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198 lines
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<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
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<title>17 May, 2023</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>Defining distinct RNA-protein interactomes of SARS-CoV-2 genomic and subgenomic RNAs</strong> -
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Host RNA binding proteins recognize viral RNA and play key roles in virus replication and antiviral defense mechanisms. SARS-CoV-2 generates a series of tiered subgenomic RNAs (sgRNAs), each encoding distinct viral protein(s) that regulate different aspects of viral replication. Here, for the first time, we demonstrate the successful isolation of SARS-CoV-2 genomic RNA and three distinct sgRNAs (N, S, and ORF8) from a single population of infected cells and characterize their protein interactomes. Over 500 protein interactors (including 260 previously unknown) were identified as associated with one or more target RNA at either of two time points. These included protein interactors unique to a single RNA pool and others present in multiple pools, highlighting our ability to discriminate between distinct viral RNA interactomes despite high sequence similarity. The interactomes indicated viral associations with cell response pathways including regulation of cytoplasmic ribonucleoprotein granules and posttranscriptional gene silencing. We validated the significance of five protein interactors predicted to exhibit antiviral activity (APOBEC3F, TRIM71, PPP1CC, LIN28B, and MSI2) using siRNA knockdowns, with each knockdown yielding increases in viral production. This study describes new technology for studying SARS-CoV-2 and reveals a wealth of new viral RNA-associated host factors of potential functional significance to infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.05.15.540806v1" target="_blank">Defining distinct RNA-protein interactomes of SARS-CoV-2 genomic and subgenomic RNAs</a>
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</div></li>
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<li><strong>Disparities in COVID-19-related trauma and internalizing symptoms across sexual orientation, race/ethnicity, and their intersection during the pandemic</strong> -
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Sexual minority individuals face elevated risk for internalizing problems due to minority stress, and internalizing problems may have been exacerbated with the onset of the COVID-19 pandemic. This study examined sexual orientation- and race/ethnicity-related mental health disparities during the first four months of COVID-19 stay-at-home orders. We investigated disparities in COVID-19-related trauma (CRT) and internalizing symptoms (depression, anxiety) in a university community sample via surveys in March-April (Wave 1) and May-June 2020 (Wave 2) cross-sectionally using t-tests and longitudinally using residualized change score regressions. The analytic sample (N = 646; M age = 25.70, SD age = 10.16 at Wave 1) comprised 350 (54.2%) non-Hispanic White and 296 (45.8%) racial/ethnic minority participants; and 514 (79.6%) heterosexual and 132 (20.4%) sexual minority participants. Except for Wave 1 CRT, sexual minority individuals reported greater symptomatology than heterosexual individuals across all outcomes at each wave and racial/ethnic minority individuals reported no differences in outcomes compared to non-Hispanic White individuals. Longitudinally, sexual minority individuals reported less recovery from CRT compared to heterosexual individuals. No similar longitudinal disparities were identified across race/ethnicity. These findings build upon a growing body of literature of mental health disparities during the COVID-19 pandemic. Results highlight the importance of examining CRT to understand the effects of the pandemic on minoritized populations, particularly sexual minority individuals. Further work is needed to elucidate the potential exacerbating effects of minority stress on these disparities.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/5jsz9/" target="_blank">Disparities in COVID-19-related trauma and internalizing symptoms across sexual orientation, race/ethnicity, and their intersection during the pandemic</a>
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</div></li>
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<li><strong>Quantifying and Realizing the Benefits of Targeting for Pandemic Response</strong> -
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To respond to pandemics such as COVID-19, policy makers have relied on interventions that target specific population groups or activities. Because targeting is operationally challenging and contentious, rigorously quantifying its benefits and designing practically implementable policies that achieve some of these benefits is critical for effective and equitable pandemic control. We propose a flexible framework that leverages publicly available data and a novel optimization algorithm based on model predictive control and trust region methods to compute optimized interventions that can target two dimensions of heterogeneity: age groups and the specific activities that individuals normally engage in. We showcase a complete implementation focused on the Ile-de-France region of France and use this case study to quantify the benefits of dual targeting and to propose practically implementable policies. We find that dual targeting can lead to Pareto improvements, reducing the number of deaths and the economic losses. Additionally, dual targeting allows maintaining higher activity levels for most age groups and, importantly, for those groups that are most confined, thus leading to confinements that are arguably more equitable. We then fit decision trees to explain the decisions and gains of dual-targeted policies and find that they prioritize confinements intuitively, by allowing increased activity levels for group-activity pairs with high marginal economic value prorated by social contacts, which generates important complementarities. Because dual targeting can face significant implementation challenges, we introduce two practical proposals inspired by real-world interventions - based on curfews and recommendations - that achieve a significant portion of the benefits without explicitly discriminating based on age.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.03.23.21254155v6" target="_blank">Quantifying and Realizing the Benefits of Targeting for Pandemic Response</a>
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</div></li>
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<li><strong>Effectiveness of Sotrovimab and Molnupiravir in community settings in England across the Omicron BA.1 and BA.2 sublineages: emulated target trials using the OpenSAFELY platform</strong> -
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Background The effectiveness of COVID-19 monoclonal antibody and antiviral therapies against severe COVID-19 outcomes is unclear. Initial benefit was shown in unvaccinated patients and before the Omicron variant emerged. We used the OpenSAFELY platform to emulate target trials to estimate the effectiveness of sotrovimab or molnupiravir, versus no treatment. Methods With the approval of NHS England, we derived population-based cohorts of non-hospitalised high-risk individuals in England testing positive for SARS-CoV-2 during periods of dominance of the BA.1 (16/12/2021-10/02/2022) and BA.2 (11/02/2022-21/05/2022) Omicron sublineages. We used the clone-censor-weight approach to estimate the effect of treatment with sotrovimab or molnupiravir initiated within 5 days after positive test versus no treatment. Hazard ratios (HR) for COVID-19 hospitalisation or death within 28 days were estimated using weighted Cox models. Results Of the 35,856 [BA.1 period] and 39,192 [BA.2 period] patients, 1,830 [BA.1] and 1,242 [BA.2] were treated with molnupiravir and 2,244 [BA.1] and 4,164 [BA.2] with sotrovimab. The estimated HRs for molnupiravir versus untreated were 1.00 (95%CI: 0.81;1.22) [BA.1] and 1.22 (0.96;1.56) [BA.2]; corresponding HRs for sotrovimab versus untreated were 0.76 (0.66;0.89) [BA.1] and 0.92 (0.79;1.06) [BA.2]. Interpretation Compared with no treatment, sotrovimab was associated with reduced risk of adverse outcomes after COVID-19 in the BA.1 period, but there was weaker evidence of benefit in the BA2 period. Molnupiravir was not associated with reduced risk in either period.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.12.23289914v1" target="_blank">Effectiveness of Sotrovimab and Molnupiravir in community settings in England across the Omicron BA.1 and BA.2 sublineages: emulated target trials using the OpenSAFELY platform</a>
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<li><strong>Predictors of Mortality in Hospitalized Patients with COVID-19: A One-Year Case-Control Study</strong> -
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Objective: To determine the associated factors with mortality, in addition to age and sex, in a high-complexity hospital in Bogota, Colombia, during the first year of the pandemic. Design: A case-control study. Setting: High-complexity center above 2,640 meters above sea level (masl) in Colombia. Methods: A case-control study was conducted on 564 patients admitted to the hospital with confirmed COVID-19. Deceased patients (n: 282) and a control group (n: 282), matched by age, sex, and month of admission, were included. Clinical and paraclinical variables were retrospectively obtained by systematic revision of clinical records. Multiple imputations by chained equation (MICE) were implemented to account for missing variables. Classification and regression trees (CART) were estimated to evaluate the interaction of associated factors on admission and their role in predicting mortality during hospitalization. Results: Most of the patients included were males in the seventh decade of life. Most of the admissions occurred between July and August 2021. Surprisingly, recovered patients reported heterogeneous symptomatology, whereas deceased patients were most likely to present respiratory distress, dyspnea, and seizures on admission. In addition, the latter group exhibited a higher burden of comorbidities and alterations in laboratory parameters. After the imputation of datasets, CART analysis estimated 14 clinical profiles based on respiratory distress, LDH, dyspnea, hemoglobin, D-dimer, ferritin, blood urea nitrogen, C-reactive protein, PaO2/FiO2, dysgeusia, total bilirubin, platelets, and gastroesophageal reflux disease. The accuracy model for prediction was 85.6% (P < 0.0001). Conclusion: Multivariate analysis yielded a reliable model to predict mortality in COVID-19. This analysis revealed new interactions between clinical and paraclinical features in addition to age and sex. Furthermore, this predictive model could offer new clues for the personalized management of this condition in clinical settings. Keywords: SARS-CoV-2, COVID-19, Mortality, Predictors, Risk Factors
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.12.23289918v1" target="_blank">Predictors of Mortality in Hospitalized Patients with COVID-19: A One-Year Case-Control Study</a>
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<li><strong>Immunoglobulin A as a key immunological molecular signature of post-COVID-19 conditions</strong> -
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COVID-19 has infected humans worldwide, causing millions of deaths or prolonged symptoms in survivors. The transient or persistent symptoms after SARS-CoV-2 infection have been defined as post-COVID-19 conditions (PCC). We conducted a study of 151 Brazilian PCC patients to analyze symptoms and immunoglobulin profiles, taking into account gender, vaccination, hospitalization and age. Fatigue and myalgia were the most common symptoms and lack of vaccination, hospitalization, and neuropsychiatric and metabolic comorbidities were relevant for the development of PCC. Analysis of serological immunoglobulins showed that IgA was higher in PCC patients, especially in the adult and elderly groups. Also, non-hospitalized and hospitalized PCC patients produced high and similar levels of IgA. Our results indicated that the detection of IgA antibodies against SARS-CoV-2 during the course of the disease could be associated with the development of PCC and may be an immunological signature to predict prolonged symptoms in COVID-19 patients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.11.23289866v1" target="_blank">Immunoglobulin A as a key immunological molecular signature of post-COVID-19 conditions</a>
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<li><strong>Understanding COVID-19 Vaccine Uptake and Hesitancy Among People With HIV in Freetown, Sierra Leone: A Cross-sectional Study</strong> -
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Objectives: People living with HIV (PWH) are at increased risk of COVID-19-related morbidity and mortality, yet less is known about COVID-19 vaccination uptake and hesitancy, especially in sub-Saharan Africa. We aimed to evaluate COVID-19 vaccine uptake and hesitancy among PWH in Sierra Leone. Methods: We conducted a cross-sectional study in a convenience sample of PWH in routine care at Connaught Hospital in Freetown, Sierra Leone from April through June 2022. We collected sociodemographic and health-related data. We used the VAX Scale, a validated instrument to assess attitudes towards COVID-19 vaccination. From the responses, we constructed hesitancy (VAX) scores, with higher scores implying negative attitudes toward vaccination. We used generalized linear models to identify factors associated with vaccine hesitancy. Results: A total of 490 PWH were enrolled (71.4% female, median age 38 years, median CD4 count 412 cells/mm3, 83.9% virologically suppressed). About 17.3% had received at least one dose of a COVID-19 vaccine. The mean VAX score was 43.14 ± 7.05, corresponding to 59.9% of participants classified as vaccine-hesitant. Preference for natural immunity (65.8%) and concerns about commercial profiteering (64.4%) were the commonest reasons for hesitancy, followed by mistrust of vaccine benefits (61.4%) and worries about future side effects (48.0%). In adjusted regression analysis, being Muslim (β = 2.563, p < 0.001) and residence in urban areas (β = 1.709, p = 0.010) were associated with greater vaccine hesitancy, while having tested ever for COVID-19 was associated with lesser vaccine hesitancy (β = -3.417, p = 0.027). Conclusion: We observed a low COVID-19 vaccine uptake and high hesitancy among PWH in Sierra Leone. Our findings underscore the need to address vaccine hesitancy as a critical element of efforts to boost COVID-19 vaccine uptake among this population in Sierra Leone.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.11.23289882v1" target="_blank">Understanding COVID-19 Vaccine Uptake and Hesitancy Among People With HIV in Freetown, Sierra Leone: A Cross-sectional Study</a>
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<li><strong>Outbreak of a carbapenem-resistant XDR Acinetobacter baumannii belonging to the International Clone II (IC2) in a clinical setting in Brazil, 2022</strong> -
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Carbapenem-resistant Acinetobacter baumannii (CRAB) is a leading cause of nosocomial infections worldwide, and the occurrence of extensively drug-resistant (XDR) lineages among them is increasing. Most of A. baumannii pandemic lineages, known as International clones, are represented by MDR/XDR CRAB strains. The IC2 is considered one of the most successful and widespread pandemic clones, however, it is rare in South America, where IC1, IC4 and IC5 are prevalent. In Brazil, besides sporadic reports, an IC2 outbreak was reported only once in Sao Paulo city during the COVID-19 pandemics. This study characterized an outbreak caused by IC2 strains (n=16) in a hospital in Rio de Janeiro in 2022. MLST (MLST Pasteur scheme) analysis revealed that all strains recovered from nosocomial infections belonged to ST2 and corresponded to CRAB presenting the XDR phenotype. In general, this broad resistance spectrum was explained by the presence of several antibiotic resistance genes (ARGs) (armA, blaTEM, blaOXA-23, blaOXA-66, and aacA4-catB8-aadA1-qacEdelta1/sul1 carried in class 1 integron). Interestingly, the strains characterized here presented a broader resistance spectrum compared to those of the unique other and contemporary IC2 outbreak in Brazil, although they shared most of the ARGs. This study stressed the possibility of the successful establishment of IC2 in Brazilian clinical settings during and after the COVID-19 pandemics in response to a series of events, such as the overuse of antibiotics, during that period.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.12.23289862v1" target="_blank">Outbreak of a carbapenem-resistant XDR Acinetobacter baumannii belonging to the International Clone II (IC2) in a clinical setting in Brazil, 2022</a>
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<li><strong>Absolute and relative excess mortality across demographic and clinical subgroups during the COVID-19 pandemic: an individual-level cohort study from a nationwide healthcare system of US Veterans</strong> -
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Background. Most analyses of excess mortality during the COVID-19 pandemic have employed aggregate data. Individual-level data from the largest integrated healthcare system in the US may enhance understanding of excess mortality. Methods. We performed an observational cohort study following patients receiving care from the Department of Veterans Affairs (VA) between 1 March 2018 and 28 February 2022. We estimated excess mortality on an absolute scale (i.e., excess mortality rates, number of excess deaths), and a relative scale by measuring the hazard ratio (HR) for mortality comparing pandemic and pre-pandemic periods, overall, and within demographic and clinical subgroups. Comorbidity burden and frailty were measured using the Charlson Comorbidity Index and Veterans Aging Cohort Study Index, respectively. Results. Of 5,905,747 patients, median age was 65.8 years and 91% were men. Overall, the excess mortality rate was 10.0 deaths/1000 person-years (PY), with a total of 103,164 excess deaths and pandemic HR of 1.25 (95% CI 1.25-1.26). Excess mortality rates were highest among the most frail patients (52.0/1000 PY) and those with the highest comorbidity burden (16.3/1000 PY). However, the largest relative mortality increases were observed among the least frail (HR 1.31, 95% CI 1.30-1.32) and those with the lowest comorbidity burden (HR 1.44, 95% CI 1.43-1.46). Conclusions. Individual-level data offered crucial clinical and operational insights into US excess mortality patterns during the COVID-19 pandemic. Notable differences emerged among clinical risk groups, emphasising the need for reporting excess mortality in both absolute and relative terms to inform resource allocation in future outbreaks.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.12.23289900v1" target="_blank">Absolute and relative excess mortality across demographic and clinical subgroups during the COVID-19 pandemic: an individual-level cohort study from a nationwide healthcare system of US Veterans</a>
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<li><strong>Heterogeneous changes in mobility in response to the SARS-CoV-2 Omicron BA.2 outbreak in Shanghai</strong> -
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The coronavirus disease 2019 (COVID-19) pandemic and the measures taken by authorities to control its spread had altered human behavior and mobility patterns in an unprecedented way. However, it remains unclear whether the population response to a COVID-19 outbreak varies within a city or among demographic groups. Here we utilized passively recorded cellular signaling data at a spatial resolution of 1km x 1km for over 5 million users and epidemiological surveillance data collected during the SARS-CoV-2 Omicron BA.2 outbreak from February to June 2022 in Shanghai, China, to investigate the heterogeneous response of different segments of the population at the within-city level and examine its relationship with the actual risk of infection. Changes in behavior were spatially heterogenous within the city and population groups, and associated with both the infection incidence and adopted interventions. We also found that males and individuals aged 30-59 years old traveled more frequently, traveled longer distances, and their communities were more connected; the same groups were also associated with the highest SARS-CoV-2 incidence. Our results highlight the heterogeneous behavioral change of the Shanghai population to the SARS-CoV-2 Omicron BA.2 outbreak and the its effect on the heterogenous spread of COVID-19, both spatially and demographically. These findings could be instrumental for the design of targeted interventions for the control and mitigation of future outbreaks of COVID-19 and, more broadly, of respiratory pathogens.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.12.23289890v1" target="_blank">Heterogeneous changes in mobility in response to the SARS-CoV-2 Omicron BA.2 outbreak in Shanghai</a>
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<li><strong>A Bayesian System to Track Outbreaks of Influenza-Like Illnesses Including Novel Diseases</strong> -
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It would be highly desirable to have a tool that detects the outbreak of a new influenza-like illness, such as COVID-19, accurately and early. This paper describes the ILI Tracker algorithm that first models the daily occurrence of a set of known influenza-like illnesses in a hospital emergency department using findings extracted from patient-care reports using natural language processing. We include results based on modeling the diseases influenza, respiratory syncytial virus, human metapneumovirus, and parainfluenza for five emergency departments in Allegheny County Pennsylvania from June 1, 2010 through May 31, 2015. We then show how the algorithm can be extended to detect the presence of an unmodeled disease which may represent a novel disease outbreak. We also include results for detecting an outbreak of an unmodeled disease during the mentioned time period, which in retrospect was very likely an outbreak of Enterovirus D68.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.10.23289799v1" target="_blank">A Bayesian System to Track Outbreaks of Influenza-Like Illnesses Including Novel Diseases</a>
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<li><strong>Regularized COVID-19 Forecast Ensemble Methods</strong> -
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Forecasts of COVID-19 outcomes play an essential role in alerting public health and government officials to the trajectory of the pandemic. The sudden and critical need for these forecasts spurred both the proliferation of diverse epidemiological transmission models from academia and industry across the United States and efforts to standardize and curate these model outputs. In many scientific domains, ensemble models, where individual forecasts are aggregated into one, have demonstrated smaller forecasting error than the individual models from which they are constructed. Using COVID-19 deaths as an index outcome, we developed and evaluated several ensemble approaches where point forecast models were combined via weighted sums based on historical individual model or ensemble model performance. We found that a simple method that minimized the error of the past performance of individual models and used L2 regularization to encourage broader distribution of weights across models outperformed a baseline mean ensemble and all other tested methods across US states for both absolute error and weighted interval scores. This suggests that performance-based ensembles can produce accurate forecasts despite training on only point forecasts and recent historical data, provided that sufficient regularization and constraints are used to capture uncertainty. Availability of an accurate and explainable ensemble forecast model can increase trust among stakeholders and the general public, thus bettering preparedness and response efforts during the COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.12.23289872v1" target="_blank">Regularized COVID-19 Forecast Ensemble Methods</a>
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<li><strong>Disrupted seasonality and association of COVID-19 with medically attended respiratory syncytial virus infections among young children in the US: January 2010-January 2023</strong> -
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Respiratory syncytial virus (RSV) infections and hospitalizations surged sharply in 2022 among young children. To assess whether COVID-19 contributed to this surge, we leveraged a real-time nation-wide US database of electronic health records (EHRs) using time series analysis from January 1, 2010 through January 31, 2023, and propensity-score matched cohort comparisons for children aged 0-5 years with or without prior COVID-19 infection. Seasonal patterns of medically attended RSV infections were significantly disrupted during the COVID-19 pandemic. The monthly incidence rate for first-time medically attended cases, most of which were severe RSV-associated diseases, reached a historical high rate of 2,182 cases per 1,0000,000 person-days in November 2022, corresponding to a related increase of 143% compared to expected peak rate (rate ratio: 2.43, 95% CI: 2.25-2.63). Among 228,940 children aged 0-5 years, the risk for first-time medically attended RSV during 10/2022-12/2022 was 6.40% for children with prior COVID-19 infection, higher than 4.30% for the matched children without COVID-19 (risk ratio or RR: 1.40, 95% CI: 1.27-1.55); and among 99,105 children aged 0-1 year, the overall risk was 7.90% for those with prior COVID-19 infection, higher than 5.64% for matched children without (RR: 1.40, 95% CI: 1.21-1.62). These data provide evidence that COVID-19 contributed to the 2022 surge of severe pediatric RSV cases.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.12.23289898v1" target="_blank">Disrupted seasonality and association of COVID-19 with medically attended respiratory syncytial virus infections among young children in the US: January 2010-January 2023</a>
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<li><strong>Composite interventions on outcomes of severely and critically ill patients with COVID-19 in Shanghai, China</strong> -
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Abstract Background: The sixty-day effects of initial composite interventions for the treatment of severely and critically ill patients with COVID-19 are not fully assessed. Methods: Using a bayesian piecewise exponential model, we analyzed the 60-day mortality, health-related quality of life (HRQoL) and disability in 1082 severely and critically patients with COVID-19 between December 8, 2022 and February 9, 2023 in Shanghai, China. The final 60-day follow-up was completed on April 10, 2023. Results: Among 1082 patients (mean age, 78.0 years), 421 [38.9%] women), 139 patients (12.9%) died within 60 days. Azvudine had a 99.8% probability of improving 2-month survival (adjusted HR, 0.44 [95% credible interval, 0.24-0.79]) and Paxlovid had a 91.9% probability of improving 2-month survival (adjusted HR, 0.71 [95% credible interval, 0.44-1.14]) compared with the control. IL-6 receptor antagonist, Baricitinib, and a-thymosin each had a high probability of benefit (99.5%, 99.4%, and 97.5%, respectively) compared to their controls, while the probability of trail-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.8%; HR, 1.64 [95% CrI, 1.06-2.50]), and glucocorticoid (91.4%; HR, 1.20 [95% CrI, 0.71-2.16]). Paxlovid, Azvudine and therapeutic anticoagulation showed significant reduction in disability (p<0.05) Conclusions: Among severely and critically ill patients with COVID-19 who received 1 or more therapeutic interventions, treatment with Azvudine had a high probability of improved 60-day mortality compared with the control, indicating its potential in resource-limited scenario. Treatment with IL-6 receptor antagonist, Baricitinib, and a-thymosin also had high probabilities of benefit of improving 2-month survival, among which a-thymosin could improve HRQoL. Treatment with Paxlovid, Azvudine and therapeutic anticoagulation could significantly reduce disability at day 60. Keyword: COVID-19; Azvudine; Paxlovid; Interleukin-6 receptor antagonist; Baricitinib, α-thymosin, Intravenous immunoglobulin
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.10.23289325v2" target="_blank">Composite interventions on outcomes of severely and critically ill patients with COVID-19 in Shanghai, China</a>
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<li><strong>Pre-pandemic humoral immunity to SARS-CoV-2 in Africa: systematic review and meta-analysis</strong> -
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Objective: To assess the evidence on the presence of antibodies cross-reactive with SARS-CoV-2 antigens in pre-pandemic samples from African populations. Methods: We performed a systematic review and meta-analysis of studies evaluating pre-pandemic African samples using pre-set assay-specific thresholds for SARS-CoV-2 seropositivity. Results: 26 articles with 156 datasets were eligible, including 3,437 positives among 29,923 measurements (11.5%) with large between-dataset heterogeneity. Positivity was similar for anti-N (14%) and anti-S antibodies (11%), higher for anti-S1 (23%) and lower for anti-RBD antibodies (7%). Positivity was similar, on average, for IgM and IgG. Positivity was seen prominently in countries where malaria transmission occurs throughout and in datasets enriched in malaria cases (14%, 95% CI, 12-15% versus 2%, 95% CI 1-2% in other datasets). Substantial SARS-CoV-2 reactivity was seen in high malaria burden with or without high dengue burden (14% and 12%, respectively), and not without high malaria burden (2% and 0%, respectively). Lower SARS-CoV-2 cross-reactivity was seen in countries and cohorts of high HIV seroprevalence. More sparse individual-level data showed associations of higher SARS-CoV-2 cross-reactivity with Plasmodium parasitemia and lower SARS-CoV-2 cross-reactivity with HIV seropositivity. Conclusions: Pre-pandemic samples from Africa show high levels of anti-SARS-CoV-2 seropositivity. Levels of cross-reactivity tracks especially with malaria prevalence.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.07.22280814v3" target="_blank">Pre-pandemic humoral immunity to SARS-CoV-2 in Africa: systematic review and meta-analysis</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>The Standard of Care Combined With Glucocorticoid in Elderly People With Mild or Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Glucocorticoid<br/><b>Sponsor</b>: Huashan Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Conducting Clinical Trials of the Medicine “Rutan Tablets 0.1g” No. 10 in the Complex Therapy of COVID-19</strong> - <b>Condition</b>: Patients With COVID-19<br/><b>Interventions</b>: Drug: The drug “Rutan 0.1”.; Other: Basic treatment<br/><b>Sponsor</b>: Research Institute of Virology, Ministry of Health of the Republic of Uzbekistan<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>Arginine Replacement Therapy in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Arginine Hydrochloride<br/><b>Sponsor</b>: Emory University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effectiveness of a Second COVID-19 Vaccine Booster in Chinese Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Intramuscularly administered Ad5-nCoV vaccine; Biological: Aerosolized Ad5-nCoV; Biological: DelNS1-2019-nCoV-RBD-OPT1; Biological: SYS6006<br/><b>Sponsor</b>: Jiangsu Province Centers for Disease Control and Prevention<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 Pilot Study Evaluating the Efficacy of the Vielight Neuro RX Gamma in the Treatment of Post COVID-19 Cognitive Impairment</strong> - <b>Condition</b>: Post COVID-19 Cognitive Impairment<br/><b>Interventions</b>: Device: Vielight Neuro RX Gamma active device; Device: Vielight Neuro RX Gamma sham device<br/><b>Sponsor</b>: Vielight 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>PAxlovid loNg cOvid-19 pRevention triAl With recruitMent In the Community in Norway</strong> - <b>Conditions</b>: Post COVID-19 Condition, Unspecified; SARS-CoV2 Infection; COVID-19<br/><b>Interventions</b>: Drug: Nirmatrelvir/ritonavir; Drug: Placebo<br/><b>Sponsors</b>: Haukeland University Hospital; University of Bergen<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>Working Towards Empowered Community-driven Approaches to Increase Vaccination and Preventive Care Engagement</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: mHealth Outreach; Other: Care Coordination<br/><b>Sponsors</b>: University of California, San Diego; San Ysidro Health 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>Role of Vit-D Supplementation on BioNTech, Pfizer Vaccine Side Effect and Immunoglobulin G Response</strong> - <b>Condition</b>: COVID-19 Respiratory Infection<br/><b>Intervention</b>: Combination Product: Vitamin-D<br/><b>Sponsor</b>: Sulaimany Polytechnic university<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>REVERSE-Long COVID-19 With Baricitinib Pilot Study</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>: Drug: Baricitinib 4 MG<br/><b>Sponsors</b>: Vanderbilt University Medical Center; Emory University; University of California, San Francisco; University of Minnesota; Vanderbilt University; Yale University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety, Tolerability and Immunogenicity of Alveavax-v1.2, a BA.2/Omicron-optimized, DNA Vaccine for COVID-19 Prevention</strong> - <b>Condition</b>: Sars-CoV-2 Infection<br/><b>Interventions</b>: Drug: Alveavax-v1.2; Drug: Janssen Ad26.COV2.S<br/><b>Sponsor</b>: Alvea Holdings, LLC<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>Post Covid-19 Dysautonomia Rehabilitation Randomized Controlled Trial</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome; Dysautonomia<br/><b>Interventions</b>: Procedure: Rehabilitation; Procedure: Standard of Care<br/><b>Sponsors</b>: Evangelismos Hospital; National and Kapodistrian University of Athens; LONG COVID GREECE; 414 Military Hospital of Special Diseases<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>COVID-19 Vaccination Detoxification in LDL-C</strong> - <b>Conditions</b>: COVID-19 Stress Syndrome; COVID-19 Vaccine Adverse Reaction; COVID-19-Associated Thromboembolism; COVID-19 Post-Intensive Care Syndrome; COVID-19-Associated Stroke; COVID-19 Respiratory Infection<br/><b>Intervention</b>: Combination Product: Atorvastatin Calcium Tablets<br/><b>Sponsor</b>: Yang I. Pachankis<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>Exercise for Health in Patients With Post-acute Sequelae of COVID-19</strong> - <b>Condition</b>: Long COVID<br/><b>Intervention</b>: Other: Rehabilitation program<br/><b>Sponsors</b>: Campus docent Sant Joan de Déu-Universitat de Barcelona; Hospital de Mataró; University of Barcelona<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>Digital Multimodal Rehabilitation for People With Post-acute COVID-19 Syndrome.</strong> - <b>Condition</b>: Post-COVID Syndrome<br/><b>Interventions</b>: Behavioral: RehabCovid_Telematic; Behavioral: RehabCovid_ImmersiveVR; Behavioral: Control_Condition<br/><b>Sponsors</b>: Consorci Sanitari de Terrassa; University of Barcelona; Universitat de Girona; Unitat Assistencial i Preventiva de l’Esport- Centre d’Alt rendiment; Politecnic University of Catalonia; Corporación Fisiogestión<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>Understanding the Determinants of Mucosal Immunity and Optimizing the Diagnosis of Infection With SARS-CoV-2 Variants</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Blood sample collection; Other: Saliva sample collection; Other: Nasopharyngeal and nasal sample collection; Other: Exhaled Breath Condensate (EBC)<br/><b>Sponsors</b>: Institut Pasteur; Biogroup Laboratoire de biologie médicale<br/><b>Not yet 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>Compounds from myrtle flowers as antibacterial agents and SARS-CoV-2 inhibitors: <em>In-vitro</em> and molecular docking studies</strong> - Plants and their related phytochemicals play a key role in the treatment of bacterial and viral infections, which inspire scientists to design and develop more efficient drugs starting from the phytochemical active scaffold. This work aims to characterize the chemical compounds of Myrtus communis essential oil (EO) from Algeria and to evaluate its in vitro antibacterial effect, as well as the in silico anti-SARS-CoV-2 activity. The chemical profile of hydrodistilled EO from myrtle flowers was…</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>Declined Humoral Immunity of Kidney Transplant Recipients to SARS-CoV-2 Vaccines</strong> - CONCLUSION: KTRs’ humoral response after SARS-CoV-2 vaccination is dramatically inhibited and wanes. Antibody levels show a significant decline over time in KTRs with hypertension; receiving triple immunosuppressive therapy or steroid-based or antimetabolite-based regimens; receiving mixed mRNA and viral vector vaccines; and with a transplant of >10 years.</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>Interactive network pharmacology and electrochemical analysis reveals electron transport-mediating characteristics of Chinese medicine formula Jing Guan Fang</strong> - BACKGROUND: Jing Guan Fang (JGF) is an anti-COVID-19 Chinese Medicine decoction comprised of five medicinal herbs to possess anti-inflammatory and antiviral properties for treatment. This study aims to electrochemically decipher the anti-coronavirus activity of JGF and show that microbial fuel cells may serve as a platform for screening efficacious herbal medicines and providing scientific bases for the mechanism of action (MOA) of TCMs.</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>Physicochemical characterization of reusable facemasks and theoretical adhesion by a challenged bacterium</strong> - CONCLUSION: Such information is valuable to understand attachment of biological particles and to contribute in the inhibition of this attachment.</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>Screening of SARS-CoV-2 antivirals through a cell-based RNA-dependent RNA polymerase (RdRp) reporter assay</strong> - COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus-2) continues to pose an international public health threat and thus far, has resulted in greater than 6.4 million deaths worldwide. Vaccines are critical tools to limit COVID-19 spread, but antiviral drug development is an ongoing global priority due to fast-spreading COVID-19 variants that may elude vaccine efficacies. The RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is an essential…</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>SARS-CoV-2 Omicron sub-lineages differentially modulate interferon response in human lung epithelial cells</strong> - Although most of the attention was focused on the characterization of changes in the Spike protein among variants of SARS-CoV-2 virus, mutations outside the Spike region are likely to contribute to virus pathogenesis, virus adaptation and escape to the immune system. Phylogenetic analysis of SARS-CoV-2 Omicron strains reveals that several virus sub-lineages could be distinguished, from BA.1 up to BA.5. Regarding BA.1, BA.2 and BA.5, several mutations concern viral proteins with antagonistic…</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>Purification and characterisation of heparin-like sulfated polysaccharides with potent anti-SARS-CoV-2 activity from snail mucus of Achatina fulica</strong> - Heparin-like sulfated polysaccharide, acharan sulfate, was purified from the mucus of an African giant snail with unique sulfated glycosaminoglycans (GAGs). This study reported on finding novel and safe heparin resources from Achatina fulica for further use as well as easy isolation and purification of the active fraction from the initial raw material. Its structure was characterised by a strong-anion exchange combined with high-performance liquid chromatography (HPLC) and nuclear magnetic…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Structure-guided optimization of adenosine mimetics as selective and potent inhibitors of coronavirus nsp14 N7-methyltransferases</strong> - The COVID-19 pandemic reveals the urgent need to develop new therapeutics targeting the SARS-CoV-2 replication machinery. The first antiviral drugs were nucleoside analogues targeting RdRp and protease inhibitors active on nsp5 Mpro. In addition to these common antiviral targets, SARS-CoV-2 codes for the highly conserved protein nsp14 harbouring N7-methyltransferase (MTase) activity. Nsp14 is involved in cap N7-methylation of viral RNA and its inhibition impairs viral RNA translation and immune…</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>Immunization with Recombinant Accessory Protein-Deficient SARS-CoV-2 Protects against Lethal Challenge and Viral Transmission</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a worldwide coronavirus disease 2019 (COVID-19) pandemic. Despite the high efficacy of the authorized vaccines, there may be uncertain and unknown side effects or disadvantages associated with current vaccination approaches. Live-attenuated vaccines (LAVs) have been shown to elicit robust and long-term protection by the induction of host innate and adaptive immune responses. In this study, we sought to verify an attenuation…</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>SARS-CoV-2 Enters Human Leydig Cells and Affects Testosterone Production In Vitro</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a SARS-like coronavirus, continues to produce mounting infections and fatalities all over the world. Recent data point to SARS-CoV-2 viral infections in the human testis. As low testosterone levels are associated with SARS-CoV-2 viral infections in males and human Leydig cells are the main source of testosterone, we hypothesized that SARS-CoV-2 could infect human Leydig cells and impair their function. We successfully detected…</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>NLRP3 Inflammasome’s Activation in Acute and Chronic Brain Diseases-An Update on Pathogenetic Mechanisms and Therapeutic Perspectives with Respect to Other Inflammasomes</strong> - Increasingly prevalent acute and chronic human brain diseases are scourges for the elderly. Besides the lack of therapies, these ailments share a neuroinflammation that is triggered/sustained by different innate immunity-related protein oligomers called inflammasomes. Relevant neuroinflammation players such as microglia/monocytes typically exhibit a strong NLRP3 inflammasome activation. Hence the idea that NLRP3 suppression might solve neurodegenerative ailments. Here we review the recent…</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>Structural and non-structural proteins in SARS-CoV-2: potential aspects to COVID-19 treatment or prevention of progression of related diseases</strong> - Coronavirus disease 2019 (COVID-19) is caused by a new member of the Coronaviridae family known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are structural and non-structural proteins (NSPs) in the genome of this virus. S, M, H, and E proteins are structural proteins, and NSPs include accessory and replicase proteins. The structural and NSP components of SARS-CoV-2 play an important role in its infectivity, and some of them may be important in the pathogenesis of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pan-sarbecovirus prophylaxis with human anti-ACE2 monoclonal antibodies</strong> - Human monoclonal antibodies (mAbs) that target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been isolated from convalescent individuals and developed into therapeutics for SARS-CoV-2 infection. However, therapeutic mAbs for SARS-CoV-2 have been rendered obsolete by the emergence of mAb-resistant virus variants. Here we report the generation of a set of six human mAbs that bind the human angiotensin-converting enzyme-2 (hACE2) receptor, rather than 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>A peptide derived from HSP60 reduces proinflammatory cytokines and soluble mediators: a therapeutic approach to inflammation</strong> - Cytokines are secretion proteins that mediate and regulate immunity and inflammation. They are crucial in the progress of acute inflammatory diseases and autoimmunity. In fact, the inhibition of proinflammatory cytokines has been widely tested in the treatment of rheumatoid arthritis (RA). Some of these inhibitors have been used in the treatment of COVID-19 patients to improve survival rates. However, controlling the extent of inflammation with cytokine inhibitors is still a challenge because…</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>Novel targeted inhibition of the IL-5 axis for drug reaction with eosinophilia and systemic symptoms syndrome</strong> - CONCLUSION: Current treatment guidelines for DRESS are based on case reports and expert opinion. Understanding the central role of eosinophils in DRESS pathogenicity emphasizes the need for future implementation of IL-5 axis blockade as steroid-sparing agents, potential therapy to steroid-resistant cases, and perhaps an alternative to CS treatment in certain DRESS patients more prone to CS toxicity.</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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