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<title>17 February, 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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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Using Managers’ Expectations for Ex-ante Policy Evaluation: Evidence from the COVID-19 Crisis</strong> -
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Evaluation of the impacts of government policies during an economic crisis is often delayed until the outcomes are realized. Policies can be better guided if they can be evaluated amid a crisis, before the realization of outcomes. This study examines whether survey data on the expectations of small business managers can help evaluate two high-stake subsidies for firms amid the COVID-19 crisis in Japan, namely, Subsidy Program for Sustaining Businesses (SPSB) and Employment Adjustment Subsidy (EAS). We evaluate the accuracy of managers’ expectations, estimate the impact of subsidies on the expected firm survival, and compare it with the estimated impact on realized survival. We find that the managers’ expectations on their future sales, survival rate, and the possibility of receiving these subsidies predict the realized outcomes, although they were highly pessimistic about their survival rates. We find that the estimated impacts of the SPSB on the expected survival rates have the same sign as the estimated impact on the realized survival rates, but the size is more than twice because of the pessimism on survival. The estimated impacts of the EAS are both insignificant. Therefore, although its impact may be overestimated, managers’ expectations are useful for selecting an effective policy.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/cnqmr/" target="_blank">Using Managers’ Expectations for Ex-ante Policy Evaluation: Evidence from the COVID-19 Crisis</a>
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</div></li>
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<li><strong>Estimates of protection against SARS-CoV-2 infection and severe COVID-19 in Germany before the 2022/2023 winter season - the IMMUNEBRIDGE project</strong> -
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Despite the need to generate valid and reliable estimates of protection against SARS-CoV-2 infection and severe course of COVID-19 for the German population in summer 2022, there was a lack of systematically collected population-based data allowing for the assessment of the protection level in real-time. In the IMMUNEBRIDGE project, we harmonised data and biosamples for nine population-/hospital-based studies (total number of participants n=33,637) to provide estimates for protection levels against SARS-CoV-2 infection and severe COVID-19 between June and November 2022. Based on evidence synthesis, we formed a combined endpoint of protection levels based on the number of self-reported infections/vaccinations in combination with nucleocapsid/spike antibody responses (“confirmed exposures”). Four confirmed exposures represented the highest protection level, and no exposure represented the lowest. Most participants were seropositive against the spike antigen; 37% of the participants ≥79 years had less than four confirmed exposures (highest level of protection) and 5% less than three. In the subgroup of participants with comorbidities, 46-56% had less than four confirmed exposures. We found major heterogeneity across federal states, with 4%-28% of participants having less than three confirmed exposures. Using serological analyses, literature synthesis and infection dynamics during the survey period, we observed moderate to high levels of protection against severe COVID-19, whereas the protection against SARS-CoV-2 infection was low across all age groups. We found relevant protection gaps in the oldest age group and amongst individuals with comorbidities, indicating a need for additional protective measures in these groups.
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</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.16.23285816v1" target="_blank">Estimates of protection against SARS-CoV-2 infection and severe COVID-19 in Germany before the 2022/2023 winter season - the IMMUNEBRIDGE project</a>
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<li><strong>Construction of Fosmid-based SARS-CoV-2 replicons for antiviral drug screening and replication analyses in biosafety level 2 facilities</strong> -
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The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has necessitated the global development of countermeasures since its outbreak. However, current therapeutics and vaccines to stop the pandemic are insufficient and this is mainly because of the emergence of resistant variants, which requires the urgent development of new countermeasures, such as antiviral drugs. Replicons, self-replicating RNAs that do not produce virions, are a promising system for this purpose because they safely recreate viral replication, enabling antiviral screening in biosafety level (BSL)-2 facilities. We herein constructed three pCC2Fos-based RNA replicons lacking some open reading frames (ORF) of SARS-CoV-2: the Dorf2-8, {Delta}orf2.4, and {Delta}orf2 replicons, and validated their replication in Huh-7 cells. The functionalities of the {Delta}orf2-8 and {Delta}orf2.4 replicons for antiviral drug screening were also confirmed. We conducted puromycin selection following the construction of the {Delta}orf2.4-puro replicon by inserting a puromycin-resistant gene into the {Delta}orf2.4 replicon. We observed the more sustained replication of the {Delta}orf2.4-puro replicon by puromycin pressure. The present results will contribute to the establishment of a safe and useful replicon system for analyzing SARS-CoV-2 replication mechanisms as well as the development of novel antiviral drugs in BSL-2 facilities.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.15.528742v1" target="_blank">Construction of Fosmid-based SARS-CoV-2 replicons for antiviral drug screening and replication analyses in biosafety level 2 facilities</a>
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<li><strong>Factors associated with adverse outcomes among patients hospitalized at a COVID-19 treatment center run by Médecins sans Frontières in Herat, Afghanistan</strong> -
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Background Though many studies on COVID have been published to date, data on COVID-19 epidemiology, symptoms, risk factors and severity in low- and middle-income countries (LMICS), such as Afghanistan are sparse. Objective To describe clinical characteristics, severity, and outcomes of patients hospitalized in the MSF COVID-19 treatment center (CTC) in Herat, Afghanistan and to assess risk factors associated with severe outcomes. Methods 1113 patients were included in this observational study between June 2020 and April 2022. Descriptive analysis was performed on clinical characteristics, complications, and outcomes of patients. Univariate description by Cox regression to identify risk factors for an adverse outcome was performed. Adverse outcome was defined as death or transfer to a level 3 intensive care located at another health facility. Finally, factors identified were included in a multivariate Cox survival analysis. Results A total of 165 patients (14.8%) suffered from a severe disease course, with a median time of 6 days (interquartile range: 2-11 days) from admission to adverse outcome. In our multivariate model, we identified male gender, age over 50, high O2 flow administered during admission, lymphopenia, anemia and O2 saturation <=93% during the first three days of admission as predictors for a severe disease course (p<0.05). Conclusion Our analysis concluded in a relatively low rate of adverse outcomes of 14.8%. This is possibly related to the fact, that the resources at an MSF-led facility are higher, in terms of human resources as well as supply of drugs and biomedical equipment, including oxygen therapy devices, compared to local hospitals. Predictors for severe disease outcomes were found to be comparable to other settings.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.15.23285976v1" target="_blank">Factors associated with adverse outcomes among patients hospitalized at a COVID-19 treatment center run by Médecins sans Frontières in Herat, Afghanistan</a>
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<li><strong>Polygenic Risk Scores for Asthma and Allergic Disease Associate with COVID-19 Severity in 9/11 Responders</strong> -
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Background. Genetic factors contribute to individual differences in the severity of coronavirus disease 2019 (COVID-19). A portion of genetic predisposition can be captured using polygenic risk scores (PRS). Relatively little is known about the associations between PRS and COVID-19 severity or post-acute COVID-19 in community-dwelling individuals. Methods. Participants in this study were 983 World Trade Center responders infected for the first time with SARS-CoV-2 (mean age at infection=56.06, standard deviation [SD]=7.37, 918 (93.4%) male, 813 (82.7%) European ancestry). Seventy-five (7.6%) responders were in the severe COVID-19 category, that included hospitalization and other adverse outcomes; 306 (31.1%) reported at least one post-acute COVID-19 symptom at the 4-week follow-up. Analyses were adjusted for population stratification and demographic covariates. Findings. In responders with European ancestry, the asthma PRS was associated with severe COVID-19 category (odds ratio [OR]=1.61, 95% confidence interval: 1.17-2.21) and more severe COVID-19 symptomatology (β=.09, p=.01), independently of respiratory disease diagnosis. The allergic disease PRS similarly associated with severe COVID-19 category (OR=1.97, [1.26-3.07]). The PRS for COVID-19 hospitalization was associated with the risk of severe COVID-19 category (OR=1.35, [1.01-1.82]), but this association was smaller than for the asthma PRS. PRS for coronary artery disease and type II diabetes were not associated with COVID-19 severity. Interpretation. Taken together, the results indicate that recently developed polygenic biomarkers for asthma, allergic disease, and COVID-19 hospitalization capture some of the individual differences in severity and clinical course of COVID-19 illness in a community population. Funding. National Institute for Occupational Safety and Health, CDC.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.30.22279383v2" target="_blank">Polygenic Risk Scores for Asthma and Allergic Disease Associate with COVID-19 Severity in 9/11 Responders</a>
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<li><strong>“Is there anything else you would like to tell us?”: An analysis of language features in text responses to a study on mental health during the COVID-19 pandemic</strong> -
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The COVID-19 pandemic and associated restrictions have been a major stressor and exacerbated mental health worldwide. Qualitative data play a unique role in documenting mental state, via both language features and content. Within a longitudinal study on mental health during the COVID-19 pandemic, we analyzed free responses to the question: “Is there anything else you would like to tell us that might be important that we did not ask about?” We applied text analysis methods to ask whether individuals who responded to the item differed from non- responders, whether there were associations between language use and psychological status, and to characterize the content of responses and how responses changed over time. 3,655 individuals provided biweekly measures of mental health and responses to the COVID-19 pandemic for 6 months. Of these, 2,497 participants provided at least one free response (9,741 total responses). Response likelihood was influenced by demographic factors and health status: Participants who were male, Asian, Black, or Hispanic were less likely to respond, and odds of responding increased with age and education as well as with a history of physical health conditions. Although mental illness history did not influence an individual’s overall likelihood of responding, it was associated with more negative sentiment, negative word use, and higher usage of first-person singular pronouns. Responses were dynamically influenced by psychological status, such that distress and loneliness were positively associated with an individuals’ likelihood to respond at a given timepoint, and predicted more negativity. Finally, responses were negative in valence overall, exhibited fluctuations linked with external events, and covered a variety of topics, with the most common being mental health and emotion. Our results identify trends in language use during the first year of the pandemic, and suggest that the both the content of responses and overall sentiment are linked to mental health.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/xczdg/" target="_blank">“Is there anything else you would like to tell us?”: An analysis of language features in text responses to a study on mental health during the COVID-19 pandemic</a>
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<li><strong>The role of serum brain injury biomarkers in individuals with a mild-to-moderate COVID infection and Long-COVID - results from the prospective population-based COVI-GAPP study</strong> -
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Background: During and after mild (no hospitalization) or moderate (hospitalization without ICU) SARS-CoV-2 infections, a wide range of symptoms, including neurological disorders have been reported. It is, however, unknown if these neurological symptoms are associated with brain injury and whether brain injury and related symptoms also emerge in patients suffering from Long-COVID. Neuronal biomarkers such as serum neurofilament light chain and glial fibrillary acidic protein can be used to elucidate neuro-axonal and astroglial injuries. We therefore investigated whether these biomarkers are associated with the COVID-19 infection status (mild-to-moderate), the associated symptoms and Long-COVID. Methods: From 146 individuals of the general population with a post-acute, mild-to-moderate SARS-CoV-2 infection, serum neurofilament light chain (sNfL; marker of intra-axonal neuronal injury) and serum glial fibrillary acidic protein (sGFAP; marker of astrocytic activation/injury) were measured. Samples were taken before, during and after (five and ten months) a SARS-CoV-2 infection. Individual symptoms and Long-COVID status were assessed using questionnaires. Results: Neurological symptoms were described for individuals after a mild and moderate COVID-19 infection, however, serum markers of brain injury (sNfL/sGFAP) did not change after an infection (sNfL: P = 0.74; sGFAP: P = 0.24) and were not associated with headache (P = 0.51), fatigue (P = 0.93), anosmia (P = 0.77) and ageusia (P = 0.47). In participants with Long-COVID, sGFAP (P = 0.038), but not sNfL (P = 0.58) significantly increased but was not associated with neurological symptoms. Conclusion: Neurological symptoms in individuals after a mild-to-moderate SARS-CoV-2 infection with and without Long-COVID were not associated with brain injury, although there was some astroglial injury observed in Long-COVID patients. Funding: The COVI-GAPP study received grants from the Innovative Medicines Initiative (IMI grant agreement number 101005177), the Princely House of Liechtenstein, the government of the Principality of Liechtenstein, and the Hanela Foundation (Switzerland). None of the funders played a role in the study design, data collection, data analysis, data interpretation, writing of the report, or decision to publish.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.15.23285972v1" target="_blank">The role of serum brain injury biomarkers in individuals with a mild-to-moderate COVID infection and Long-COVID - results from the prospective population-based COVI-GAPP study</a>
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<li><strong>Characteristics and outcomes of 7620 Multiple Sclerosis patients admitted with COVID-19 in the United States</strong> -
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Background At the start of the COVID-19 pandemic, several experts raised concerns about its impact on Multiple Sclerosis (MS) patients. Several small sample studies were published throughout the pandemic highlighting certain risk factors and outcomes. This study aims to provide a perspective using the biggest inpatient database from the United States. Method We screened for COVID-19 cases between April to December 2020, via the 2020 National Inpatient Sample (NIS). Characteristics of COVID-19 patients with and without MS were studied. The odds of mortality, mechanical ventilation and non-invasive ventilation were also analyzed. Finally, we investigated the risk factors of various outcomes among MS patients. Results We identified 1,628,110 hospitalizations with COVID-19, including 7620 (0.5%) MS patients. 68.6% of MS cases were Whites, and 63.3% were covered by Medicare. Compared to non-MS patients, MS patients with COVID-19 were mostly Females, had depression, peripheral vascular disease, and smoked. However, MS patients had lower cases of alcohol abuse, obesity, hyperlipidemia, diabetes, hypertension, CKD, or maintenance dialysis. MS patients with COVID-19 were also younger (mean age 60.65 years vs. 62.60 years, p<0.01). 8.9% of MS patients with COVID-19 did not survive their hospitalization, and it was lower than non-MS cases (12.9%, aOR 0.783, 95% CI 0.721-0.852, p<0.01). Less MS patients with COVID-19 needed non-invasive ventilation (4.5% vs. 6.4%, aOR 0.790, 95% CI 0.706-0.883, p<0.01) and mechanical ventilation (9.0% vs. 11.2%, aOR 1.017, 95% CI 0.937-1.104, p=0.687). Furthermore, MS patients with COVID-19 reported higher odds of non-invasive ventilation if they were of ages 60 and above (aOR 2.124, p<0.01), had chronic pulmonary disease (aOR 1.691, p<0.01), obesity (aOR 1.69, p<0.01), and diabetes (aOR 1.573, p<0.01). Private insurance beneficiaries showed reduced risk compared to Medicare (aOR 0.523, p<0.01). Similarly, for mechanical ventilation, those ages 60 and above (aOR 1.404, p<0.01), alcohol abuse (aOR 6.404, p<0.01), obesity (aOR 1.417, p<0.01), diabetes (aOR 1.992, p<0.01), hypertension (aOR 1.269, p=0.016), or dialysis (aOR 3.003, p<0.01) had higher odds, while females (aOR 0.700, p<0.01), smokers (aOR 0.588, p<0.01), and those with depression (aOR 0.698, p<0.01) or hyperlipidemia (aOR 0.711, p<0.01) showed reduced odds. Our study further found higher odds of mortality among those of age 60 and above (aOR 3.813, p<0.01), chronic pulmonary disease (aOR 1.739, p<0.01), obesity (aOR 1.425, p<0.01), CKD (aOR 1.982, p<0.01), or a history of old MI (aOR 1.864, p<0.01) while females (aOR 0.610, p<0.01), smokers (aOR 0.770, p<0.01), as well as those with depression (aOR 0.695, p<0.01), and hyperlipidemia (aOR 0.769, p<0.01) showed better outcomes. Blacks had lower odds of dying (aOR 0.636, p<0.01), whereas Hispanics had higher odds of dying (aOR 1.674, p<0.01), compared to Whites. Medicaid and Privately insured patients had lower odds of dying compared to Medicare i.e. (aOR 0.435, p<0.01), and (aOR 0.488, p<0.01), respectively. Conclusion We found several differences in patient characteristics among MS and non-MS patients with COVID-19. MS patients were also less likely to die or require non-invasive ventilation than non-MS patients. Further risk factors influencing the different outcomes among MS patients were also identified.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.15.23285994v1" target="_blank">Characteristics and outcomes of 7620 Multiple Sclerosis patients admitted with COVID-19 in the United States</a>
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<li><strong>Adaptive metrics for an evolving pandemic: A dynamic approach to area-level COVID-19 risk designations</strong> -
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Throughout the COVID-19 pandemic, policymakers have proposed risk metrics, such as the CDC Community Levels, to guide local and state decision-making. However, risk metrics have not reliably predicted key outcomes and often lack transparency in terms of prioritization of false positive versus false negative signals. They have also struggled to maintain relevance over time due to slow and infrequent updates addressing new variants and shifts in vaccine- and infection-induced immunity. We make two contributions to address these weaknesses of risk metrics. We first present a framework to evaluate predictive accuracy based on policy targets related to severe disease and mortality, allowing for explicit preferences toward false negative versus false positive signals. This approach allows policymakers to optimize metrics for specific preferences and interventions. Second, we propose a novel method to update risk thresholds in real-time. We show that this adaptive approach to designating areas as high risk improves performance over static metrics in predicting 3-week-ahead mortality and intensive care usage at both state and county levels. We also demonstrate that with our approach, using only new hospital admissions to predict 3-week-ahead mortality and intensive care usage has performed consistently as well as metrics that also include cases and inpatient bed usage. Our results highlight that a key challenge for COVID-19 risk prediction is the changing relationship between indicators and outcomes of policy interest. Adaptive metrics therefore have a unique advantage in a rapidly evolving pandemic context.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.15.23285969v1" target="_blank">Adaptive metrics for an evolving pandemic: A dynamic approach to area-level COVID-19 risk designations</a>
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<li><strong>Post-COVID syndrome is associated with capillary alterations, macrophage infiltration and distinct transcriptomic signatures in skeletal muscles</strong> -
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The SARS-CoV-2 pandemic not only resulted in millions of acute infections worldwide, but also caused innumerable cases of post-infectious syndromes, colloquially referred to as long COVID. Due to the heterogeneous nature of symptoms and scarcity of available tissue samples, little is known about the underlying mechanisms. We present an in-depth analysis of skeletal muscle biopsies obtained from eleven patients suffering from enduring fatigue and post-exertional malaise after an infection with SARS-CoV-2. Compared to two independent historical control cohorts, patients with post-COVID exertion intolerance had fewer capillaries, thicker capillary basement membranes and increased numbers of CD169+ macrophages. SARS-CoV-2 RNA could not be detected in the muscle tissues, but transcriptomic analysis revealed distinct gene signatures compared to the two control cohorts, indicating immune dysregulations and altered metabolic pathways. We hypothesize that the initial viral infection may have caused immune-mediated structural changes of the microvasculature, potentially explaining the exercise-dependent fatigue and muscle pain.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.15.23285584v1" target="_blank">Post-COVID syndrome is associated with capillary alterations, macrophage infiltration and distinct transcriptomic signatures in skeletal muscles</a>
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<li><strong>Early Treatment, Inflammation and Post-COVID Conditions</strong> -
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ABSTRACT Background: Post-COVID conditions (PCC) are common and have significant morbidity. Risk factors for PCC include advancing age, female sex, obesity, and diabetes mellitus. Little is known about early treatment, inflammation, and PCC. Methods: Among 883 individuals with confirmed SARS-CoV-2 infection participating in a randomized trial of CCP vs. control plasma with available biospecimens and symptom data, the association between early COVID treatment, cytokine levels and PCC was evaluated. Cytokine and chemokine levels were assessed at baseline, day 14 and day 90 using a multiplexed sandwich immuosassay (Mesoscale Discovery). Presence of any self-reported PCC symptoms was assessed at day 90. Associations between COVID treatment, cytokine levels and PCC were examined using multivariate logistic regression models. Results: One-third of the 882 participants had day 90 PCC symptoms, with fatigue (14.5%) and loss of smell (14.5%) being most common. Cytokine levels decreased from baseline to day 90. In a multivariable analysis including diabetes, body mass index, race, and vaccine status, female sex (adjusted odds ratio[AOR]=2.70[1.93-3.81]), older age (AOR=1.32[1.17-1.50]), and elevated baseline levels of IL-6 (AOR=1.59[1.02-2.47]) were associated with development of PCC. There was a trend for decreased PCC in those with early CCP treatment (<5 days after symptom onset) compared to late CCP treatment. Conclusion: Increased IL-6 levels were associated with the development of PCC and there was a trend for decreased PCC with early CCP treatment in this predominately unvaccinated population. Future treatment studies should evaluate the effect of early treatment and anti-IL-6 therapies on PCC development.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.13.23285855v1" target="_blank">Early Treatment, Inflammation and Post-COVID Conditions</a>
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<li><strong>A large-scale serological survey in pets from October 2020 through June 2021 in France shows significantly higher exposure to SARS-CoV-2 in cats</strong> -
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect many animals, including pets such as dogs and cats. Many studies have documented infection in companion animals by bio-molecular and serological methods. However, only a few have compared seroprevalence in cats and dogs from the general population, and these studies were limited by small sample sizes and collections over short periods. Our goal was to obtain a more accurate evaluation of seroprevalence in companion animals in France and to determine whether cats and dogs differ in their exposure to SARS-CoV-2. For this purpose, we conducted an extensive SARS-CoV-2 serological survey of 2036 cats and 3577 dogs sampled by veterinarians during medical examinations in clinics throughout France. Sampling was carried out from October 2020 through June 2021, a period encompassing the second and third waves of SARS-CoV-2 infections in humans in the country. Using a microsphere immunoassay targeting receptor binding domain and trimeric spike protein, we found 7.1% seroprevalence in pets, in a subset of 308 seropositive samples, 26.3% had neutralizing antibodies. We found that cats were significantly more likely to test positive than dogs, with seropositivity rates of 9.3% and 5.9% in cats and dogs, respectively. Finally, data for both species showed that seroprevalence was lower in older animals and was not associated with the date of sampling or the sex of the animal. Our results show that cats are significantly more sensitive to SARS-CoV-2 than dogs, in line with experimental studies showing that cats are more susceptible than dogs. This study reinforces that pets are commonly infected or exposed to SARS-CoV-2, emphasizing the importance of a One-Health approach to the SARS-CoV-2 pandemic and raising the question of vaccination of companion animals in close contact with humans.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.12.23.521567v2" target="_blank">A large-scale serological survey in pets from October 2020 through June 2021 in France shows significantly higher exposure to SARS-CoV-2 in cats</a>
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<li><strong>Wastewater genomic surveillance tracks the spread of the SARS-CoV-2 Omicron variant across England</strong> -
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Background Many countries have moved into a new stage of managing the SARS-CoV-2 pandemic with minimal restrictions and reduced testing in the population, leading to reduced genomic surveillance of virus variants in individuals. Wastewater-based epidemiology (WBE) can provide an alternative means of tracking virus variants in the population but is lacking verifications of its comparability to individual testing data. Methods We analysed more than 19,000 samples from 524 wastewater sites across England at least twice a week between November 2021 and February 2022, capturing sewage from >70% of the English population. We used amplicon-based sequencing and the phylogeny based de-mixing tool Freyja to estimate SARS-CoV-2 variant frequencies and compared these to the variant dynamics observed in individual testing data from clinical and community settings. Findings We show that wastewater data can reconstruct the spread of the Omicron variant across England since November 2021 in close detail and aligns closely with epidemiological estimates from individual testing data. We also show the temporal and spatial spread of Omicron within London. Our wastewater data further reliably track the transition between Omicron subvariants BA1 and BA2 in February 2022 at regional and national levels. Interpretation Our demonstration that WBE can track the fast-paced dynamics of SARS-CoV-2 variant frequencies at a national scale and closely match individual testing data in time shows that WBE can reliably fill the monitoring gap left by reduced individual testing in a more affordable way.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.15.23285942v1" target="_blank">Wastewater genomic surveillance tracks the spread of the SARS-CoV-2 Omicron variant across England</a>
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<li><strong>Quantification of early nonpharmaceutical interventions 1 aimed at slowing transmission of Coronavirus Disease 2019 in the Navajo Nation and surrounding states (Arizona, Colorado, New Mexico, and Utah)</strong> -
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During an early period of the Coronavirus Disease 2019 (COVID-19) pandemic, the Navajo Nation, much like New York City, experienced a relatively high rate of disease transmission. Yet, between January and October 2020, it experienced only a single period of growth in new COVID-19 cases, which ended when cases peaked in May 2020. The daily number of new cases slowly decayed in the summer of 2020 until late September 2020. In contrast, the surrounding states of Arizona, Colorado, New Mexico, and Utah all experienced at least two periods of growth in the same time frame, with second surges beginning in late May to early June. To investigate the causes of this difference, we used a compartmental model accounting for distinct periods of non-pharmaceutical interventions (NPIs) (e.g., behaviors that limit disease transmission) to analyze the epidemic in each of the five regions. We used Bayesian inference to estimate region-specific model parameters from regional surveillance data (daily reports of new COVID-19 cases) and to quantify uncertainty in parameter estimates and model predictions. Our results suggest that NPIs in the Navajo Nation were sustained over the period of interest, whereas in the surrounding states, NPIs were relaxed, which allowed for subsequent surges in cases. Our region-specific model parameterizations allow us to quantify the impacts of NPIs on disease incidence in the regions of interest.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.15.23285971v1" target="_blank">Quantification of early nonpharmaceutical interventions 1 aimed at slowing transmission of Coronavirus Disease 2019 in the Navajo Nation and surrounding states (Arizona, Colorado, New Mexico, and Utah)</a>
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<li><strong>On the Impact of Mass Screening for SARS-CoV-2 through Self-Testing in Greece</strong> -
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The emergence of COVID-19 stressed country health systems up to the point of triggering compulsory public health interventions to flatten the epidemic curve. Most of the interventions during the first year of the pandemic were non-pharmaceutical and aimed to reduce the contact rate of the people, which reduced the transmission rate of all respiratory pathogens, but had a large social and financial burden. SARS-CoV-2 specific interventions included screening, that is testing of asymptomatic people, which was largely facilitated by the availability of self-testing lateral flow antigen detection devices. The importance of self-testing interventions in controlling COVID-19 epidemic is not well-documented. We study as a paradigm-model the self-testing COVID-19 mass screening program that was implemented in Greece, involving large, susceptible populations taking tests routinely and pre-emptively so as to enable early detection of infections. Using a novel compartmental model we quantify the effectiveness of the program in curbing the COVID-19 pandemic. Conservative estimates indicate that the program reduced the reproductive number by 4%, hospital admissions by 25% and deaths by 20%, which translated into approximately 20,000 averted hospitalizations and 2,000 averted deaths between April-December 2021. Self-testing mass screening programs are efficient interventions with minimal social and financial burden, thus they are invaluable tools to be considered in pandemic preparedness.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.15.23285963v1" target="_blank">On the Impact of Mass Screening for SARS-CoV-2 through Self-Testing in Greece</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>MG Granules Improve COVID-19 Efficacy and Safety of Convalescent Exercise Tolerance</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Manzi Guben granules<br/><b>Sponsors</b>: Second Affiliated Hospital, School of Medicine, Zhejiang University; The First Affiliated Hospital of Zhejiang Chinese Medical University; Hangzhou Hospital of Traditional Chinese Medicine; Suzhou Hospital of Traditional Chinese Medicine<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>Effects of Pilates in Patients With Post- -COVID-19 Syndrome: Controlled and Randomized Clinical Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Procedure: Pilates Exercises<br/><b>Sponsor</b>: Michele de Aguiar Zacaria<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>Heterologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine in Children 12-17 Years of Age</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: SARS-CoV-2 subunit protein recombinant vaccine<br/><b>Sponsors</b>: PT Bio Farma; Faculty of Medicine Universitas Padjadjaran<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>Improving Adherence to COVID-19 Prevention Behaviours: Test of Persuasive Messages</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Persuasive Appeal<br/><b>Sponsor</b>: University of Calgary<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>Incidence of COVID-19 Following Vaccination in Botswana Against SARS CoV 2</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: AZD 1222<br/><b>Sponsors</b>: Botswana Harvard AIDS Institute Partnership; AstraZeneca; Botswana Ministry of Health<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>Study Evaluating GS-5245 in Nonhospitalized Participants With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: GS-5245; Drug: GS-5245 Placebo<br/><b>Sponsor</b>: Gilead Sciences<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study To Assess The Efficacy and Safety of HH-120 Nasal Spray for the Treatment of Mild COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: HH-120 nasal spray; Drug: Placebo Comparator<br/><b>Sponsor</b>: Huahui Health<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study for Efficacy and Safety Assessment of the Drug RADAMIN®VIRO for COVID-19 Postexposure Prophylaxis</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Double-Stranded RNA sodium salt; Drug: Placebo<br/><b>Sponsor</b>: Promomed, 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>Study of Flonoltinib Maleate Tablets in the Treatment of Severe Novel Coronavirus (COVID-19) Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: VV116+SOC; Drug: SOC<br/><b>Sponsor</b>: Chengdu Zenitar Biomedical Technology Co., Ltd<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Access the Efficacy and Safety of STI-1558 in Adult Subjects With Mild or Moderate (COVID-19)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: STI-1558; Drug: STI-1558 placebo<br/><b>Sponsor</b>: Zhejiang ACEA 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>Pirfenidone in Adult Hospitalized Patients With COVID-19</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: Pirfenidone Oral Product; Drug: Pirfenidone placebo<br/><b>Sponsor</b>: Capital Medical University<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>Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cells in the Treatment of Long COVID-19</strong> - <b>Condition</b>: Long COVID-19<br/><b>Intervention</b>: Biological: UC-MSCs<br/><b>Sponsor</b>: Shanghai East 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>CONFIDENCE: a Multicomponent Clinic-based Intervention to Promote COVID-19 Vaccine Intention and Uptake Among Diverse Youth and Adolescents</strong> - <b>Condition</b>: COVID-19 Vaccination<br/><b>Intervention</b>: Behavioral: CONFIDENCE<br/><b>Sponsors</b>: University of Massachusetts, Worcester; Merck Sharp & Dohme LLC; Baystate Health<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>Cognitive Rehabilitation for People With Cognitive Covid19</strong> - <b>Condition</b>: Long Covid19<br/><b>Intervention</b>: Behavioral: Cognitive rehabilitation<br/><b>Sponsors</b>: University College, London; Bangor University; St George’s University Hospitals NHS Foundation Trust; University of Brighton; University Hospital Southampton NHS Foundation Trust; Greater Manchester Mental Health NHS Foundation Trust<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>Washing COVID-19 Away With a Hypertonic Seawater Nasal Irrigation Solution</strong> - <b>Condition</b>: SARS-CoV2 Infection<br/><b>Intervention</b>: Other: Hypertonic seawater solution<br/><b>Sponsor</b>: Larissa University Hospital<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>Effect of DPP4/CD26 expression on SARS‑CoV‑2 susceptibility, immune response, adenosine (derivatives m<sup>6</sup><sub>2</sub>A and CD) regulations on patients with cancer and healthy individuals</strong> - The worldwide COVID‑19 pandemic was brought on by a new coronavirus (SARS Cov‑2). A marker/receptor called Dipeptidyl peptidase 4/CD26(DPP4/CD26) may be crucial in determining susceptibility to tumors and coronaviruses. However, the regulation of DPP4 in COVID‑invaded cancer patients and its role on small molecule compounds remain unclear. The present study used the Human Protein Atlas, Monaco, and Schmiedel databases to analyze the expression of DPP4 in human tissues and immune cells. 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>P2X7 purinergic receptor: A potential target in heart diseases (Review)</strong> - The P2X7 purinergic receptor (P2X7R) is a non‑selective cation channel activated by high levels of adenosine triphosphate that are commonly present in serious conditions. Activation of this purinergic receptor is closely related to the development of various disease states including inflammatory and neurodegenerative disorders, orthopedic diseases and types of cancer. Accumulating evidence has shown that the P2X7R plays a crucial role in the development of various heart diseases. For example,…</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 OM-85 bacterial lysate: a new tool against SARS-CoV-2?</strong> - The emergence of SARS-CoV-2, a novel coronavirus, caused the global Coronavirus disease of 2019 (COVID-19) pandemic. Because SARS-CoV-2 mutates rapidly, vaccines that induce immune responses against viral components critical for target cell infection strongly mitigate but do not abrogate viral spread, and disease rates remain high worldwide. Complementary treatments are therefore needed to reduce the frequency and/or severity of SARS-CoV-2 infections. OM-85, a standardized lysate of 21 bacterial…</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>Renin-Angiotensin-Aldosterone Axis Inhibition Improves Outcome of Diabetic Patients with Chronic Hypertension and COVID-19: An Iranian Perspective</strong> - CONCLUSIONS: The current study suggests that ACE inhibitors and ARBs are associated with decreased mortality, ICU admission, and better ICU survival in the diabetic subgroup of hypertensive patients.</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>Nanoscale Interaction Mechanisms of Antiviral Activity</strong> - Nanomaterials have now found applications across all segments of society including but not limited to energy, environment, defense, agriculture, purification, food medicine, diagnostics, and others. The pandemic and the vulnerability of humankind to emerging viruses and other infectious diseases has renewed interest in nanoparticles as a potential new class of antivirals. In fact, a growing body of evidence in the literature suggests nanoparticles may have activity against multiple viruses…</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 Investigational Anti-SARS-CoV-2 Agent Ensitrelvir “S-217622”: A Very Promising Potential Universal Broad-Spectrum Antiviral at the Therapeutic Frontline of Coronavirus Species</strong> - Lately, nitrogenous heterocyclic antivirals, such as nucleoside-like compounds, oxadiazoles, thiadiazoles, triazoles, quinolines, and isoquinolines, topped the therapeutic scene as promising agents of choice for the treatment of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and their accompanying ailment, the coronavirus disease 2019 (COVID-19). At the same time, the continuous emergence of new strains of SARS-CoV-2, like the Omicron variant and its multiple…</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>High SARS-CoV-2 tropism and activation of immune cells in the testes of non-vaccinated deceased COVID-19 patients</strong> - CONCLUSIONS: Our findings indicate that high angiotensin II levels and activation of mast cells and macrophages may be critical for testicular pathogenesis. Importantly, our findings suggest that patients who become critically ill may exhibit severe alterations and harbor the active virus in the testes.</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 chitooligosaccharide on the inhibition of SARS-CoV-2 main protease</strong> - CONCLUSION: This study provides the theoretical basis to develop targeted Mpro inhibitors for the screening and application of anti-novel coronavirus drugs.</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 dithiocarbamates selectively inhibit 3CL protease of SARS-CoV-2 and other coronaviruses</strong> - Since end of 2019, the global and unprecedented outbreak caused by the coronavirus SARS-CoV-2 led to dramatic numbers of infections and deaths worldwide. SARS-CoV-2 produces two large viral polyproteins which are cleaved by two cysteine proteases encoded by the virus, the 3CL protease (3CL^(pro)) and the papain-like protease, to generate non-structural proteins essential for the virus life cycle. Both proteases are recognized as promising drug targets for the development of anti-coronavirus…</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>Screen for Modulation of Nucleocapsid Protein Condensation Identifies Small Molecules with Anti-Coronavirus Activity</strong> - Biomolecular condensates formed by liquid-liquid phase separation have been implicated in multiple diseases. Modulation of condensate dynamics by small molecules has therapeutic potential, but so far, few condensate modulators have been disclosed. The SARS-CoV-2 nucleocapsid (N) protein forms phase-separated condensates that are hypothesized to play critical roles in viral replication, transcription, and packaging, suggesting that N condensation modulators might have anti-coronavirus 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>Synthesis, X-ray crystal structure, Hirshfeld surface analysis and computational investigation into the potential inhibitory action of novel 6-(<em>p</em>-tolyl)-2-((<em>p</em>-tolyl)thio)methyl-7<em>H</em>-[1.2.4]triazolo[5,1-<em>b</em>][1,3,4]thiadiazine inhibits the main protease of COVID-19</strong> - In recent times, the novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now become a worldwide pandemic. With over 71 million confirmed cases, even though the effectiveness and side effects of the specific drugs and vaccines approved for this disease are still limited. Scientists and researchers from all across the world are working to find a vaccine and a cure for COVID-19 by using large-scale drug discovery and analysis….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The effect of vitamin C supplementation on favipiravir-induced oxidative stress and proinflammatory damage in livers and kidneys of rats</strong> - Favipiravir (FPV), an effective antiviral agent, is a drug used to treat influenza and COVID-19 by inhibiting the RNA-dependent RNA polymerase (RdRp) of RNA viruses. FPV has the potential to increase oxidative stress and organ damage. The purpose of this study was to demonstrate the oxidative stress and inflammation caused by FPV in the liver and kidneys of rats, as well as to investigate the curative effects of vitamin C (VitC). A total of 40 Sprague-Dawley male rats were randomly and equally…</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>Supporting and inhibiting factors of accepting COVID-19 booster vaccination in the elderly in north Jakarta, Indonesia</strong> - CONCLUSIONS: Most of the elderly displayed positive attitudes concerning booster shots, but it was discovered that some barriers need to be removed.</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>Comparison of the mucosal and systemic antibody responses in Covid-19 recovered patients with one dose of mRNA vaccine and unexposed subjects with three doses of mRNA vaccines</strong> - CONCLUSION: The booster benefited all subjects to obtain neutralizing antibody (NAb) against omicron BA.1 variant in plasma while only the Covid-19 recovered subjects had an extra enrichment in nasal NAb against omicron BA.1 variant.</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 development and validation of the pandemic medication-assisted treatment questionnaire for the assessment of pandemic crises impact on medication management and administration for patients with opioid use disorders</strong> - Pandemic and the globally applied restriction measures mainly affect vulnerable population groups, such as patients with opioid use disorders. Towards inhibiting SARS-Cov-2 spread, the medication-assisted treatment (MAT) programs follow strategies targeting the reduction of in-person psychosocial interventions and an increase of take-home doses. However, there is no available instrument to examine the impact of such modifications on diverse health aspects of patients under MAT. The aim of this…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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