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<title>22 April, 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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<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>Novel Estimates Reveal Subnational Heterogeneities in Disease-Relevant Contact Patterns in the United States</strong> -
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The spread and transmission dynamics of directly transmitted airborne pathogens, such as SARS-CoV-2, are fundamentally determined by in-person contact patterns. Reliable quantitative estimates of contact patterns are critical to modeling and reducing the spread of directly transmitted infectious diseases. While national-level contact data are available in many countries, including the United States, local-level estimates of age-specific contact patterns are key since disease dynamics and public health policy vary by geography. However, collecting contact data for each state would require a very large sample and be prohibitively expensive. To overcome this challenge, we develop a flexible model to estimate age-specific contact patterns at the subnational level using national-level interpersonal contact data. Our model is based on dynamic multilevel regression with poststratification. We apply this approach to a national sample of interpersonal contact data collected by the Berkeley Interpersonal Contact Study (BICS). Results illustrate important state-level variation in levels and trends of contacts across the US.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/87e32/" target="_blank">Novel Estimates Reveal Subnational Heterogeneities in Disease-Relevant Contact Patterns in the United States</a>
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</div></li>
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<li><strong>Peptide derived nanobody inhibits entry of SARS-CoV-2 variants</strong> -
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Emergence of the new escape mutants of the SARS-CoV-2 virus has escalated its penetration among the human population and has reinstated its status as a global pandemic. Therefore, developing effective antiviral therapy against emerging SARS variants and other viruses in a short period of time becomes essential. Blocking the SARS-CoV-2 entry into human host cells by disrupting the spike glycoprotein-ACE2 interaction has been already exploited for vaccine development and monoclonal antibody therapy. Unlike the previous reports, our study used a 9 amino acid peptide from the receptor-binding motif (RBM) of Spike (S) protein as an epitope. We report the identification of an efficacious nanobody N1.2 that blocks the entry of pseudovirus containing SARS-CoV-2 spike as the surface glycoprotein. Moreover, we observe a more potent neutralizing effect against both the hCoV19 (Wuhan/WIV04/2019) and the Omicron (BA.1) pseudotyped spike virus with a bivalent version of the nanobody. In summary, our study presents a faster and efficient methodology to use peptide sequences from a protein-receptor interaction interface as epitopes for screening nanobodies against potential pathogenic targets. This approach can also be widely extended to target other viruses and pathogens in the future.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.04.21.489021v1" target="_blank">Peptide derived nanobody inhibits entry of SARS-CoV-2 variants</a>
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<li><strong>Lung spatial profiling reveals a T cell signature in COPD patients with fatal SARS-CoV-2 infection</strong> -
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Rationale: People with pre-existing lung diseases like chronic obstructive pulmonary disease (COPD) are more likely to get very sick from SARS-CoV-2 disease 2019 (COVID-19), but an interrogation of the immune response to COVID-19 infection, spatial throughout the lung structure is lacking in patients with COPD. Objectives: To profile the immune microenvironment of lung parenchyma, airways, and vessels of never- and ever-smokers with or without COPD, whom all died of COVID-19, using spatial transcriptomic and proteomic profiling. Findings: The parenchyma, airways, and vessels of COPD patients, compared to control lungs had: 1) significant enrichment for lung resident CD45RO+ memory T cells; 2) downregulation of genes associated with T cell antigen-priming and memory T cell differentiation; 3) higher expression of proteins associated with SARS-CoV-2 entry and major receptor ubiquitously across the ROIs and in particular the lung parenchyma, despite similar SARS-CoV-2 structural gene expression levels. Conclusions: The lung parenchyma, airways, and vessels of COPD patients have increased T-lymphocytes with a blunted memory T cell response and a more invasive SARS- CoV-2 infection pattern, and may underlie the higher death toll observed with COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.04.20.488968v1" target="_blank">Lung spatial profiling reveals a T cell signature in COPD patients with fatal SARS-CoV-2 infection</a>
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<li><strong>Pediatric nasal epithelial cells are less permissive to SARS-CoV-2 replication compared to adult cells</strong> -
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Children typically experience more mild symptoms of COVID-19 when compared to adults. There is a strong body of evidence that children are also less susceptible to SARS-CoV-2 infection with the ancestral viral isolate. However, the emergence of SARS-CoV-2 variants of concern (VOCs) has been associated with an increased number of pediatric infections. Whether this is the result of widespread adult vaccination or fundamental changes in the biology of SARS-CoV-2 remains to be determined. Here, we use primary nasal epithelial cells from children and adults, differentiated at an air-liquid interface to show that the ancestral SARS-CoV-2 replicates to significantly lower titers in the nasal epithelial cells of children compared to those of adults. This was associated with a heightened antiviral response to SARS-CoV-2 in the nasal epithelial cells of children. Importantly, the Delta variant also replicated to significantly lower titres in the nasal epithelial cells of children. This trend was markedly less pronounced in the case of Omicron. It is also striking to note that, at least in terms of viral RNA, Omicron replicated better in pediatric NECs compared to both Delta and the ancestral virus. Taken together, these data show that the nasal epithelium of children supports lower infection and replication of ancestral SARS-CoV-2, although this may be changing as the virus evolves.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.03.08.434300v3" target="_blank">Pediatric nasal epithelial cells are less permissive to SARS-CoV-2 replication compared to adult cells</a>
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<li><strong>COVID-19 outcomes by cancer status, type, treatment, and vaccination</strong> -
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Background: Observational studies have identified patients with cancer as a potential subgroup of individuals at elevated risk of severe SARS-CoV-2 (COVID-19) disease and mortality. Early studies showed an increased risk of COVID-19 mortality for cancer patients, but it is not well understood how this association varies by cancer site, cancer treatment, and vaccination status. Methods: Using electronic health record data from an academic medical center, we identified 259,893 individuals who were tested for or diagnosed with COVID-19 from March 10, 2020, to February 2, 2022. Of these, 41,218 tested positive for COVID-19 of whom 10,266 had a past or current cancer diagnosis. We conducted Firth- corrected, covariate-adjusted logistic regression to assess the association of cancer status, cancer type, and cancer treatment with four COVID-19 outcomes: hospitalization, intensive care unit (ICU) admission, mortality, and a composite “severe COVID-19” outcome which is the union of the first three outcomes. We examine the effect of the timing of cancer diagnosis and treatment relative to COVID diagnosis, and the effect of vaccination. Results: Cancer status was associated with higher rates of severe COVID-19 infection [OR (95% CI): 1.18 (1.08, 1.29)], hospitalization [OR (95% CI): 1.18 (1.06, 1.28)], and mortality [OR (95% CI): 1.22 (1.00, 1.48)]. These associations were driven by patients whose most recent initial cancer diagnosis was within the past three years. Chemotherapy receipt was positively associated with all four COVID-19 outcomes (e.g., severe COVID [OR (95% CI): 1.96 (1.73, 2.22)], while receipt of either radiation or surgery alone were not associated with worse COVID-19 outcomes. Among cancer types, hematologic malignancies [OR (95% CI): 1.62 (1.39, 1.88)] and lung cancer [OR (95% CI): 1.81 (1.34, 2.43)] were significantly associated with higher odds of hospitalization. Hematologic malignancies were associated with ICU admission [OR (95% CI): 1.49 (1.11, 1.97)] and mortality [OR (95% CI): 1.57 (1.15, 2.11)], while melanoma and breast cancer were not associated with worse COVID-19 outcomes. Vaccinations were found to reduce the frequency of occurrence for the four COVID-19 outcomes across cancer status but those with cancer continued to have elevated risk of severe COVID [cancer OR (95% CI) among those fully vaccinated: 1.69 (1.10, 2.62)] relative to those without cancer even among vaccinated. Conclusion: Our study provides insight to the relationship between cancer diagnosis, treatment, cancer type, vaccination, and COVID-19 outcomes. Our results indicate that it is plausible that specific diagnoses (e.g., hematologic malignancies, lung cancer) and treatments (e.g., chemotherapy) are associated with worse COVID-19 outcomes. Vaccines significantly reduce the risk of severe COVID-19 outcomes in individuals with cancer and those without, but cancer patients are still at higher risk of breakthrough infections and more severe COVID outcomes even after vaccination. These findings provide actionable insights for risk identification and targeted treatment and prevention strategies.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.19.22274047v1" target="_blank">COVID-19 outcomes by cancer status, type, treatment, and vaccination</a>
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<li><strong>The impact of community asymptomatic rapid antigen testing on COVID-19 hospital admissions: a synthetic control study</strong> -
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Objective: To analyse the impact on hospital admissions for COVID-19 of large-scale, voluntary, public open access rapid testing for SARS-CoV-2 antigen in Liverpool (UK) between 6th November 2020 and 2nd January 2021. Design: Synthetic control analysis comparing hospital admissions for small areas in the intervention population to a group of control areas weighted to be similar in terms of prior COVID-19 hospital admission rates and socio-demographic factors. Intervention: COVID-SMART (Systematic Meaningful Asymptomatic Repeated Testing), a national pilot of large-scale, voluntary rapid antigen testing for people without symptoms of COVID-19 living or working in the City of Liverpool, deployed with the assistance of the British Army from the 6th November 2020 in an unvaccinated population. This pilot informed the UK roll-out of SARS-CoV-2 antigen rapid testing, and similar policies internationally. Main outcome measure: Weekly COVID-19 hospital admissions for neighbourhoods in England. Results: The intensive introduction of COVID-SMART community testing was associated with a 43% (95% confidence interval: 29% to 57%) reduction in COVID-19 hospital admissions in Liverpool compared to control areas for the initial period of intensive testing with military assistance in national lockdown from 6th November to 3rd December 2020. A 25% (11% to 35%) reduction was estimated across the overall intervention period (6th November 2020 to 2nd January 2021), involving fewer testing centres, before England9s national roll-out of community testing, after adjusting for regional differences in Tiers of COVID-19 restrictions from 3rd December 2020 to 2nd January 2021. Conclusions: The world9s first voluntary, city-wide SARS-CoV-2 rapid antigen testing pilot in Liverpool substantially reduced COVID-19 hospital admissions. Large scale asymptomatic rapid testing for SARS-CoV-2 can help reduce transmission and prevent hospital admissions.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.19.22274050v1" target="_blank">The impact of community asymptomatic rapid antigen testing on COVID-19 hospital admissions: a synthetic control study</a>
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<li><strong>Investigating Attitudes, Motivations and Key Influencers for vaccine uptake among late adopters of COVID-19 vaccination in Africa</strong> -
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Background: The rapid development of vaccines in response to the COVID-19 pandemic has provided an effective tool for the management of COVID-19. In Africa COVID-19 vaccine uptake is poor; with 15% vaccine coverage compared to the WHO target of 70%. An important factor has been vaccine hesitancy, understanding late adopters of vaccination can provide insights into the attitudes, motivations and influences that can enhance vaccine uptake. Methods: Between January 4 – February 11, 2022, we conducted a survey among adults presenting for their first dose of a COVID-19 vaccine almost 12-months after the vaccination program began. Vaccines were free and provided at clinics and outreach centers in Harare, Zimbabwe. The questionnaire assessed environmental and individual factors (attitudes, barriers, motivations, key influencers, and information sources) that influenced the decision to present for vaccination. Baseline socio- demographic data and responses to survey questions were summarized using descriptive statistics. Binary logistic regression models were developed to understand factors associated with vaccine confidence. Results: 1016 adults were enrolled into the study, 508 (50%) were female, 126 (12.4%) had HIV co-infection. The median age was 30 years (IQR 22 – 39). Women were more likely to have negative views about the COVID-19 vaccine compared to men (OR 1.51 (95%CI 1.16, 1.97, p=0.002). Women compared to men and older adults (>= 40 years) compared with youth (18-25 years) were more likely to have ‘major concerns’ about vaccines. Most concerns were about safety with 602 (59.3%) concerned about immediate and 520 (51.2%) about long-term health effects of vaccines. People living with HIV (PLWH) were more likely to perceive vaccines as safe (OR 1.71 (95%CI: 1.07, 2.74, p=0.025), effective (1.68 (95%CI: 1.07, 2.64, p=0.026) and to trust regulatory systems for approving vaccines (OR 1.79 (95% CI: 1.11, 2.89, p=0.017) compared to those without HIV. Internet users were less likely to perceive vaccines as safe (OR 0.72 (95% CI: 0.55, 0.95, p=0.021), effective (OR 0.61 (95% CI: 0.47, 0.80, p<0.001) or trust regulatory processes for approving vaccines (OR 0.64 (95% CI: 0.48, 0.85, p=0.002) compared to non-internet users. Social influence was a key factor in the decision to be vaccinated with family members being the primary key influencers for 560 (55.2%) participants. The most important reason for receiving the COVID-19 vaccine today for 715 (70.4%) participants was the protection of individual health. The most trusted source of information regarding the vaccine was the Ministry of Health (79.7%) and the radio, television and social media were the preferred sources for obtaining this information. Social media was a more likely source for youth and those with higher levels of education. Conclusion: Improving vaccine coverage will need targeted communication strategies that address negative perceptions of vaccines and associated safety and effectiveness concerns. Leveraging normative behavior as a social motivator for vaccination will be important as close social networks are key influences of vaccination. Traditional media remains important for health communication in Africa and should be strengthened to counter social media-based misinformation that drives concerns about safety and effectiveness particularly among internet users.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.20.22274081v1" target="_blank">Investigating Attitudes, Motivations and Key Influencers for vaccine uptake among late adopters of COVID-19 vaccination in Africa</a>
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<li><strong>Accuracy of US CDC COVID-19 Forecasting Models</strong> -
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Accurate predictive modeling of pandemics is essential for optimally distributing resources and setting policy. Dozens of case predictions models have been proposed but their accuracy over time and by model type remains unclear. In this study, we analyze all US CDC COVID-19 forecasting models, by first categorizing them and then calculating their mean absolute percent error, both wave-wise and on the complete timeline. We compare their estimates to government- reported case numbers, one another, as well as two baseline models wherein case counts remain static or follow a simple linear trend. The comparison reveals that more than one-third of models fail to outperform a simple static case baseline and two-thirds fail to outperform a simple linear trend forecast. A wave-by-wave comparison of models revealed that no overall modeling approach was superior to others, including ensemble models, and error in modeling has increased over time during the pandemic. This study raises concerns about hosting these models on official public platforms of health organizations including the US-CDC which risks giving them an official imprimatur and further raising concerns if utilized to formulate policy. By offering a universal evaluation method for pandemic forecasting models, we expect this work to serve as the starting point towards the development of more sophisticated models.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.20.22274097v1" target="_blank">Accuracy of US CDC COVID-19 Forecasting Models</a>
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<li><strong>Effectiveness of Primary and Booster COVID-19 mRNA Vaccination against Infection Caused by the SARS-CoV-2 Omicron Variant in People with a Prior SARS-CoV-2 Infection</strong> -
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Importance: The benefit of primary and booster vaccination in people who experienced prior SARS-CoV-2 infection remains unclear. Objective: To estimate the effectiveness of a primary (two-dose) and booster (third dose) vaccination against Omicron infection among previously infection people. Design: Test-negative case-control study. Setting: Yale New Haven Health System facilities serving southern Connecticut communities. Participants: Vaccine eligible people who received SARS-CoV-2 RT-PCR testing between November 1, 2021, and January 31, 2022. Exposure: COVID-19 mRNA primary and booster vaccination. Main Outcomes and Measures: We conducted two analyses, each with an outcome of Omicron BA.1 variant infection (S-gene target failure defined) and each stratified by prior SARS-CoV-2 infection status. We estimated the effectiveness of primary vaccination during the period before and during booster eligibility (14-149 and ≥150 days, respectively, after 2nd dose) and of booster vaccination (≥14 days after booster dose). To test whether booster vaccination reduced the risk of infection beyond that of the primary series, we compared the odds among boosted and booster eligible people. Results: Overall, 10,676 cases and 119,397 controls were included (median age: cases: 35 years, controls: 39 years). Among cases and controls, 6.1% and 7.8% had a prior infection. The effectiveness of primary vaccination 14-149 days after 2nd dose was 36.1% (95% CI, 7.1-56.1%) and 28.5% (95% CI, 20.0-36.2%) for people with and without prior infection, respectively. The effectiveness of booster vaccination was 45.8% (95% CI, 20.0-63.2%) and 56.9% (95% CI, 52.1-61.2%) in people with and without prior infection, respectively. The odds ratio comparing boosted and booster eligible people with prior infection was 0.83 (95% CI, 0.56-1.23), whereas the odds ratio comparing boosted and booster eligible people without prior infection was 0.51 (95% CI, 0.46-0.56). Conclusions and Relevance: Primary vaccination provided significant but limited protection against Omicron BA.1 infection among people with and without prior infection. While booster vaccination was associated with additional protection in people without prior infection, it was not associated with additional protection among people with prior infection. These findings support primary vaccination in people regardless of prior infection status but suggest that infection history should be considered when evaluating the need for booster vaccination.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.19.22274056v2" target="_blank">Effectiveness of Primary and Booster COVID-19 mRNA Vaccination against Infection Caused by the SARS-CoV-2 Omicron Variant in People with a Prior SARS-CoV-2 Infection</a>
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<li><strong>Risk and severity of SARS-CoV-2 reinfections during 2020-2022 in Vojvodina, Serbia: a population-level study</strong> -
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Background: Data on the rate and severity of reinfections with SARS-CoV-2 in real-world settings are scarce and the effects of booster vaccination on reinfection risk are unknown. Methods: In a retrospective cohort study, all SARS- CoV-2 laboratory-confirmed residents of Vojvodina, registered in the database of the Institute of Public Health of Vojvodina, between March 6, 2020 and October 31, 2021, were followed for reinfection >90 days after primary infection. Data were censored at the end of follow-up (January 31, 2022) or death. The risk of reinfection was visualized with Kaplan-Meier plots. To examine whether vaccination protected from reinfection, the subset of Vojvodina residents with primary infection in 2020 (March 6-December 31) were matched (1:2) with controls without reinfection. Results: Until January 31, 2022, 13,792 reinfections were recorded among 251,104 COVID-19 primary infections (5.49%). Most reinfections (86.8%) were recorded in January 2022. Reinfections were mostly mild (99.2%). Hospitalizations were uncommon (1.08% vs. 3.70% in primary infection) and COVID-19 deaths were very rare (n=20, case fatality rate 0.15%). The overall incidence rate of SARS-CoV-2 reinfections was 5.99 (95% CI 5.89-6.09) per 1,000 person-months for those who survived the first three months after primary infection. The reinfection risk was estimated as 0.76% at six months, 1.36% at nine months, 4.96% at 12 months, 16.7% at 15 months, and 18.9% at 18 months. Among 34 second reinfections, none resulted in hospitalization or death. Unvaccinated (OR=1.23; 95%CI=1.14-1.33), incompletely (OR=1.33; 95%CI=1.08-1.64) or completely vaccinated (OR=1.50; 95%CI=1.37-1.63), were modestly more likely to be reinfected compared with those who received a third (booster) vaccine dose. Conclusions: SARS-CoV-2 reinfections were exceptionally uncommon until the end of 2021 but became common with the advent of the Omicron variant. Very few reinfections were severe. A vaccination booster dose may modestly reduce reinfection risk.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.08.22273571v2" target="_blank">Risk and severity of SARS-CoV-2 reinfections during 2020-2022 in Vojvodina, Serbia: a population-level study</a>
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<li><strong>Determinants of SARS-CoV-2 anti-spike antibody levels following BNT162b2 vaccination: cross-sectional analysis of 6,000 SIREN study participants</strong> -
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Background: Understanding immunological responses to SARS-CoV-2 vaccinations is integral to the management of SARS-CoV-2. We aimed to investigate determinants of antibody response to the BNT162b2 vaccine. Methods: A cross- sectional analysis of anti-spike binding antibodies in serum samples from healthcare workers after one or two doses. Post-vaccination interval was restricted to ≥21 days after dose 1, ≥14 days after dose 2. The primary outcome was anti-S titres with explanatory variables dose, previous infection, dosing interval, age, ethnicity, and comorbidities. Multivariable linear regression was also conducted. Results: Participants (n=5,871) included 3,989 post-dose 1, 1,882 post-dose 2. In SARS-CoV-2 infection naive, 99.65% seroconverted after dose 1 and >99.9% seroconverted after dose 2. Geometric mean anti-S titre in the naive cohort was 75.48 Binding Antibody Units/ml after dose 1, 7,049 BAU/ml after dose 2. Anti-S titres were higher in those with previous infection (2,111 BAU/ml post-dose 1, 16,052 BAU/ml post- dose 2), and increased with time between infection and vaccination: 3 months 1,970 (1,506-2,579) vs 9 months; 13,759 (8,097-23,379). Longer dosing intervals increased antibody response post-dose 2: 11-fold higher with a longer interval (>10 weeks) than those with shorter intervals, across all age-groups. Younger participants had higher mean titres (>2.2-fold higher). Multivariable regression modelling corroborated the above associations, and also found higher titres associated with being female or from an ethnic minority but lower titres among immunocompromised participants. Conclusion: The number of antigen exposures and timing between vaccinations plays a significant role in the magnitude of the post-vaccination antibody response, with implications for long-term protection and post-booster antibody responses.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.21.22274025v1" target="_blank">Determinants of SARS-CoV-2 anti- spike antibody levels following BNT162b2 vaccination: cross-sectional analysis of 6,000 SIREN study participants</a>
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<li><strong>Monoclonal Antibodies for Treatment of SARS-CoV-2 Infection During Pregnancy</strong> -
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Abstract IMPORTANCE Monoclonal antibody (mAb) treatment decreases hospitalization and death in high-risk outpatients with mild to moderate COVID-19. However, no studies have evaluated adverse events and effectiveness of mAbs in pregnant persons compared to no mAb treatment. OBJECTIVE To determine the frequency of drug-related adverse events and obstetric-associated safety outcomes after treatment with mAb compared to no mAb treatment, and the association between mAb treatment and a composite of 28-day COVID-19-related hospital admission or emergency department visit, COVID-19-associated delivery, or mortality. DESIGN, SETTING, PARTICIPANTS Propensity-score matched cohort study of persons aged 12 years of age or older with a pregnancy episode and any documented positive SARS-CoV-2 test (polymerase chain reaction or antigen test) in the UPMC health system from April 30, 2021 to January 21, 2022. EXPOSURES Bamalanivmab and etesevimab, casirivimab and imdevimab, or sotrovimab treatment compared to no mAb treatment. MAIN OUTCOMES AND MEASURES Drug-related adverse events, obstetric-associated safety outcomes among persons who delivered, and a risk-adjusted composite of 28-day COVID-19-related hospital admission or ED visit, COVID-19-associated delivery, or mortality. RESULTS Among 944 pregnant persons (median [IQR] age 30 [26, 33] years, White (79.5%, N=750), median [IQR] Charlson Comorbidity Index Score 0 (0,0)), 552 persons received mAb treatment (58%). Median gestational age at COVID-19 diagnosis or treatment was 179 days (IQR: 123, 227), and most persons received sotrovimab (69%, N=382). Of those with known vaccination status, 178 (62%) were fully vaccinated. Drug-related adverse events were uncommon (N=8, 1.4%), and there were no differences in any obstetric-associated outcome among 276 persons who delivered. After propensity score matching, the frequency of the composite 28-day COVID-19-associated outcome was 4.0 per 100 persons (95% CI 1.9, 6.2) in mAb-treated compared to 3.7 per 100 persons (95% CI 1.7, 5.8) in non-treated controls (risk difference = 0.31 per 100 persons [95% CI -2.6, 3.3). There were no deaths among mAb-treated patients compared to 1 death in the non-treated controls (p = 0.24). There were more non-COVID-19-related hospital admissions in the mAb- treated persons (risk difference 2.8 per 100 persons (95% CI 1.1, 4.5)). CONCLUSIONS AND RELEVANCE In pregnant persons with mild to moderate COVID-19, adverse events after mAb treatment were mild and rare. There was no difference in obstetric-associated safety outcomes between mAb treatment and no treatment among persons who delivered. MAb treatment was associated with similar 28-day COVID-19-associated outcomes and more non-COVID-19-related hospital admissions compared to no mAb treatment.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.20.22274090v1" target="_blank">Monoclonal Antibodies for Treatment of SARS-CoV-2 Infection During Pregnancy</a>
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<li><strong>Elevated plasma Complement Factor H Regulating Protein 5 is associated with venous thromboembolism and COVID-19 severity</strong> -
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Venous thromboembolism (VTE), comprising both deep vein thrombosis (DVT) and pulmonary embolism (PE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. We used multiplex proteomics profiling to screen plasma from patients with suspected acute VTE, and a case-control study of patients followed up after ending anticoagulant treatment for a first VTE. With replication in 5 independent studies, together totalling 1137 patients and 1272 controls, we identify Complement Factor H Related Protein (CFHR5), a regulator of the alternative pathway of complement activation, as a novel VTE associated plasma biomarker. Using GWAS analysis of 2967 individuals we identified a genome-wide significant pQTL signal on chr1q31.3 associated with CFHR5 levels. We showed that higher CFHR5 levels are associated with increased thrombin generation in patient plasma and that recombinant CFHR5 enhances platelet activation in vitro. Thrombotic complications are a frequent feature of COVID-19; in hospitalised patients we found CFHR5 levels at baseline were associated with short-time prognosis of disease severity, defined as maximum level of respiratory support needed during hospital stay. Our results indicate a clinically important role for regulation of the alternative pathway of complement activation in the pathogenesis of VTE and pulmonary complications in acute COVID-19. Thus, CFHR5 is a potential diagnostic and/or risk predictive plasma biomarker reflecting underlying pathology in VTE and acute COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.20.22274046v1" target="_blank">Elevated plasma Complement Factor H Regulating Protein 5 is associated with venous thromboembolism and COVID-19 severity</a>
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<li><strong>Immune response to 2-dose BNT162b2 vaccination and risk of SARS-CoV-2 breakthrough infection: The Shieldvacc-2 study</strong> -
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It is uncertain to which extent antibody and T-cell responses after vaccination against SARS-CoV-2 are associated with reduced risk of breakthrough infection and whether their measurement enhances risk prediction. We conducted a phase-4 open-label clinical trial in the pre-omicron era, enrolling 2,760 individuals aged ≥16 years 35±8 days after having received the second dose of BNT162b2 (baseline 15-21 May 2021). Over a median 5.9-month of follow-up, we identified incident SARS-CoV-2 breakthrough infections using weekly antigen tests, a confirmatory PCR test, and/or serological evidence for incident infection. We quantified relative risks adjusted for age, sex, and prior SARS-CoV-2 infection for different immunological parameters and assessed improvements in risk discrimination. In contrast to the T-cell response, higher plasma levels of binding antibodies and antibodies in a surrogate neutralization assay were associated with reduced risk of breakthrough infection. Furthermore, assessment of anti-spike IgG levels enhanced prediction of breakthrough infection and may therefore be a suitable measurable correlate of protection in practice.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.19.22273872v1" target="_blank">Immune response to 2-dose BNT162b2 vaccination and risk of SARS-CoV-2 breakthrough infection: The Shieldvacc-2 study</a>
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<li><strong>Genetic diversity and spatiotemporal distribution of SARS-CoV-2 alpha variant in India</strong> -
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After the spill to humans, in the timeline of SARS-CoV-2, several positively selected variants have emerged. A phylogeographic study on these variants can reveal their spatial and temporal distribution. In December 2020, the alpha variant of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which has been designated as a variant of concern (VOC) by WHO, was discovered in the southeastern United Kingdom (UK). Slowly, it expanded across India, with a considerable number of cases, particularly in North India. The study focuses on determining the prevalence and expansion of the alpha variants in various parts of India. The genetic diversity estimation helped us understand various evolutionary forces that have shaped the spatial distribution of this variant during the peak. Overall, our study paves the way to understand the evolution and expansion of a virus variant.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.20.22274084v1" target="_blank">Genetic diversity and spatiotemporal distribution of SARS-CoV-2 alpha variant in India</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Performance Evaluation of the Bio-Self™ COVID-19 Antigen Home Test</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Device: Bio-Self COVID-19 Antigen Home Test; Device: Standard of Care COVID-19 Test; Diagnostic Test: RT-PCR Test<br/><b>Sponsors</b>: BioTeke USA, LLC; CSSi Life Sciences<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Functional Capacity in Patients Post Mild COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: Cardiopulmonary exercise test (CPET)<br/><b>Sponsor</b>: Rambam Health Care Campus<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>Circuit Training Program in Post COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Circuit Training Exercise Program; Other: Aerobic Training Exercise Program<br/><b>Sponsor</b>: Riphah International University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effect of Home-based Rehabilitation Program After COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Add-on telerehabilitation and home-based rehabilitation; Behavioral: Home-based rehabilitation alone<br/><b>Sponsor</b>: <br/>
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National Taiwan University Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluate the Safety and Immunogenicity of Ad5 COVID-19 Vaccines for Booster Use in Children Aged 6-17 Years.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: 1 Nebulized inhalation for booster groups; Biological: 2 Nebulized inhalation for booster groups; Biological: 3 Nebulized inhalation for booster groups; Biological: 4 Nebulized inhalation for booster groups; Biological: 5 Intramuscular injection for booster groups; Biological: 6 Intramuscular injection for booster groups; Biological: 7 Intramuscular injection for booster groups; Biological: 8 Intramuscular injection for booster groups; Biological: 9 Intramuscular injection for booster groups; Biological: 10 Intramuscular injection for booster groups; Biological: 11 Nebulized inhalation for booster groups; Biological: 12 Nebulized inhalation for booster groups; Biological: 13 Nebulized inhalation for booster groups; Biological: 14 Nebulized inhalation for booster groups; Biological: 15 Intramuscular injection for booster groups; Biological: 16 Intramuscular injection for booster groups; Biological: 17 Intramuscular injection for booster groups; Biological: 18 Intramuscular injection for booster groups; Biological: 19 Intramuscular injection for booster groups; Biological: 20 Intramuscular injection for booster groups; Biological: 21 Nebulized inhalation for primary groups; Biological: 22 Nebulized inhalation for primary groups; Biological: 23 Nebulized inhalation for primary groups; Biological: 24 Nebulized inhalation for primary groups<br/><b>Sponsor</b>: <br/>
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Seventh Medical Center of PLA General Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Non-inferiority Trial on Treatments in Early COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Sotrovimab; Drug: Tixagevimab Cilgavimab; Drug: Nirmatrelvir Ritonavir<br/><b>Sponsors</b>: Azienda Ospedaliera Universitaria Integrata Verona; Agenzia Italiana del Farmaco; Azienda Sanitaria-Universitaria Integrata di Udine<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>Immunogenicity and Safety Study of Recombinant Two-Component COVID-19 Vaccine (CHO Cell)(ReCOV)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant two-component COVID-19 vaccine (CHO cell); Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsor</b>: Jiangsu Rec- Biotechnology Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity，Safety and Cross - Immune Response With the Strains of the Booster Immunization Using an Inactivated COVID-19 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Inactivated COVID-19 Vaccine<br/><b>Sponsor</b>: Sinovac Research and Development 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 Immunogenicity and Safety of Two Recombinant Protein COVID-19 Vaccines in Population Aged ≥18 Years as Booster Vaccines</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: SCTV01C; Biological: SCTV01E; Biological: Sinopharm inactivated COVID-19 vaccine; Biological: mRNA-1273<br/><b>Sponsor</b>: Sinocelltech Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine in Population Aged ≥18 Years</strong> - <b>Conditions</b>: SARS-CoV-2 Infection; COVID-19<br/><b>Interventions</b>: Biological: SCTV01E; Biological: Comirnaty<br/><b>Sponsor</b>: Sinocelltech Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of JT001 (VV116) Compared With Paxlovid</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: JT001; Drug: Paxlovid<br/><b>Sponsor</b>: <br/>
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Vigonvita Life Sciences<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Aerobic Exercise and Covid-19 Survivors With Post-Intensive Care Syndrome (Pics)</strong> - <b>Conditions</b>: COVID-19; Post Intensive Care Syndrome<br/><b>Interventions</b>: <br/>
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Other: Aerobic Exercise Training; Other: Home Plan<br/><b>Sponsor</b>: Riphah International University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Interleukine 6 (IL6) Assay for Predicting Failure of Spontaneous Breathing in Patients With COVID-19 Acute Respiratory Distress Syndrome</strong> - <b>Condition</b>: COVID-19 Acute Respiratory Distress Syndrome<br/><b>Interventions</b>: <br/>
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Biological: IL6 assessment; Biological: CRP and PCT assessment<br/><b>Sponsor</b>: <br/>
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Centre Hospitalier Henri Duffaut - Avignon<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 Single Arm Phase-IV Study to Determine Reactogenicity and Immunogenicity of Delayed COVID-19 Vaccine Schedule in Children</strong> - <b>Conditions</b>: Vaccine Reaction; COVID-19; Children, Only<br/><b>Intervention</b>: <br/>
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Biological: BNT162b2 Pfizer-BioNTech/Comirnaty<br/><b>Sponsors</b>: KK Women’s and Children’s Hospital; Duke- NUS Graduate 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>Pilot Trial on Immunosuppression Modulation to Increase SARS-CoV-2 Vaccine Response in Kidney Transplant Recipients</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Immunosuppression reduction; Other: No immunosuppression reduction<br/><b>Sponsor</b>: Medical University of Vienna<br/><b>Active, not recruiting</b></p></li>
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<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>ER Stress in COVID-19 and Parkinson’s Disease: In Vitro and In Silico Evidences</strong> - The outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signifies a serious worldwide concern to public health. Both transcriptome and proteome of SARS-CoV-2-infected cells synergize the progression of infection in host, which may exacerbate symptoms and/or progression of other chronic diseases such as Parkinson’s disease (PD). Oxidative stress is a well-known cause of endoplasmic reticulum (ER) stress observed in both SARS-CoV-2 and PD. In the current…</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>Combined administration of inhaled DNase, baricitinib and tocilizumab as rescue treatment in COVID-19 patients with severe respiratory failure</strong> - Aiming to reduce mortality in COVID-19 with severe respiratory failure (PaO2/FiO2 < 100 mmHg), we administered a combined rescue treatment (COMBI) on top of standard-of-care (SOC: dexamethasone/heparin) consisted of inhaled DNase to dissolve thrombogenic neutrophil extracellular traps, plus agents against cytokine-mediated hyperinflammation, namely anti-IL-6-receptor tocilizumab and JAK1/2 inhibitor baricitinib. COMBI group (n = 22) was compared with similar groups that had received SOC alone (n…</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>Water Extract of the Chaga Medicinal Mushroom, Inonotus obliquus (Agaricomycetes), Inhibits SARS-CoV-2 Replication in Vero E6 and Vero Cell Culture Experiments</strong> - The antiviral properties of water extracts from pharmaceutical raw materials of the chaga mushroom, Inonotus obliquus, were studied against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). All studies with infectious materials were carried out in an isolated virological laboratory of the State Research Center of Virology and Biotechnology Vector of Rospotrebnadzor, which has a sanitary and epidemiological conclusion for the right to work with pathogenic biological agents of I-II…</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>Secretory autophagy maintains proteostasis upon lysosome inhibition</strong> - The endolysosome system plays central roles in both autophagic degradation and secretory pathways, including the release of extracellular vesicles and particles (EVPs). Although previous work reveals important interconnections between autophagy and EVP-mediated secretion, our understanding of these secretory events during endolysosome inhibition remains incomplete. Here, we delineate a secretory autophagy pathway upregulated in response to endolysosomal inhibition, which mediates EVP-associated…</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>Metronidazole, acyclovir and tetrahydrobiopterin may be promising to treat COVID-19 patients, through interaction with interleukin-12</strong> - COVID-19 patients have shown overexpressed serum levels of several pro-inflammatory cytokines, leading to a high mortality rate due to numerous complications. Also, previous studies demonstrated that the metronidazole (MTZ) administration reduced pro-inflammatory cytokines and improved the treatment outcomes for inflammatory disorders. However, the effect and mechanism of action of MTZ on cytokines have not been studied yet. Thus, the current study aimed to identify anti-cytokine therapeutics…</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 Needle-free Microjet Drug Injector Using Er:YAG LASER: A Completely New Concept of Trans-Dermal Drug Delivery System</strong> - CONCLUSION: This study showed that a novel needle-free microjet injector using Er:YAG LASER can introduce beneficial, liquid, aesthetic drugs into the papillary dermal layer (depth of 300um) with minimal epidermal damage. This article is protected by copyright. All rights reserved.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety Learning in Anxiety, Pavlovian Conditioned Inhibition and COVID Concerns</strong> - Experimental studies of fear conditioning have identified the effectiveness of safety signals in inhibiting fear and maintaining fear-motivated behaviors. In fear conditioning procedures, the presence of safety signals means that the otherwise expected feared outcome will not now occur. Differences in the inhibitory learning processes needed to learn safety are being identified in various psychological and psychiatric conditions. However, despite early theoretical interest, the role of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Kinase Inhibitors as Potential Therapeutic Agents in the Treatment of COVID-19</strong> - Corona virus is quickly spreading around the world. The goal of viral management is to disrupt the virus’s life cycle, minimize lung damage, and alleviate severe symptoms. Numerous strategies have been used, including repurposing existing antivirals or drugs used in previous viral outbreaks. One such strategy is to repurpose FDA-approved kinase inhibitors that are potential chemotherapeutic agents and have demonstrated antiviral activity against a variety of viruses, including MERS, SARS-CoV-1,…</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>Methylene blue in management of COVID19</strong> - CONCLUSION: No statistically significant difference in outcome measures like Spo2, duration of hospital stay or inflammatory markers. A general trend of fall in inflammatory markers and O2 requirements in group receiving methylene blue but this difference was not consistantly statistically significant.</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 Profiling in COVID-19 Patients with Different Severities by Using Spike Variant Protein Microarrays</strong> - The disease progression of COVID-19 varies from mild to severe, even death. However, the link between COVID-19 severities and humoral immune specificities is not clear. Here, we developed a multiplexed spike variant protein microarray (SVPM) and utilized it for quantifying neutralizing activity, drug screening, and profiling humoral immunity. First, we demonstrated the competition between antispike antibody and ACE2 on SVPM for measuring the neutralizing activity against multiple spike variants….</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>Porcine Epidemic Diarrhea Virus nsp7 Inhibits Interferon-Induced JAK-STAT Signaling through Sequestering the Interaction between KPNA1 and STAT1</strong> - Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic enteric coronavirus that causes high mortality in piglets. Interferon (IFN) responses are the primary defense mechanism against viral infection; however, viruses always evolve elaborate strategies to antagonize the antiviral action of IFN. Previous study showed that PEDV nonstructural protein 7 (nsp7), a component of the viral replicase polyprotein, can antagonize ploy(I:C)-induced type I IFN production. Here, we found that PEDV nsp7…</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>Does government intervention affect CO<sub>2</sub> emission reduction effect of producer service agglomeration? Empirical analysis based on spatial Durbin model and dynamic threshold model</strong> - Achieving carbon peak and carbon neutrality is an inherent requirement for countries to promote green recovery and transformation of the global economy after the COVID-19 pandemic. As “a smoke-free industry,” producer services agglomeration (PSA) may have significant impacts on CO(2) emission reduction. Therefore, based on the nightlight data to calculate the CO(2) emissions of 268 cities in China from 2005 to 2017, this study deeply explores the impact and transmission mechanism of PSA on CO(2)…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Famotidine activates the vagus nerve inflammatory reflex to attenuate cytokine storm</strong> - Background. Severe COVID-19 is characterized by pro-inflammatory cytokine release syndrome (cytokine storm) which causes high morbidity and mortality. Recent observational and clinical studies suggest famotidine, a histamine 2 receptor (H2R) antagonist widely used to treat gastroesophageal reflux disease , attenuates the clinical course of COVID-19. Because evidence is lacking for a direct antiviral activity of famotidine, a proposed mechanism of action is blocking the effects of histamine…</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>Receptor binding domain of SARS-CoV-2 is a functional αv-integrin agonist</strong> - Among the novel mutations distinguishing SARS-CoV-2 from similar respiratory coronaviruses is a K403R substitution in the receptor-binding domain (RBD) of the viral spike (S) protein within its S1 region. This amino acid substitution occurs near the angiotensin-converting enzyme 2 (ACE2)-binding interface and gives rise to a canonical RGD adhesion motif that is often found in native extracellular matrix proteins, including fibronectin. In the present study, the ability of recombinant S1-RBD to…</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 Roles of APOBEC-mediated RNA Editing in SARS-CoV-2 Mutations, Replication and Fitness</strong> - During COVID-19 pandemic, mutations of SARS-CoV-2 produce new strains that can be more infectious or evade vaccines. Viral RNA mutations can arise from misincorporation by RNA-polymerases and modification by host factors. Analysis of SARS-CoV-2 sequence from patients showed a strong bias toward C-to-U mutation, suggesting a potential mutational role by host APOBEC cytosine deaminases that possess broad anti-viral activity. We report the first experimental evidence demonstrating that APOBEC3A,…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SYSTEM FOR MONITORING COVID-19 PATIENTS USING A VIRTUAL TELEPRESENCE ROBOT</strong> - Attached Separately - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN356991740">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MASCARA FACIAL PARA LA INHALACION DE SUBSTANCIAS NEBULIZADAS, CON SISTEMA DE ASPIRACION INCORPORADO</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=ES355538276">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MACHINE LEARNING TECHNIQUE TO ANALYZE THE WORK PRESSURE OF PARAMEDICAL STAFF DURING COVID 19</strong> - Machine learning technique to analyse the work pressure of paramedical staff during covid 19 is the proposed invention that focuses on identifying the stress levels of paramedical staff. The invention focuses on analysing the level of stress that is induced on the paramedical staff especially during pandemic. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=IN353347401">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种吡咯烷酮中间体的合成方法</strong> - 本发明涉及药物中间体合成技术领域，尤其是一种吡咯烷酮中间体的合成方法，包括以下步骤：化合物1溶液和有机锂试剂溶液泵入连续反应器，反应生成锂氢交换中间体，再泵入卤代乙腈与中间态发生反应生成化合物2；化合物2用固定床反应装置内进行氢化反应，后处理得到化合物3；将化合物3的溶液和氨水溶液泵入连续反应器生成酰胺化合物4；化合物4和脱水剂使用恒流泵泵入连续化反应器，生成化合物5或其氨基上有保护基的中间体；应用串联连续反应技术，将传统釜式数步反应改进为连续化工艺，解决了传统釜式反应的放大效应问题，降低了含金属试剂以及高压氢化等危险反应的安全风险进而避免了超低温反应釜和高压氢化釜等设备，提高了生产效率。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN357081864">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一株表达新冠病毒S1蛋白单克隆抗体杂交瘤细胞系及中和活性抗体</strong> - 本发明属于细胞工程与免疫学领域，具体涉及一株表达新冠病毒S1蛋白单克隆抗体杂交瘤细胞系及中和活性抗体。本发明筛选获得一株能高效稳定分泌表达新冠病毒S1蛋白单克隆抗体的杂交瘤细胞系以及其分泌的新冠病毒S1蛋白单克隆抗体；利用普通细胞培养皿培养本发明的重组杂交瘤细胞系，产量可达10mg/L，且纯度能达90%以上；本发明的单抗具有高中和活性，单抗浓度为0.00103μg/mL时即可抑制50％以上新冠假病毒活性，是目前所报告的新冠单抗中和活性最佳的。本发明提供的杂交瘤细胞系或单克隆抗体在新冠病毒的血清学检测、制备新冠病毒感染的试剂或药物及制备新冠病毒抗原或抗体检测的试剂中具有重要的应用价值。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN357081918">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>基于SARS-CoV-2的S蛋白的疫苗及其用途</strong> - 本公开提供了基于SARS‑CoV‑2的S蛋白的疫苗及其用途，并具体涉及重组SARS‑CoV‑2刺突蛋白(S蛋白)及编码其的mRNA和DNA。本公开还涉及包含编码重组S蛋白的DNA序列的重组质粒。本公开的重组质粒经转录得到mRNA，其包含SEQ ID NO.12所示的序列。本公开进一步涉及包含前述mRNA的mRNA‑载体颗粒例如脂质纳米颗粒(LNP)和组合物例如疫苗组合物。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN356073372">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>CBD Covid 19 Protection</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU353359094">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种双价可电离脂质化合物、组合物及其应用</strong> - 本发明涉及核酸药物递送技术领域，特别是关于一种双价可电离脂质化合物、组合物及其应用。本发明提供多种可以递送核酸药物的可电离阳离子脂质，具备较强的可设计性、可生物降解性及高效的体内外转染效率，由其组成的脂质纳米递送系统用于递送mRNA，在细胞水平上，优于目前上市的产品，并且在动物水平也具有良好的递送效率，可以作为核酸药物的递送新的方法，促进核酸药物的发展。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN356073405">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种双价可电离脂质化合物、组合物及其应用</strong> - 本发明涉及核酸药物递送技术领域，特别是关于一种双价可电离脂质化合物、组合物及其应用。本发明提供多种可以递送核酸药物的可电离阳离子脂质，具备较强的可设计性、可生物降解性及高效的体内外转染效率，由其组成的脂质纳米递送系统用于递送mRNA，在细胞水平上，优于目前上市的产品，并且在动物水平也具有良好的递送效率，可以作为核酸药物的递送新的方法，促进核酸药物的发展。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN356073406">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>新冠肺炎CT图像分割方法及终端设备</strong> - 本发明公开了一种新冠肺炎CT图像分割方法及终端设备，方法包括获取待分割新冠肺炎CT图像；将该图像输入至训练好的分割模型中，得到新冠肺炎病灶区域的图像；其中分割模型包括依次连接的多个下采样模块和下采样模块对应的上采样模块；每个采样模块均包括依次连接的第一提取单元和第二提取单元；上述两个提取单元的卷积模块均为结构重参数化卷积模块。本发明的结构重参数化卷积模块为训练时使用多分支结构，加强模型表达能力，推理时使用单路结构，加快推理速度，快速得出诊断结果。同时，为从不同尺度特征图中学习分层表示，加强模型对图像边缘信息提取，并使梯度更快回流，上采样每一侧输出都连接混合损失函数，实现图像的像素级分割。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN356073393">link</a></p></li>
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