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190 lines
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<title>16 March, 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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<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>Lapses in the person radar: ADHD symptoms predict difficulty in interpersonal distancing</strong> -
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<div>
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Objective: Across contexts, from social cognition to the COVID-19 pandemic response, individual variation in the regulation of interpersonal distance has typically been viewed as a voluntary choice. Here we examine the frequency of unintentional lapses in interpersonal distancing, and their relationship with childhood ADHD symptoms. Method: We administered a novel measure of difficulty in interpersonal distancing across 3 undergraduate samples (total N = 1,233), in addition to measures of recalled childhood ADHD symptoms, mind wandering and hyperfocus. Results: Almost all (>97%) participants reported unintentional lapses in maintaining interpersonal distance, with 16% experiencing such lapses frequently. Thirty percent of the variance in these reports was accounted for by attentional traits: Inattentive and hyperactive/impulsive ADHD symptoms jointly predicted difficulties with interpersonal distancing, with the former relationship fully mediated by hyperfocus and spontaneous mind wandering. Conclusion: Both inattentive and hyperactive/impulsive ADHD symptoms confer vulnerability to frequent unintentional lapses in interpersonal distancing.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/2yrfj/" target="_blank">Lapses in the person radar: ADHD symptoms predict difficulty in interpersonal distancing</a>
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</div></li>
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<li><strong>Peg-interferon Lambda Single Dose Treatment for COVID-19: A Call to Avoid another Hydroxychloroquine Fiasco.</strong> -
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In this perspective, I counter-argue a claim that was recently made that a single dose of Peg-interferon lambda can significantly lower incidence of COVID-19 hospitalizations or emergency department visits. Some major flaws in a recently published article that suggested this benefit are discussed while asking the global authorities to learn from the prior mistakes and to be of utmost caution when considering its final decision regarding adoption of a single dose of Peg-interferon lambda to manage COVID-19. It has been declined to be published by the respective NEJM that published the fraudulent claim without any comment and it’s reasonable that many journals might be hesitant to allow a peer review. However, no matter my argument could seem harsh, the loss of millions of lives due to corrupted American journals and health care authorities that allowed failure pharmacotherapeutics to manage COVID-19 patients in return of billions of dollars profits is much harsher and I’ll not be surprised if this preprint follows numerous previous ones that I was tired and eventually gave up and stopped seeking to find a peer review opportunity.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/5xd6q/" target="_blank">Peg-interferon Lambda Single Dose Treatment for COVID-19: A Call to Avoid another Hydroxychloroquine Fiasco.</a>
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</div></li>
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<li><strong>Changes in Environmental Stress over COVID-19 Pandemic Likely Contributed to Failure to Replicate Adiposity Phenotype Associated with Krtcap3</strong> -
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<div>
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We previously identified Keratinocyte-associated protein 3, Krtcap3, as an obesity-related gene in female rats where a whole-body Krtcap3 knock-out (KO) led to increased adiposity compared to wild-type (WT) controls when fed a high-fat diet (HFD). We sought to replicate this work to better understand the function of Krtcap3 but were unable to reproduce the adiposity phenotype. In the current work, WT female rats ate more compared to WT in the prior study, with corresponding increases in body weight and fat mass, while there were no changes in these measures in KO females between the studies. The prior study was conducted before the COVID-19 pandemic, while the current study started after initial lock-down orders and was completed during the pandemic with a generally less stressful environment. We hypothesize that the environmental changes impacted stress levels and may explain the failure to replicate our results. Analysis of corticosterone (CORT) at euthanasia showed a significant study by genotype interaction where WT had significantly higher CORT relative to KO in Study 1, with no differences in Study 2. These data suggest that decreasing Krtcap3 expression may alter the environmental stress response to influence adiposity. We also found that KO rats in both studies, but not WT, experienced a dramatic increase in CORT after their cage mate was removed, suggesting a separate connection to social behavioral stress. Future work is necessary to confirm and elucidate the finer mechanisms of these relationships, but these data indicate the possibility of Krtcap3 as a novel stress gene.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.15.532439v1" target="_blank">Changes in Environmental Stress over COVID-19 Pandemic Likely Contributed to Failure to Replicate Adiposity Phenotype Associated with Krtcap3</a>
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</div></li>
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<li><strong>Homologous Ad26.COV2.S vaccination results in reduced boosting of humoral responses in hybrid immunity, but elicits antibodies of similar magnitude regardless of prior infection</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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The impact of previous SARS-CoV-2 infection on the durability of Ad26.COV2.S vaccine-elicited responses, and the effect of homologous boosting has not been well explored. We followed a cohort of healthcare workers for 6 months after receiving the Ad26.COV2.S vaccine and a further one month after they received an Ad26.COV2.S booster dose. We assessed longitudinal spike-specific antibody and T cell responses in individuals who had never had SARS-CoV-2 infection, compared to those who were infected with either the D614G or Beta variants prior to vaccination. Antibody and T cell responses elicited by the primary dose were durable against several variants of concern over the 6 month follow-up period, regardless of infection history. However, at 6 months after first vaccination, antibody binding, neutralization and ADCC were as much as 33-fold higher in individuals with hybrid immunity compared to those with no prior infection. Antibody cross-reactivity profiles of the previously infected groups were similar at 6 months, unlike at earlier time points suggesting that the effect of immune imprinting diminishes by 6 months. Importantly, an Ad26.COV2.S booster dose increased the magnitude of the antibody response in individuals with no prior infection to similar levels as those with previous infection. The magnitude of spike T cell responses and proportion of T cell responders remained stable after homologous boosting, concomitant with a significant increase in long-lived early differentiated CD4 memory T cells. Thus, these data highlight that multiple antigen exposures, whether through infection and vaccination or vaccination alone, result in similar boosts after Ad26.COV2.S vaccination.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.15.23287288v1" target="_blank">Homologous Ad26.COV2.S vaccination results in reduced boosting of humoral responses in hybrid immunity, but elicits antibodies of similar magnitude regardless of prior infection</a>
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</div></li>
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<li><strong>Latin-American Registry of Cardiovascular Disease and COVID-19: Final Results</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: COVID-19 is a global disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Patients with a severe or critical illness can develop respiratory and cardiovascular complications. This study aimed to describe a Latin American and Caribbean (LA&C) population with COVID-19 to provide information related to this disease, in-hospital cardiovascular complications and in-hospital mortality. Methods: The CARDIO COVID-19-20 Registry is an observational, multicenter, ambispective, and hospital-based registry of patients with confirmed COVID-19 infection that required in-hospital treatment in LAC. Enrollment of patients started on May 01, 2020, and ended on June 30, 2021. Results: The CARDIO COVID-19-20 Registry included 3260 patients from 44 institutions of 14 LA&C countries. 63.2% patients were male and median age was 61.0 years old. Most common comorbidities were overweight/obesity (49.7%), hypertension (49.0%), and diabetes mellitus (26.7%). Most frequent cardiovascular complications were cardiac arrhythmia (9.1%), decompensated heart failure (8.5%), and pulmonary embolism (3.9%). 53.5% of patients were admitted to Intensive Care Unit (ICU), and median length of stay at the ICU was 10.0 days. Support required in ICU included invasive mechanical ventilation (34.2%), vasopressors (27.6%), inotropics (10.3%) and vasodilators (3.7%). Rehospitalization after 30-day post discharge was 7.3%. In-hospital mortality and 30-day post discharge was 25.5% and 2.6%, respectively. Conclusions: The LA&C population with COVID-19 patients and hospitalization, has a considerable burden of cardiovascular diseases related to a worse prognosis. It is necessary to carry out a more specific analysis to determine risk factors for cardiovascular outcome.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.15.23287304v1" target="_blank">Latin-American Registry of Cardiovascular Disease and COVID-19: Final Results</a>
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</div></li>
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<li><strong>Left ventricular global longitudinal strain as a parameter of mild myocardial dysfunction in athletes after COVID-19</strong> -
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Background Whether impaired left ventricular (LV) function contributes to persistent cardiopulmonary symptoms or decreased exercise capacity after COVID-19 remains unclear. The aim of this prospective study was to determine differences in LV global longitudinal strain (GLS) between athletes who did not have a history of LV dysfunction but had a positive COVID-19 test (PCAt) and healthy control (CON) athletes and relate them to symptoms during COVID-19. Methods We performed 151 transthoracic echocardiographies in our high-performance laboratory. GLS was determined in four-, two-, and three-chamber views and assessed offline by a blinded investigator in 88 PCAt (35% women) at a median of two months after COVID-19 who trained at least three times per week with more than 20 MET per week and 52 CONs from the German national squad (38% women). Results GLS was significantly lower (GLS -18.53 ±1.94% vs. -19.94±1.42%, p<0.001) and diastolic function significantly reduced (E/A 1.54±0.52 vs. 1.66±0.43, p=0.020; E`l 0.15±0.04 vs. 0.17±0.04, p=0.009; E/E9l 5.74±1.74 vs. 5.22±1.36, p=0.024) in PCAt. There was no association between GLS and acute symptoms like resting dyspnea, exertional dyspnea during or after COVID-19, palpitations, chest pain or increased resting heart rate. However, there was a trend toward lower GLS in PCAt with subjectively perceived performance limitation (p=0.054). Conclusions In a cohort of athletes at a median two months after COVID-19, significantly lower GLS and diastolic function were observed, suggesting mild myocardial dysfunction. GLS could be used as a screening element during return-to-sport examinations.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.14.23287258v1" target="_blank">Left ventricular global longitudinal strain as a parameter of mild myocardial dysfunction in athletes after COVID-19</a>
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<li><strong>Modeling COVID-19 vaccination strategies in LMICs considering uncertainty in viral evolution and immunity</strong> -
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Vaccines against the SARS-CoV-2 virus were developed in record time, but their distribution has been highly unequal. With demand saturating in high-income countries, many low- and middle-income countries (LMIC) finally have an opportunity to acquire COVID-19 vaccines. But the pandemic has taken its toll, and a majority of LMIC populations have partial immunity to COVID-19 disease due primarily to viral infection. This existing immunity, combined with resource limitations, raises the question of how LMICs should prioritize COVID-19 vaccines relative to other competing health priorities. We modify an established computational model, Covasim, to address these questions in four diverse country-like settings under a variety of viral evolution, vaccine delivery, and novel immunity scenarios. Under continued Omicron-like viral evolution and mid-level immunity assumptions, results show that COVID-19 vaccines could avert up to 2 deaths per 1,000 doses if administered to high-risk (60+) populations as prime+boost or annual boosting campaigns. Similar immunization efforts reaching healthy children and adults would avert less than 0.1 deaths per 1,000 doses. Together, these modeling results can help to support normative guidelines and programmatic decision making towards objectively maximizing population health.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.15.23287285v1" target="_blank">Modeling COVID-19 vaccination strategies in LMICs considering uncertainty in viral evolution and immunity</a>
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</div></li>
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<li><strong>Living alone and mental health: parallel analyses in longitudinal population surveys and electronic health records prior to and during the COVID-19 pandemic</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Objectives: To describe the mental health gap between those who live alone and those who live with others, and to examine whether the COVID-19 pandemic had an impact on this gap. Design: Ten population based prospective cohort studies, and a retrospective descriptive cohort study based on electronic health records (EHRs). Setting: UK Longitudinal population-based surveys (LPS), and primary and secondary care records within the OpenSAFELY-TPP database. Participants: Participants from the LPS were included if they had information on living status in early 2020, valid data on mental ill-health at the closest pre-pandemic assessment and at least once during the pandemic, and valid data on a key minimum set of covariates. The EHR dataset included 16 million adults registered with primary care practices in England using TPP SystmOne software on 1st February 2020, with at least three months of registration, valid address data, and living in households of <16 people. Main outcome measures: In the LPS, self-reported survey measures of psychological distress and life satisfaction were assessed in the nearest pre-pandemic sweep and three periods during the pandemic: April-June 2020, July-October 2020, and November 2020-March 2021. In the EHR analyses, outcomes were morbidity codes recorded in primary or secondary care between March 2018 and January 2022 reflecting the diagnoses of depression, self-harm, anxiety, obsessive compulsive disorder, eating disorders, and severe mental illnesses. Results: The LPS consisted of 37,544 participants (15.2% living alone) and we found greater psychological distress (SMD: 0.09 (95% CI: 0.04, 0.14) and lower life satisfaction (SMD: -0.22 (95% CI: -0.30, -0.15) in those living alone pre-pandemic, and the gap between the two groups stayed similar after the onset of the pandemic. In the EHR analysis of almost 16 million records (21.4% living alone), codes indicating mental health conditions were more common in those who lived alone compared to those who lived with others (e.g., depression 26 and severe mental illness 58 cases more per 100,000). Recording of mental health conditions fell during the pandemic for common mental health disorders and the gap between the two groups narrowed. Conclusions: Multiple sources of data indicate that those who live alone experience greater levels of common and severe mental illnesses, and lower life satisfaction. During the pandemic this gap in need remained, however, there was a narrowing of the gap in service use, suggesting greater barriers to healthcare access for those who live alone.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.15.23287292v1" target="_blank">Living alone and mental health: parallel analyses in longitudinal population surveys and electronic health records prior to and during the COVID-19 pandemic</a>
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<li><strong>Post-COVID-19 syndrome and related dysautonomia affect patients life and work productivity</strong> -
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Background: A significant percentage of COVID-19 patients experience post-COVID-19 symptoms and signs. Post-COVID-19 syndrome affects physical and mental health of patients in several ways. Aim: To investigate the impact of post-COVID-19 syndrome and related dysautonomia on patients life and work productivity. Methods: We conducted a cross-sectional study in Greece using an online questionnaire. Study population included 108 workers over 18 years old that have been diagnosed with post-COVID-19 syndrome. Patients were recruited from the Long COVID Greece patients society. We measured demographic and clinical characteristics of patients, resilience, and social support. Results: Among patients, 68.5% stated that post-COVID-19 syndrome affected their daily life to a great extent, 25% to a moderate level, and 6.5% to a small extent. Moreover, 56.5% stated that post-COVID-19 syndrome affected their work productivity to a great extent, 27.8% to a moderate level, and 15.7% to a small extent. Multivariable analysis identified that females and patients with post-COVID-19 dysautonomia had more problems in their daily life. Moreover, increased duration of COVID-19 symptoms was associated with increased daily problems. Increased resilience was related with fewer problems in daily life. Also, we found that patients with post-COVID-19 dysautonomia had less work productivity. Moreover, increased duration of COVID-19 symptoms was associated with more problems in work. Resilience was related with increased work productivity. Conclusions: Post-COVID-19 syndrome and related dysautonomia affect significantly patients daily and work life. Also, resilience is an important preventive factor improving patients life. Policy makers should develop and implement educational programs to improve patients life. Healthcare professionals should be aware of the post-COVID-19 syndrome and its consequences in order to understand post-COVID-19 patients and their problems.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.15.23287298v1" target="_blank">Post-COVID-19 syndrome and related dysautonomia affect patients life and work productivity</a>
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<li><strong>Association of radiological severity with inflammatory biomarkers for prognostic prediction in patients with COVID-19</strong> -
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Background: Covid 19 caused by SARSCoV2 has become a pandemic. It has a rapid disease progression and causes severe and fatal complications. Associating radiological severity with effective biomarkers like CRP, leucocytes, lymphocytes, DDimer, would be helpful in screening, categorizing patient, preventing serious complications. Aims and Objectives: The aim of the study was to investigate association between levels of inflammatory biomarkers and correlate it with HRCT chest finding to identify patients at risk of fatal complications. Materials and Methods: It was a retrospective monocentric observational study undertaken at Ibn Tofail hospital COVID19 dedicated center. 177 Patients>18 year of age who were admitted from september 1, 2020 up to november 30,2020 with laboratory confirmed diagnosis of Covid19 were included in the study. Data was collected on demography, disease severity, laboratory measurements, radiology imaging retrospectively from records of patients. The disease severity was classified into light, mild to severe and critic based on CT Severity scoring. HRCT Chest and inflammatory biomarkers were sent in every patient at the time of admission and the outcome was recorded. Results: There were 116 male patients, 61 female patients in our study. Average age of patients having severe lung involvement is 61.9years, whereas Average age of patients having non-severe lung involvement is 56.8 years and showed significant association with severity of lung involvement (p value : 0.017). Severity of lung involvement according to HRCT chest findings was greater in patients with both raised values of CRP <0.001), DDimer (P value 0.032) and low values of lymphocytes (P value : 0.001) . Capillary oxygen SATURATION was also found to be significantly associated with radiological severity among covid19 patients. Compared with CRP, leukocytes, lymphocytes, and DDimeres levels, the CT severity score had higher sensitivity, specificity, and overall accuracy in predicting severe, critical cases, and short term mortality. Conclusion: the severity of Covid19 disease is correlated with radiological severity andinflammatory markers thereby it will help in immediate categorization of patients into different risk groups following diagnosis, to ensure optimal resource allocation.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.14.23287265v1" target="_blank">Association of radiological severity with inflammatory biomarkers for prognostic prediction in patients with COVID-19</a>
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<li><strong>Epithelial galectin-3 induces mitochondrial complex inhibition and cell cycle arrest of CD8+ T Cells in severe/critical ill COVID-19</strong> -
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Several studies have identified the presence of functionally depleted CD8+ T cells in COVID-19 patients, and particularly abnormally reduced CD8+ T cells in severe/critical patients, which may be a major cause of disease progression and poor prognosis. In this study, a proliferating-depleted CD8+ T cell phenotype was observed in severe/critical COVID-19 patients through scRNA-seq and scTCR-seq analysis. These CD8+ T cells were subsequently found to be characterized by cell cycle arrest and downregulation of mitochondrial biogenesis and respiratory chain complex genes. Cellchat analysis revealed that the Galectin signaling pathways between infected lung epithelial cells and CD8+ T cells play the key role in inducing CD8+ T cell reduction and dysfunction in severe/critical COVID-19. We used SARS-COV-2 ORF3a to transfect A549 epithelial cells, and co-cultured with CD8+ T cells. The ex vivo experiments confirmed that galectin-3 inhibited the transcription of mitochondrial respiratory chain complex III/IV genes in CD8+ T cells by suppressing the nuclear translocation of nuclear respiratory factor 1 (NRF1). In addition, the regulatory effect of galectin-3 was correlated with the activation of ERK signaling and/or the inhibition of Akt signaling. Galectin-3 inhibitor, TD-139, promoted nuclear translocation of NRF1, and enhanced mitochondrial respiratory chain complex III/IV gene expression and mitochondrial biogenesis, then restore the expansion ability of CD8+ T cells. Our study improved the understanding the immunopathogenesis and provided new target for the prevention and treatment of severe/critical COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.14.532609v1" target="_blank">Epithelial galectin-3 induces mitochondrial complex inhibition and cell cycle arrest of CD8+ T Cells in severe/critical ill COVID-19</a>
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<li><strong>scMinerva: an Unsupervised Graph Learning Framework with Label-efficient Fine-tuning for Single-cell Multi-omics Integrated Analysis</strong> -
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<div>
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Single-cell multi-omics is a rapidly growing field in biomedicine, where multiple biological contents, such as the epigenome, genome, and transcriptome, can be measured simultaneously. Despite its potential, the integrated analysis and prediction of cellular states based on this complex multi-omics data pose significant challenges due to data sparsity, high noise, and computational overhead. To address these challenges, we developed scMinerva, an unsupervised framework for single-cell multi-omics integrated analysis. The learned embeddings from the multi-omics data enable accurate integrated classification of cell types and stages. Specifically, we construct a heterogeneous graph from multiple omics and propose a novel biased random walk algorithm omics2vec, which can learn the heterogeneous biological graph in a way that balances both local and global network structures. scMinerva successfully outperforms existing unsupervised methods on various simulated and real-world datasets when fine-tuned by very few labels. Additionally, scMinerva demonstrates strong label efficiency, is robust to fluctuation in data quality, allows one omics to compensate for weakness in others and could effectively classify cells with different annotation granularities. Furthermore, we showcase scMinerva’s ability to accurately provide prospective biomarkers and predict cell differentiation trends for COVID-19-infected cells, through the joint analysis of multi-omics data.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.05.28.493838v2" target="_blank">scMinerva: an Unsupervised Graph Learning Framework with Label-efficient Fine-tuning for Single-cell Multi-omics Integrated Analysis</a>
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<li><strong>The real-world effectiveness of an intranasal spray A8G6 antibody cocktail in the post-exposure prophylaxis of COVID-19</strong> -
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Background: Due to the continuous appearance of novel SARS-CoV-2 variants that are resistant to approved antibodies and leading to the epidemic rebound, several approved neutralizing antibodies have been paused for their usage against COVID-19. Previously, we identified A8G6, an antibody combination of two synergic SARS-CoV-2 neutralizing antibodies 55A8 and 58G6, that showed broad neutralizing activities against Omicron variants. When administrated by the nasal spray delivery system, A8G6 showed promising efficacy in COVID-19 animal models and also showed favorable safety profile in preclinical models as well as in a first-in-human trial. The aim of this study is to evaluate the real-world efficacy of A8G6 neutralizing antibody nasal spray in post-exposure prevention of COVID-19. Methods: From November 27, 2022 to January 31, 2023, an open-label, non-randomized, two-arm, blank-controlled, investigator-initiated trial was conducted in Chongqing, China. High-risk healthy participants (18-65 years) within 72 hours after close contact to SARS-CoV-2 infected individuals were recruited and received a three-dose (1.4 mg/dose) A8G6 nasal spray treatment daily or no treatment (blank control) for 7 consecutive days. The primary end points were 1) the occurrence of positive SARS-CoV-2 RT-PCR cases in A8G6 treated group vs blank control group at the end of day 7; 2) time to SARS-CoV-2 positive conversion at the end of day 7. The secondary end points were 1) viral load of SARS-CoV-2 when participants became SARS-CoV-2 positive; 2) the time from SARS-CoV-2 infection to negative COVID-19 conversion. Safety end point of the nasal spray AG86 was analyzed by recording adverse events during the whole course of this trial. This study was registered with Chictr.org (ChiCTR2200066416). Findings: Of 513 enrolled participants, 173 in the A8G6 treatment group and 340 in the blank-control group were included in the analysis. SARS-CoV-2 infection occurred in 151/340 (44.4%) subjects in the blank control group and 12/173 (6.9%) subjects with the A8G6 treatment group. The result indicates that the intranasal spray A8G6 reduces the risk of SARS-CoV-2 infection (HR=0.12, 95% CI, 0.07-0.22; p<0.001). The prevention efficacy of the A8G6 treatment within 72-hours exposure was calculated to be 84.4% (95% CI: 74.4%-90.4%). Moreover, compared to the blank-control group, the time from the SARS-CoV-2 negative to the positive COVID-19 conversion was significantly longer in the AG86 treatment group (mean time: 3.4 days in the A8G6 treatment group vs 2.6 days in the control group, p=0.019). In the secondary end-point analysis, the A8G6 nasal treatment had no effects on the viral load at baseline SARS-CoV-2 RT-PCR positivity and the time of the negative COVID-19 conversion (viral clearance). Finally, 5 participants (3.1%) in the treatment group reported general adverse effects. We did not observe any severe adverse effects related to the A8G6 treatment in this study. Interpretation: In this study, the intranasal spray AG86 antibody cocktail showed potent efficacy for prevention of SARS-CoV-2 infection in close contacts of COVID-19 patients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.14.23287255v1" target="_blank">The real-world effectiveness of an intranasal spray A8G6 antibody cocktail in the post-exposure prophylaxis of COVID-19</a>
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<li><strong>Engineering Nanomolar Potent Protein-based Inhibitors for Papain-like Protease Guided by Residue Correlation Network</strong> -
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We developed a rational protocol with a minimal number of mutated residues to create highly potent and selective protein-based inhibitors. Guided by an interaction and dihedral correlation network of ubiquitin (Ub) and MERS coronaviral papain-like protease (PLpro) complex, our designed ubiquitin variant (UbV) with 3 mutated residues (A46F, K48E, and E64Y) resulted in a ~3,500-fold increase in functional inhibition as compared with the wild-type Ub (wtUb). Further optimization with C-terminal R74N and G75S mutations led to a KD of 1.5 nM and IC50 of 9.7 nM and 27,000-fold and 5,500-fold increases in affinity and potency and selectivity, respectively, without destabilizing the UbV structure. This approach effectively designs tight binding inhibitors, which assists the development of therapeutics for COVID-19 and other coronaviruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.15.532709v1" target="_blank">Engineering Nanomolar Potent Protein-based Inhibitors for Papain-like Protease Guided by Residue Correlation Network</a>
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<li><strong>Rapidly Adaptable Multiplexed Yeast Surface Display Serological Assay for Immune Escape Screening of SARS-CoV-2 Variants</strong> -
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With numerous variations in the Spike protein, including concentrated mutations in the receptor-binding domain (RBD), the SARS-CoV-2 Omicron variant significantly shifted in the trajectory of the COVID-19 pandemic. To understand individual patient risk profiles in the face of rapidly emerging variants, there is an interest in sensitive serological tests capable of analyzing patient IgG response to multiple variants in parallel. Here, we present a serological test based on yeast surface display and serum biopanning that characterizes immune profiles against SARS-CoV-2 RBD variants. We used this yeast-based multi-variant serology method to examine IgG titers from 30 serum samples derived from COVID-19-convalescent and vaccinated individuals in Switzerland and assessed the relative affinity of polyclonal serum IgG for Wuhan (B lineage), Delta (B.1.617.2 lineage), and Omicron (B.1.1.529 lineage) RBD domains. We validated and benchmarked our system against a commercial lateral flow assay and showed strong concordance. Our assay demonstrates that serum IgGs from patients recovered from severe COVID-19 between March-June 2021 bound tightly to both original Wuhan and Delta RBD variants, but became indistinguishable from background when assayed against Omicron, representing an affinity loss of >10-20 fold. Our yeast immunoassay is easily tailored and parallelized with newly emerging RBD variants.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.17.23286074v2" target="_blank">Rapidly Adaptable Multiplexed Yeast Surface Display Serological Assay for Immune Escape Screening of SARS-CoV-2 Variants</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Performance Evaluation of the CareSuperb™ COVID-19 Antigen Home Test</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: CareSuperb COVID-19 Antigen Home Test Kit<br/><b>Sponsor</b>: AccessBio, Inc.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Use of E-health Based Exercise Intervention After COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Exercise training using an e-health tool<br/><b>Sponsors</b>: Norwegian University of Science and Technology; University of Oslo<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>Effect of Selected Types of Breathing Exercises on Different Outcome Measures in Covid-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: breathing exercise<br/><b>Sponsor</b>: Basma Mosaad Abd-elrahman Abushady<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>Effect Of Calcitriol On Neutrophil To Lymphocytes Ratio And High Sensitivity C-Reactive Protein Covid-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Calcitriol; Other: Placebo<br/><b>Sponsor</b>: Universitas Sebelas Maret<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>Clinical Study for the Efficacy and Safety of Ropeginterferon Alfa-2b in Moderate COVID19.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: P1101 (Ropeginterferon alfa-2b); Procedure: SOC<br/><b>Sponsor</b>: National Taiwan University Hospital<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase I Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102)</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant variant COVID-19 vaccine(Sf9 cell)<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase II Clinical Trial of Recombinant Variant COVID-19 Vaccine (Sf9 Cell) (WSK-V102)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant variant COVID-19 vaccine (Sf9 cell); Biological: Recombinant COVID-19 vaccine (CHO cell); Biological: Recombinant COVID-19 vaccine (Sf9 cell)<br/><b>Sponsor</b>: WestVac Biopharma Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Compare QLS1128 With Placebo in Symptomatic Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: QLS1128; Drug: Placebo<br/><b>Sponsor</b>: Qilu 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>Effect of Kinesio Tape Versus Diaphragmatic Breathing Exercise In Post COVID-19</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Interventions</b>: Other: Pursed lip breathing; Other: Cognitive Behavior Therapy; Other: Diaphragmatic breathing exercise; Other: Kinesio tape<br/><b>Sponsor</b>: Cairo 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>Study of WPV01 Compared With Placebo in Patients With Mild/Moderate COVID-19 Infection</strong> - <b>Condition</b>: COVID-19 Infection<br/><b>Interventions</b>: Drug: WPV01; Drug: Placebo<br/><b>Sponsor</b>: Westlake Pharmaceuticals (Hangzhou) 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>Hydrogen-Oxygen Generator With Nebulizer for Adjuvant Treatment of Novel Coronavirus Disease 2019 (COVID-19)</strong> - <b>Conditions</b>: Covid19; Hydrogen-oxygen Gas; AMS-H-03<br/><b>Interventions</b>: Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03; Device: OLO-1 Medical Molecular Sieve Oxygen Generator<br/><b>Sponsor</b>: Guangzhou Institute of Respiratory Disease<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>ARVAC-A New Recombinant Coronavirus Disease 2019 (COVID-19)</strong> - <b>Condition</b>: COVID-19 Vaccine<br/><b>Interventions</b>: Biological: Gamma Variant RBD-based ARVAC-CG vaccine; Biological: Omicron Variant RBD-based ARVAC-CG vaccine; Biological: Bivalent RBD-based ARVAC-CG vaccine; Other: Placebo<br/><b>Sponsors</b>: Mónica Edith Lombardo; Universidad Nacional de San Martín (UNSAM); National Council of Scientific and Technical Research, Argentina; Laboratorio Pablo Cassará S.R.L.<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>Oxygen Atomizing Inhalation of EGCG in the Treatment COVID-19 Pneumonia in Cancer Patients</strong> - <b>Conditions</b>: COVID-19 Pneumonia; Neoplasms Malignant<br/><b>Interventions</b>: Drug: EGCG; Drug: Placebo<br/><b>Sponsor</b>: Shandong Cancer Hospital and Institute<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Use of Photobiomodulation in the Treatment of Oral Complaints of Long COVID-19.A Randomized Controlled Trial.</strong> - <b>Conditions</b>: Xerostomia; COVID-19; Long COVID; Persistent COVID-19<br/><b>Interventions</b>: Combination Product: Institutional standard treatment for xerostomia and Long Covid; Radiation: Photobiomodulation Therapy; Radiation: Placebo Photobiomodulation Therapy<br/><b>Sponsor</b>: University of Nove de Julho<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>Balneotherapy for Patients With Post-acute Coronavirus Disease (COVID) Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Other: Balneotherapy and aquatic exercises<br/><b>Sponsors</b>: Parc de Salut Mar; Caldes de Montbui’s City Council; Consorcio Centro de Investigación Biomédica en Red (CIBER); European Regional Development Fund<br/><b>Completed</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>A confirmed COVID-19 in a patient with newly diagnosed hypertension and preexisting type 2 diabetes mellitus: a case report</strong> - CONCLUSION: Poor blood glucose management in the case of COVID-19 may increase the pathogen’s susceptibility, the likelihood that patients will be admitted to the hospital, and the likelihood that mortality will be enhanced.</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>Zilucoplan in immune-mediated necrotising myopathy: a phase 2, randomised, double-blind, placebo-controlled, multicentre trial</strong> - BACKGROUND: Immune-mediated necrotizing myopathy (IMNM) is an autoimmune myopathy characterised by proximal muscle weakness, high creatine kinase (CK) values, and autoantibodies recognizing 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) or the signal recognition particle (SRP). There are currently no approved therapies for IMNM and many patients experience active disease despite off-label treatment with intravenous immunoglobulin, glucocorticoids, and immunosuppressants. Detection 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>Delivery of anti-microRNA-21 by lung-targeted liposomes for pulmonary fibrosis treatment</strong> - Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder with a low survival rate. Pulmonary fibrosis is one of the complications of COVID-19 and has a high prevalence in COVID-19 patients. Currently, no effective therapies other than lung transplantation are available to cure IPF and post-COVID-19 pulmonary fibrosis. MicroRNAs are small non-coding RNAs that mediate the development and progression of pulmonary fibrosis, thus making them potent drug candidates for this serious disease….</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>Insights of different analytical approaches for estimation of budesonide as COVID-19 replication inhibitor in its novel combinations: green assessment with AGREE and GAPI approaches</strong> - Simple, direct, rapid, and sensitive HPLC and spectrophotometric methods were established for simultaneous estimation of a novel combination of budesonide and azelastine (BUD/AZL) in their laboratory-prepared mixture and dosage form according to the medicinally recommended ratio 1:4.28. Budesonide is an important inhalation corticosteroid that plays a vital role in the inhibition of COVID-19 replication and cytokine production. The first chromatographic method was created for the simultaneous…</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 multi-organoid platform identifies CIART as a key factor for SARS-CoV-2 infection</strong> - COVID-19 is a systemic disease involving multiple organs. We previously established a platform to derive organoids and cells from human pluripotent stem cells to model SARS-CoV-2 infection and perform drug screens^(1,2). This provided insight into cellular tropism and the host response, yet the molecular mechanisms regulating SARS-CoV-2 infection remain poorly defined. Here we systematically examined changes in transcript profiles caused by SARS-CoV-2 infection at different multiplicities 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>Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients</strong> - CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the ‘cytokine storm’ in COVID-19.</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>Teicoplanin derivatives block spike protein mediated viral entry as pan-SARS-CoV-2 inhibitors</strong> - The rapid emergence of highly transmissible SARS-CoV-2 variants poses serious threat to the efficacy of vaccines and neutralizing antibodies. Thus, there is an urgent need to develop new and effective inhibitors against SARS-CoV-2 and future outbreaks. Here, we have identified a series of glycopeptide antibiotics teicoplanin derivatives that bind to the SARS-CoV-2 spike (S) protein, interrupt its interaction with ACE2 receptor and selectively inhibit viral entry mediated by S protein….</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>Paving New Roads Using <em>Allium sativum</em> as a Repurposed Drug and Analyzing its Antiviral Action Using Artificial Intelligence Technology</strong> - CONCLUSIONS: The COVID-19 pandemic has triggered interest among researchers to conduct future research on molecular docking with clinical trials before releasing salutary remedies against the deadly malady.</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>Brevicillin, a novel lanthipeptide from the genus Brevibacillus with antimicrobial, antifungal and antiviral activity</strong> - CONCLUSION: This study provides detailed description of a novel lanthipeptide and demonstrates its effective antibacterial, antifungal and anti-SARS-CoV-2 activity.</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 residual humoral immune response against SARS-CoV-2 by a surrogate virus neutralization test (sVNT) 9 months after BNT162b2 primary vaccination</strong> - The humoral response to SARS-CoV-2 vaccination has shown to be temporary, although may be more prolonged in vaccinated individuals with a history of natural infection. We aimed to study the residual humoral response and the correlation between anti-Receptor Binding Domain (RBD) IgG levels and antibody neutralizing capacity in a population of health care workers (HCWs) after 9 months from COVID-19 vaccination. In this cross-sectional study, plasma samples were screened for anti-RBD IgG using a…</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 Antiviral Activity of Gemcitabine Derivatives against Influenza Virus and Severe Acute Respiratory Syndrome Coronavirus 2</strong> - Gemcitabine is a nucleoside analogue of deoxycytidine and has been reported to be a broad-spectrum antiviral agent against both DNA and RNA viruses. Screening of a nucleos(t)ide analogue-focused library identified gemcitabine and its derivatives (compounds 1, 2a, and 3a) blocking influenza virus infection. To improve their antiviral selectivity by reducing cytotoxicity, 14 additional derivatives were synthesized in which the pyridine rings of 2a and 3a were chemically modified….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A novel mAb broadly neutralizes SARS-CoV-2 VOCs in vitro and in vivo, including the Omicron variants</strong> - Novel immune escape variants have emerged as SARS-CoV-2 continues to spread worldwide. Many of the variants cause breakthrough infections in vaccinated populations, posing great challenges to current antiviral strategies targeting the immunodominance of the receptor-binding domain within the spike protein. Here, we found that a novel broadly neutralizing monoclonal antibody (mAb), G5, provided efficient protection against SARS-CoV-2 variants of concern (VOCs) in vitro and in vivo. A single dose…</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>Mucosal immunization with Ad5-based vaccines protects Syrian hamsters from challenge with omicron and delta variants of SARS-CoV-2</strong> - SARS-CoV-2 variant clades continue to circumvent antibody responses elicited by vaccination or infection. Current parenteral vaccination strategies reduce illness and hospitalization, yet do not significantly protect against infection by the more recent variants. It is thought that mucosal vaccination strategies may better protect against infection by inducing immunity at the sites of infection, blocking viral transmission more effectively, and significantly inhibiting the evolution of new…</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>2-Deoxy-D-Glucose: A Novel Pharmacological Agent for Killing Hypoxic Tumor Cells, Oxygen Dependence-Lowering in Covid-19, and Other Pharmacological Activities</strong> - The nonmetabolizable glucose analog 2-deoxy-D-glucose (2-DG) has shown promising pharmacological activities, including inhibition of cancerous cell growth and N-glycosylation. It has been used as a glycolysis inhibitor and as a potential energy restriction mimetic agent, inhibiting pathogen-associated molecular patterns. Radioisotope derivatives of 2-DG have applications as tracers. Recently, 2-DG has been used as an anti-COVID-19 drug to lower the need for supplemental oxygen. In the present…</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>Potential Regulation of NF-κB by Curcumin in Coronavirus-Induced Cytokine Storm and Lung Injury</strong> - The current pandemic coronavirus disease-19 (COVID-19) is still a global medical and economic emergency with over 244 million confirmed infections and over 4.95 million deaths by October 2021, in less than 2 years. Severe acute respiratory syndrome (SARS), the Middle East respiratory syndrome coronavirus (MERS), and COVID-19 are three recent coronavirus pandemics with major medical and economic implications. Currently, there is no effective treatment for these infections. One major pathological…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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