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<title>03 July, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>The decline of COVID-19 severity and lethality over two years of pandemic</strong> -
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Undernotification of SARS-CoV-2 infections has been a major obstacle to the tracking of critical quantities such as infection attack rates and the probability of severe and lethal outcomes. We use a model of SARS-CoV-2 transmission and vaccination informed by epidemiological and genomic surveillance data to estimate the number of daily infections occurred in Italy in the first two years of pandemic. We estimate that the attack rate of ancestral lineages, Alpha, and Delta were in a similar range (10-17%, range of 95% CI: 7-23%), while that of Omicron until February 20, 2022, was remarkably higher (51%, 95%CI: 33-70%). The combined effect of vaccination, immunity from natural infection, change in variant features, and improved patient management massively reduced the probabilities of hospitalization, admission to intensive care, and death given infection, with 20 to 40-fold reductions during the period of dominance of Omicron compared to the initial acute phase.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.01.22277137v1" target="_blank">The decline of COVID-19 severity and lethality over two years of pandemic</a>
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</div></li>
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<li><strong>Increased disparity in routine infant vaccination during COVID-19</strong> -
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Background COVID-19 restrictions and its impact on healthcare resources have reduced routine infant vaccine uptake, although some report that this effect was short-lived. These prior studies mostly described entire populations, but disparities in uptake may have changed during the pandemic due to differential access to healthcare. Objectives We aimed to examine disparities in the reduction in routine infant vaccine uptake during the COVID-19 pandemic in Manitoba, Canada. Methods We assessed vaccine uptake for routine infant vaccines for a pre-pandemic and pandemic subcohort. We assessed how the reduction in vaccine uptake differed by gender, neighborhood income quintile and region of residence. For each evaluation age, we limited the pandemic subcohort to children reaching this milestone age on/before November 30, 2021. Results Vaccine uptake was about 5-10% lower during the pandemic. The groups most vulnerable to COVID-19 saw the largest reductions in vaccine uptake, with an ongoing downward trend throughout the pandemic. Children in the lowest income neighborhoods saw a 17% reduction in diphtheria, tetanus, and acellular pertussis dose 4 uptake at 24 months, 4.4-fold that of high-income neighborhoods, and an 11% reduction in measles, mumps, rubella (MMR) vaccine uptake at 24 months, 5.6-fold that of high-income neighborhoods. The largest reductions were for low-income Northern residents and smallest for high-income Winnipeg residents, e.g. 16-fold larger for MMR at 24 months (79:94 pre-pandemic to 65:93 during the pandemic). Conclusions While privileged children have similar high vaccine uptake as before the pandemic, children in populations hardest hit by COVID-19 continue seeing concerning reductions in routine infant vaccination. It is imperative that infant vaccination rates are increased, especially in communities with lower socioeconomic status, as a failure to do so could lead to persistent rebound epidemics in the most vulnerable populations.
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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/10.1101/2022.06.30.22277115v1" target="_blank">Increased disparity in routine infant vaccination during COVID-19</a>
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</div></li>
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<li><strong>Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection</strong> -
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The chronic infection hypothesis for novel SARS-CoV-2 variant emergence is increasingly gaining credence following the appearance of Omicron. Here we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral loads. During the infection, we found an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately two-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution led to the emergence and persistence of at least three genetically distinct genotypes suggesting the establishment of spatially structured viral populations continually reseeding different genotypes into the nasopharynx. Finally, using unique molecular indexes for accurate intrahost viral sequencing, we tracked the temporal dynamics of genetic diversity to identify advantageous mutations and highlight hallmark changes for chronic infection. Our findings demonstrate that untreated chronic infections accelerate SARS-CoV-2 evolution, ultimately providing opportunity for the emergence of genetically divergent and potentially highly transmissible variants as seen with Delta and Omicron.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.29.22276868v1" target="_blank">Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection</a>
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<li><strong>Rucaparib blocks SARS-CoV-2 virus binding to cells and interleukin-6 release in a model of COVID-19</strong> -
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Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 virus, is a major global health challenge, as there is no efficient treatment for the moderate to severe disease. ADP-ribosylation events are involved in regulating the life cycle of coronaviruses and the inflammatory reactions of the host, hence we assessed the repurposing of registered PARP inhibitors for the treatment of COVID-19. We detected high levels of oxidative stress and strong PARylation in all cell types in the lungs of COVID-19 patients. Interestingly, rucaparib, unlike other PARP inhibitors, reduced SARS-CoV-2 infection rate through binding to the conserved 493-498 amino acid region located in the spike-ACE2 interface in the spike protein and prevented viruses from binding to ACE2. In addition, the spike protein-induced overexpression of IL-6, a key cytokine in COVID-19, was inhibited by rucaparib at pharmacologically relevant concentrations. These findings build a case for repurposing rucaparib for treating COVID-19 disease.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.30.22277079v1" target="_blank">Rucaparib blocks SARS-CoV-2 virus binding to cells and interleukin-6 release in a model of COVID-19</a>
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</div></li>
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<li><strong>Real World Evidence of Effectiveness of COVID-19 Vaccines and Anti SARS-CoV-2 Monoclonal Antibodies Against Post-Acute Sequelae of SARS-CoV-2 Infection</strong> -
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Background: We evaluated the effectiveness of COVID-19 vaccines and monoclonal antibodies (mAb) against Post-Acute Sequelae of SARS-CoV-2 infection (PASC), an emerging public health problem. Methods and Findings: In a retrospective cohort study, we identified patients with clinically significant PASC using a COVID-19 specific, electronic medical record-based surveillance and outcomes registry from an 8-hospital tertiary healthcare system in the greater Houston metropolitan (primary analyses). Analyses were then replicated across a global research network database. We included all adults (>= 18) who survived beyond 28-days of their index infection. PASC was defined as experiencing constitutional (palpitations, malaise / fatigue, headache) or systemic (sleep disorder, shortness of breath, mood / anxiety disorders, cough, and cognitive impairment) symptoms beyond 28-day post-infection period. Instances of PASC were excluded if the symptoms were present pre-COVID or if they resolved within four weeks of initial infection. We fit multivariable logistic regression models and report estimated likelihood of PASC associated with vaccination or mAb treatment as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Primary analyses included 53,239 subjects (54.9% female), of whom 5,929, 11.1% (CI: 10.9 - 11.4), experienced PASC. Both, vaccinated breakthrough cases (vs. unvaccinated) and mAb treated patients (vs. untreated) had lower likelihoods for developing PASC, aOR (CI): 0.58 (0.52, 0.66), and 0.77 (0.69, 0.86), respectively. Vaccination was associated with decreased odds of developing all constitutional and systemic symptoms except for taste and smell changes. For all symptoms, vaccination was associated with lower likelihood of experiencing PASC compared to mAb treatment. Replication analysis found almost identical frequency of PASC (11.2%) and similar protective effects against PASC for the COVID-19 vaccine: aOR (CI) 0.25 (0.21 - 0.30) and mAb treatment: 0.62 (0.59 - 0.66). Discussion: Although both COVID-19 vaccines and mAbs decreased the likelihood of PASC, at present, vaccination is the most effective tool to potentially prevent long-term clinical and socio-economic consequences of COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.30.22277105v1" target="_blank">Real World Evidence of Effectiveness of COVID-19 Vaccines and Anti SARS-CoV-2 Monoclonal Antibodies Against Post-Acute Sequelae of SARS-CoV-2 Infection</a>
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<li><strong>B cell response six months after SARS-CoV-2 mRNA vaccination in people living with HIV under antiretroviral therapy</strong> -
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Abstract Background SARS-CoV-2 mRNA vaccines have demonstrated high immunogenicity in healthy subjects and preliminary results for people living with HIV (PLWHIV) are promising too. We have previously reported the persistence of spike-specific circulating IgG and memory B cells in healthy adults up to six months after mRNA SARS-CoV-2 vaccination. Unfortunately, limited longitudinal data are available for PLWHIV and no evidence of persistent spike-specific B cells have been reported yet. Methods We investigated the humoral response and the persistence of spike-specific memory B cells up to six months after vaccination with two doses of mRNA vaccines in 84 PLWHIV under ART and compared them to healthy controls (HCs). Humoral response was analyzed with enzyme-linked immunosorbent assay and with an angiotensin-converting enzyme 2 (ACE2) and receptor binding domain (RBD) inhibition assay. PBMCs were analyzed with a cytofluorimetric approach for B cell phenotyping. Findings Spike-specific IgG peaked 1 month after second dose and persisted up to six months after vaccination with no significant differences compared to HCs. The stratification of patients according to CD4+ T cell count showed a significantly lower IgG response in case of CD4<350/μ, remarking the relevance of immune reconstitution. The ability of IgG of blocking the binding between ACE2 and RBD was detected in 58.4% of PLWHIV, compared to 86.2% in HCs. The amount of circulating spike-specific memory B cells detected in PLWHIV six months after vaccination was not significantly different from HCs, while there was prevalence of antigen-specific double negative (IgD-/CD27-) cells, compared to controls. Interpretation In conclusion, the majority of PLWHIV developed spike-specific humoral and B cell responses that persist for at least six months after SARS-CoV-2 mRNA vaccination. However, hints of HIV-dependent immune impairment were revealed by altered spike-specific B cell phenotypes and by reduced spike-specific humoral response in patients with low CD4+ T cell count (<350/μl).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.01.22277132v1" target="_blank">B cell response six months after SARS-CoV-2 mRNA vaccination in people living with HIV under antiretroviral therapy</a>
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<li><strong>Religiosity, Beliefs in the Supernatural, Perceived Social Support, Resilience, and Well-being of University Students during the COVID-19 pandemic.</strong> -
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The COVID-19 pandemic infection control measures had severely impacted mental well-being providing an insight into possible protective parameters. With religion always playing a role during challenging times, this study investigated the effects of beliefs on the supernatural and religiosity on the mental well-being of university students during the COVID19 pandemic and how social support and resilience can mitigate this effect. 185 university students aged between 17 to 42 years old responded to online surveys on their theistic beliefs, religiosity, well-being, perceived support, and resilience. Pearson’s correlations and single and sequential mediation analyses showed that theistic beliefs did not significantly predict well-being (r = .05) while religiosity mediated the relationship (r = .18, effect size = .035). Sequential mediation analysis showed that resilience and perceived social support did not mediate the relationship between religiosity and well-being. Perceived social support alone significantly mediated religiosity and well-being with an effect size of .039. Religiosity was found to be a mediator and both resilience, while perceived social support was non-significantly positively associated with well-being. Analysing the open-ended questions on the students’ beliefs in the supernatural and paranormal, as well as the impact of the pandemic restrictions on their interests, insights where the majority of them did not attribute supernatural causes to the pandemic were garnered. In line with previous studies during the pandemic, the students also reported having too little social interaction and too much time with family to affect them negatively. The findings reveal how several factors were associated with well-being as well as the relationship between religiosity and well-being that may aid in the mental well-being of future challenging times.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/pqz2t/" target="_blank">Religiosity, Beliefs in the Supernatural, Perceived Social Support, Resilience, and Well-being of University Students during the COVID-19 pandemic.</a>
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<li><strong>Self-Reported Use of COVID-19 Immunologic Test Results to Inform Decisions About Daily Activities and COVID-19 Vaccination</strong> -
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Importance: Despite widespread use of clinical diagnostic tests to assess prior exposure to SARS-CoV-2, limited evidence exists regarding how test results affect patient behaviors and decision-making. Objective: To understand the rationale behind ordering diagnostic T-cell receptor (TCR) immunosequencing for assessment of prior SARS-CoV-2 infection and evaluate how test results affect patient behaviors, including day-to-day activities and decisions about vaccination. Design: Mandatory demographic information and clinical characteristics were collected for all individuals ordering T-DetectTM COVID. Study participants completed a one-time survey that included additional questions about demographics and clinical characteristics, relevant interactions with healthcare providers, reasons for ordering diagnostic TCR immunosequencing, and the utility of test results. Setting: US participants ordering T-Detect COVID between February 2021 and March 2022. Participants: Of the 806 individuals who underwent diagnostic TCR immunosequencing, provided informed consent, and were sent the email survey, 718 completed the survey (response rate, 89.1%). At the time of receiving the test report, 25.5% of participants had been vaccinated against COVID-19, 29.7% reported a previous COVID-19 infection, and 25.6% were immunocompromised. Main Outcome(s) and Measure(s): Patient demographics and clinical characteristics were reported using descriptive statistics. Additional analyses explored trends in reported data over time and evaluated reasons for ordering diagnostic TCR immunosequencing and behaviors among participant subgroups (vaccinated or unvaccinated individuals and those with positive or negative test results). Logistic regression analysis evaluated factors that increased the likelihood of post-test vaccination. Results: Study participants ordered diagnostic TCR immunosequencing to understand their health status (55.0%) and to inform decision-making about daily activities (43.6%) and vaccination (38.3%). Most participants (92.1%) ordered diagnostic TCR immunosequencing for themselves without consulting their physician. Testing negative for prior SARS-CoV-2 infection was associated with increased likelihood of subsequent COVID-19 vaccination (31.0% vs 6.9%; median time to vaccination, 17.0 days vs 47.5 days), which was confirmed by logistic regression analysis. Conclusions and Relevance: This report presents patient-reported clinical utility of a commercial COVID-19 assay based on an immune response readout. Our findings suggest that participants used diagnostic TCR immunosequencing results to inform decisions about daily activities and COVID-19 vaccination. Trial Registration: Not applicable.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.01.22277108v1" target="_blank">Self-Reported Use of COVID-19 Immunologic Test Results to Inform Decisions About Daily Activities and COVID-19 Vaccination</a>
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<li><strong>The changing landscape of respiratory viruses contributing to respiratory hospitalisations: results from a hospital-based surveillance in Quebec, Canada, 2012-13 to 2021-22</strong> -
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Background. A comprehensive description of the combined effect of SARS-CoV-2 and respiratory viruses (RV) other than SARS-CoV-2 (ORV) on hospitalisations is lacking. Aim. To compare viral etiology of acute respiratory infections (ARI) hospitalisations before and during two pandemic years from a surveillance network in Quebec, Canada. Method. We compared detection of ORV and SARS-CoV-2 during 2020-21 and 2021-22 to 8 pre-pandemic influenza seasons in patients hospitalised with ARI who were tested systematically by a multiplex PCR. Results. During pre-pandemic influenza seasons, overall RV detection was 92.7% (1,493) (48.3% respiratory syncytial virus (RSV)) in children and 62.8% (4,339) (40.1% influenza) in adults. Overall RV detection in 2020-21 was 58.6% (29) in children (all ORV) and 43.7% (333) in adults (3.4% ORV, 40.3% SARS-CoV2, both including coinfections). In 2021-22 overall RV detection was 91.0% (201) in children (82.8% ORV, 8.1% SARS-CoV-2, both including coinfections) and 55.5% (527) in adults (14.1% ORV, 41.4% SARS-CoV-2, both including coinfections). Virtually no influenza was detected in 2020-21 and in 2021-22 up to epi-week 2022-9 presented here; no RSV was detected in 2020-21. In 2021-22, detection of RSV was comparable to pre-pandemic years but with an unusually early season. There were significant differences in ORV and SARS-CoV-2 detection between time periods and age groups. Conclusion. Significant continuous shifts in age distribution and viral etiology of ARI hospitalisations occurred during two pandemic years. This reflects evolving RV epidemiology and underscores the need for increased scrutiny of ARI hospitalisation etiology to inform tailored public health recommendations.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.01.22277061v1" target="_blank">The changing landscape of respiratory viruses contributing to respiratory hospitalisations: results from a hospital-based surveillance in Quebec, Canada, 2012-13 to 2021-22</a>
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<li><strong>Phase 2 randomised placebo-controlled trial of spironolactone and dexamethasone versus dexamethasone in COVID-19 hospitalised patients in Delhi</strong> -
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Background: In this phase 2 randomised placebo-controlled clinical trial, we hypothesised that blocking mineralocorticoid receptors with spironolactone in patients with COVID-19 is safe and may reduce illness severity. Methods: Hospitalised patients with confirmed COVID-19 were randomly allocated to low dose oral spironolactone (50mg day 1, then 25mg once daily for 21 days) or standard care in a 2:1 ratio. Both groups received dexamethasone 6mg for 10 days. Group allocation was blinded to the patient and research team. Primary outcomes were time to recovery, defined as the number of days until patients achieved WHO Ordinal Scale (OS) category less than or equal to 3, and the effect of spironolactone on aldosterone, D-dimer, angiotensin II and Von Willebrand Factor (VWF). Results: 120 patients were recruited in Delhi from 01 February to 30 April 2021. 74 were randomly assigned to spironolactone and dexamethasone (SpiroDex), and 46 to dexamethasone alone (Dex). There was no significant difference in the time to recovery between SpiroDex and Dex groups (SpiroDex median 4.5 days, Dex median 5.5 days, p = 0.055). SpiroDex patients had lower aldosterone levels on day 7 and lower D-dimer levels on days 4 and 7 (day 7 D-dimer mean SpiroDex 1.15 mcg/mL, Dex 3.15 mcg/mL, p = 0.0004). There was no increase in adverse events in patients receiving SpiroDex. Post hoc analysis demonstrated reduced clinical deterioration (pre specified as escalating to WHO OS category >4) in the SpiroDex group vs Dex group (5.4% vs 19.6%). Conclusion: Low dose oral spironolactone in addition to dexamethasone was safe and reduced D-Dimer and aldosterone. Although time to recovery was not significantly reduced, fewer patients progressed to severe disease. Phase 3 randomised controlled trials with spironolactone should be considered.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.01.22277163v1" target="_blank">Phase 2 randomised placebo-controlled trial of spironolactone and dexamethasone versus dexamethasone in COVID-19 hospitalised patients in Delhi</a>
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<li><strong>DIFFERENTIAL SARS-COV-2 ANTIGEN SPECIFICITY OF THE HUMORAL RESPONSE IN INACTIVATED VIRUS-VACCINATED, CONVALESCENT, AND BREAKTHROUGH SUBJECTS</strong> -
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Analytical methods for the differential determination between natural infection with SARS-CoV-2 vs. immunity elicited by vaccination or infection after immunization (breakthrough cases) represent attractive new research venues in the context of the ongoing COVID-19 pandemic caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). Herein, we set out to compare humoral responses against several SARS-CoV-2 structural and non-structural proteins in infected unvaccinated (convalescent), vaccinated, as well as vaccinated and infected (breakthrough) individuals. Our results indicate that immunization with an inactivated SARS-CoV-2 vaccine (CoronaVac) induces significantly higher levels of IgG antibodies against the membrane (M) protein of SARS-CoV-2 as compared to convalescent subjects both, after the primary vaccination schedule and after a booster dose. Moreover, we found that CoronaVac-immunized individuals, after receiving a third vaccine shot, display equivalent levels of N-specific IgG antibodies as convalescents subjects. Regarding non-structural viral proteins, for the two viral proteins ORF3a and NSP8, IgG antibodies were produced in more than 50% of the convalescent subjects. Finally, a logistic regression model and a receiver operating characteristic (ROC) analysis show that combined detection of M and N proteins may be useful as a biomarker to differentiate breakthrough cases from vaccinated and convalescent individuals that did not receive prior vaccination. Taken together, these results suggest that multiple SARS-CoV-2 antigens may be used as differential biomarkers for distinguishing natural infection from vaccination.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.01.22277165v1" target="_blank">DIFFERENTIAL SARS-COV-2 ANTIGEN SPECIFICITY OF THE HUMORAL RESPONSE IN INACTIVATED VIRUS-VACCINATED, CONVALESCENT, AND BREAKTHROUGH SUBJECTS</a>
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<li><strong>Transcriptional Profiles Analysis of COVID-19 and Malaria Patients Reveals Potential Biomarkers in Children</strong> -
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The clinical presentation overlap between malaria and COVID-19 poses special challenges for rapid diagnosis in febrile children. In this study, we collected RNA-seq data of children with malaria and COVID-19 infection from the public databases as raw data in fastq format paired end files. A group of six, five and two biological replicates of malaria, COVID-19 and healthy donors respectively were used for the study. We conducted differential gene expression analysis to visualize differences in the expression profiles. Using edgeR, we explored particularly the expressed genes in different phenotype groups relative to the healthy samples where 1084 genes and 2495 genes were differentially expressed in the malaria samples and COVID-19 samples respectively. Highly expressed genes in the COVID-19 samples were associated with biological processes such as cell division (CCDC124) and SLC12A5-AS1 a lncRNA gene associated with NK-cell while in the malaria samples were associated with biological processes such as immune response (CTSL), T cell activation (RSAD2) and proteolysis (LAP3). By comparing both malaria and COVID-19, the overlaps of 62 differentially expressed genes patterns were identified. Among the shared genes, the hemoglobin complexes and lipid mediators are highly expressed. We found six genes such as CYB5R3, RSAD2, ALOX15, HBQ1, HBM and PNPLA2 associated with malaria and COVID-19 diseases in children, which can be further validated as potential biomarkers. Our study provided new insights for further investigation of the biological pattern in hosts with malaria and COVID-19 coinfection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.30.498338v1" target="_blank">Transcriptional Profiles Analysis of COVID-19 and Malaria Patients Reveals Potential Biomarkers in Children</a>
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<li><strong>The coevolutionary mosaic of bat betacoronavirus emergence risk</strong> -
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Pathogen evolution is one of the least predictable components of disease emergence, particularly in nature. Here, building on principles established by the geographic mosaic theory of coevolution, we develop a quantitative, spatially-explicit framework for mapping the evolutionary risk of viral emergence. Driven by interest in diseases like SARS, MERS, and COVID-19, we examine the global biogeography of bat-origin betacoronaviruses, and find that coevolutionary principles suggest geographies of risk that are distinct from the hotspots and coldspots of host richness. Further, our framework helps explain patterns like a unique pool of merbecoviruses in the Neotropics, a recently-discovered lineage of divergent nobecoviruses in Madagascar, and–most importantly–hotspots of diversification in southeast Asia, sub-Saharan Africa, and the Middle East that correspond to the site of previous zoonotic emergence events. Our framework may help identify hotspots of future risk that have also been previously overlooked, like west Africa and the Indian subcontinent, and may more broadly help researchers understand how host ecology shapes the evolution and diversity of pandemic threats.
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🖺 Full Text HTML: <a href="https://ecoevorxiv.org/8mgv6/" target="_blank">The coevolutionary mosaic of bat betacoronavirus emergence risk</a>
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<li><strong>The 1968 Influenza Pandemic and COVID-19 Outcomes</strong> -
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Past pandemic experience can affect health outcomes in future pandemics. This paper focuses on the last major influenza pandemic in 1968 (H3N2), which killed up to 100,000 people in the US. We find that places with high influenza mortality in 1968 experienced 1-4% lower COVID-19 death rates. Our identification strategy isolates variation in COVID-19 rates across people born before and after 1968. In places with high 1968 influenza incidence, older cohorts experience lower COVID-19 death rates relative to younger ones. The relationship holds using county and patient-level data, as well as in hospital and nursing home settings. Results do not appear to be driven by systemic or policy-related factors, instead suggesting an individual-level response to prior influenza pandemic exposure. The findings merit investigation into potential biological and immunological mechanisms that account for these differences–and their implications for future pandemic preparedness.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.10.23.21265403v2" target="_blank">The 1968 Influenza Pandemic and COVID-19 Outcomes</a>
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<li><strong>Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5 compared with previous waves in the Western Cape Province, South Africa</strong> -
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Objective: We aimed to compare clinical severity of Omicron BA.4/BA.5 infection with BA.1 and earlier variant infections among laboratory-confirmed SARS-CoV-2 cases in the Western Cape, South Africa, using timing of infection to infer the lineage/variant causing infection. Methods: We included public sector patients aged ≥20 years with laboratory-confirmed COVID-19 between 1-21 May 2022 (BA.4/BA.5 wave) and equivalent prior wave periods. We compared the risk between waves of (i) death and (ii) severe hospitalization/death (all within 21 days of diagnosis) using Cox regression adjusted for demographics, comorbidities, admission pressure, vaccination and prior infection. Results: Among 3,793 patients from the BA.4/BA.5 wave and 190,836 patients from previous waves the risk of severe hospitalization/death was similar in the BA.4/BA.5 and BA.1 waves (adjusted hazard ratio (aHR) 1.12; 95% confidence interval (CI) 0.93; 1.34). Both Omicron waves had lower risk of severe outcomes than previous waves. Prior infection (aHR 0.29, 95% CI 0.24; 0.36) and vaccination (aHR 0.17; 95% CI 0.07; 0.40 for boosted vs. no vaccine) were protective. Conclusion: Disease severity was similar amongst diagnosed COVID-19 cases in the BA.4/BA.5 and BA.1 periods in the context of growing immunity against SARS-CoV-2 due to prior infection and vaccination, both of which were strongly protective.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.28.22276983v2" target="_blank">Outcomes of laboratory-confirmed SARS-CoV-2 infection during resurgence driven by Omicron lineages BA.4 and BA.5 compared with previous waves in the Western Cape Province, South Africa</a>
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</div></li>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<ul>
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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>Immuno-bridging Study of COVID-19 Protein Subunit Recombinant Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: COVID-19 Protein Subunit Recombinant Vaccine; Biological: Active Comparator<br/><b>Sponsors</b>: PT Bio Farma; Fakultas Kedokteran Universitas Indonesia; Faculty of Medicine Universitas Diponegoro; Faculty of Medicine Universitas Andalas; Faculty of Medicine Universitas Hassanudin<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Learn About the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With COVID-19 Who Are Immunocompromised</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Nirmatrelvir; Drug: Ritonavir; Drug: Placebo for nirmatrelvir; Drug: Placebo for ritonavir<br/><b>Sponsor</b>: Pfizer<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Randomized Controlled Trial of a Digital, Self-testing Strategy for COVID-19 Infection in South Africa.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Device: Abbott Panbio rapid antigen self-tests; Other: COVIDSmart CARE! app<br/><b>Sponsors</b>: McGill University Health Centre/Research Institute of the McGill University Health Centre; University of Cape Town Lung Institute<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>Discussing COVID-19 Vaccines in Private Facebook Groups</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Gist messages on COVID-19 vaccination; Behavioral: COVID-19 vaccine information<br/><b>Sponsor</b>: George Washington University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety Study of One Booster Dose of Trivalent COVID-19 Vaccine (Vero Cell), Inactivated</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Trivalent COVID-19 Vaccine (Vero Cell), Inactivated, Prototype Strain, Delta Strain and Omicron Strain; Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>: Sinovac Biotech (Colombia) S.A.S.; Sinovac Life Sciences 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>Home-Based Exercise Tele-Rehabilitation After COVID-19</strong> - <b>Condition</b>: Post SARS-CoV2 (COVID-19)<br/><b>Intervention</b>: Other: Tele-exercise<br/><b>Sponsors</b>: VA Office of Research and Development; Baltimore Veterans Affairs Medical Center; Salem Veterans Affairs Medical Center<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>IMM-BCP-01 in Mild to Moderate COVID-19</strong> - <b>Conditions</b>: SARS-CoV2 Infection; COVID-19<br/><b>Interventions</b>: Drug: IMM-BCP-01; Drug: Placebo<br/><b>Sponsors</b>: Immunome, Inc.; United States Department of Defense<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety, Tolerability, and Immunogenicity of SARS-CoV-2 Variant (COVID-19 Omicron) mRNA Vaccine (Phase 1)</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: ABO1009-DP<br/><b>Sponsor</b>: Suzhou Abogen Biosciences Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate Safety, Tolerability, and Immunogenicity of SARS-CoV-2 Variant (COVID-19) mRNA Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: ABO1009-DP; Biological: ABO-CoV.617.2; Other: Placebo<br/><b>Sponsor</b>: Suzhou Abogen Biosciences 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>Can Intensive Insulin Therapy Improve Outcomes of COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Dysglycemia<br/><b>Interventions</b>: Drug: Insulin; Drug: Subcutaneous Insulin<br/><b>Sponsor</b>: Benha University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mesenchymal Stromal Cells for the Treatment of Patients With COVID-19.</strong> - <b>Conditions</b>: COVID-19 Pneumonia; COVID-19<br/><b>Interventions</b>: Biological: Mesenchymal stem cell; Other: Placebo<br/><b>Sponsors</b>: Paulo Brofman; Conselho Nacional de Desenvolvimento Científico e Tecnológico<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate Immunogenicity and Safety of MVC-COV1901 Vaccine Compared With AZD1222</strong> - <b>Condition</b>: COVID-19 Vaccine<br/><b>Interventions</b>: Biological: MVC-COV1901; Biological: AZD1222<br/><b>Sponsor</b>: Medigen Vaccine Biologics Corp.<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>Laser Therapy on Tension-type Cephalea and Orofacial Pain in Post-covid-19 Patients</strong> - <b>Conditions</b>: Tension-Type Headache; Orofacial Pain; COVID-19<br/><b>Intervention</b>: Radiation: Photobimodulation<br/><b>Sponsor</b>: University of Nove de Julho<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>Study of Self-Amplifying Messenger Ribonucleic Acid (samRNA) Vaccines Against COVID-19 in Healthy Adults and People Living With Human Immunodeficiency Virus (HIV)</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2<br/><b>Interventions</b>: Drug: GRT-R912, samRNA-Spikebeta-TCE11; Drug: GRT-R914, samRNA-Spikebeta-TCE9; Drug: GRT-R918, samRNA-SpikeOmicron-N-TCE11<br/><b>Sponsor</b>: Gritstone bio, Inc.<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 Phase 1b Study of a Q-Griffithsin Intranasal Spray for Broad-spectrum Coronavirus Prophylaxis</strong> - <b>Condition</b>: COVID-19 Prevention<br/><b>Interventions</b>: Drug: Q-Griffithsin 3.0; Drug: Q-Griffithsin 6.0<br/><b>Sponsors</b>: Kenneth Palmer; United States Department of Defense<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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<ul>
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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>Tissue Repair Strategies: What We Have Learned From COVID-19 in the Application of MSCs Therapy</strong> - Coronavirus disease 2019 (COVID-19) infection evokes severe proinflammatory storm and pulmonary infection with the number of confirmed cases (more than 200 million) and mortality (5 million) continue to surge globally. A number of vaccines (e.g., Moderna, Pfizer, Johnson/Janssen and AstraZeneca vaccines) have been developed over the past two years to restrain the rapid spread of COVID-19. However, without much of effective drug therapies, COVID-19 continues to cause multiple irreversible organ…</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>Recapitulating infection, thermal sensitivity and antiviral treatment of seasonal coronaviruses in human airway organoids</strong> - BACKGROUND: Human seasonal coronaviruses usually cause mild upper-respiratory tract infection, but severe complications can occur in specific populations. Research into seasonal coronaviruses is limited and robust experimental models are largely lacking. This study aims to establish human airway organoids (hAOs)-based systems for seasonal coronavirus infection and to demonstrate their applications in studying virus-host interactions and therapeutic development.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A multi-pronged evaluation of aldehyde-based tripeptidyl main protease inhibitors as SARS-CoV-2 antivirals</strong> - As an essential enzyme of SARS-CoV-2, the COVID-19 pathogen, main protease (M^(Pro)) is a viable target to develop antivirals for the treatment of COVID-19. By varying chemical compositions at both P2 and P3 positions and the N-terminal protection group, we synthesized 18 tripeptidyl M^(Pro) inhibitors that contained also an aldehyde warhead and β-(S-2-oxopyrrolidin-3-yl)-alaninal at the P1 position. Systematic characterizations of these inhibitors were conducted, including their in vitro…</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>Pandemic COVID-19, an update of current status and new therapeutic strategies</strong> - The global COVID-19 pandemic is underway. In recent weeks, several countries throughout the globe, and particularly in Europe, have experienced an exponential increase in the number of individuals infected with COVID-19, probably induced by a new variant of SARS-CoV-2, called the “Omicron variant.” Mass vaccination against COVID-19 continues worldwide. Are authorized mRNA vaccines effective against the new Omicron variant? Recently, several pharmaceutical companies have developed oral antiviral…</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 a broad range of SARS-CoV-2 variants by antiviral phytochemicals in hACE2 mice</strong> - Although several vaccines and antiviral drugs against SARS-CoV-2 are currently available, control and prevention of COVID-19 through these interventions is limited due to inaccessibility and economic issues in some regions and countries. Moreover, incomplete viral clearance by ineffective therapeutics may lead to rapid genetic evolution, resulting in the emergence of new SARS-CoV-2 variants that may escape the host immune system as well as currently available COVID-19 vaccines. Here, we report…</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>Rapid Assessment of Biological Activity of Ag-Based Antiviral Coatings for the Treatment of Textile Fabrics Used in Protective Equipment Against Coronavirus</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants have rapidly spread worldwide, causing coronavirus disease (COVID-19) with numerous infected cases and millions of deaths. Therefore, developing approaches to fight against COVID-19 is currently the most priority goal of the scientific community. As a sustainable solution to stop the spread of the virus, a green dip-coating method is utilized in the current work to prepare antiviral Ag-based coatings to treat cotton…</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 pilot phase Ib/II study of whole-lung low dose radiation therapy (LDRT) for the treatment of severe COVID-19 pneumonia: First experience from Africa</strong> - CONCLUSION: LDRT was feasible, safe and shows promise in the management of severe COVID-19 pneumonia including in patients progressing on conventional systemic treatment. Additional phase II trials are warranted to identify patients most likely to benefit from LDRT.</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 platform for attenuating immune hyperactivity using EXO-CD24 in Covid-19 and beyond</strong> - A small but significant proportion of Covid19 patients develop life-threatening cytokine storm. We have developed a new anti-inflammatory drug, EXO-CD24, a combination of an immune checkpoint (CD24) and a delivery platform (exosomes). CD24 inhibits the NF-kB pathway and the production of cytokines/chemokines. EXO-CD24 discriminates Damage- from Pathogen-Associated Molecular Patterns (DAMPs and PAMPs) therefore does not interfere with viral clearance. EXO-CD24 was produced and purified from…</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>Antiviral effects of coinage metal-based nanomaterials to combat COVID-19 and its variants</strong> - The world has been suffering from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, and millions of people have been infected through human-to-human transmission and lost their lives within months. Although multidisciplinary scientific approaches have been employed to fight against this deadly pandemic, various mutations and diverse environments keep producing constraints in treating SARS-CoV-2. Indeed, the efficacy of the developed vaccines has been limited, and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cepharanthine: A Promising Old Drug against SARS-CoV-2</strong> - Recently, the inhibiting effects of a clinically approved drug Cepharanthine on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have attracted widespread attention and discussion. However, the public does not understand the relevant research progress very well. This paper aims to introduce a brief history of studies on the effects of cepharanthine against SARS-CoV-2, including “discovery of anti-SARS-CoV-2 activity of cepharanthine in vitro”, "potential mechanisms of cepharanthine…</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>Therapeutic role of traditionally used Indian medicinal plants and spices in combating COVID-19 pandemic situation</strong> - The coronavirus disease (COVID-19) caused by SARS-CoV-2 is a big challenge and burning issue to the scientific community and doctors worldwide. Globally, COVID-19 has created a health disaster and adversely affects the economic growth. Although some vaccines have already emerged, no therapeutic medication has yet been approved by FDA for the treatment of COVID-19 patients. Traditionally, we have been using different medicinal plants like neem, tulsi, tea, and many spices like garlic, ginger,…</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>Structure basis for inhibition of SARS-CoV-2 by the feline drug GC376</strong> - No abstract</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>Artemisinin inhibits neutrophil and macrophage chemotaxis, cytokine production and NET release</strong> - Immune cell chemotaxis to the sites of pathogen invasion is critical for fighting infection, but in life-threatening conditions such as sepsis and Covid-19, excess activation of the innate immune system is thought to cause a damaging invasion of immune cells into tissues and a consequent excessive release of cytokines, chemokines and neutrophil extracellular traps (NETs). In these circumstances, tempering excessive activation of the innate immune system may, paradoxically, promote recovery. Here…</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>Effect of a 2-week interruption in methotrexate treatment versus continued treatment on COVID-19 booster vaccine immunity in adults with inflammatory conditions (VROOM study): a randomised, open label, superiority trial</strong> - BACKGROUND: Immunosuppressive treatments inhibit vaccine-induced immunity against SARS-CoV-2. We evaluated whether a 2-week interruption of methotrexate treatment immediately after the COVID-19 vaccine booster improved antibody responses against the S1 receptor-binding domain (S1-RBD) of the SARS-CoV-2 spike protein compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases.</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 adverse inflammatory response of tobacco smoking in COVID-19 patients: biomarkers from proteomics and metabolomics</strong> - Whether tobacco smoking affects the occurrence and development of COVID-19 is still a controversial issue, and potential biomarkers to predict the adverse outcomes of smoking in the progression of COVID-19 patients have not yet been elucidated. To further uncover their linkage and explore the effective biomarkers, three proteomics and metabolomics databases (i.e. smoking status, COVID-19 status, and basic information of population) from human serum proteomic and metabolomic levels were…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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