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190 lines
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>25 August, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Basic Psychological Needs, Quality of Motivation, and Protective Behavior Intentions: A Nationally Representative Survey</strong> -
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Objective: Citizens’ volitional engagement in protective behaviors is essential for successful pandemic management, as much of the required adherence is beyond authorities’ control and difficult to monitor. Building on the Self-Determination Theory (SDT), this study examines how basic psychological need satisfaction (BPNS) related to COVID-19 behavioral measures is associated with the quality of motivation (autonomous vs. controlled), and whether this quality of motivation is predictive of the intention to wear a face mask and to avoid meeting others. Methods: Cross-sectional survey study involving a nationally representative sample (N = 2272) was conducted in Finland in May 2021, when protective behaviors were recommended to prevent acceleration of the epidemic. Mann-Whitney U tests, Kruskal-Wallis tests, linear regression analysis, and multinomial logistic regression were conducted. Results: All three psychological needs were positively related to autonomous motivation (all p<.001). Satisfaction of autonomy (β = .234) and relatedness (β = .402) had larger effects than competence (β = .091). Autonomous motivation (range Exp(B) = 1.82‒3.55, p = .001) was consistently related to intention to wear a mask and intention to avoid meeting people. Controlled motivation (range Exp(B) = .66‒.93, p = .001‒.457) was associated with decreased protective behavior intentions. The effects of amotivation (range Exp(B) = .65‒1.02, p = .001‒.911) varied across analyses. Conclusions: Fostering autonomous motivation could increase adherence to protective behaviors in situations without clear mandates. The results also suggest that increasing perceptions of pressure or appealing to personal risk and fear may not advance adherence as effectively.
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🖺 Full Text HTML: <a href="https://osf.io/qgvua/" target="_blank">Basic Psychological Needs, Quality of Motivation, and Protective Behavior Intentions: A Nationally Representative Survey</a>
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<li><strong>ENHANCED RECOMBINATION AMONG SARS-COV-2 OMICRON VARIANTS CONTRIBUTES TO VIRAL IMMUNE ESCAPE.</strong> -
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SARS-CoV-2 virus evolution occurs as a result of antigenic drift and shift. Although antigenic drift has been extensively studied, antigenic shift, which for SARS-CoV-2 occurs through genetic recombination, has been examined scarcely. To gain a better understanding of the emergence and prevalence of recombinant SARS-CoV-2 lineages through time and space, we analyzed SARS-CoV-2 genome sequences from public databases. Our study revealed an extraordinary increase in the emergence of SARS-CoV-2 recombinant lineages during the Omicron wave, particularly in Northern America and Europe. This phenomenon was independent of sequencing density or genetic diversity of circulating SARS-CoV-2 strains. In SARS-CoV-2 genomes, recombination breakpoints were found to be more concentrated in the 3- UTR followed by ORF1a. Additionally, we noted enrichment of certain amino acids in the spike protein of recombinant lineages, which have been reported to confer immune escape from neutralizing antibodies, increase ACE2 receptor binding, and enhance viral transmission in some cases. Overall, we report an important and timely observation of accelerated recombination in the currently circulating Omicron variants and explore their potential contribution to viral fitness, particularly immune escape.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.23.504936v1" target="_blank">ENHANCED RECOMBINATION AMONG SARS-COV-2 OMICRON VARIANTS CONTRIBUTES TO VIRAL IMMUNE ESCAPE.</a>
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<li><strong>Predicting antiviral resistance mutations in SARS-CoV-2 main protease with computational and experimental screening</strong> -
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The main protease (Mpro) of SARS-CoV-2 is essential for viral replication and has been the focus of many drug discovery efforts since the start of the COVID-19 pandemic. Nirmatrelvir (NTV) is an inhibitor of SARS-CoV-2 Mpro that is used in the combination drug Paxlovid for the treatment of mild to moderate COVID-19. However, with increased use of NTV across the globe, there is a possibility that future SARS-CoV-2 lineages will evolve resistance to NTV. Early prediction and monitoring of resistance mutations could allow for measures to slow the spread of resistance and for the development of new compounds with activity against resistant strains. In this work, we have used in silico mutational scanning and inhibitor docking of Mpro to identify potential resistance mutations. Subsequent in vitro experiments revealed five mutations (N142L, E166M, Q189E, Q189I, and Q192T) that reduce the potency of NTV and of a previously identified non-covalent cyclic peptide inhibitor of Mpro. The E166M mutation reduced the half-maximal inhibitory concentration (IC50) of NTV 24-fold, and 118-fold for the non-covalent peptide inhibitor. Our findings inform the ongoing genomic surveillance of emerging SARS-CoV-2 lineages.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.24.505060v1" target="_blank">Predicting antiviral resistance mutations in SARS-CoV-2 main protease with computational and experimental screening</a>
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<li><strong>Knowledge, attitude, and practices of ward attendant and housekeeping staffs towards dead body care of COVID-19 patients at tertiary care hospital : A cross sectional study</strong> -
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Background : Healthcare workers worked untiringly during entire pandemic period and taken efforts to protect individuals, families and communities in adverse situations with stretched resources. Among health care workers role of ward attendant and housekeeping staffs have been very significant particularly in infection control practices and dead body management. Present study aim is to gain an understanding of the knowledge, attitudes, and practices (KAP) of ward attendant and housekeeping staffs towards dead body management. Methods: Hospital-based cross-sectional study design was conducted among ward attendant and housekeeping staffs working in COVID units. A total of 62 participants were selected using simple random sampling technique. Self-administered questionnaire was used to collect data. Binary logistic regression model was used to see association between outcome and independent variables. Result: Present study found mean knowledge, attitude and practice score of participants were 6.1, 49.9 and 12.28 indicates good knowledge, positive attitude and inappropriate practice towards dead body care. Study result also shows that odds of good knowledge were not significantly associated with demographic variables. However, the participants who did not receive any training on dead body care were found to have positive attitude towards dead body care(AOR=3.90,95%CI=1.092-13.92), whereas gender (AOR=1.85,95%CI=.430-7.96), working experience in COVID units (AOR=99.5,95%CI=.913-98.8) and educational qualification (AOR=30.33,95%CI=1.5-577) were significantly associated with practice of dead body care of COVID-19 patients. Conclusion: The study found that majority of participants were having good knowledge, positive attitude and inappropriate practice towards dead body care of COVID-19 patients. Hospital administration should conduct regular training of dead body care of COVID-19 patients for all the housekeeping staffs and ward attendant to minimise the risk of exposure to infections and better management of dead bodies.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.23.22279058v1" target="_blank">Knowledge, attitude, and practices of ward attendant and housekeeping staffs towards dead body care of COVID-19 patients at tertiary care hospital : A cross sectional study</a>
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<li><strong>Tuberculosis severity associates with variants and eQTLs related to vascular biology and infection-induced inflammation</strong> -
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Background: Tuberculosis (TB) remains a major public health problem globally, even compared to COVID-19. Genome-wide studies have failed to discover genes that explain a large proportion of genetic risk for adult pulmonary TB, and even fewer have examined genetic factors underlying TB severity, an intermediate trait impacting disease experience, quality of life, and risk of mortality. No prior severity analyses used a genome-wide approach. Methods and Findings: As part of our ongoing household contact study in Kampala, Uganda, we conducted a genome-wide association study (GWAS) of TB severity measured by TBScore, in two independent cohorts of culture-confirmed adult TB cases (n=149 and n=179). We identified 3 SNPs (P<1.0 x 10-7) including one on chromosome 5, rs1848553, that was GWAS significant (meta-analysis p=2.97x10-8). All three SNPs are in introns of RGS7BP and have effect sizes corresponding to clinically meaningful reductions in disease severity. RGS7BP is highly expressed in blood vessels and plays a role in infectious disease pathogenesis. Other genes with suggestive associations defined gene sets involved in platelet homeostasis and transport of organic anions. To explore functional implications of the TB severity-associated variants, we conducted eQTL analyses using expression data from Mtb-stimulated monocyte-derived macrophages. A single variant (rs2976562) associated with monocyte SLA expression (p=0.03) and subsequent analyses indicated that SLA downregulation following MTB stimulation associated with increased TB severity. Src Like Adaptor (SLAP-1), encoded by SLA, is highly expressed in immune cells and negatively regulates T cell receptor signaling, providing a potential mechanistic link to TB severity. Conclusions: These analyses reveal new insights into the genetics of TB severity with regulation of platelet homeostasis and vascular biology being central to consequences for active TB patients. This analysis also reveals genes that regulate inflammation can lead to differences in severity. Our findings provide an important step in improving TB patient outcomes.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.23.22279140v1" target="_blank">Tuberculosis severity associates with variants and eQTLs related to vascular biology and infection-induced inflammation</a>
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<li><strong>SARS-CoV-2 variant dynamics across US states show consistent differences in effective reproduction numbers</strong> -
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Accurately estimating relative transmission rates of SARS-CoV-2 variants remains a scientific and public health priority. Recent studies have used the sample proportions of different variants from genetic sequence data to describe variant frequency dynamics and relative transmission rates, but frequencies alone cannot capture the rich epidemiological behavior of SARS-CoV-2. Here, we extend methods for inferring the effective reproduction number of an epidemic using confirmed case data to jointly estimate variant-specific effective reproduction numbers and frequencies of co- circulating variants using cases and sequences across states in the US from January 2021 to March 2022. Our method can be used to infer structured relationships between effective reproduction numbers across time series allowing us to estimate fixed variant-specific growth advantages. We use this model to estimate the effective reproduction number of SARS-CoV-2 Variants of Concern and Variants of Interest in the United States and estimate consistent growth advantages of particular variants across different locations.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.12.09.21267544v2" target="_blank">SARS-CoV-2 variant dynamics across US states show consistent differences in effective reproduction numbers</a>
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<li><strong>New Insights into How JUUL Electronic Cigarette Aerosols and Aerosol Constituents Affect SARS-CoV-2 Infection of Human Bronchial Epithelial Cells</strong> -
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Background: The relationship between the use of tobacco products and SARS-CoV-2 infection is poorly understood and controversial. Most studies have been done with tobacco cigarettes, while few have examined the effect of electronic cigarettes (ECs) on SARS-CoV-2 infection. We tested the hypothesis that EC fluids and aerosols with high concentrations of nicotine promote SARS-COV-2 infection by increasing viral entry into human respiratory epithelial cells. Methods: Responses of BEAS-2B cells to authentic JUUL aerosols or their individual constituents (propylene glycol (PG)/vegetable glycerin (VG) and nicotine) were compared using three exposure platforms: submerged culture, air-liquid-interface (ALI) exposure in a cloud chamber, and ALI exposure in a Cultex system, which produces authentic heated EC aerosols. SARS-CoV-2 infection machinery was assessed using immunohistochemistry and Western blotting. Specifically, the levels of the SARS-CoV-2 receptor ACE2 (angiotensin converting enzyme 2) and a spike modifying enzyme, TMPRSS2 (transmembrane serine protease 2), were evaluated. Following each exposure, lentivirus pseudoparticles with spike protein and a green-fluorescent reporter were used to test viral penetration and the susceptibility of BEAS-2B cells to infection. Results: Nicotine, EC fluids, and authentic JUUL aerosols increased both ACE2 levels and TMPRSS2 activity, which in turn increased viral particle entry into cells. While most data were in good agreement across the three exposure platforms, cells were more responsive to treatments when exposed at the ALI in the Cultex system, even though the exposures were brief and intermittent. In the Cultex system, PG/VG, PG/VG/nicotine, and JUUL aerosols significantly increased infection above clean air controls. However, both the PG/VG and JUUL treatments were significantly lower than nicotine/PG/VG. PG/VG increased infection only in the Cultex system, which produces heated aerosol. Conclusion: Our data are consistent with the conclusion that authentic JUUL aerosols or their individual constituents (nicotine or PG/VG) increase SARS-CoV-2 infection. The strong effect produced by nicotine was modulated in authentic JUUL aerosols, demonstrating the importance of studying mixtures and aerosols from actual EC products. These data support the idea that vaping increases the likelihood of contracting COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.23.505031v1" target="_blank">New Insights into How JUUL Electronic Cigarette Aerosols and Aerosol Constituents Affect SARS-CoV-2 Infection of Human Bronchial Epithelial Cells</a>
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<li><strong>Design and Analysis of Outcomes following SARS-CoV-2 Infection in Veterans</strong> -
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<b>Background</b>: Understanding how SARS-CoV-2 infection impacts long-term patient outcomes requires identification of comparable persons with and without infection. We report the design and implementation of a matching strategy employed by the Department of Veterans Affairs (VA) COVID-19 Observational Research Collaboratory (CORC) to develop comparable cohorts of SARS-CoV-2 infected and uninfected persons for the purpose of inferring potential causative long-term adverse effects of SARS-CoV-2 infection in the Veteran population. <b>Methods</b>: In a retrospective cohort study, we identified VA health care system patients who were and were not infected with SARS-CoV-2 on a rolling monthly basis. We generated matched cohorts utilizing a combination of exact and time-varying propensity score matching based on electronic health record (EHR)-derived covariates that can be confounders or risk factors across a range of outcomes. <b>Results</b>: From an initial pool of 126,689,864 person-months of observation, we generated final matched cohorts of 208,536 Veterans infected between March 2020-April 2021 and 3,014,091 uninfected Veterans. Matched cohorts were well-balanced on all 38 covariates used in matching after excluding patients for: no VA health care utilization; implausible age, weight, or height; living outside of the 50 states or Washington, D.C.; prior SARS-CoV-2 diagnosis per Medicare claims; or lack of a suitable match. Most Veterans in the matched cohort were male (88.3%), non-Hispanic (87.1%), white (67.2%), and living in urban areas (71.5%), with a mean age of 60.6, BMI of 31.3, Gagne comorbidity score of 1.4 and a mean of 2.3 CDC high-risk conditions. The most common diagnoses were hypertension (61.4%), diabetes (34.3%), major depression (32.2%), coronary heart disease (28.5%), PTSD (25.5%), anxiety (22.5%), and chronic kidney disease (22.5%). <b>Conclusions</b>: This successful creation of matched SARS-CoV-2 infected and uninfected patient cohorts from the largest integrated health system in the United States will support cohort studies of outcomes derived from EHRs and sample selection for qualitative interviews and patient surveys. These studies will increase our understanding of the long-term outcomes of Veterans who were infected with SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.23.22279120v1" target="_blank">Design and Analysis of Outcomes following SARS-CoV-2 Infection in Veterans</a>
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<li><strong>Integrated Immunopeptidomics and Proteomics Study Reveals Imbalanced Innate and Adaptive Immune Responses to SARS-Cov-2 Infection</strong> -
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We present an integrated immunopeptidomics and proteomics study of SARS-Cov-2 infection to comprehensively decipher the changes in host cells in response to viral infection. Our results indicated that innate immune response in Calu-3 cells was initiated by TLR3, followed by activation of interferon signaling pathway. Host cells also present viral antigens to the cell surface through both Class I and Class II MHC system for recognition by adaptive immune system. SARS-Cov-2 infection led to the disruption of antigen presentation as demonstrated by higher level of HLA proteins from the flow-through of MHC immunoprecipitation. Glycosylation analysis of HLA proteins from the elution and flow-through of immunoprecipitation revealed that the synthesis and degradation of HLA protein was affected by SARS-Cov-2 infection. This study provided many useful information to study the host response to SARS-Cov-2 infection and would be helpful for the development of therapeutics and vaccine for Covid-19 and future pandemic.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.23.504798v1" target="_blank">Integrated Immunopeptidomics and Proteomics Study Reveals Imbalanced Innate and Adaptive Immune Responses to SARS-Cov-2 Infection</a>
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<li><strong>A Deep Learning Approach to Forecast Short-Term COVID-19 Cases and Deaths in the US</strong> -
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Since the US reported its first COVID-19 case on January 21, 2020, the science community has been applying various techniques to forecast incident cases and deaths. To date, providing an accurate and robust forecast at a high spatial resolution has proved challenging, even in the short term. Here we present a novel multi-stage deep learning model to forecast the number of COVID-19 cases and deaths for each US state at a weekly level for a forecast horizon of 1 to 4 weeks. The model is heavily data driven, and relies on epidemiological, mobility, survey, climate, and demographic. We further present results from a case study that incorporates SARS-CoV-2 genomic data (i.e. variant cases) to demonstrate the value of incorporating variant cases data into model forecast tools. We implement a rigorous and robust evaluation of our model - specifically we report on weekly performance over a one-year period based on multiple error metrics, and explicitly assess how our model performance varies over space, chronological time, and different outbreak phases. The proposed model is shown to consistently outperform the CDC ensemble model for all evaluation metrics in multiple spatiotemporal settings, especially for the longer-term (3 and 4 weeks ahead) forecast horizon. Our case study also highlights the potential value of virus genomic data for use in short-term forecasting to identify forthcoming surges driven by new variants. Based on our findings, the proposed forecasting framework improves upon the available forecasting tools currently used to support public health decision making with respect to COVID-19 risk.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.23.22279132v1" target="_blank">A Deep Learning Approach to Forecast Short-Term COVID-19 Cases and Deaths in the US</a>
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<li><strong>Post-COVID syndrome prevalence and risk factors in children and adolescents: A population-based serological study</strong> -
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Objectives Post-COVID syndrome remain poorly studied in children and adolescents. In this study, we aimed to investigate the prevalence and risk factors of pediatric post-COVID in a population-based sample, stratifying by serological status. Study design We used data from the SEROCoV-KIDS cohort study (State of Geneva, Switzerland), which included children (aged 6 months to 17 years) selected from random samples drawn from state registries or who had a household member participating in a COVID-19 seroprevalence study conducted by our group. Children were tested for anti-SARS-CoV-2 N antibodies. Parents filled in a questionnaire on persistent symptoms in their children (lasting over 12 weeks) compatible with post-COVID syndrome. Results From December 1st, 2021 to February 16th, 2022, 1034 children were included, among whom 570 (55.1%) were seropositive. The sex- and age-adjusted prevalence of persistent symptoms among seropositive children was 9.1% (95%CI: 6.7;11.8) and 5.0% (95%CI: 3.0;7.1) among seronegatives, with an adjusted prevalence difference (ΔaPrev) of 4.1% (95%CI: 1.1;7.3). After stratification by age group, the prevalence was higher among adolescents aged 12-17 years (ΔaPrev=8.3%, 95%CI: 3.5;13.5) than among younger children (0.0%, 95%CI: -5.2;5.2 among 6-11 years old and 4.2%; 95%CI: -4.4;13.3 among 0-5 years old). The most frequently declared persistent symptoms among seropositives were smell loss, trouble concentrating and abdominal pain. Older age, having a chronic condition and lower socioeconomic conditions were identified as risk factors. Conclusion A significant proportion of seropositive children, particularly adolescents, experienced persistent symptoms. While there is a need for further investigation, growing evidence of pediatric post-COVID syndrome urges early screening and primary care management.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.24.22279150v1" target="_blank">Post-COVID syndrome prevalence and risk factors in children and adolescents: A population-based serological study</a>
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<li><strong>Effective Matrix Designs for COVID-19 Group Testing</strong> -
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Grouping samples with low prevalence of positives into pools and testing these pools can achieve considerable savings in testing resources compared with individual testing in the context of COVID-19. We review published pooling matrices, which encode the assignment of samples into pools and describe decoding algorithms, which decode individual samples from pools. Based on the findings we propose new one-round pooling designs with high compression that can efficiently be decoded by combinatorial algorithms. This expands the admissible parameter space for the construction of pooling matrices compared to current methods. By arranging samples in a grid and using polynomials to construct pools, we develop direct formulas for an Algorithm (Polynomial Pools (PP)) to generate assignments of samples into pools. Designs from PP guarantee to correctly decode all samples with up to a specified number of positive samples. PP includes recent combinatorial methods for COVID-19, and enables new constructions that can result in more effective designs. For low prevalences of COVID-19, group tests can save resources when compared to individual testing. Constructions from the recent literature on combinatorial methods have gaps with respect to the designs that are available. We develop a method (PP), which generalizes previous constructions and enables new designs that can be advantageous in various situations.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.23.22279137v1" target="_blank">Effective Matrix Designs for COVID-19 Group Testing</a>
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<li><strong>Symptom presentation among SARS-CoV-2 positive cases and the impact of COVID-19 vaccination; three prospective household cohorts</strong> -
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<b>OBJECTIVE:</b> Using data from European prospective household studies, we systematically compared the symptom burden of the wild-type and Alpha variant infected individuals versus the Omicron BA.1 and BA.2 infected individuals across paediatric and adult age-groups. In addition, we measured the impact of COVID-19 vaccination on the Omicron symptom burden. <b>METHODS:</b> The household transmission studies were conducted during the wild-type and Alpha period (April 2020 to April 2021) and the early Omicron BA.1 and BA.2 dominant period (January to March 2022). All three studies used similar protocols. Households were prospectively followed from detection of the first SARS-CoV-2 index case until at least day 21 including (repeated) PCR testing, paired serology and daily symptom reporting for all household members. To avoid possible index-case ascertainment bias, we restricted analyses to secondary household cases. Age-stratified SARS-CoV-2 symptom burden was compared for wild-type/Alpha versus Omicron infections and for primary versus primary plus booster series vaccinated adult cases. <b>FINDINGS:</b> In total 216 secondary cases from wild-type/Alpha, and 130 from the Omicron period were included. Unvaccinated children <12 years experienced more symptoms and higher maximum and cumulative severity scores during the Omicron compared to the wild-type/Alpha period (p=0.004, p=0.011 and p=0.075, respectively). In adults, disease duration and maximum and cumulative severity scores were reduced during the Omicron period. Adjusted for age, gender and prior immunity Omicron was associated with lower odds for loss of smell or taste (Odds Ratio [OR]: 0.14; 95%CI 0.03-0.50), and higher, but non-significant odds for upper respiratory symptoms, fever and fatigue (ORs varying between 1.85-2.23). Comparing primary versus primary plus booster vaccinated adult cases during the Omicron period no differences were observed in disease severity or duration (p≥0.12). <b>INTERPRETATION:</b> In children, the Omicron variant causes higher symptom burden compared to the wild-type/Alpha. Adults experienced a lower symptom burden possibly due to prior vaccination. A shift in most frequently reported symptoms occurred with a marked reduction in loss of smell or taste during the Omicron period. An additional effect of booster vaccination on symptom severity in infected adults compared to primary series only, could not be demonstrated.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.19.22278985v2" target="_blank">Symptom presentation among SARS-CoV-2 positive cases and the impact of COVID-19 vaccination; three prospective household cohorts</a>
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<li><strong>Individuals with recent prior SARS-CoV-2 infection are at reduced risk of Omicron infection and associated hospitalization</strong> -
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Omicron sub-lineages such as BA2.12.1 and BA5 have breached prior infection-induced immunity and vaccine-induced immunity. This capacity of Omicron to reinfect patients calls for a characterization of vaccination, infection, and reinfection patterns. We analyzed de-identified longitudinal electronic health records for 389,746 individuals (88,679 fully-vaccinated, 184,205 boosted, 73,184 with prior infection) across a multi-state health system. Compared to individuals with only full vaccination, the rates of SARS-CoV-2 infections in the Omicron era were reduced for individuals with additional prior infection (1.4 to 1.8-fold reduced, depending on vaccine status) or booster vaccination (1.3 to 2.0-fold reduced). Although prior infection was associated with lower incidence of SARS-CoV-2 infection, we found that the relative risk (RR) of infections for individuals with prior infection has increased during Omicron. During October, 2021, RR was 0.11 [0.10-0.13, 95% CI] while during May, 2022, it increased to 0.57 [0.46-0.68, 95% CI], suggesting an increase in reinfections with Omicron. Furthermore, we found that time since prior infection is associated with risk of reinfection, providing evidence of waning immunity. Prior infections before June, 2021, were associated with marginal reduction in risk of infection (eg., RR = 0.80 [0.68-0.90] for prior infection during January, 2021), while recent prior infections were associated with significant reduction in risk (eg., RR = 0.24 [0.20-0.29, 95% CI] for prior infection during November, 2021). Despite an observed increase in reinfections and vaccine breakthrough infections, our findings emphasize the protective effect of natural and vaccine immunity, with prior infection providing ~6 months of protection from reinfection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.10.22278641v2" target="_blank">Individuals with recent prior SARS-CoV-2 infection are at reduced risk of Omicron infection and associated hospitalization</a>
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<li><strong>What ACH is equivalent to an N95 for protection from SARS-Cov-2 and other airborne contaminants?</strong> -
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Air filtration has limited effectiveness to stop spread of COVID-19 at near-field (e.g. talking close by), but potential to emulate far-field equivalent of N95 with 95% reduction of particles (20x) from airborne particulate sources. A wide range of air change per hour (ACH) recommendations for air filtration exist, ranging from 2 to 12 ACH (CDC, CDPH, etc.) and verifying ACH often involves an inert airborne contaminant (e.g. salt water) which can be disruptive in occupied rooms. We describe simpler procedures using an optical particle counter to track decay of ambient aerosols (0.3 μm diameter) and measure ACH from exponential decay coefficients in a room and whole house. Surface deposition in an unventilated room without ventilation or filtration was 0.6 ACH using ambient aerosols, and 3 to 17 using low-noise generating HEPA purifiers ($299-$999, reported CADR 114 to 1360 cfm) and Do-It-Yourself (DIY) air purifiers ($55-$160, 1“-5”, MERV 13-16, 1-filter box-fans and 4-filter Corsi-Rosenthal boxes). CADR estimated using ACH and volume of room/house per dollar varied 4x from below 80 cfm / $100 for tested HEPA purifiers at their highest speed (for maximum CADR) up to above 350 cfm / $100 run with tested DIY air purifiers running on lowest speed (for reduced noise generation). Differences in CADR were observed in room versus house, and purifiers with higher airspeed had higher than expected CADR, possibly reflecting better mixing. Using 0.6 ACH as baseline for unventilated rooms, at least 12 ACH if not more is required for far-field protection equivalent to N95 respirators (95%), and this ACH can be achieved using either HEPA or DIY air filtration in a room or building and verified with ambient aerosols. These results offer independent, experimentally-derived interpretation of the 12 ACH recommended for airborne infection isolation rooms (AIIR) by CDC and WHO.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.09.22278555v7" target="_blank">What ACH is equivalent to an N95 for protection from SARS-Cov-2 and other airborne contaminants?</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>A Clinical Study to Evaluate the Efficacy and Safety of SIM0417 Orally Co-Administered With Ritonavir in Symptomatic Adult Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SIM0417; Drug: 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>Self-management of Post COVID-19 Syndrome Using Wearable Biometric Technology</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Self-management of post COVID-19 respiratory outcomes<br/><b>Sponsor</b>: University of Manitoba<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>Clinical Study to Compare Efficacy and Safety of Casirivimab and Imdevimab Combination, Remdesivir and Favipravir in Hospitalized COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Casirivimab and Imdevimab Drug Combination; Drug: Remdesivir; Drug: Favipiravir<br/><b>Sponsor</b>: Mansoura University Hospital<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Role of BCG Vaccine in the Clinical Evolution of COVID-19 and in the Efficacy of Anti-SARS-CoV-2 Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: BCG (Bacillus Calmette-Guérin) vaccine; Other: Placebo<br/><b>Sponsors</b>: Oswaldo Cruz Foundation; University of Sao Paulo; Federal University of Juiz de Fora<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>Performance Evaluation of LumiraDx COVID-19 (SARS-CoV-2) Ag ULTRA Test (ASPIRE-2)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Diagnostic Test: Nasal Swab; Diagnostic Test: Nasopharyngeal swab<br/><b>Sponsor</b>: LumiraDx UK Limited<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>Social Network Diffusion of COVID-19 Prevention for Diverse Criminal Legal Involved Communities</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Education; Other: Motivational<br/><b>Sponsor</b>: University of Chicago<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 2a Trial to Evaluate Safety and Immunogenicity of COVID-19 Vaccine Strategies in HIV-infected/Uninfected Adults.</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Ad26.COV2.S (VAC31518, JNJ-78436735) Vaccine, SARS-CoV-2 rS (CovovaxTM), BNT162b2 (Pfizer)<br/><b>Sponsors</b>: The Aurum Institute NPC; Coalition for Epidemic Preparedness Innovations<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of Booster Immunization With COVID-19 Vaccine,Inactivated Co -Administration With Influenza Vaccine and Pneumococcal Polysaccharide Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Adult group in immunogenicity and safety study of combined immunization; Biological: Elderly group in immunogenicity and safety study of combined immunization; Biological: Adult group in safety observation study of combined immunization; Biological: Elderly group in safety observation study of combined immunization<br/><b>Sponsor</b>: Sinovac Biotech Co., Ltd<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluate the Safety and Efficacy of Allogeneic Umbilical Cord Mesenchymal Stem Cells in Patients With COVID-19</strong> - <b>Condition</b>: COVID-19 Infection<br/><b>Interventions</b>: Biological: Allogeneic umbilical cord mesenchymal stem cells; Biological: Controlled normal saline<br/><b>Sponsor</b>: Ever Supreme Bio Technology Co., Ltd.<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>Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Interventions</b>: Drug: Temelimab 54mg/kg; Drug: Placebo<br/><b>Sponsor</b>: GeNeuro SA<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>The Effects of a Sublingual Sprayable Microemulsion of Vitamin D on Inflammatory Markers in COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Vitamin D Deficiency<br/><b>Intervention</b>: Dietary Supplement: Vitamin D 25 (OH) 12000 IU in the form of a sublingual sprayable microemulsion<br/><b>Sponsor</b>: Pauls Stradins Clinical University Hospital<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>UNAIR Inactivated COVID-19 Vaccine Phase 3</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines<br/><b>Interventions</b>: Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg; Biological: CoronaVac Biofarma COVID-19 Vaccine<br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; Biotis Pharmaceuticals, Indonesia<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>Hydrogen-Oxygen Generator With Nebulizer for Rehabilitation Treatment of COVID-19</strong> - <b>Conditions</b>: COVID-19; AMS-H-03; Hydrogen-oxygen Gas<br/><b>Interventions</b>: Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03; Other: basic treatment<br/><b>Sponsor</b>: Shanghai Zhongshan 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>Canadian Adaptive Platform Trial for Long COVID</strong> - <b>Condition</b>: Long COVID, Post COVID Condition, Post Acute Sequelae of COVID-19<br/><b>Interventions</b>: Drug: Ibudilast; Dietary Supplement: Whey Protein Isolate; Drug: Pentoxifylline; Other: Placebo<br/><b>Sponsor</b>: University Health Network, Toronto<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>Clinical Trial of Jinzhen Oral Liquid in Treating Children With COVID-19 Infection</strong> - <b>Conditions</b>: COVID-19; Child, Only<br/><b>Intervention</b>: Drug: Jinzhen oral liquid or Jinhuaqinggan granules<br/><b>Sponsor</b>: The Affiliated Hospital of Qingdao University<br/><b>Recruiting</b></p></li>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Role of tannic acid against SARS-cov-2 cell entry by targeting the interface region between S-protein-RBD and human ACE2</strong> - Coronavirus disease 2019 (COVID-19) was caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 utilizes human angiotensin converting enzyme 2 (hACE2) as the cellular receptor of its spike glycoprotein (SP) to gain entry into cells. Consequently, we focused on the potential of repurposing clinically available drugs to block the binding of SARS-CoV-2 to hACE2 by utilizing a novel artificial-intelligence drug screening approach. Based on the structure…</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>Case report: Application of nirmatrelvir/ritonavir to treat COVID-19 in a severe aplastic anemia child after allogeneic hematopoietic stem cell transplantation</strong> - We present a case report of successful treatment with nirmatrelvir/ritonavir (Paxlvoid) for a severe aplastic anemia child with COVID-19, cytopenia, and mixed chimerism of donor hematopoietic cells at 3 months after allogeneic hematopoietic stem cell transplantation. After the 5-day entire course of treatment, the clinical symptoms were relieved, cycle threshold values of ORF1a/b and N genes increased from 22.60 and 22.15 to 34.52 and 33.84, respectively, and the peripheral blood counts…</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>Roles and functions of SARS-CoV-2 proteins in host immune evasion</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades the host immune system through a variety of regulatory mechanisms. The genome of SARS-CoV-2 encodes 16 non-structural proteins (NSPs), four structural proteins, and nine accessory proteins that play indispensable roles to suppress the production and signaling of type I and III interferons (IFNs). In this review, we discussed the functions and the underlying mechanisms of different proteins of SARS-CoV-2 that evade the host…</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>Identifying inhibitors of NSP16-NSP10 of SARS-CoV-2 from large databases</strong> - The COVID-19 pandemic, which has already claimed millions of lives, continues to pose a serious threat to human health, requiring the development of new effective drugs. Non-structural proteins of SARS-CoV-2 play an important role in viral replication and infection. Among them, NSP16 (non-structured protein 16) and its cofactor NSP10 (non-structured protein 10) perform C2’-O methylation at the 5’ end of the viral RNA, which promotes efficient virus replication. Therefore, the NSP16-NSP10 complex…</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>Contribution of Lipid Mediators in Divergent Outcomes following Acute Bacterial and Viral Lung Infections in the Obese Host</strong> - Obesity is considered an important comorbidity for a range of noninfectious and infectious disease states including those that originate in the lung, yet the mechanisms that contribute to this susceptibility are not well defined. In this study, we used the diet-induced obesity (DIO) mouse model and two models of acute pulmonary infection, Francisella tularensis subspecies tularensis strain SchuS4 and SARS-CoV-2, to uncover the contribution of obesity in bacterial and viral disease. Whereas DIO…</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>Shufeng Jiedu capsule inhibits inflammation and apoptosis by activating A2AAR and inhibiting NF-κB to alleviate LPS-induced ALI</strong> - CONCLUSIONS: According to the results of this study, SFJDC can reduce inflammation and inhibit apoptosis. A2AAR activation and regulation of NF-κB expression are thought to make SFJDC anti-inflammatory and anti-apoptotic. A wide range of active ingredients may result in an anti-inflammatory and antipyretic effect with SFJDC.</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>Lessons from the Failure to Complete a Trial of Denosumab in Women With a Pathogenic BRCA1/2 Variant Scheduling Risk-Reducing Salpingo-Oophorectomy</strong> - Female carriers of pathogenic/likely pathogenic (P/LP) BRCA1/2 variants are at increased risk of developing breast and ovarian cancer. Currently, the only effective strategy for ovarian cancer risk reduction is risk-reducing bilateral salpingo-oophorectomy (RR-BSO), which carries adverse effects related to early menopause. There is ongoing investigation of inhibition of the RANK ligand (RANKL) with denosumab as a means of chemoprevention for breast cancer in carriers of BRCA1 P/LP 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>Characterization of Entry Pathways, Species-Specific Angiotensin-Converting Enzyme 2 Residues Determining Entry, and Antibody Neutralization Evasion of Omicron BA.1, BA.1.1, BA.2, and BA.3 Variants</strong> - The SARS-CoV-2 Omicron variants were first detected in November 2021, and several Omicron lineages (BA.1, BA.2, BA.3, BA.4, and BA.5) have since rapidly emerged. Studies characterizing the mechanisms of Omicron variant infection and sensitivity to neutralizing antibodies induced upon vaccination are ongoing by several groups. In the present study, we used pseudoviruses to show that the transmembrane serine protease 2 (TMPRSS2) enhances infection of BA.1, BA.1.1, BA.2, and BA.3 Omicron 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>Molecular mechanisms and therapeutic target of NETosis in diseases</strong> - Evidence shows that neutrophils can protect the host against pathogens in multiple ways, including the formation and release of neutrophil extracellular traps (NETs). NETs are web-like structures composed of fibers, DNA, histones, and various neutrophil granule proteins. NETs can capture and kill pathogens, including bacteria, viruses, fungi, and protozoa. The process of NET formation is called NETosis. According to whether they depend on nicotinamide adenine dinucleotide phosphate (NADPH),…</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>Reinforcement sensitivity theory may predict COVID-19 infection outcome and vulnerability</strong> - Research suggests that specific behavior patterns may be related with the outcome and vulnerability of a COVID-19 infection; nevertheless, much of this information has been obtained by means of psychological paradigms that are not based on research conducted using experimental designs. Thus, the purpose of the present study was to identify behavior patterns associated with COVID-19 outcome and vulnerability from the point of view of the Reinforcement Sensitivity Theory. A total of 464 college…</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 Remarkable Roles of the Receptor for Advanced Glycation End Products (RAGE) and Its Soluble Isoforms in COVID-19: The Importance of RAGE Pathway in the Lung Injuries</strong> - The respiratory symptoms of acute respiratory distress syndrome (ARDS) in the coronavirus disease 2019 (COVID-19) patients is associated with accumulation of pre-inflammatory molecules such as advanced glycation end-products (AGES), calprotectin, high mobility group box family-1 (HMGB1), cytokines, angiotensin converting enzyme 2 (ACE2), and other molecules in the alveolar space of lungs and plasma. The receptor for advanced glycation end products (RAGEs), which is mediated by the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exposure to phenytoin associates with a lower risk of post-COVID cognitive deficits: a cohort study</strong> - Post-COVID cognitive deficits (often referred to as ‘brain fog’) are common and have large impacts on patients’ level of functioning. No specific intervention exists to mitigate this burden. This study tested the hypothesis, inspired by recent experimental research, that post-COVID cognitive deficits can be prevented by inhibiting receptor-interacting protein kinase. Using electronic health record data, we compared the cognitive outcomes of propensity score-matched cohorts of patients with…</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 a rapid semiquantitative lateral flow assay for the prediction of serum neutralizing activity against SARS-CoV-2 variants</strong> - CONCLUSIONS: The ichroma™ COVID-19 nAb assay, with appropriate variant cut-offs, can be useful for the monitoring of anti-SARS-CoV-2 immunization and may provide a rapid prediction of protection, especially in individuals with significant levels of NAbs.</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>Plant-derived compounds effectively inhibit the main protease of SARS-CoV-2: An in silico approach</strong> - The current coronavirus disease 2019 (COVID-19) pandemic, caused by the coronavirus 2 (SARS-CoV-2), involves severe acute respiratory syndrome and poses unprecedented challenges to global health. Structure-based drug design techniques have been developed targeting the main protease of the SARS-CoV-2, responsible for viral replication and transcription, to rapidly identify effective inhibitors and therapeutic targets. Herein, we constructed a phytochemical dataset of 1154 compounds using deep…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Discovery of novel potential inhibitors of TMPRSS2 and Mpro of SARS-CoV-2 using E-pharmacophore and docking-based virtual screening combined with molecular dynamic and quantum mechanics</strong> - The pandemic of coronavirus disease is caused by the SARS-CoV-2 which is considered a global health issue. The main protease of COVID 19 (Mpro) has an important role in viral multiplication in the host cell. Inhibiting Mpro is a novel approach to drug discovery and development. Also, transmembrane serine proteases (TMPSS2) facilitate viral activation by cleavage S glycoproteins, thus considered one of the essential host factors for COVID-19 pathogenicity. Computational tools were widely used to…</p></li>
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