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<title>22 May, 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>Shared genetic etiology and causality between COVID-19 and venous thromboembolism: evidence from genome-wide cross trait analysis and bi-directional Mendelian randomization study</strong> -
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Venous thromboembolism (VTE) occurs in up to one third patients with COVID-19. VTE and COVID-19 may share a common genetic architecture in etiology, which has not been comprehensively investigated. In this study, we leveraged summary-level data from the latest COVID‐19 host genetics consortium and UK Biobank to study the genetic commonality between COVID-19 traits and VTE. We found a positive genetic correlation between COVID-19 hospitalization and VTE (rg = 0.2320, P-value= 0.0092). The cross-trait analysis identified shared genetic loci between VTE and COVID-19 traits, including 8 for severe COVID-19, 11 for COVID-19 hospitalization, and 7 for SARS-CoV-2 infection. We identified seven novel mapped genes (LINC00970, TSPAN15, ADAMTS13, F5, DNAJB4, SLC39A8 and OBSCN) that were enriched for expression in the lung tissue, and in coagulation and immune related pathways. Eight genetic loci were found to share causal variants between COVID-19 and VTE, which are localized in the ABO, ADAMTS13 and FUT2 gene regions. Bi-directional Mendelian randomization analysis did not suggest a causal relationship between VTE and COVID-19 traits. Our study advances the understanding of shared genetic etiology of COVID-19 and VTE at the molecular and functional levels.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.21.22275413v1" target="_blank">Shared genetic etiology and causality between COVID-19 and venous thromboembolism: evidence from genome-wide cross trait analysis and bi-directional Mendelian randomization study</a>
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<li><strong>The negative impact of COVID-19 on working memory revealed using a rapid online quiz</strong> -
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Although coronavirus disease 2019 (COVID-19) affects the respiratory system, it can also have neurological consequences leading to cognitive deficits such as memory problems. The aim of our study was to assess the impact of COVID-19 on working memory function. We developed and implemented an online anonymous survey with a working memory quiz incorporating aspects of gamification to engage participants. 5428 participants successfully completed the survey and memory quiz between 8 th December 2020 and 5 th July 2021 (68.6% non-COVID-19 and 31.4% COVID-19). Most participants (93.3%) completed the survey and memory quiz relatively rapidly (mean time of 8.84 minutes). Categorical regression was used to assess the contribution of COVID status, age, time post-COVID (number of months elapsed since having had COVID), symptoms, ongoing symptoms and gender, followed by non-parametric statistics. A principal component analysis explored the relationship between subjective ratings and objective memory scores. The objective memory scores were significantly correlated with participants’ own assessment of their cognitive function. The factors significantly affecting memory scores were COVID status, age, time post-COVID and ongoing symptoms. Our main finding was a significant reduction in memory scores in all COVID groups (self-reported, positive-tested and hospitalised) compared to the non-COVID group. Memory scores for all COVID groups combined were significantly reduced compared to the non-COVID group in every age category 25 years and over, but not for the youngest age category (18-24 years old). We found that memory scores gradually increased over a period of 17 months post-COVID-19. However, those with ongoing COVID-19 symptoms continued to show a reduction in memory scores. Our findings demonstrate that COVID-19 negatively impacts working memory function, but only in adults aged 25 years and over. Moreover, our results suggest that working memory deficits with COVID-19 can recover over time, although impairments may persist in those with ongoing symptoms.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.20.22275380v1" target="_blank">The negative impact of COVID-19 on working memory revealed using a rapid online quiz</a>
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<li><strong>Serial infection with SARS-CoV-2 Omicron BA.1 and BA.2 following three-dose COVID-19 vaccination</strong> -
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SARS-CoV-2 Omicron infections are common among individuals who are vaccinated or have recovered from prior variant infection, but few reports have documented serial Omicron infections. We characterized SARS-CoV-2 humoral responses in a healthy young person who acquired laboratory-confirmed Omicron BA.1.15 ten weeks after a third dose of BNT162b2, and BA.2 thirteen weeks later. Responses were compared to those of 124 COVID-19 naive vaccinees. One month after the second and third vaccine doses, the participant9s wild-type and BA.1-specific IgG, ACE2 competition and virus neutralization activities were average for a COVID-19 naive triple-vaccinated individual. BA.1 infection boosted the participant9s responses to the cohort >95th percentile, but even this strong “hybrid” immunity failed to protect against BA.2. Moreover, reinfection increased BA.1 and BA.2-specific responses only modestly. Results illustrate the risk of Omicron infection in fully vaccinated individuals and highlight the importance of personal and public health measures as vaccine-induced immune responses wane.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.19.22275026v1" target="_blank">Serial infection with SARS-CoV-2 Omicron BA.1 and BA.2 following three-dose COVID-19 vaccination</a>
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<li><strong>Bias-adjusted predictions of county-level vaccination coverage from the COVID-19 Trends and Impact Survey</strong> -
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The potential for bias in non-representative, large-scale, low-cost survey data can limit their utility for population health measurement and public health decision-making. We developed a multi-step regression framework to bias- adjust vaccination coverage predictions from the large-scale US COVID-19 Trends and Impact Survey that included post- stratification to the American Community Survey and secondary normalization to an unbiased reference indicator. As a case study, we applied this framework to generate county-level predictions of long-run vaccination coverage among children ages 5 to 11 years. Our vaccination coverage predictions suggest a low ceiling on long-term national coverage (46%), detect substantial geographic heterogeneity (ranging from 11% to 91% across counties in the US), and highlight widespread disparities in the pace of scale-up in the three months following Emergency Use Authorization of COVID-19 vaccination for 5 to 11 year-olds. Generally, our analysis demonstrates an approach to leverage differing strengths of multiple sources of information to produce estimates on the time-scale and geographic-scale necessary for proactive decision-making. The utility of large-scale, low-cost survey data for improving population health measurement is amplified when these data are combined with other representative sources of data.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.18.22275217v1" target="_blank">Bias-adjusted predictions of county-level vaccination coverage from the COVID-19 Trends and Impact Survey</a>
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<li><strong>Early experience with modified dose nirmatrelvir/ritonavir in dialysis patients with coronavirus disease-2019</strong> -
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Introduction: Nirmatrelvir/Ritonavir was approved for use in high risk outpatients with coronavirus disease (COVID-19). However, patients with severe chronic kidney disease, including patients on dialysis, were excluded from the phase 3 trial, and currently the drug is not recommended below a glomerular filtration rate of 30 ml/min/1.73m2 . Based on available pharmacological data and principles, we developed a modified dose which was lower, and administered at longer intervals.We administered nirmatrelvir/ritonavir as 300/100 mg on day one, followed by 150/100 mg daily from day two to day five. In this case series, we report the initial experience with this modified dose regimen. Methods: This is a retrospective chart review, conducted after obtaining institutional board approval. Demographic and outcome data was abstracted from the electronic medical record for dialysis patients who developed COVID-19 during the period of study and received nirmatrelvir/ritonavir. The principal outcomes we describe are symptom resolution, and safety data with the modified dose regimen in the dialysis patients. Results: 19 patients developed COVID-19 during the period of study of whom 15 received nirmatrelvir/ritonavir. 47% of them were female and 67% had diabetes. Most patients had received three doses of the vaccine (80%) while 13% were unvaccinated. Potential drug interactions concerns were common (median 2 drugs per patient) with amlodipine and atorvastatin being the commonest drugs requiring dose modification. Nirmatrelvir/ritonavir use was associated with symptom resolution in all patients, and was well tolerated. One patient had a rebound of symptoms, which improved in 2 more days. There were no COVID-19 related hospitalizations or deaths in any of the patients. Conclusion: In this case series of 15 hemodialysis patients with COVID-19, a modified dose of nirmatrelvir/ritonavir use, with pharmacist support for drug interaction management, was associated with symptom resolution, and was well tolerated with no serious adverse effects.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.18.22275234v1" target="_blank">Early experience with modified dose nirmatrelvir/ritonavir in dialysis patients with coronavirus disease-2019</a>
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<li><strong>BNT162b2 induces robust cross-variant SARS-CoV-2 immunity in children</strong> -
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Currently available mRNA vaccines are extremely safe and effective to prevent severe SARS-CoV-2 infections. However, the emergence of novel variants of concerns has highlighted the importance of high population-based vaccine rates to effectively suppress viral transmission and breakthrough infections. While initially left out from vaccine efforts, children have become one of the most affected age groups and are key targets to stop community and household spread. Antibodies are central for vaccine induced protection and emerging data points to the importance of additional Fc effector functions like opsononophagocytosis or cytotoxicity, particularly in the context of variants of concern that escape neutralizing antibodies. Here, we observed delayed induction and reduced magnitude of vaccine induced antibody titers in children 5-11 years receiving two doses of the age recommended 10 μg dose of the Pfizer SARS-CoV-2 BNT162b2 vaccine compared to adolescents (12-15 years) or adults receiving the 30 μg dose. Conversely, children mounted equivalent or more robust neutralization and opsonophagocytic functions at peak immunogenicity, pointing to a qualitatively more robust humoral functional response in children. Moreover, broad cross-variants of concern responses were observed across children, with enhanced IgM and parallel IgG cross-reactivity to variants of concern (VOCs) in children compared to adults. Collectively, these data argue that despite the lower magnitude of the BNT162b2 induced antibody response in children, vaccine induced immunity in children target VOCs broadly and exhibit enhanced functionality that may contribute to attenuation of disease.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.18.22275283v1" target="_blank">BNT162b2 induces robust cross-variant SARS-CoV-2 immunity in children</a>
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<li><strong>Exploring barriers and facilitators to physical activity during the COVID-19 pandemic: a qualitative study</strong> -
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Objectives Quantitative data show that physical activity (PA) reduced during the COVID-19 pandemic, with differential impacts across demographic groups. Qualitative research is limited, so reasons for this have not been explored in-depth. This study aimed to understand barriers and facilitators to PA during the pandemic, focusing on groups more likely to have been affected by restrictions, and to map these onto the Capability, Opportunity, Motivation Model of Behaviour (COM-B). Design Semi-structured qualitative interview study. Methods One-to-one telephone/videocall interviews were conducted with younger (aged 18-24) and older adults (aged 70+), those with long-term physical health conditions or mental health conditions, and parents of young children, probing about their experiences of PA. Barriers and facilitators were identified using reflexive thematic analysis, and themes were mapped onto COM-B dimensions. Results 116 participants were included (18-93 years old, 61% female, 71% White British). Key themes were the importance of the outdoor environment, impact of COVID-19 restrictions, fear of contracting COVID-19, and level of engagement with home exercise. Caring responsibilities and conflicting priorities were a barrier. PA as a method of socialising, establishing new routines, and the importance of PA for protecting mental health were motivators. Most themes mapped onto the physical opportunity (environmental factors) and reflective motivation (evaluations and plans) COM-B domains. Conclusions Future interventions should increase physical opportunity and reflective motivation for PA during pandemics, to avoid further negative health outcomes following periods of lockdown. Strategies could include tailoring PA guidance depending on location and giving education on the health benefits of PA.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.18.22275240v1" target="_blank">Exploring barriers and facilitators to physical activity during the COVID-19 pandemic: a qualitative study</a>
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<li><strong>Targeting SARS-CoV-2 superspreading infections could dramatically improve the efficiency of epidemic control strategies in resource-limited contexts</strong> -
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Background: Superspreading infections play an important role in the SARS-CoV-2 pandemic. Superspreading is caused primarily by heterogeneity in social contact rates, and therefore represents an opportunity for targeting surveillance and control via consideration of social network topologies, particularly in resource-limited settings. Yet, it remains unclear how to implement such surveillance and control, especially when network data is unavailable. Methods: We evaluated the efficiency of a testing strategy that targeted potential superspreading individuals based on their degree centrality on a social network compared to a random testing strategy in the context of low testing capacity. We simulated SARS-CoV-2 dynamics on two contact networks from rural Madagascar and measured the epidemic duration, infection burden, and tests needed to end the epidemics. In addition, we examined the robustness of this approach when individuals9 true degree centralities were unknown and were instead estimated via readily-available socio- demographic variables. Findings: Targeted testing of potential superspreaders reduced the infection burden by 40-63% at low testing capacities, while requiring between 45-78% fewer tests compared to random testing. Further, targeted testing remained more efficient when the true network topology was unknown and prioritization was based on socio demographic characteristics. Interpretation: Incorporating social network topology into epidemic control strategies is an effective public health strategy for health systems suffering from low testing capacity and can be implemented via socio- demographic proxies when social networks are unknown.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.20.22275359v1" target="_blank">Targeting SARS-CoV-2 superspreading infections could dramatically improve the efficiency of epidemic control strategies in resource-limited contexts</a>
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<li><strong>Building Medical Rehabilitation System with Safety and Without Interruption for the Patients with Coronavirus Disease 2019 Using the Functional Resonance Analysis Method (FRAM)</strong> -
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Introduction Coronavirus disease 2019 (COVID-19) is an indication for rehabilitation medicine, especially in severe cases. However, there has been no systematic development of a safe and uninterrupted provision system of medical rehabilitation for patients and medical staff with COVID-19. The Functional Resonance Analysis method (FRAM) is used to analyze performance in a socio-technical system. In FRAM, each Function is viewed from six aspects: Input, Output, Preconditions, Resources, Control, and Time. These aspects define each Function and reveal connections between Functions. In this study, we analyzed a safe and uninterrupted provision system for medical rehabilitation for severely ill COVID-19 patients using FRAM to prepare for possible problems in the future. Methods The subject of analysis was the provision system for medical rehabilitation for patients with COVID-19 at the Rehabilitation Center of Hyogo College of Medicine College Hospital. The analysis was conducted by dividing a 21-month rehabilitation period beginning April 2020 into 5 phases, and analyzing each phase using FRAM. The first four phases were retrospective analyses, and the fifth phase was a prospective analysis. Results Our results showed that the number of rehabilitation physicians, consultation systems, and full-time therapists was adjusted and the system providing rehabilitation was modified during each phase. Discussion Elements of Function, such as preconditions, control, and resources, require modification in each phase. In the process of adding and deleting these elements, it became clear that it was necessary to deal with new characteristics of SARS-CoV-2 infection. Retrospective system analysis using FRAM may contribute to the planning of measures necessary for the implementation of rehabilitation medicine prospectively.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.18.22275242v1" target="_blank">Building Medical Rehabilitation System with Safety and Without Interruption for the Patients with Coronavirus Disease 2019 Using the Functional Resonance Analysis Method (FRAM)</a>
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<li><strong>B cells, BAFF and interferons in MIS-C</strong> -
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Multisystem Inflammatory Syndrome in Children associated with COVID-19 (MIS-C) is a late complication of pediatric COVID-19, which follows weeks after original SARS-CoV-2 infection, regardless of its severity. It is characterized by hyperinflammation, neutrophilia, lymphopenia and activation of T cells with elevated IFN-γ. Observing production of autoantibodies and parallels with systemic autoimmune disorders, such as systemic lupus erythematodes (SLE), we explored B cell phenotype and serum levels of type I, II and III interferons, as well as the cytokines BAFF and APRIL in a cohort of MIS-C patients and healthy children after COVID-19. We documented a significant elevation of IFN-γ, but not IFN-α and IFN-λ in MIS-C patients. BAFF was elevated in MIS-C patient sera and accompanied by decreased BAFFR expression on all B cell subtypes. The proportion of plasmablasts was significantly lower in patients compared to healthy post-COVID children. We noted the presence of ENA Ro60 autoantibodies in 4/35 tested MIS-C patients. Our work shows the involvement of humoral immunity in MIS-C and hints at parallels with the pathophysiology of SLE, with autoreactive B cells driven towards autoantibody production by elevated BAFF.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.18.22275245v1" target="_blank">B cells, BAFF and interferons in MIS-C</a>
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<li><strong>Evaluation of the ID NOW Among Symptomatic Individuals During the Omicron Wave</strong> -
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BACKGROUND Point of Care SARS CoV 2 devices, such as the Abbott ID NOW have great potential, to help combat the COVID19 pandemic. Starting in December, 2020, the ID NOW was implemented throughout the province of Alberta, Canada (population 4.4 million) in various settings. We aimed to assess the ID NOW performance during the BA.1 Omicron wave and compare it to previous waves. METHODS The ID NOW was assessed in two distinct locations among symptomatic individuals: acute care (emergency room, urgent care, and hospitalized patients) and community assessment centres (AC) during the period January 5 to 18, 2022. Starting January 5, Omicron represented >95% of variants detected in our population. For every individual tested, two swabs were collected: one for ID NOW testing and the other for either reverse- transcriptase polymerase chain reaction (RT-PCR) confirmation of negative ID NOW results or for variant testing of positive ID NOW results. RESULTS A total of 3,041 paired samples were analyzed (1,139 RTPCR positive). 1,873 samples were from 42 COVID-19 AC and 1,168 from 69 rural hospitals. ID NOW sensitivity for symptomatic individuals presenting to community AC and patients in hospital was 96.0% [95% confidence interval (CI) 94.5 to 97.3%, n=830 RTPCR positive], and 91.6% (95% CI 87.9 to 94.4%, n=309 RTPCR positive), respectively. SARS CoV 2 positivity rate was very high for both populations (44.3% at AC, 26.5% in hospital). CONCLUSIONS Sensitivity of ID NOW SARS CoV 2, compared to RTPCR, is very high during the BA.1 Omicron wave, and is significantly higher when compared to previous SARS CoV 2 variant waves.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.19.22275316v1" target="_blank">Evaluation of the ID NOW Among Symptomatic Individuals During the Omicron Wave</a>
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<li><strong>Estimating Vaccine-Preventable COVID-19 Deaths Under Counterfactual Vaccination Scenarios in the United States</strong> -
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Importance: With an abundant supply of COVID-19 vaccines becoming available in spring and summer 2021, the major barrier to high vaccination rates in the United States has been a lack of vaccine demand. This has contributed to a higher rate of deaths from SARS-CoV-2 infections amongst unvaccinated individuals as compared to vaccinated individuals. It is important to understand how low vaccination rates directly impact deaths resulting from SARS-CoV-2 infections in unvaccinated populations across the United States. Objective: To estimate a lower bound on the number of vaccine- preventable deaths from SARS-CoV-2 infections under various scenarios of vaccine completion, for every state of the United States. Design, Setting, and Participants: This counterfactual simulation study varies the rates of complete vaccination coverage under the scenarios of 100%, 90% and 85% coverage of the adult (18+) population of the United States. For each scenario, we use U.S. state-level demographic information in conjunction with county-level vaccination statistics to compute a lower bound on the number of vaccine-preventable deaths for each state. Exposures: COVID-19 vaccines, SARS-CoV-2 infection Main Outcomes and Measures: Death from SARS-CoV-2 infection Results: Between January 1st, 2021 and April 30th, 2022, there were 641,305 deaths due to COVID-19 in the United States. Assuming each state continued peak vaccination capacity after initially achieving its peak vaccination rate, a vaccination rate of 100% would have led to 322,324 deaths nationally, that of 90% would have led to 415,878 deaths, and that of 85% would have led to 463,305 deaths. As a comparison, using the state with the highest peak vaccination rate (per million population each week) for all the states, a vaccination rate of 100% would have led to 302,344 deaths nationally, that of 90% would have led to 398,289 deaths, and that of 85% would have led to 446,449 deaths. Conclusions and Relevance: Once COVID-19 vaccine supplies peaked across the United States, if there had been 100% COVID-19 vaccination coverage of the over 18+ population, a conservative estimate of 318,981 deaths could have been potentially avoided through vaccination. For a 90% vaccination coverage, we estimate at least 225,427 deaths averted through vaccination, and at least 178,000 lives saved through vaccination for an 85% vaccination coverage.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.05.19.22275310v1" target="_blank">Estimating Vaccine-Preventable COVID-19 Deaths Under Counterfactual Vaccination Scenarios in the United States</a>
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</div></li>
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<li><strong>Acute Vaping of a golden Syrian Hamster is Feasible and Leads to Nicotine-Dependent Respiratory Tract Inflammation</strong> -
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Introduction: E-cigarette vaping has become a major portion of nicotine consumption, especially for children and young adults. Although it is branded as a safer alternative to cigarette smoking, murine and rat models of sub-acute and chronic e-cigarette vaping exposure have shown many pro-inflammatory changes in the respiratory tract. An acute vaping exposure paradigm has not been demonstrated in the golden Syrian hamster, and the hamster is a readily available small animal model that has the unique benefit of becoming infected with and transmitting SARS-CoV-2 without genetic alteration to the animal or virus. Methods: Using a two-day, whole-body vaping exposure protocol in male golden Syrian hamsters, we evaluated serum cotinine, bronchoalveolar lavage cells, lung and nasal histopathology, and gene expression in the nasopharynx and lung through RT-qPCR. Depending on the presence of nonnormality or outliers, statistical analysis was performed by ANOVA or Kruskal-Wallis tests. For tests that were statistically significant (p-value <0.05), post- hoc Tukey-Kramer and Dunn’s tests, respectively, were performed to make pairwise comparisons between groups. Results: In nasal tissue, RT-qPCR analysis revealed nicotine-dependent increases in genes associated with type 1 inflammation (CCL-5 and CXCL-10), fibrosis (TGF-{beta}), and a nicotine-independent decrease in the vasculogenesis/angiogenesis gene VEGF-A. In the lung, nicotine-dependent increases in the expression of genes involved in the renin-angiotensin pathway (ACE, ACE2), coagulation (tissue factor, Serpine-1), extracellular matrix remodeling (MMP-2, MMP-9), type 1 inflammation (IL-1{beta}, TNF-, and CXCL-10), fibrosis (TGF-{beta} and Serpine-1), oxidative stress response (SOD-2), neutrophil extracellular traps release (ELANE), and vasculogenesis and angiogenesis (VEGF-A) were identified. Conclusion: To our knowledge, this is the first demonstration that the Syrian hamster is a viable model of e-cig induced inhalational injury. In addition, this is the first report that e-cig vaping with nicotine can increase tissue factor gene expression in the lung. Our results show that even an acute exposure to e-cigarette vaping causes significant upregulation in the respiratory tract of pathways involving the renin-angiotensin system, coagulation, extracellular matrix remodeling, type 1 inflammation, fibrosis, oxidative stress response, NETosis, vasculogenesis, and angiogenesis.
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</div>
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.20.492852v1" target="_blank">Acute Vaping of a golden Syrian Hamster is Feasible and Leads to Nicotine-Dependent Respiratory Tract Inflammation</a>
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</div></li>
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<li><strong>Omicron breakthrough infections in vaccinated or previously infected hamsters</strong> -
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The second and third years of the SARS-CoV-2 pandemic have been marked by the repeated emergence and replacement of variants with genetic and phenotypic distance from the ancestral strains, the most recent examples being Delta and Omicron. Here we describe a hamster contact exposure challenge model to assess protection conferred by vaccination or prior infection against re-infection. We found that 2-doses of self-amplifying RNA vaccine based on the ancestral spike ameliorated weight loss following Delta infection and decreased viral loads, but had minimal effect on Omicron/BA.1 infection. Prior infection with ancestral or Alpha variant was partially protective against Omicron/BA.1 infection, whereas all animals previously infected with Delta and exposed to Omicron became infected, although shed less virus. We further tested whether prior infection with Omicron/BA.1 protected from re-infection with Delta or Omicron/BA.2. Omicron/BA.1 was protective against Omicron/BA.2, but not Delta reinfection, again showing Delta and Omicron have a very large antigenic distance. Indeed, cross-neutralisation assays with human antisera from otherwise immunonaive individuals (unvaccinated and no known prior infection), confirmed a large antigenic distance between Delta and Omicron. Prior vaccination followed by Omicron or Delta breakthrough infection led to a higher degree of cross-reactivity to all tested variants. To conclude, cohorts whose only immune experience of COVID is Omicron/BA.1 infection may be particularly vulnerable to future circulation of Delta or Delta-like derivatives. In contrast, repeated exposure to antigenically distinct spikes, via infection and or vaccination drives a more cross-reactive immune response, both in hamsters and people.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.20.492779v1" target="_blank">Omicron breakthrough infections in vaccinated or previously infected hamsters</a>
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</div></li>
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<li><strong>Structural basis for substrate selection by the SARS-CoV-2 replicase</strong> -
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The SARS-CoV-2 RNA-dependent RNA polymerase coordinates viral RNA synthesis as part of an assembly known as the replication-transcription complex (RTC). Accordingly, the RTC is a target for clinically approved antiviral nucleoside analogs, including remdesivir. Faithful synthesis of viral RNAs by the RTC requires recognition of the correct nucleotide triphosphate (NTP) for incorporation into the nascent RNA. To be effective inhibitors, antiviral nucleoside analogs must compete with the natural NTPs for incorporation. How the SARS-CoV-2 RTC discriminates between the natural NTPs, and how antiviral nucleoside analogs compete, has not been discerned in detail. Here, we use cryo-electron microscopy to visualize the RTC bound to each of the natural NTPs in states poised for incorporation. Furthermore, we investigate the RTC with the active metabolite of remdesivir, remdesivir triphosphate (RDV-TP), highlighting the structural basis for the selective incorporation of RDV-TP over its natural counterpart ATP. Our results elucidate the suite of interactions required for NTP recognition, informing the rational design of antivirals. Our analysis also yields insights into nucleotide recognition by the nsp12 NiRAN, an enigmatic catalytic domain essential for viral propagation. The NiRAN selectively binds GTP, strengthening proposals for the role of this domain in the formation of the 5’ RNA cap.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.20.492815v1" target="_blank">Structural basis for substrate selection by the SARS-CoV-2 replicase</a>
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</div></li>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Role of Glutathione Deficiency and MSIDS Variables in Long COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Dietary Supplement: NAC (N-acetyl cysteine) , Alpha lipoic acid (ALA), liposomal glutathione (GSH)<br/><b>Sponsors</b>: University of California, Irvine; Hudson Valley Healing Arts Center<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Evaluate the Efficacy of IN STI-9199 in Treating Symptomatic COVID-19 in Outpatient Adults and Adolescents</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: STI-9199; Drug: Placebo<br/><b>Sponsor</b>: <br/>
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Sorrento Therapeutics, 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>A Study to Evaluate the Safety and Immunogenicity of Omicron COVID-19 Vaccine (Vero Cell), Inactivated in Population 18 Years Old of Age and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>: China National Biotec Group Company Limited; Beijing Institute of Biological Products Co Ltd.; Shulan (Hangzhou) 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>Study on Sequential Immunization of Omicron Inactivated COVID-19 Vaccine and Prototype Inactivated COVID-19 Vaccine in Population Aged 18 Years Old and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Omicron COVID-19 Vaccine (Vero Cell), Inactivated; Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>: <br/>
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China National Biotec Group Company Limited; Beijing Institute of Biological Products Co Ltd.; Hunan Provincial Center for Disease Control and Prevention<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>Neuro-inflammation and Post-infectious Fatigue in Individuals With and Without COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Radiation: [18F]DPA-714 positron emission tomography (PET) scan<br/><b>Sponsors</b>: Amsterdam UMC, location VUmc; ZonMw: The Netherlands Organisation for Health Research and Development<br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase II Safety Single-arm Study of CDK4/6 Inhibition With Palbociclib in Hospitalized, Moderate COVID-19 Cases to Prevent Thromboinflammation</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Palbociclib<br/><b>Sponsor</b>: biotx.ai GmbH<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase I Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: COVID-19 mRNA vaccine; Biological: Placebo<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>Phase II Clinical Trial of COVID-19 mRNA Vaccine in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: COVID-19 mRNA vaccine; Biological: Placebo<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>THEMBA II T-Cell Vaccine: Vaccination With saRNA COVID-19 Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: AAHI-SC2 Vaccine; Biological: AAHI- SC3 Vaccine; Biological: EUA or approved vaccine<br/><b>Sponsor</b>: ImmunityBio, Inc.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>To Evaluate SSD8432/Ritonavir in Adults With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SSD8432 dose; Drug: SSD8432 placebo<br/><b>Sponsor</b>: Jiangsu Simcere Pharmaceutical 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 and Safety of DXP604 in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: DXP604<br/><b>Sponsor</b>: <br/>
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Wuhan Institute of Biological Products 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>Evaluation of SSD8432 and Ritonavir in Adult Subjects With COVID-19 Placebo-Controlled, Phase II Clinical Study</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SSD8432 dose1; Drug: SSD8432 dose2; Drug: SSD8432Placebo<br/><b>Sponsor</b>: Jiangsu Simcere Pharmaceutical 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>Sequential Immunization of Two Doses of Inactivated COVID-19 Vaccine (Omicron) in Vaccinated Population Aged 18 Years and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: BIBP Omicron Inactivated COVID-19 vaccine (Vero Cell); Biological: WIBP Omicron Inactivated COVID-19 vaccine (Vero Cell); Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>: China National Biotec Group Company Limited; Beijing Institute of Biological Products Co Ltd.; Wuhan Institute of Biological Products Co., Ltd; The University of Hong Kong<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 of Booster Immunization of COVID-19 Vaccine (Vero Cell), Inactivated (Omicron Variant) in Healthy People Aged 18 Years and Above</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: COVID-19 Vaccine (Vero cell), Inactivated (Omicron variant); Biological: COVID-19 Vaccine (Vero cell), Inactivated (CZ strain)<br/><b>Sponsor</b>: <br/>
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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>To Evaluate SSD8432/ Ritonavir in Adults With COVID-19</strong> - <b>Condition</b>: COVID-19 Patients<br/><b>Interventions</b>: Drug: SSD8432 dose 1/Ritonavir; Drug: SSD8432 dose 2/Ritonavir<br/><b>Sponsor</b>: Jiangsu Simcere Pharmaceutical Co., Ltd.<br/><b>Recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Circulatory Cytokine Levels as a Predictor of Disease Severity in COVID-19: A Study from Western India</strong> - CONCLUSION: Elevated IL-6 levels lead to adverse clinical events so IL-6 level might serve as a potential prognostic marker for severity of disease in COVID-19. Inhibition of IL-6 might be helpful to prevent serious adverse events in COVID-19 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>Effect of herbal compounds on coronavirus; a systematic review and meta-analysis</strong> - CONCLUSION: Due to the variety of study methods, definitive conclusions are not possible. However, in this study, we attempted to gather all the available evidence on the effect of plant compounds on SARS-COV-2 to be used for the development and use of promising antiviral agents against this virus and other coronaviruses. Trypthantrin, Sambucus extract, S. cusia extract, Boceprevir and Indigole B, dioica agglutinin urtica had a good effect on reducing the virus titer. Also among the compounds…</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>Recombinant human interferon-α1b inhibits SARS-CoV-2 better than interferon-α2b in vitro</strong> - No abstract</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Design, synthesis and evaluation of inhibitors of the SARS-CoV-2 nsp3 macrodomain</strong> - A series of amino acid based 7H-pyrrolo[2,3-d]pyrimidines were designed and synthesized to discern the structure activity relationships against the SARS-CoV-2 nsp3 macrodomain (Mac1), an ADP-ribosylhydrolase that is critical for coronavirus replication and pathogenesis. Structure activity studies identified compound 15c as a low-micromolar inhibitor of Mac1 in two ADP-ribose binding assays. This compound also demonstrated inhibition in an enzymatic assay of Mac1 and displayed a thermal shift…</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>Role of LL-37 in thrombotic complications in patients with COVID-19</strong> - Blood clot formation induced by dysfunctional coagulation is a frequent complication of coronavirus disease 2019 (COVID-19) and a high-risk factor for severe illness and death. Neutrophil extracellular traps (NETs) are implicated in COVID-19-induced immunothrombosis. Furthermore, human cathelicidin, a NET component, can perturb the interaction between the SARS-CoV-2 spike protein and its ACE2 receptor, which mediates viral entry into cells. At present, however, the levels of cathelicidin…</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>Comparative evaluation of flavonoids reveals the superiority and promising inhibition activity of silibinin against SARS-CoV-2</strong> - Flavonoids are phenolic compounds naturally found in plants and commonly consumed in diets. Herein, flavonoids were sequentially evaluated by a comparative in silico study associated with systematic literature search. This was followed by an in vitro study and enzyme inhibition assays against vital SARS-CoV-2 proteins including spike (S) protein, main protease (M^(pro) ), RNA-dependent RNA-polymerase (RdRp), and human transmembrane serine protease (TMPRSS2). The results obtained revealed 10…</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>Disease-associated dysbiosis and potential therapeutic role of Akkermansia muciniphila, a mucus degrading bacteria of gut microbiome</strong> - The unique functionality of Akkermansia muciniphila in gut microbiota indicates it to be an indispensable microbe for human welfare. The importance of A. muciniphila lies in its potential to convert mucin into beneficial by-products, regulate intestinal homeostasis and maintain gut barrier integrity. It is also known to competitively inhibit other mucin-degrading bacteria and improve metabolic functions and immunity responses in the host. It finds a pivotal perspective in various diseases and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Expanding the spectrum of the hyperferritinemic syndrome, from pathogenic mechanisms to clinical observations, and therapeutic implications</strong> - From the introduction of hyperferritinemic syndrome concept, a growing body of evidence has suggested the role of ferritin as a pathogenic mediator and a relevant clinical feature in the management of patients with inflammatory diseases. From a pathogenic point of view, ferritin may directly stimulate the aberrant immune response by triggering the production of pro-inflammatory mediators in inducing a vicious pathogenic loop and contributing to the occurrence of cytokine storm syndrome. 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>Longitudinal analyses reveal distinct immune response landscapes in lung and intestinal tissues from SARS- CoV-2-infected rhesus macaques</strong> - The pathological and immune response of individuals with COVID-19 display different dynamics in lung and intestine. Here, we depict the single-cell transcriptional atlas of longitudinally collected lung and intestinal tissue samples from SARS-CoV-2-infected monkeys at 3 to 10 dpi. We find that intestinal enterocytes are degraded at 3 days post- infection but recovered rapidly, revealing that infection has mild effects on the intestine. Crucially, we observe suppression of the inflammatory…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In vitro characterization of the furin inhibitor MI-1851: Albumin binding, interaction with cytochrome P450 enzymes and cytotoxicity</strong> - The substrate-analog furin inhibitor MI-1851 can suppress the cleavage of SARS-CoV-2 spike protein and consequently produces significant antiviral effect on infected human airway epithelial cells. In this study, the interaction of inhibitor MI-1851 was examined with human serum albumin using fluorescence spectroscopy and ultrafiltration techniques. Furthermore, the impacts of MI-1851 on human microsomal hepatic cytochrome P450 (CYP) 1A2, 2C9, 2C19, 2D6 and 3A4 activities were assessed based on…</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>Folic acid: a potential inhibitor against SARS-CoV-2 nucleocapsid protein</strong> - CONTEXT: Coronavirus disease 2019 is a global pandemic. Studies suggest that folic acid has antiviral effects. Molecular docking shown that folic acid can act on SARS-CoV-2 Nucleocapsid Phosphoprotein (SARS-CoV-2 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>HDAC Inhibition as Potential Therapeutic Strategy to Restore the Deregulated Immune Response in Severe COVID-19</strong> - The COVID-19 pandemic has had a devastating impact worldwide and has been a great challenge for the scientific community. Vaccines against SARS-CoV-2 are now efficiently lessening COVID-19 mortality, although finding a cure for this infection is still a priority. An unbalanced immune response and the uncontrolled release of proinflammatory cytokines are features of COVID-19 pathophysiology and contribute to disease progression and worsening. Histone deacetylases (HDACs) have gained interest in…</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>Intranasal Delivery of Thermostable Subunit Vaccine for Cross-Reactive Mucosal and Systemic Antibody Responses Against SARS-CoV-2</strong> - Despite the remarkable efficacy of currently approved COVID-19 vaccines, there are several opportunities for continued vaccine development against SARS-CoV-2 and future lethal respiratory viruses. In particular, restricted vaccine access and hesitancy have limited immunization rates. In addition, current vaccines are unable to prevent breakthrough infections, leading to prolonged virus circulation. To improve access, a subunit vaccine with enhanced thermostability was designed to eliminate 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>Importance of Influenza Anti-Hemagglutinin Antibodies During the SARS-CoV-2 Pandemic in the 2019/2020 Epidemic Season in Poland</strong> - BACKGROUND The aim of this study was to determine the level of anti-hemagglutinin antibodies in the serum of recovered patients during the SARS-CoV-2 pandemic in the 2019/2020 epidemic season in Poland, and the course of COVID-19. MATERIAL AND METHODS The material for the study consisted of the sera of COVID-19 convalescents obtained from the following 9 Regional Blood Donation and Blood Supply Centers located in 8 voivodeships. The hemagglutination inhibition reaction assay (HAI) using 8 viral…</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>Nanocomposites of Graphene Oxide-Silver Nanoparticles for Enhanced Antibacterial Activity: Mechanism of Action and Medical Textiles Coating</strong> - The resistance of microorganisms to antibiotics is a crucial problem for which the application of nanomaterials is among a growing number of solutions. The aim of the study was to create a nanocomposite (composed of graphene oxide and silver nanoparticles) with a precise mode of antibacterial action: what enables textiles to be coated in order to exhibit antibacterial properties. A characterization of nanomaterials (silver nanoparticles and graphene oxide) by size distribution, zeta potential…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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