by infecting primary human airway epithelial cells. Moreover, to assess the possibility of drug screening in this model, we demonstrate the efficacy of the broad-spectrum antiviral Remdesivir. This whole-organ scale lung infection model represents a step towards modelling viral infection of human cells in a 3D context, providing a powerful tool to investigate the mechanisms of the early stages of pathogenic infections and the development of effective treatment strategies for respiratory diseases.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.01.526441v1" target="_blank">Lung viral infection modelling in a bioengineered whole-organ</a>
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<li><strong>sciCSR infers B cell state transition and predicts class-switch recombination dynamics using single-cell transcriptomic data</strong> -
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Class-switch recombination (CSR) is an integral part of B cell maturation. Steady-state analyses of isotype distribution (e.g. B cell receptor [BCR] repertoire analysis of snapshots during an immune response) do not directly measure CSR dynamics, which is crucial in understanding how B cell maturation is regulated across time. We present sciCSR (pronounced ‘scissor’, single-cell inference of class switch recombination), a computational pipeline which analyses CSR events and dynamics of B cells from single-cell RNA-sequencing (scRNA-seq) experiments. sciCSR re-analyses transcriptomic sequence alignments to differentiate productive heavy-chain immunoglobulin transcripts from germline “sterile” transcripts. From a snapshot of B cell scRNA-seq data, a Markov state model is built by the pipeline to infer the dynamics and direction of CSR. Applying sciCSR on SARS-CoV-2 vaccination time-course scRNA-seq data, we observe that sciCSR predicts, using data from an earlier timepoint in the collected time-course, the isotype distribution of BCR repertoires of subsequent timepoints with high accuracy (cosine similarity approximately 0.9). sciCSR also recapitulates CSR patterns in mouse models where B cell maturation was perturbed using gene knockouts. sciCSR infers cell state transitions using processes specific to B cells, identifies transitions which are often missed by conventional RNA velocity analyses, and can reveal insights into the regulation of CSR and the dynamics of B cell maturation during an immune response.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.02.526789v1" target="_blank">sciCSR infers B cell state transition and predicts class-switch recombination dynamics using single-cell transcriptomic data</a>
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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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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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🖺 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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<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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🖺 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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<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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🖺 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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<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>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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase 2/Phase 3 Study To Evaluate The Efficacy And Safety Of Ramatroban Along With The Standard Of Care In Subjects Hospitalized For COVID Pneumonia</strong> - <b>Conditions</b>: COVID-19 Pneumonia; COVID-19 Respiratory Infection<br/><b>Interventions</b>: Drug: Ramatroban; Drug: Placebo<br/><b>Sponsors</b>: KARE Biosciences; JSS Medical Research Inc.; Biomedical Advanced Research and Development Authority; Open Philanthropy; Charak Laboratories India Pvt. Ltd; Charak Foundation; BioLink Life Sciences, Inc.<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>JAK-STAT inhibition reduces endothelial pro-thrombotic activation and leukocyte- endothelial pro-adhesive interactions</strong> - BACKGROUND: Vascular activation is characterized by increased pro-inflammatory, pro- thrombotic, and pro-adhesive signaling. Several chronic and acute conditions, including Bcr-abl- negative myeloproliferative neoplasms (MPNs), graft-versus-host disease (GVHD), and COVID- 19 have been noted to have increased activation of the janus kinase (JAK)-signal transducer and downstream activator of transcription (STAT) pathways. Two notable inhibitors of the JAK- STAT pathway are ruxolitinib (JAK1/2…</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>A novel compound targets the feline infectious peritonitis virus nucleocapsid protein and inhibits viral replication in cell culture</strong> - Feline infectious peritonitis (FIP) is a serious viral illness in cats, caused by feline coronavirus. Once a cat develops clinical FIP, the prognosis is poor. The effective treatment strategy for coronavirus infections with immunopathological complications such as SARS-CoV-2, MERS, and FIP is focused on antiviral and immunomodulatory agents to inhibit virus replication and enhance the protective immune response. In this manuscript we report the binding and conformational alteration of feline…</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 spike protein promotes RPE cell senescence via the ROS/P53/P21 pathway</strong> - SARS-Cov-2 infection, which has caused the COVID-19 global pandemic, triggers cellular senescence. In this study, we investigate the role of the SARS-COV-2 spike protein (S-protein) in regulating the senescence of RPE cells. The results showed that administration or overexpression of S-protein in ARPE-19 decreased cell proliferation with cell cycle arrest at the G1 phase. S-protein increased SA-β-Gal positive ARPE-19 cells with high expression of P53 and P21, senescence-associated inflammatory…</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 E3 ligase RNF5 restricts SARS-CoV-2 replication by targeting its envelope protein for degradation</strong> - The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a severe global health crisis; its structural protein envelope (E) is critical for viral entry, budding, production, and induction of pathology which makes it a potential target for therapeutics against COVID-19. Here, we find that the E3 ligase RNF5 interacts with and catalyzes ubiquitination of E on the 63rd lysine, leading to its degradation by 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>SSRIs differentially modulate the effects of pro-inflammatory stimulation on hippocampal plasticity and memory via sigma 1 receptors and neurosteroids</strong> - Certain selective serotonin reuptake inhibitors (SSRIs) have anti-inflammatory effects in preclinical models, and recent clinical studies suggest that fluvoxamine can prevent deterioration in patients with COVID-19, possibly through activating sigma 1 receptors (S1Rs). Here we examined potential mechanisms contributing to these effects of fluvoxamine and other SSRIs using a well-characterized model of pro-inflammatory stress in rat hippocampal slices. When hippocampal slices are exposed acutely…</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 IL-6 signaling prevents serum-induced umbilical cord artery dysfunction from severe COVID-19 patients</strong> - Coronavirus disease 2019 (COVID-19) infection has a negative impact on the cytokine profile of pregnant women. Increased levels of pro-inflammatory cytokines seem to be correlated with the severity of the disease, in addition to predisposing to miscarriage or premature birth. Pro-inflammatory cytokines increase the generation of reactive oxygen species (ROS). It is unclear how interleukin-6 (IL-6) found in the circulation of severe COVID-19 patients might affect gestational health, particularly…</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>Emerging role of microRNAs and long non-coding RNAs in COVID-19 with implications to therapeutics</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection which is commonly known as COVID-19 (COronaVIrus Disease 2019) has creeped into the human population taking tolls of life and causing tremendous economic crisis. It is indeed crucial to gain knowledge about their characteristics and interactions with human host cells. It has been shown that the majority of our genome consists of non-coding RNAs. Non-coding RNAs including micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs)…</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>Antisense oligonucleotides to therapeutically target SARS-CoV-2 infection</strong> - Although the COVID-19 pandemic began over three years ago, the virus responsible for the disease, SARS-CoV-2, continues to infect people across the globe. As such, there remains a critical need for development of novel therapeutics against SARS-CoV-2. One technology that has remained relatively unexplored in COVID-19 is the use of antisense oligonucleotides (ASOs)-short single-stranded nucleic acids that bind to target RNA transcripts to modulate their expression. In this study, ASOs targeted…</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>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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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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