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<title>08 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>Racial Disparities in Hesitancy and Utilization of Monoclonal Antibody Infusion Treatment of COVID-19</strong> -
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Background and Methods: We conducted a single center cross-sectional study to investigate racial disparities in the hesitancy and utilization of monoclonal antibody (mAb) treatment of COVID-19 among treatment eligible patients who were referred to the infusion center between January 4, 2021 and May 14, 2021. Results: Among the 2,406 eligible participants, African Americans were significantly more likely to underutilize mAb treatment (OR 1.8; 95% CI 1.5-2.1) and miss treatment opportunities due to monoclonal hesitancy (OR 1.7, 95% CI 1.3-2.1). Conclusion: Addressing racial disparities in mAb delivery is an opportunity to bridge the racial inequities in COVID-19 care.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.07.22277360v1" target="_blank">Racial Disparities in Hesitancy and Utilization of Monoclonal Antibody Infusion Treatment of COVID-19</a>
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</div></li>
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<li><strong>How is the COVID-19 pandemic impacting our life, mental health, and well-being? Design and preliminary findings of the pan-Canadian longitudinal COHESION Study</strong> -
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Abstract With the advent of the COVID-19 pandemic, in-person social interactions and opportunities for accessing resources that sustain health and well-being have drastically reduced. We therefore designed the pan-Canadian population-based prospective COVID-19: HEalth and Social Inequities across Neighbourhoods (COHESION) cohort to provide deeper understanding of how the COVID-19 pandemic context affects mental health and well-being, key determinants of health, and health inequities. This paper presents the design of the two-phase COHESION Study, and descriptive results from the first phase conducted between May 2020 and September 2021. During that period, the COHESION research platform collected monthly data linked to COVID-19 such as infection and vaccination status, perceptions and attitudes regarding pandemic-related measures, and information on participants’ physical and mental health, well-being, sleep, loneliness, resilience, substances use, living conditions, social interactions, activities, and mobility. The 1,268 people enrolled in the Phase 1 COHESION Study are for the most part from Ontario (47%) and Quebec (33%), aged 48 ± 16 years [mean± standard deviation (SD)], and mainly women (78%), White (85%), with a university degree (63%), and living in large urban centers (70%). According to the 298 ± 68 (mean ± SD) prospective questionnaires completed each month in average, the first year of follow-up reveals significant temporal variations in standardized indexes of well-being, loneliness, anxiety, depression, and psychological distress. The COHESION Study will allow identifying trajectories of mental health and well-being while investigating their determinants and how these may vary by subgroup, over time, and across different provinces in Canada, in the unique context of the COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.26.22275645v2" target="_blank">How is the COVID-19 pandemic impacting our life, mental health, and well-being? Design and preliminary findings of the pan-Canadian longitudinal COHESION Study</a>
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</div></li>
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<li><strong>Remote self-report and speech-in-noise measures predict clinical audiometric thresholds</strong> -
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The COVID-19 pandemic highlighted the need for remote, but reliable hearing tests. Previous studies used remote testing but did not directly compare results in the same listeners with standard lab testing. Digits-in-noise (DIN) is a reliable speech-in-noise test that can be self-administered remotely. This study investigated the predictive validity of a self-administered DIN test and a commonly used self-report, the speech, spatial, and qualities of hearing (SSQ-12), for lab-based, supervised DIN and audiometry. Speech reception thresholds (SRTs) of 34 adults (18-64 y/o), 16 normal-hearing (NH) and 18 hearing-impaired (HI), were measured at home (remote-DIN) and in the lab (lab-DIN). All DIN testing used English digits 0-9, binaurally presented as triplets in different speech-shaped noise maskers (broadband, low-pass filtered at 2, 4, 8 kHz). Audiometry was administered during lab testing. An SSQ-12 e-version was completed by participants at home. As expected, NH listeners had significantly higher SSQ scores, and remote- and lab-DIN SRTs than HI listeners. All test versions of DIN were significantly correlated with pure-tone-average (PTA), with the 2-kHz filtered test the best predictor, explaining 50% of variance in PTA. SSQ also significantly predicted PTA. Overall, DIN-SRTs were better predictors of audiograms than the SSQ. Remote-DIN correlated significantly with lab-DIN, and there was no significant mean difference between remote- and lab-DIN. Test-retest reliability was measured for broadband remote-DIN. High, significant intraclass correlation coefficients indicated strong internal consistency of the remote-DIN. This study shows that remote SSQ-12 and DIN are valid screening tools for capturing important aspects of auditory function.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.09.22274843v2" target="_blank">Remote self-report and speech-in-noise measures predict clinical audiometric thresholds</a>
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</div></li>
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<li><strong>Humoral and cellular immune responses to CoronaVac assessed up to one year after vaccination</strong> -
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Background: The Sinovac SARS-CoV-2 inactivated vaccine (CoronaVac) has been demonstrated to be safe, well tolerated, and efficacious in preventing mild and severe Covid-19. Although different studies have demonstrated its short-term immunogenicity, long-term cellular and humoral response evaluations are still lacking. Methods: Cellular and humoral responses were assessed after enrollment of volunteers in the PROFISCOV phase 3 double-blind, randomized, placebo-controlled clinical trial to evaluate CoronaVac. Assays were performed using flow cytometry to evaluate cellular immune response and an antigen binding electrochemiluminescence assay to detect antigen-specific antibodies to the virus. Results: Fifty-three volunteers were selected for long term assessment of their SARS-CoV-2-specific immune responses. CD4+ T cell responses (including circulating follicular helper (cTfh, CD45RA- CXCR5+) expressing CD40L, as well as non-cTfh cells expressing CXCR3) were observed early upon the first vaccine dose, increased after the second dose, remaining stable for 6-months. Memory CD4+ T cells were detected in almost all vaccinees, the majority being central memory T cells. IgG levels against Wuhan/WH04/2020 N, S and receptor binding domain (RBD) antigens and the variants of concern (VOCs, including B.1.1.7/Alpha, B.1.351/Beta and P.1/Gamma) S and RBD antigens peaked 14 days after the second vaccine shot, and were mostly stable for a 1-year period. Conclusions: CoronaVac two-doses regimen is able to induce a potent and durable SARS-CoV-2 specific cellular response. The cellular reaction is part of a coordinated immune response that includes high levels of specific IgG levels against parental and SARS-CoV-2 VOC strains, still detected after one year. Funding: Fundacao Butantan, Instituto Butantan and Sao Paulo Research Foundation (FAPESP) (grants 2020/10127-1 and 2020/06409-1). This work has also been supported by NIH contract 75N93019C00065 (A.S, D.W). PATH facilitated reagent donations for this work with support by the Bill & Melinda Gates Foundation (INV-021239). Under the grant conditions of the foundation, a Creative Commons Attribution 4.0 generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.03.16.22272513v2" target="_blank">Humoral and cellular immune responses to CoronaVac assessed up to one year after vaccination</a>
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<li><strong>Prevalence and factors associated with antigen test positivity following SARS-CoV-2 infection among healthcare workers in Los Angeles</strong> -
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Surges of SARS-CoV-2 infections among healthcare workers (HCWs) have led to critical staffing shortages. From January 4 to February 4, 2022, we implemented a return-to-work antigen testing program for HCWs and 870 HCWs participated. Antigen test positivity was 60.5% for those ≤5 days from symptom onset or positive PCR and 47.4% were positive at day 7. Antigen positivity was associated with receiving a booster vaccination and being ≤6 days from symptom onset or PCR test, but not age or a symptomatic infection. Rapid antigen testing can be a useful tool to guide return-to-work and isolation precautions for HCWs following infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.06.22277341v1" target="_blank">Prevalence and factors associated with antigen test positivity following SARS-CoV-2 infection among healthcare workers in Los Angeles</a>
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<li><strong>Duration of immune protection of SARS-CoV-2 natural infection against reinfection in Qatar</strong> -
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BACKGROUND: The future of the SARS-CoV-2 pandemic hinges on virus evolution and duration of immune protection of natural infection against reinfection. We investigated duration of protection afforded by natural infection, the effect of viral immune evasion on duration of protection, and protection against severe reinfection, in Qatar, between February 28, 2020 and June 5, 2022. METHODS: Three national, matched, retrospective cohort studies were conducted to compare incidence of SARS-CoV-2 infection and COVID-19 severity among unvaccinated persons with a documented SARS-CoV-2 primary infection, to incidence among those infection-naive and unvaccinated. Associations were estimated using Cox proportional-hazard regression models. RESULTS: Effectiveness of pre-Omicron primary infection against pre-Omicron reinfection was 85.5% (95% CI: 84.8-86.2%). Effectiveness peaked at 90.5% (95% CI: 88.4-92.3%) in the 7th month after the primary infection, but waned to ~70% by the 16th month. Extrapolating this waning trend using a Gompertz curve suggested an effectiveness of 50% in the 22nd month and <10% by the 32nd month. Effectiveness of pre-Omicron primary infection against Omicron reinfection was 38.1% (95% CI: 36.3-39.8%) and declined with time since primary infection. A Gompertz curve suggested an effectiveness of <10% by the 15th month. Effectiveness of primary infection against severe, critical, or fatal COVID-19 reinfection was 97.3% (95% CI: 94.9-98.6%), irrespective of the variant of primary infection or reinfection, and with no evidence for waning. Similar results were found in sub-group analyses for those ≥50 years of age. CONCLUSIONS: Protection of natural infection against reinfection wanes and may diminish within a few years. Viral immune evasion accelerates this waning. Protection against severe reinfection remains very strong, with no evidence for waning, irrespective of variant, for over 14 months after primary infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.06.22277306v1" target="_blank">Duration of immune protection of SARS-CoV-2 natural infection against reinfection in Qatar</a>
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<li><strong>Quantifying the impact of vaccines and booster doses on COVID-19 in the U.S.</strong> -
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The 2019 coronavirus (COVID-19) pandemic continues to have a devastating impact on health systems and economies across the globe, with the United States (U.S.) among the worse impacted nations. Implementing public health measures in tandem with effective vaccination strategies is instrumental in halting the transmission of the virus and curtailing the burden of the pandemic. Currently, the U.S. Food and Drug Administration has authorized the use of the PfizerBioNTech, Moderna, and the Johnson & Johnson vaccines to prevent COVID-19 in the U.S. However, these vaccines have varying efficacies (≈ 95% for the Pfizer-BioNTech and Moderna vaccines and ≈ 70% for the Johnson & Johnson vaccine) and waning effects against major COVID-19 strains, hence, understanding their impact on the incidence of COVID-19 in the U.S. is critical. Here, we formulate and use mathematical models 1) to investigate the impact of each vaccine type and booster doses (single/double) on the incidence of COVID-19 in the U.S., and 2) to predict future trends of the disease in the U.S., if existing control measures are reinforced or relaxed. The models are fitted to part of the new daily confirmed case data from the U.S., and validated using the remaining part of the daily data, as well as the full cumulative case data. The fitting and numerical simulations of the models show a 44% (71%) reduction in the reproduction number (number of new daily confirmed cases) at the peak during the wave in which vaccination peaked compared to the preceding wave. Additionally, the estimated disease transmission rate is ≈ 3 times higher for the Omicron variant. Simulations of the model show that in the absence of booster shots, the time to elimination of community transmission in the U.S. would have increased by at least two months compared to the baseline case. However, had more people (i.e., 70% of the fully vaccinated population) been boosted by mid-August 2021, ≈ 78% of the daily incidence could have been prevented as at the time the first case of Omicron was reported in the U.S. Our findings suggest that booster shots with the Pfizer-BioNTech or Moderna vaccines conferred superior protection than those with the Johnson & Johnson vaccine. Furthermore, the simulations show that the baseline value of the new daily cases at the peak of the Omicron variant in January 2022 would have dropped significantly (by ≈ 20%) if a fourth dose of the Pfizer-BioNTech or Moderna vaccine was administered at the start of the Omicron wave. Specifically, three million cumulative cases in the U.S. could have been averted between late November 2021 and March 2022. The study proves that early administration of vaccines and booster doses could have significantly reduced the surge in cases and the observed peak size. In particular, we showed that, while late boosting will result in an increase in the number of cases (compared to the baseline value), early boosting will lead to a decrease in the number of cases. Additionally, we showed that a second booster dose using the Pfizer-BioNTech or Moderna vaccine is important in curtailing the burden of the pandemic in the U.S. Particularly if this second dose is administered soon after the first dose. Furthermore, the study shows that early relaxation of existing control measures can lead to a more devastating wave, especially if both vaccination and transmission rate reducing measures such as mask-use are relaxed simultaneous. Keywords: COVID-19 pandemic; Vaccine efficacy; Booster doses; Delta and Omicron variants; Waning vaccine-derived and natural immunity; Infectious disease models.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.06.22277303v1" target="_blank">Quantifying the impact of vaccines and booster doses on COVID-19 in the U.S.</a>
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<li><strong>Understanding the dynamic relation between wastewater SARS-CoV-2 signal and clinical metrics throughout the pandemic</strong> -
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Wastewater surveillance (WWS) of SARS-CoV-2 was proven to be a reliable and complementary tool for population-wide monitoring of COVID-19 disease incidence but was not as rigorously explored as an indicator for disease burden throughout the pandemic. Prior to global mass immunization campaigns and during the spread of the wildtype COVID-19 and the Alpha variant of concern (VOC), viral measurement of SARS-CoV-2 in wastewater was a leading indicator for both COVID-19 incidence and disease burden in communities. As the two-dose vaccination rates escalated during the spread of the Delta VOC in Jul. 2021 through Dec. 2021, relations weakened between wastewater signal and community COVID-19 disease incidence and maintained a strong relationship with clinical metrics indicative of disease burden (new hospital admissions, ICU admissions, and deaths). Further, with the onset of the vaccine-resistant Omicron BA.1 VOC in Dec. 2021 through Mar. 2022, wastewater again became a strong indicator of both disease incidence and burden during a period of limited natural immunization (no recent infection), vaccine escape, and waned vaccine effectiveness. Lastly, with the populations regaining enhanced natural and vaccination immunization shortly prior to the onset of the Omicron BA.2 VOC in mid-Mar 2022, wastewater is shown to be a strong indicator for both disease incidence and burden. Hospitalization-to-wastewater ratio is further shown to be a good indicator of VOC virulence when widespread clinical testing is limited. In the future, WWS is expected to show moderate indication of incidence and strong indication of disease burden in the community during future potential seasonal vaccination campaigns.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.06.22277318v1" target="_blank">Understanding the dynamic relation between wastewater SARS-CoV-2 signal and clinical metrics throughout the pandemic</a>
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<li><strong>Association between nursing home crowding and outbreak-associated respiratory infection and death prior to the COVID-19 pandemic between 2014 and 2019 in Ontario, Canada</strong> -
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Importance: Resident crowding in nursing homes is associated with larger SARS-CoV-2 outbreaks. However, this association has not been previously documented for non-SARS-CoV-2 respiratory infections. Objective: We sought to measure the association between nursing home crowding and respiratory infections in Ontario nursing homes prior to the COVID-19 pandemic. Design, Setting, and Participants: We conducted a retrospective cohort study of nursing home residents in Ontario, Canada over a five-year period prior to the COVID-19 pandemic, between September 2014 and August 2019. Exposure: Using administrative data, we estimated the crowding index equal to the mean number of residents per bedroom and bathroom (residents / [0.5<em>bedrooms+0.5</em>bathrooms]). Outcomes: The incidence of outbreak-associated infections and mortality per 100 nursing home residents per year. We also examined infection and mortality outcomes for outbreaks due to 7 specific pathogens: coronaviruses (OC43, 229E, NL63, HKU1), influenza A, influenza B, human metapneumovirus, parainfluenza virus, respiratory syncytial virus, rhinovirus/enterovirus. Results: There was one or more respiratory outbreak in 93.9% (588/626) nursing homes in Ontario. There were 4,921 outbreaks involving 64,829 cases of respiratory infection, and 1,969 deaths. Outbreaks attributable to a single identified pathogen were principally caused by influenza A (29%), rhinovirus (11.7%), influenza B (8.1%), and respiratory syncytial virus (6.1%). Among homes, 42.7% (251/588) homes had a high crowding index (≥ 2.0). After adjustment, more crowded homes had higher outbreak-associated respiratory infection incidence (aRR 1.89; 95% 1.64-2.18) and mortality incidence (aRR 2.28; 95% 1.84- 2.84). More crowded homes had higher adjusted estimates of the incidence of infection and mortality for each of the 7 respiratory pathogens examined. Conclusions and Relevance: Residents of crowded nursing homes experienced more respiratory-outbreak infections and mortality due to influenza and other non-SARS-CoV-2 respiratory pathogens. Decreasing crowding in nursing homes is an important patient safety target beyond the COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.06.22277066v1" target="_blank">Association between nursing home crowding and outbreak-associated respiratory infection and death prior to the COVID-19 pandemic between 2014 and 2019 in Ontario, Canada</a>
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<li><strong>Cardiac Post-acute Sequelae of SARS-CoV-2 in Community- Dwelling Adults: Cross-sectional Study</strong> -
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Objective To examine risk factors for cardiac-related PASC in community-dwelling adults after acute coronavirus disease 2019 (COVID-19) infection. Methods We performed a cross-sectional analysis among adults who tested positive for COVID-19. Outcomes were self-reported cardiac-related PASC. We conducted stepwise multivariable logistic regression to assess association between the risk factors (existing cardiovascular disease, pre-existing conditions, days since positive test, COVID hospitalization, age, sex, education, income) and cardiac-related PASC. Results In a sample of 442 persons, mean(SD) age was 45.4 (16.2) years, 71% were female, 13% were black, 46% had pre-existing conditions, 23% had CV risk factors, and 4% had CV illness (CVD). Prevalence of cardiac PASC were 43% and newly diagnosed cardiac conditions was 27%. The odds for cardiac-related PASC were higher among persons with underlying pre-existing conditions (adjusted odds ratio aOR: 2.00, 95% CI:1.28-3.10) and among those who were hospitalized (aOR: 3.03, 95%CI:1.58-5.83). Conclusions More than a third of persons with COVID-19 reported cardiac-related PASC symptoms. Underlying CVD, pre-existing diseases, age, and COVID-19 hospitalization are possible risk factors for cardiac-related PASC symptoms. COVID-19 may exacerbate CV risk factors and increase risk of complications.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.05.22277260v1" target="_blank">Cardiac Post-acute Sequelae of SARS-CoV-2 in Community- Dwelling Adults: Cross-sectional Study</a>
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<li><strong>Wastewater-Based Epidemiology for SARS-CoV-2 Biomarkers: Evaluation of Normalization Methods in Small and Large Communities in Southern Germany</strong> -
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In the context of the COVID-19 pandemic, wastewater-based epidemiology (WBE) emerged as a useful tool to account for the prevalence of SARS-CoV-2 infections on a population scale. In this study we analyzed wastewater samples from three large (> 300,000 people served) and four small (< 25,000 people served) communities throughout southern Germany from August to December 2021, capturing the fourth infection wave in Germany dominated by the Delta variant (B.1.617.2). As dilution can skew the SARS-CoV-2 biomarker concentrations in wastewater, normalization to wastewater parameters can improve the relationship between SARS-CoV-2 biomarker data and clinical prevalence data. In this study, we investigated the suitability and performance of various normalization parameters. Influent flow data showed strong relationships to precipitation data; accordingly, flow-normalization reacted distinctly to precipitation events. Normalization by surrogate viruses CrAssphage and Pepper Mild Mottle Virus showed varying performance for different sampling sites. The best normalization performance was achieved with a mixed fecal indicator calculated from both surrogate viruses. Analyzing the temporal and spatial variation of normalization parameters proved to be useful to explain normalization performance. Overall, our findings indicate that the performance of surrogate viruses, flow and hydro-chemical data is site-specific. We recommend to test the suitability of normalization parameters individually for specific sewage systems.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.07.22277349v1" target="_blank">Wastewater-Based Epidemiology for SARS-CoV-2 Biomarkers: Evaluation of Normalization Methods in Small and Large Communities in Southern Germany</a>
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<li><strong>PERSISTENT IMMUNITY AFTER MILD SARS CoV-2 INFECTION - THE CoNAN-LONG TERM STUDY -</strong> -
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Objectives: Understanding persistent cellular and humoral immune responses to SARS-CoV-2 will be of major importance to terminate the ongoing pandemic. Here we assessed long-term immunity in individuals with mild COVID-19 up to one year after a localized SARS-CoV-2 outbreak. Methods: CoNAN was a longitudinal population-based cohort study performed 1.5 months, 6 months and 12 months after a SARS-CoV-2 outbreak in a rural German community. We performed a time series of five different IgG immunoassays assessing SARS-CoV-2 antibody responses on serum samples from individuals that had been tested positive after a SARS-CoV-2 outbreak as well as in control individuals who had a negative PCR result. These analyses were complemented with the determination of spike-antigen specific TH cell responses in the same individuals. Results: All infected participants presented as asymptomatic or mild cases. Participants initially tested positive for SARS-CoV-2 infection either with PCR, antibody testing, or both had a rapid initial decline in the serum antibody levels in all serological test but showed a persisting and robust TH cell immunity as assessed by the detection of SARS-CoV-2 specificity of TH cells for up to one year after infection. Conclusion: Our data support the notion of a robust T cell immunity in mild and asymptomatic cases of SARS-CoV-2 up to one year after infection. We show that antibody titers decline over one year, but considering several test results, complete seroconversion is rare. Trial Registration: German Clinical Trials Register DRKS00022416.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.05.22277237v1" target="_blank">PERSISTENT IMMUNITY AFTER MILD SARS CoV-2 INFECTION - THE CoNAN-LONG TERM STUDY -</a>
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<li><strong>Drivers of COVID-19 policy stringency in 175 countries and territories: COVID-19 cases and deaths, gross domestic products per capita, and health expenditures</strong> -
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Objective: To understand the associations of COVID-19 cases and deaths with policy stringency globally and regionally. Methods: We modeled the marginal effects of new COVID-19 cases and deaths on policy stringency (scored 0-100) in 175 countries and territories, adjusting for gross domestic product (GDP) per capita and health expenditure (% of GDP). Time periods examined were March-August 2020, September 2020-February 2021, and March-August 2021. Results: Policy response to new cases and deaths was faster and more stringent early in the COVID-19 pandemic (March-August 2020) compared to subsequent periods. New deaths were more strongly associated with stringent policies than new cases. In an average week, 1 new death per 100,000 people was associated with a stringency increase of 2.1 units in March-August 2020, 1.3 units in September 2020-February 2021, and 0.7 units in March-August 2021. New deaths in Africa and the Western Pacific were associated with more stringency than in other regions. Higher health expenditure was associated with less stringent policies. GDP per capita did not have consistent patterns of associations with stringency. Conclusions: Our findings demonstrate the need for enhanced mortality surveillance to ensure policy alignment during health emergencies. Countries that invest less of their GDP in health are inclined to enact stringent policies during health emergencies than countries with more significant health expenditure.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.05.22277269v1" target="_blank">Drivers of COVID-19 policy stringency in 175 countries and territories: COVID-19 cases and deaths, gross domestic products per capita, and health expenditures</a>
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<li><strong>Effects of SARS-CoV-2 Alpha, Beta, and Delta variants, age, vaccination, and prior infection on infectiousness of SARS-CoV-2 infections</strong> -
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In 2021, Qatar experienced considerable incidence of SARS-CoV-2 infection that was dominated sequentially by the Alpha, Beta, and Delta variants. Using the cycle threshold (Ct) value of an RT-qPCR-positive test to proxy the inverse of infectiousness, we investigated infectiousness of SARS-CoV-2 infections by variant, age, sex, vaccination status, prior infection status, and reason for testing in a random sample of 18,355 RT-qPCR-genotyped infections. Regression analyses were conducted to estimate associations with the Ct value of RT-qPCR-positive tests. Compared to Beta infections, Alpha and Delta infections demonstrated 2.56 higher Ct cycles (95% CI: 2.35-2.78), and 4.92 fewer cycles (95% CI: 4.67- 5.16), respectively. The Ct value declined gradually with age and was especially high for children <10 years of age, signifying lower infectiousness of small children. Children <10 years of age had 2.18 higher Ct cycles (95% CI: 1.88-2.48) than those 10-19 years of age. Compared to unvaccinated individuals, the Ct value was higher among individuals who had received one or two vaccine doses, but the Ct value decreased gradually with time since the second-dose vaccination. Ct value was 2.07 cycles higher (95% CI: 1.42-2.72) for those with a prior infection than those without prior infection. The Ct value was lowest among individuals tested because of symptoms and was highest among individuals tested as a travel requirement. Delta was substantially more infectious than Beta. Prior immunity, whether due to vaccination or prior infection, is associated with lower infectiousness of breakthrough infections, but infectiousness increases gradually with time since the second-dose vaccination.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.05.22277257v1" target="_blank">Effects of SARS-CoV-2 Alpha, Beta, and Delta variants, age, vaccination, and prior infection on infectiousness of SARS-CoV-2 infections</a>
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<li><strong>Multimodal surveillance of SARS-CoV-2 at a university enables development of a robust outbreak response framework</strong> -
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Universities are particularly vulnerable to infectious disease outbreaks and are also ideal environments to study transmission dynamics and evaluate mitigation and surveillance measures when outbreaks occur. Here, we introduce a SARS-CoV-2 surveillance and response framework based on high-resolution, multimodal data collected during the 2020-2021 academic year at Colorado Mesa University. We analyzed epidemiological and sociobehavioral data (demographics, contact tracing, and wifi-based co-location data) alongside pathogen surveillance data (wastewater, random, and reflexive diagnostic testing; and viral genomic sequencing of wastewater and clinical specimens) to characterize outbreak dynamics and inform policy decisions. We quantified group attributes that increased disease risk, and highlighted parallels between traditional and wifi-based contact tracing. We additionally used clinical and environmental viral sequencing to identify cryptic transmission, cluster overdispersion, and novel lineages or mutations. Ultimately, we used distinct data types to identify information that may help shape institutional policy and to develop a model of pathogen surveillance suitable for the future of outbreak preparedness.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.06.22277314v1" target="_blank">Multimodal surveillance of SARS-CoV-2 at a university enables development of a robust outbreak response framework</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>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>Generation of SARS-CoV-2-specific T Lymphocytes From Recovered Donors and Administration to High-risk COVID-19 Patients</strong> - <b>Condition</b>: Severe COVID-19<br/><b>Interventions</b>: Biological: Coronavirus-2-specific T cells; Other: standard of care (SOC)<br/><b>Sponsors</b>: George Papanicolaou Hospital; General Hospital Of Thessaloniki Ippokratio<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>Evaluate the Efficacy and Safety of FB2001 in Hospitalized Patients With Moderate to Severe COVID-19 (BRIGHT Study)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: FB2001; Drug: FB2001 placebo<br/><b>Sponsor</b>: Frontier Biotechnologies Inc.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety 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>A Study to Evaluate the Efficacy of PanCytoVir™ for the Treatment of Non-Hospitalized Patients With COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: PanCytoVir™ (probenecid); Drug: Placebo<br/><b>Sponsor</b>: TrippBio, Inc.<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>Value of Montelukast as a Potential Treatment of Post COVID-19 Persistent Cough</strong> - <b>Condition</b>: Post COVID-19<br/><b>Intervention</b>: Drug: Montelukast Sodium Tablets<br/><b>Sponsor</b>: Assiut 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>Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study</strong> - <b>Condition</b>: Post-COVID19 Condition<br/><b>Interventions</b>: Combination Product: Plasma Exchange Procedure; Other: Sham Plasma Exchange Procedure<br/><b>Sponsors</b>: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; IrsiCaixa; Banc de Sang i Teixits<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety, 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>A Study to Evaluate the Safety and Immunogenicity of Ad5-vector Based Vaccine Against Coronavirus Variants in Adults (≥18 Years) Immunized With 2 Doses of mRNA Vaccines Plus One Dose of Booster AZD1222 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Bivalent Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector); Biological: Bivalent Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) for Inhalation; Biological: mRNA-based COVID-19 vaccine<br/><b>Sponsor</b>: CanSino Biologics Inc.<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-field Magnetic Resonance Imaging in Pediatric Post Covid-19</strong> - <b>Conditions</b>: COVID-19; COVID-19 Respiratory Infection; Long COVID<br/><b>Interventions</b>: Diagnostic Test: Low-field magnetic resonance imaging; Diagnostic Test: Nailfold capillaroscopy; Diagnostic Test: Spiroergometry; Diagnostic Test: Realtime deformability cytometry<br/><b>Sponsor</b>: University of Erlangen-Nürnberg Medical School<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>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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<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>Individual and Synergistic Anti-Coronavirus Activities of SOCS1/3 Antagonist and Interferon α1 Peptides</strong> - Suppressors of Cytokine Signaling (SOCS) are intracellular proteins that negatively regulate the induction of cytokines. Amongst these, SOCS1 and SOCS3 are particularly involved in inhibition of various interferons. Several viruses have hijacked this regulatory pathway: by inducing SOCS1and 3 early in infection, they suppress the host immune response. Within the cell, SOCS1/3 binds and inhibits tyrosine kinases, such as JAK2 and TYK2. We have developed a cell penetrating peptide from 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>Gasdermin-D activation by SARS-CoV-2 triggers NET and mediate COVID-19 immunopathology</strong> - CONCLUSION: These results demonstrated that GSDMD-dependent NETosis plays a critical role in COVID-19 immunopathology and suggests GSDMD as a novel potential target for improving the COVID-19 therapeutic strategy.</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>Hydroxypropyl-beta-cyclodextrin (HP-BCD) inhibits SARS-CoV-2 replication and virus-induced inflammatory cytokines</strong> - COVID-19 is marked by extensive damage to the respiratory system, often accompanied by systemic manifestations, due to both viral cytopathic effects and hyperinflammatory syndrome. Therefore, the development of new therapeutic strategies or drug repurposing aiming to control virus replication and inflammation are required to mitigate the impact of the disease. Hydroxypropyl-beta-cyclodextrin (HP-BCD) is a cholesterol-sequestering agent with antiviral activity that has been demonstrated against…</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>How Reproducible Are QM/MM Simulations? Lessons from Computational Studies of the Covalent Inhibition of the SARS-CoV-2 Main Protease by Carmofur</strong> - This work explores the level of transparency in reporting the details of computational protocols that is required for practical reproducibility of quantum mechanics/molecular mechanics (QM/MM) simulations. Using the reaction of an essential SARS-CoV-2 enzyme (the main protease) with a covalent inhibitor (carmofur) as a test case of chemical reactions in biomolecules, we carried out QM/MM calculations to determine the structures and energies of the reactants, the product, and the transition…</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>Repositioning Therapeutics for SARS-CoV-2: Virtual Screening of Plant-based Anti-HIV Compounds as Possible Inhibitors against COVID-19 Viral RdRp</strong> - CONCLUSION: The present study suggested that these potential drug candidates can be further subjected to in vitro and in vivo studies that may help develop effective anti-COVID-19 drugs.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Specificity and Confirmation of SARS-CoV-2 Serological Test Methods in Emergency Department Populations across the United States</strong> - CONCLUSIONS: The specificity of the serological assays evaluated in a large, diverse emergency department population was >99% and did not vary by geographical site. A confirmatory algorithm with an automated pseudo-neutralization assay allowed testing on the same specimen while reducing the false positivity rate and increasing the value of serology screening methods.</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>Antibody responses and risk factors associated with impaired immunological outcomes following two doses of BNT162b2 COVID-19 vaccination in patients with chronic pulmonary diseases</strong> - INTRODUCTION: Responses to COVID-19 vaccination in patients with chronic pulmonary diseases are poorly characterised. We aimed to describe humoral responses following two doses of BNT162b2 mRNA COVID-19 vaccine and identify risk factors for impaired responses.</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>Reactogenic sleepiness after COVID-19 vaccination. A hypothesis involving orexinergic system linked to inflammatory signals</strong> - Coronavirus disease 2019 (COVID-19) represents a global healthcare crisis that has led to morbidity and mortality on an unprecedented scale. While studies on COVID-19 vaccines are ongoing, the knowledge about the reactogenic symptoms that can occur after vaccination and its generator mechanisms can be critical for healthcare professionals to improve compliance with the future vaccination campaign. Because sleep and immunity are bidirectionally linked, sleepiness or sleep disturbance side effects…</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>Peritoneal M2 macrophage-derived extracellular vesicles as natural multitarget nanotherapeutics to attenuate cytokine storms after severe infections</strong> - Cytokine storms are a primary cause of multiple organ damage and death after severe infections, such as SARS-CoV-2. However, current single cytokine-targeted strategies display limited therapeutic efficacy. Here, we report that peritoneal M2 macrophage-derived extracellular vesicles (M2-EVs) are multitarget nanotherapeutics that can be used to resolve cytokine storms. In detail, primary peritoneal M2 macrophages exhibited superior anti-inflammatory potential than immobilized cell lines….</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>Title: Cloaking the ACE2 receptor with salivary cationic proteins inhibits SARS-CoV-2 entry</strong> - Saliva contributes to the innate immune system, which suggests that it can prevent SARS-CoV-2 entry. We studied the ability of healthy salivary proteins to bind to angiotensin-converting enzyme 2 (ACE2) using biolayer interferometry and pull-down assays. Their effects on binding between the receptor-binding domain of the SARS-CoV-2 spike protein S1 (S1) and ACE2 were determined using an enzyme-linked immunosorbent assay. Saliva bound to ACE2 and disrupted the binding of S1 to ACE2 and four…</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>Current status and prospects of IL-6-targeting therapy</strong> - INTRODUCTION: Persistent and excess IL-6 production often contributes to a variety of immune diseases. IL-6-targeting therapy was first approved for Castleman disease, then rheumatoid arthritis, and now it is broadly used. Furthermore, it has been approved not only for chronic and acute inflammatory diseases but also for autoantibody-induced diseases such as neuromyelitis optica spectrum disorder and interstitial lung disease due to systemic sclerosis.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In vitro evaluation of antiviral activity of Sisybrium irio (Khaksi) against SARS-COV-2</strong> - SARS-CoV-2 pandemic, drawn attention to the need of virus culture. In vitro SARS-COV-2 culture was performed to carry out therapeutic, environmental and virus genome studies. Isolation of virus from nasopharyngeal swab was performed by inoculating virus positive samples in available cell lines. SARS-CoV-2 topography was observed by using Scanning Electron Microscopy (SEM). Virus specificity was defined by serological confirmation through neutralization assay with COVID 19 convalescent sera. 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>An outlook on potential protein targets of COVID-19 as a druggable site</strong> - CONCLUSION: Using cryo-electron microscopy or X-ray diffraction, hundreds of crystallographic data of SARS-CoV-2 proteins have been published including structural and non-structural proteins. These proteins have a significant role at different aspects in the viral machinery and presented themselves as potential target for drug designing and therapeutic interventions. Also, there are few host cell proteins which helps in SARS-CoV-2 entry and proteolytic cleavage required for viral infection.</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>Istradefylline, an adenosine A2a receptor antagonist, inhibits the CD4<sup>+</sup> T-cell hypersecretion of IL-17A and IL-8 in humans</strong> - Extracellular adenosine produced from ATP plays a role in energy processes, neurotransmission, and inflammatory responses. Istradefylline is a selective adenosine A2a receptor (A2aR) antagonist used for the treatment of Parkinson’s disease. We previously showed using mouse models that adenosine primes hypersecretion of interleukin (IL)-17A via A2aR, which plays a role in neutrophilic inflammation models in mice. This finding suggests that adenosine is an endogenous modulator of neutrophilic…</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 COVID-19 ORAL DRUG MOLNUPIRAVIR IS A CES2 SUBSTRATE: POTENTIAL DRUG-DRUG INTERACTIONS AND IMPACT OF CES2 GENETIC POLYMORPHISM IN VITRO</strong> - Molnupiravir is one of the two COVID-19 oral drugs that were recently granted the emergency use authorization by the Food and Drug Administration (FDA). Molnupiravir is an ester and requires hydrolysis to exert antiviral activity. Carboxylesterases constitute a class of hydrolases with high catalytic efficiency. Humans express two major carboxylesterases (CES1 and CES2) that differ in substrate specificity. Based on the structural characteristics of molnupiravir, this study was performed to…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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