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<title>27 October, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Supply Chain Resilience Strategies During COVID-19: A Case of Apparel Manufacturers</strong> -
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<div>
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There are many natural and other disruptions to businesses and supply chains in this dynamic and uncertain business world. Facing those disruptions and surviving the company becomes highly challenging. Global apparel value chains have been severely disrupted by the COVID- 19 pandemic, which has delayed their recovery in the short term. This study explores how the sector mitigates challenges during the pandemic and the steps the industry should focus on in the new-normal era. Using a multidisciplinary approach, this study conducted an evidence- based case study method. Through secondary data, it was examined short-term and long-term strategies executed by the industry. Due to the scattered nature of the supply chain and the labour intensity, the apparel sector faced significant challenges compared to other businesses. However, the industry rebounded after the pandemic by adopting short-term and medium-term resilient strategies. This cross-case analysis discusses the challenges faced by apparel manufacturers during the COVID-19 pandemic in different countries. The industry adopted short-term and long-term solutions to recoup from the COVID-19 storm. The findings provide an opening for the researchers to explore the viability of the strategies adopted by the industry. Also, the results open avenues how for exploring other techniques to be assumed to be resilient in unexpected situations like COVID-19.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/z7g9e/" target="_blank">Supply Chain Resilience Strategies During COVID-19: A Case of Apparel Manufacturers</a>
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<li><strong>Occupational risk of SARS-CoV-2 infection: a nationwide register-based study of the Danish workforce during the Covid-19 pandemic 2020-21</strong> -
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Abstract (word count 246) Objectives Most earlier studies of occupational risk of Covid-19 covering the entire workforce are based on relatively rare outcomes such as hospital admission and mortality. This study examines the incidence of SARS-CoV-2 infection by occupational group based upon real-time polymerase chain reaction tests (RT-PCR). Methods The cohort includes 2.4 million Danish employees, 20-69 years of age. All data were retrieved from public registries. The sex-specific incidence rate ratios (IRR) of first-occurring positive RT-PCR test from week 8 of 2020 through week 50 of 2021 were computed by Poisson regression for each 4-digit DISCO-08 job code with more than 100 employees (337 in men; 297 in women). Occupational groups with low risk of workplace infection according to a job exposure matrix constituted the reference group. Risk estimates were adjusted by demographic, social and health characteristics including household size, completed Covid-19 vaccination, pandemic wave and occupation-specific frequency of testing. Results The IRR of a SARS-CoV-2 infection was elevated in 34 occupations comprising 12 % of male employees and 45 occupations comprising 41 % of female employees. All IRR estimates were below 2.0. Decreased IRRs were observed in 85 occupations in men but none in women. Discussion We observed a modestly increased risk of SARS-CoV-2 infection among employees in numerous occupations indicating a large potential for prevention actions, especially in the female workforce. Cautious interpretation of observed risk in specific occupations is needed because of methodological issues inherent in analyses of RT-PCR-test results and because of multiple statistical tests.
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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/10.1101/2022.10.25.22281247v1" target="_blank">Occupational risk of SARS-CoV-2 infection: a nationwide register-based study of the Danish workforce during the Covid-19 pandemic 2020-21</a>
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</div></li>
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<li><strong>Which curve are we flattening? The disproportionate impact of COVID-19 among economically marginalized communities in Ontario, Canada, was unchanged from wild-type to omicron</strong> -
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Economically marginalized communities have faced disproportionately higher risks for infection and death from COVID-19 across Canada. It was anticipated that health disparities would dissipate over time and during subsequent waves. We used person-level surveillance and neighbourhood-level income data to explore, using Lorenz curves and Gini coefficients, magnitude of inequalities in COVID-19 hospitalizations and deaths over five waves of COVID-19 in Ontario, Canada (population 14 million) between February 26, 2020 and February 28, 2022. We found that despite attempts at equity-informed policies alongside fluctuating levels of public health measures, inequalities in hospitalizations and deaths by income remained at levels observed during the first wave - prior to vaccination, discussion or implementation of equity-informed policies - and despite rising levels of hybrid immunity. There was no change in the magnitude of inequalities across all waves evaluated. Our findings indicate that interventions did not sufficiently address differential exposure risks amplified at the intersections of household crowding and size, workplace exposures, and systemic barriers to prevention and care (including access to therapeutics). Equity and effectiveness of programs are inherently linked and ongoing evaluation of both is central to inform the public health response to future waves of COVID-19 and other rapidly emergent pandemics.
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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/10.1101/2022.10.24.22281104v1" target="_blank">Which curve are we flattening? The disproportionate impact of COVID-19 among economically marginalized communities in Ontario, Canada, was unchanged from wild-type to omicron</a>
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<li><strong>A rapid review of Supplementary air filtration systems in health service settings. September 2022.</strong> -
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The aerosol spread of SARS-CoV-2 has been a major challenge for healthcare facilities and there has been increased use of supplementary air filtration to mitigate SARS-CoV-2 transmission. Appropriately sized supplementary room air filtration systems could greatly reduce aerosol levels throughout ward spaces. Portable air filtration systems, such as those combining high efficiency particulate air (HEPA) filters and ultraviolet (UVC) light sterilisation, may be a scalable solution for removing respiratory viruses such as SARS-CoV-2. This rapid review aimed to assess the effectiveness of supplementary air cleaning devices in health service settings such as hospitals and dental clinics (including, but not limited to HEPA filtration, UVC light and mobile UVC light devices) to reduce the transmission of SARS-CoV-2. One systematic review (Daga et al. 2021), three observational studies (Conway Morris et al. 2022, Thuresson et al. 2022, Sloof et al. 2022), one modelling study, (Buchan et al. 2020) and two experimental studies (Barnewall & Bischoff 2021, Snelling et al. 2022) were found. Outcome measures included symptom scores, presence of SARS-CoV-2 RNA in sample counts, general particulate matter counts, viral counts, and relative risk of SARS-CoV-2 exposure. From real world settings, the systematic review assessed the effectiveness of HEPA filtration in dental clinics (Daga et al. 2021), two additional observational studies assessed HEPA and UV light in UK hospital settings (Conway Morris et al. 2022, Sloof et al. 2022) and one observational study included mobile HEPA-filtration units in Swedish hospitals (Thuresson et al. 2022). Studies were published from 2020 onwards. Real world evidence suggests supplementary air systems have the potential to reduce SARS-CoV-2 in the air and subsequently reduce transmission or infection rates but further research, with study designs having lower risk of bias, is required. HEPA filters alongside UVC light could provide the most notable reductions in SARS-CoV-2 counts, although the supporting evidence relates to HEPA/UVC filtration, and this review does not provide evidence on the effectiveness of other potential supplementary air filtration systems that could be used. Evidence is limited on the optimum air changes per hour needed and the positioning of air filtration units in rooms.
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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/10.1101/2022.10.25.22281493v1" target="_blank">A rapid review of Supplementary air filtration systems in health service settings. September 2022.</a>
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</div></li>
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<li><strong>COVID-19 prognostic model using Bayesian networks learnt on patient data</strong> -
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The response to the ongoing second wave of the COVID-19 pandemic can be helped by giving medical professionals access to models learned on patient data. To achieve this, we learned a Bayesian network model to predict risk of ICU admission, death and time of stay in the hospital from patient history, initial vital signs, initial laboratory tests and medication. Data were obtained from patients that were admitted to an HM hospital with suspicion of COVID-19 until 24/04/2020, excluding unconfirmed diagnosis, those who were admitted before the epidemic started in Madrid, had an outcome that was not discharge or death or died within 24 hours of presentation. Relevant variables for the model were selected with help from medical professionals. We learned the model using Bayesian search as implemented in GeNIe. Of 2,307 patients in the dataset, 679 were excluded. With the remaining 1,645 patients, we learned a model that predicted death with 86.4% accuracy. Some of the initial variables were discarded because they were independent of the outcomes of interest conditioned on some of the other variables. This high redundancy might be useful to build simpler tests for the severity of COVID-19. We show how the model can be used at different stages of patient admission and even with only partial information about the patient. This can be done by clinicians that want a fast second opinion or a summary of the available data from previous patients similar to the one at hand. We then include how we plan to improve the model with extra patient data and how it could be expanded to other contexts, like for example, an epidemiological one.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.24.22281436v1" target="_blank">COVID-19 prognostic model using Bayesian networks learnt on patient data</a>
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<li><strong>Prospective cohort study of Cryptosporidium infection and shedding in infants and their households</strong> -
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Background. Cryptosporidium spp are responsible for significant diarrheal morbidity and mortality in under-five children. There is no vaccine, thus a focus on prevention is paramount. Prior studies suggest that person-to-person spread may be an important pathway for transmission to young children. Here we describe a longitudinal cohort study of 100 families with infants to determine rates of cryptosporidiosis within households during the COVID-19 pandemic. Methods. Families living in Mirpur, Bangladesh with one infant age 6-8 months were enrolled and followed with weekly illness survey and stool testing for Cryptosporidium for 8 months. Results. From December 2020 to August 2021, 100 families were enrolled. Forty-four percent of index children, and 35% of siblings had at least one Cryptosporidium infection. Shedding of Cryptosporidium occurred for a mean of 19 days (sd 8.3 days) in index infants, 16.1 days (sd 11.6) in children 1-5 years, and 16.2 days (sd 12.8) in adults. A longer duration of Cryptosporidium shedding was associated with growth faltering in infants. There was a spike in Cryptosporidium cases in May 2021, which coincided with a spike in SARS-CoV-2 cases in the region. Conclusion. In this intensive, longitudinal study of Cryptosporidium infection in families we found high rates of cryptosporidiosis in infants and children, and prolonged parasite shedding, especially among malnourished children. These data support that transmission within the household is an important route of exposure for young infants, and that treatment of non-diarrheal infection to interrupt person-to-person transmission within the home may be essential for preventing cryptosporidiosis in infants.
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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/10.1101/2022.10.25.22281515v1" target="_blank">Prospective cohort study of Cryptosporidium infection and shedding in infants and their households</a>
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<li><strong>Saliva-based COVID-19 Rapid Antigen Test: a practical and accurate alternative mass screening method</strong> -
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As SARS-CoV-2 and its variants continue to spread, a reliable and convenient alternative to nasopharyngeal swabbing and RT-PCR testing is needed. To test the usability and performance of saliva sample collection, saliva, nasal and nasopharyngeal swab specimens were collected from a total of 338 individuals consisting of confirmed COVID-19 patients and healthy subjects. To evaluate the diagnostic accuracy of self-collected and performed SARS-CoV-2 rapid antigen test on saliva and nasal swabs specimens, we compared its performance to nasopharyngeal swab specimen RT-PCR as a comparator test. In saliva specimens, the positive percent agreement was 90.14%, and the negative percent agreement was 99.61%, while in nasal swab specimens, the positive percent agreement was 91.55%, and the negative percent agreement was 100%, both meeting the sensitivity and specificity criteria required by the FDA. Therefore, when considering both the reliability and convenience of testing, we found saliva testing to be the better method for large-scale and frequent self-testing.
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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/10.1101/2022.10.24.22278691v1" target="_blank">Saliva-based COVID-19 Rapid Antigen Test: a practical and accurate alternative mass screening method</a>
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</div></li>
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<li><strong>Bell’s Palsy Following SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis</strong> -
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Background and Objective Bell9s palsy (BP) has been considered as a serious adverse event following the SARS-CoV-2 vaccination. Many studies have reported BP following vaccination, although neither a causative relationship nor a prevalence of the condition higher than the general population has been established. The outcomes of interest were to compare BP incidence among (a) SARS-CoV-2 vaccine recipients, (b) nonrecipients in the placebo or unvaccinated cohorts, (c) different types of SARS-CoV-2 vaccines, and (d) SARS-CoV-2 infected vs. SARS-CoV-2 vaccinated individuals. Methods We performed a systematic search through MEDLINE (via PubMed), Web of Science, Scopus, Cochrane library, and Google Scholar from the inception to August 15, 2022. We included articles reporting individuals receiving any SARS-CoV-2 vaccine in whom BP had occurred. Studies reporting facial paralysis due to etiologies other than BP were excluded. Random- and fixed-effects meta-analyses using the Mantel-Haenszel method were conducted for the quantitative synthesis. Newcastle-Ottawa scale (NOS) was used to assess the quality. The study was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, and the protocol was registered with PROSPERO (CRD42022313299). Analyses were carried out using the R, version 4.2.1 (R package 9meta9 version 5.2-0). Results Fifty studies were included, of which 17 entered the quantitative synthesis. First, pooling four phase-3 randomized controlled trials (RCT) indicated BP occurrence was significantly higher in SARS-CoV-2 vaccines (77, 525 doses) compared to placebo (66, 682 doses) (OR = 3.00, 95% CI = 1.10 - 8.18, I2 = 0%). Second, pooling nine observational studies of mRNA SARS-CoV-2 vaccine doses (13, 518,026) and matched unvaccinated individuals (13, 510,701) revealed no significant increase in the odds of BP in the vaccinated group compared to the unvaccinated group (OR: 0.70 (95% CI 0.42-1.16), I2=94%). The third meta-analysis suggested that post-vaccination BP among first dose Pfizer/BioNTech recipients (22,760,698) did not significantly differ from that in first dose Oxford/AstraZeneca recipients (22,978,880) (OR = 0.97, 95% CI = 0.82 - 1.15, I2 = 0%). According to the fourth meta-analysis, BP was significantly more commonly reported after SARS-CoV-2 infection (2,641,398) than after SARS-CoV-2 vaccinations (36,988,718) (RR = 4.03, 95% CI = 1.78 - 9.12, I2 = 96%). Conclusion Our meta-analysis suggests a higher incidence of BP among vaccinated vs. placebo groups. BP occurrence did not significantly differ between Pfizer/BioNTech and Oxford/AstraZeneca vaccines. SARS-CoV-2 infection posed a significantly greater risk for BP than SARS-CoV-2 vaccines.
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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/10.1101/2022.10.26.22281537v1" target="_blank">Bell’s Palsy Following SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis</a>
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<li><strong>Covid-19 pandemic has polarized the society toward negative and positive traits depending on a person’s resilience and certain predispositions</strong> -
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The Covid-19 pandemic has caused a major disruption affecting almost all aspects of health, social and economic dimensions of our lives on an almost unprecedented global scale. While Covid-19 itself is, first and foremost, a pernicious physical illness, its highly contagious nature has caused significant psychological stress with occasional dire mental health consequences which are still not fully understood. To address this issue, we have conducted a longitudinal study by administering standard self-reporting questionnaires covering five major personalities and six mental traits of subjects before and a few months after the outbreak. Results revealed the distribution of population scores to become more extreme in either positive or negative trait directions despite the stability of average trait scores across the population. Higher resilience was found to be positively correlated with improved trait scores post-pandemic. Further investigations showed that certain predispositions could have an effect on trait score change post-Covid depending on the subject9s pre-Covid scores. In particular, in the subjects with moderate scores, there was a significant negative correlation between the positive trait scores and the post minus pre-positive trait scores. By examining various traits and personalities, these findings depict a more thorough picture of the pandemic9s impact on society9s psychological well-being and reveal certain predispositions and vulnerabilities that shape the mental health landscape in the post-Covid period with implications for mental health policies in dealing with Covid-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.25.22281466v1" target="_blank">Covid-19 pandemic has polarized the society toward negative and positive traits depending on a person’s resilience and certain predispositions</a>
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<li><strong>What is the current state of public health system preparedness for infectious disease emergencies? A scoping review</strong> -
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Background: The COVID-19 pandemic continues to demonstrate the risks and profound health impacts that result from infectious disease emergencies. Emergency preparedness has been defined as the knowledge, capacity and organizational systems that governments, response and recovery organizations, communities and individuals develop to anticipate, respond to, or recover from emergencies. This scoping review explored recent literature on priority areas and indicators for public health emergency preparedness (PHEP) with a focus on infectious disease emergencies. Methods: Using scoping review methodology, a comprehensive search was conducted for indexed and grey literature with a focus on records published from 2017 and 2020 onward, respectively. Records were included if they: a) described PHEP, b) focused on an infectious emergency, and c) were published in an Organization for Economic Co-operation and Development country. An evidence-based all-hazards Resilience Framework for PHEP consisting of 11 elements was used as a reference point to identify additional areas of preparedness that have emerged in recent publications. The findings were summarized thematically. Results: The included publications largely aligned with the all-hazards Resilience Framework for PHEP. In particular, the elements related to collaborative networks, community engagement, risk analysis and communication were frequently observed across the publications included in this review. Emergent themes were identified that expand on the Resilience Framework for PHEP. These were related to mitigating inequities, public health capacities (vaccination, laboratory system capacity, infection prevention and control capacity, financial investment in infrastructure, public health legislation, phases of preparedness), scientific capacities (research and evidence-informed decision making, climate and environmental health), and considerations for health system capacity. Conclusions: The themes from this review contribute to the evolving understanding of critical public health preparedness actions; however, there was a paucity of recent evidence on PHEP indicators. The themes can expand on the 11 elements outlined in the Resilience Framework for PHEP, specifically relevant to infectious disease emergencies and risks. Further research will be important to validate these findings, and expand understanding of how refinements to PHEP frameworks and indicators can support public health practice.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.25.22281308v1" target="_blank">What is the current state of public health system preparedness for infectious disease emergencies? A scoping review</a>
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<li><strong>Effects of the COVID-19 pandemic on hospital admissions and inpatient mortality in Kenya</strong> -
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Background: The impact of COVID-19 in Africa remains poorly defined. We sought to describe trends in hospitalisation due to all medical causes, pneumonia-specific admissions, and inpatient mortality in Kenya before and during the first five waves of the COVID-19 pandemic in Kenya. Methods: We conducted a hospital-based observational study of patients admitted to 13 public referral facilities in Kenya from January 2018 to December 2021. The pre-COVID population included patients admitted before 1 March 2020. We fitted time series models to compare observed and predicted trends for each outcome. To estimate the impact of the COVID-19 pandemic we calculated incidence rate ratios (IRR) and corresponding 95% confidence intervals (CI) from negative binomial mixed-effects models. Results: Out of 302,703 patients (range 7453 to 27168) hospitalised across the 13 surveillance sites 84,337 (55.2%) were aged 15 years and older. Compared with the pre-COVID period, hospitalisations declined markedly among adult (IRR 0.68, 95% CI 0.63 to 0.73) and paediatric (IRR 0.67, 95% CI 0.62 to 0.73) patients. Adjusted in-hospital mortality also declined among both adult (IRR 0.83, 95% CI 0.77 to 0.89) and paediatric (IRR 0.85, 95% CI 0.77 to 0.94) admissions. Pneumonia-specific admissions among adults were higher during the pandemic (IRR 1.75, 95% CI 1.18 to 2.59), while the paediatric pneumonia cases were lower than pre-pandemic levels in the first year of the pandemic and elevated in late 2021 (IRR 0.78, 95% CI 0.51 to 1.20). Conclusions: Contrary to initial predictions, the COVID-19 pandemic was associated with lower rates of hospitalisation and in-hospital mortality, despite increased pneumonia admissions among adults. These trends were sustained after the withdrawal of containment measures that resulted in the disruption of essential health services, suggesting a role for additional factors that warrant further investigation.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.25.22281489v1" target="_blank">Effects of the COVID-19 pandemic on hospital admissions and inpatient mortality in Kenya</a>
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<li><strong>For She had Eyes and Chose Preprints - Social Media Impact, Citation and Publication rates of Ophthalmology preprints</strong> -
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Abstract Background: Preprinting, is the sharing of non-peer reviewed, unpublished scholarly manuscripts. Across many fields of medicine, an exponential rise of manuscripts being posted to preprint servers has been observed. This has exploded during the COVID19 pandemic where early dissemination of information was critical, or where COVID19 priority disrupted the publication dynamics and priorities in other areas. We examined the characteristics of ophthalmology related preprints in this study. Methods: We searched the bioRxiv and medRxiv servers for preprints relating to field of ophthalmology. Preprints were screened by title and abstract to ensure they were related to the field of ophthalmology. Outcomes included number of tweets, upper bound followers of tweeters, number of citations, news outlets reports and dates posted/published. If a preprint was published the same outcomes were collected for the published version to allow for comparisons, as well as journal publisher and cite score. Results: After screening, a total of 720 preprints met our inclusion criteria. 420 of the preprints went on to be published. The publication rate of the preprints was 58.3%. The median number of tweets received on preprints was 3.5, IQR 5.5. 98.75% of preprints were tweeted about. Citation rate was 40.14%. The average number of days from date posted on server to date published was 180.5+/-124 days. Regression analysis revealed that tweets as a preprint predicts tweets as a published article, P=0.0135. citations as a preprint predicts citations as a published article, P<0.001. The average cite score was 8.5+/-6.2 among those preprints that we published in journals. 16.66% of papers were published by Elsevier (n = 70). 3.19% of preprints were COVID19 related, with significant differences found between them and non-COVID19 preprints in terms of number of tweets and number of citations. Conclusions: Ophthalmology preprints are increasing across preprint servers. This maybe to bypass publication times and allow early dissemination of work, as well as increase visibility and citations. We identified that preprint citations and tweets predict published version citation and tweets.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.25.22281523v1" target="_blank">For She had Eyes and Chose Preprints - Social Media Impact, Citation and Publication rates of Ophthalmology preprints</a>
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<li><strong>Severe COVID-19 is associated with fungal colonization of the nasopharynx and potent induction of IL-17 responses in the nasal epithelium</strong> -
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Recent case reports and epidemiological data suggest fungal infections represent an under-appreciated complication among people with severe COVID-19. However, the frequency of fungal colonization in patients with COVID-19 and associations with specific immune responses in the airways remain incompletely defined. We previously generated a single-cell RNA-sequencing (scRNA-seq) dataset characterizing the upper respiratory microenvironment during COVID-19, and mapped the relationship between disease severity and the local behavior of nasal epithelial cells and infiltrating immune cells. Our study, in agreement with findings from related human cohorts, demonstrated that a profound deficiency in host immunity, particularly in type I and type III interferon signaling in the upper respiratory tract, is associated with rapid progression to severe disease and worse clinical outcomes. We have now performed further analysis of this cohort and identified a subset of participants with severe COVID-19 and concurrent detection of Candida species-derived transcripts within samples collected from the nasopharynx and trachea. Here, we present the clinical characteristics of these individuals, including confirmatory diagnostic testing demonstrating elevated serum (1, 3)-β-D-glucan and/or confirmed fungal culture of the predicted pathogen. Using matched single-cell transcriptomic profiles of these individuals9 respiratory mucosa, we identify epithelial immune signatures suggestive of IL-17 stimulation and anti-fungal immunity. Further, we observe significant expression of anti-fungal inflammatory cascades in the nasal and tracheal epithelium of all participants who went on to develop severe COVID-19, even among participants without detectable genetic material from fungal pathogens. Together, our data suggests that IL-17 stimulation - in part driven by Candida colonization - and blunted type I/III interferon signaling represents a common feature of severe COVID-19 infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.25.22281528v1" target="_blank">Severe COVID-19 is associated with fungal colonization of the nasopharynx and potent induction of IL-17 responses in the nasal epithelium</a>
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<li><strong>A Digital Biomarker for Identifying Changes in Daily Activity Patterns</strong> -
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Malnutrition and dehydration are strongly associated with increased cognitive and functional decline in people living with dementia (PLWD), as well as an increased rate of hospitalisations in comparison to their healthy counterparts. Extreme changes in eating and drinking behaviours can often lead to mal- nutrition and dehydration, accelerating the progression of cognitive and functional decline and resulting in a marked reduction in quality of life. Unfortunately, there are currently no established methods by which to objectively detect such changes. Here, we present the findings of a quantitative analysis conducted on in-home monitoring data collected from 73 households of PLWD. The Coronavirus 2019 (COVID-19) pandemic has previously been shown to have dramatically altered the behavioural habits, particularly the eating and drinking habits, of PLWD. Using the COVID-19 pandemic as a natural experiment, we show that there are significant changes in eating and drinking habits at the group level within a subset of 21 households of PLWD that were continuously monitored for 499 days, with an overall increase in day-time activities and a decrease in night-time activity observed in both single and multiple occupancy households. We further present preliminary results suggesting it is possible to proactively detect episodic and gradual changes in behaviours. Together, these results pave the way to introduce improvements into the monitoring of PLWD in naturalistic settings and for shifting from reactive to proactive care.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.25.22281467v1" target="_blank">A Digital Biomarker for Identifying Changes in Daily Activity Patterns</a>
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<li><strong>Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines</strong> -
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COVID-19 manifests with a wide spectrum of clinical phenotypes, ranging from asymptomatic and mild to severe and critical. Severe and critical COVID-19 patients are characterized by marked changes in the myeloid compartment, especially monocytes. However, little is known about the epigenetic alterations that occur in these cells during hyperinflammatory responses in severe COVID-19 patients. In this study, we obtained the DNA methylome and transcriptome of peripheral blood monocytes from severe COVID-19 patients. DNA samples extracted from CD14+CD15- monocytes of 48 severe COVID-19 patients and 11 healthy controls were hybridized on MethylationEPIC BeadChip arrays. In parallel, single-cell transcriptomics of 10 severe COVID-19 patients were generated. CellPhoneDB was used to infer changes in the crosstalk between monocytes and other immune cell types. We observed DNA methylation changes in CpG sites associated with interferon-related genes and genes associated with antigen presentation, concordant with gene expression changes. These changes significantly overlapped with those occurring in bacterial sepsis, although specific DNA methylation alterations in genes specific to viral infection were also identified. We also found these alterations to comprise some of the DNA methylation changes occurring during myeloid differentiation and under the influence of inflammatory cytokines. A progression of DNA methylation alterations in relation to the Sequential Organ Failure Assessment (SOFA) score was found to be related to interferon-related genes and T-helper 1 cell cytokine production. CellPhoneDB analysis of the single-cell transcriptomes of other immune cell types suggested the existence of altered crosstalk between monocytes and other cell types like NK cells and regulatory T cells. Our findings show the occurrence of an epigenetic and transcriptional reprogramming of peripheral blood monocytes, which could be associated with the release of aberrant immature monocytes, increased systemic levels of pro-inflammatory cytokines, and changes in immune cell crosstalk in these patients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.24.22281485v1" target="_blank">Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines</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>Use of Multiple Doses of Convalescent Plasma in Mechanically Intubated Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Multiple doses of anti-SARS-CoV-2 Convalescent Plasma<br/><b>Sponsors</b>: Hospital Regional Dr. Rafael Estévez; Complejo Hospitalario Dr. Arnulfo Arias Madrid; Hospital Santo Tomas; Hospital Punta Pacífica, Pacífica Salud; Insituto Conmemorativo Gorgas de Estudios para la Salud; Sociedad Panameña de Hematología; Institute of Scientific Research and High Technology Services (INDICASAT AIP); University of Panama; Sistema Nacional de Investigación de Panamá<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>Open Multicenter Study for Assessment of Efficacy and Safety of Molnupiravir in Adult Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Molnupiravir (Esperavir); Drug: Standard of care<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>COVID-19 Testing and Vaccine Literacy for Women With Criminal Legal System Involvement</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Behavioral: Tri-City COVID Attitudes Study<br/><b>Sponsor</b>: University of Kansas Medical Center<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>JT001 (VV116) for the Treatment of COVID-19</strong> - <b>Condition</b>: Mild to Moderate COVID-19<br/><b>Interventions</b>: Drug: JT001; Drug: Placebo<br/><b>Sponsors</b>: Shanghai Vinnerna Biosciences Co., Ltd.; Sponsor GmbH<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>Boost Intentions and Facilitate Action to Promote COVID-19 Booster Take-up</strong> - <b>Conditions</b>: COVID-19; Vaccines<br/><b>Interventions</b>: Behavioral: Eligibility reminder; Behavioral: Link to a narrow set of vaccine venues; Behavioral: Link to a broad set of vaccine venues; Behavioral: Doctors’ recommendation and value of vaccine<br/><b>Sponsor</b>: University of California, Los Angeles<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Efficacy of Medications COVID-19</strong> - <b>Condition</b>: Severe Covid-19<br/><b>Intervention</b>: Drug: Oral bedtime melatonin<br/><b>Sponsor</b>: Hospital San Carlos, Madrid<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>Effects of Prompt to Bundle COVID-19 Booster and Flu Shot</strong> - <b>Conditions</b>: COVID-19; Vaccines<br/><b>Interventions</b>: Behavioral: Reminder to boost protection against COVID-19; Behavioral: Flu Tag Along; Behavioral: COVID-19 Booster & Flu Bundle<br/><b>Sponsor</b>: University of California, Los Angeles<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>Information Provision and Consistency Framing to Increase COVID-19 Booster Uptake</strong> - <b>Conditions</b>: COVID-19; Vaccines<br/><b>Interventions</b>: Behavioral: Reminder that facilitates action; Behavioral: Consistency framing; Behavioral: Information provision about the uniqueness of the bivalent booster; Behavioral: Information provision about bivalent booster eligibility; Behavioral: Information provision about the severity of COVID-19 symptoms<br/><b>Sponsor</b>: University of California, Los Angeles<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>Respiratory Muscles After Inspiratory Muscle Training After COVID-19</strong> - <b>Conditions</b>: COVID-19; Diaphragm Injury<br/><b>Intervention</b>: Device: Inspiratory Muscle Training (IMT)<br/><b>Sponsors</b>: RWTH Aachen University; Philipps University Marburg Medical Center<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>OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients: a Randomized Factorial Controlled Strategy Trial</strong> - <b>Conditions</b>: COVID-19; Immunodeficiency<br/><b>Interventions</b>: Drug: Paxlovid 5 days; Drug: Paxlovid 10 days; Drug: Tixagevimab and Cilgavimab<br/><b>Sponsors</b>: ANRS, Emerging Infectious Diseases; University Hospital, Geneva<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Combined Modified RNA Vaccine Candidates Against COVID-19 and Influenza</strong> - <b>Conditions</b>: Influenza, Human; COVID-19<br/><b>Interventions</b>: Biological: bivalent BNT162b2 (original/Omi BA.4/BA.5); Biological: qIRV (22/23); Biological: QIV<br/><b>Sponsors</b>: BioNTech SE; Pfizer<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 Preliminary Exploratory Study to Evaluate the Safety and Immunogenicity of Omicron Variant Bivalent Vaccine V-01-B5</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Biological: V-01/V-01-B5; Biological: V-01-351/V-01-B5; Biological: V-01<br/><b>Sponsor</b>: Livzon Pharmaceutical Group Inc.<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>Exploratory Clinical Study to Evaluation of the Safety and Immunogenicity of Bivalent Vaccine V-01D-351</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Interventions</b>: Biological: V-01D-351; Biological: CoronaVac<br/><b>Sponsor</b>: Livzon Pharmaceutical Group Inc.<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>COVID-19 MP Biomedicals SARS-CoV-2 Ag OTC: Clinical Evaluation</strong> - <b>Conditions</b>: SARS-CoV2 Infection; COVID-19<br/><b>Interventions</b>: Device: iCura COVID-19 Antigen Rapid Home Test; Device: RT-PCR Test<br/><b>Sponsors</b>: MP Biomedicals, LLC; EDP Biotech<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>COVID-19 MP Biomedicals Rapid SARS-CoV-2 Antigen Test Usability</strong> - <b>Conditions</b>: Sars-CoV-2 Infection; COVID-19<br/><b>Intervention</b>: Device: Rapid SARS-CoV-2 Antigen Test<br/><b>Sponsors</b>: MP Biomedicals, LLC; EDP Biotech<br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The potential for traditional Chinese therapy in treating sleep disorders caused by COVID-19 through the cholinergic anti-inflammatory pathway</strong> - Since the outbreak of Coronavirus disease (COVID-19) in 2019, it has spread rapidly across the globe. Sleep disorders caused by COVID-19 have become a major concern for COVID-19 patients and recovered patients. So far, there’s no effective therapy on this. Traditional Chinese therapy (TCT) has a great effect on sleep disorders, with rare side effects and no obvious withdrawal symptoms. The cholinergic anti-inflammatory pathway, a neuroregulatory pathway in the central nervous system that uses…</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>Temporal proteomic analyses of human lung cells distinguish high pathogenicity influenza viruses and coronaviruses from low pathogenicity viruses</strong> - Newly re-emerging viruses are of significant global concern. In late 2019, a new coronavirus, SARS-CoV-2, emerged in China and soon spread worldwide, causing the COVID-19 pandemic, which to date has caused >6 M deaths. There has been a wealth of studies on this new virus since its emergence. The coronaviruses consist of many animal and human pathogens, with some of the human coronavirus, such as strain OC43, normally causing only mild cold-like symptoms. Viruses usurp host cellular processes to…</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>Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis</strong> - We and others have previously shown that the SARS-CoV-2 accessory protein ORF6 is a powerful antagonist of the interferon (IFN) signaling pathway by directly interacting with Nup98-Rae1 at the nuclear pore complex (NPC) and disrupting bidirectional nucleo-cytoplasmic trafficking. In this study, we further assessed the role of ORF6 during infection using recombinant SARS-CoV-2 viruses carrying either a deletion or a well characterized M58R loss-of-function mutation in ORF6. We show that ORF6…</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 SARS-CoV-2 IgA neutralising antibody responses in convalescent plasma</strong> - CONCLUSION: Overall, convalescent plasma IgA contributed to the neutralising antibody response of wild-type SARS-CoV-2 RBD and various RBD mutations. However, this response displayed large heterogeneity and was less potent than IgG.</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>Small-Molecule RAF265 as an Antiviral Therapy Acts against PEDV Infection</strong> - Porcine epidemic diarrhea virus (PEDV), a member of the family Coronaviridae, causes acute diarrhea, vomiting, dehydration, and high mortality in newborn piglets, and has caused significant economic losses in the pig industry. There are currently no specific drugs available to treat PEDV. Viruses depend exclusively on the cellular machinery to ensure an efficient replication cycle. In the present study, we found that small-molecule RAF265, an anticancer drug that has been shown to be a potent…</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>Antiviral Activity of <em>Ficus rubiginosa</em> Leaf Extracts against HSV-1, HCoV-229E and PV-1</strong> - Ficus rubiginosa plant extract showed antimicrobial activity, but no evidence concerning its antiviral properties was reported. The antiviral activity of the methanolic extract (MeOH) and its n-hexane (H) and ethyl acetate (EA) fractions against Herpes simplex virus-1 (HSV-1), Human coronavirus (HCoV) -229E, and Poliovirus-1 (PV-1) was investigated in the different phases of viral infection in the VERO CCL-81 cell line. To confirm the antiviral efficacy, a qPCR was conducted. The recorded…</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 Syntenin Inhibitor Blocks Endosomal Entry of SARS-CoV-2 and a Panel of RNA Viruses</strong> - Viruses are dependent on host factors in order to efficiently establish an infection and replicate. Targeting the interactions of such host factors provides an attractive strategy to develop novel antivirals. Syntenin is a protein known to regulate the architecture of cellular membranes by its involvement in protein trafficking and has previously been shown to be important for human papilloma virus (HPV) infection. Here, we show that a highly potent and metabolically stable peptide inhibitor…</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>Optimization of Anti-SARS-CoV-2 Treatments Based on Curcumin, Used Alone or Employed as a Photosensitizer</strong> - Curcumin, the bioactive compound of the spice Curcuma longa, has already been reported as a potential COVID-19 adjuvant treatment due to its immunomodulatory and anti-inflammatory properties. In this study, SARS-CoV-2 was challenged with curcumin; moreover, curcumin was also coupled with laser light at 445 nm in a photodynamic therapy approach. Curcumin at a concentration of 10 μM, delivered to the virus prior to inoculation on cell culture, inhibited SARS-CoV-2 replication (reduction >99%)…</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 Cellular Assay for Spike/ACE2 Fusion: Quantification of Fusion-Inhibitory Antibodies after COVID-19 and Vaccination</strong> - Not all antibodies against SARS-CoV-2 inhibit viral entry, and hence, infection. Neutralizing antibodies are more likely to reflect real immunity; however, certain tests investigate protein/protein interaction rather than the fusion event. Viral and pseudoviral entry assays detect functionally active antibodies but are limited by biosafety and standardization issues. We have developed a Spike/ACE2-dependent fusion assay, based on a split luciferase. Hela cells stably transduced with Spike and 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>Design of Three Residues Peptides against SARS-CoV-2 Infection</strong> - The continuous and rapid spread of the COVID-19 pandemic has emphasized the need to seek new therapeutic and prophylactic treatments. Peptide inhibitors are a valid alternative approach for the treatment of emerging viral infections, mainly due to their low toxicity and high efficiency. Recently, two small nucleotide signatures were identified in the genome of some members of the Coronaviridae family and many other human pathogens. In this study, we investigated whether the corresponding amino…</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>Metalloprotease-Dependent S2’-Activation Promotes Cell-Cell Fusion and Syncytiation of SARS-CoV-2</strong> - SARS-CoV-2 cell-cell fusion and syncytiation is an emerging pathomechanism in COVID-19, but the precise factors contributing to the process remain ill-defined. In this study, we show that metalloproteases promote SARS-CoV-2 spike protein-induced syncytiation in the absence of established serine proteases using in vitro cell-cell fusion assays. We also show that metalloproteases promote S2’-activation of the SARS-CoV-2 spike protein, and that metalloprotease inhibition significantly reduces 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>Simultaneous Detection of RIG-1, MDA5, and IFIT-1 Expression Is a Convenient Tool for Evaluation of the Interferon-Mediated Response</strong> - In this study, we developed a novel, multiplex qPCR assay for simultaneous detection of RIG-1, MDA5, and IFIT-1 at the mRNA level. The assay was validated in A549 cells transfected with in vitro transcribed RNAs. Both exogenous RNA-GFP and self-amplifying (saRNA-GFP) induced significant expression of RIG-1, MDA5, IFIT-1, as well as type I and III interferons. In contrast, native RNA from intact A549 cells did not upregulate expression of these genes. Next, we evaluated RIG-1, MDA5, and IFIT-1…</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>Baculovirus-Free SARS-CoV-2 Virus-like Particle Production in Insect Cells for Rapid Neutralization Assessment</strong> - Virus-like particles (VLPs) resemble authentic virus while not containing any genomic information. Here, we present a fast and powerful method for the production of SARS-CoV-2 VLP in insect cells and the application of these VLPs to evaluate the inhibition capacity of monoclonal antibodies and sera of vaccinated donors. Our method avoids the baculovirus-based approaches commonly used in insect cells by employing direct plasmid transfection to co-express SARS-CoV-2 envelope, membrane, and spike…</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 SARS-CoV-2 Antibody Levels after a Third Heterologous and Homologous BNT162b2 Booster Dose</strong> - This study aimed to determine the anti-S (receptor binding protein) RBD IgG antibody titers formed against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and the neutralizing antibody inhibition percentages (nAb IH%) in blood samples taken after two doses of inactive or mRNA-based vaccine and a booster dose. Volunteers with two doses of inactivated CoronaVac (heterologous group; n = 75) and BioNTech (BNT)162b2 mRNA vaccine (homologous group; n = 75) were included in this study. All…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity of a Fractional Dose of mRNA BNT162b2 COVID-19 Vaccine for Primary Series and Booster Vaccination among Healthy Adolescents</strong> - Primary series vaccination with BNT162b2 followed by a booster 5 months later has been recommended for healthy adolescents. We aimed to describe the immunogenicity in a fractional dose of BNT162b2. Adolescents aged 12-18 years were randomized into six arms for primary series administration: 3wPZ30/30 (reference group), 3wPZ30/20, 3wPZ20/20, 6wPZ30/30, 6wPZ30/20, and 6wPZ20/20 μg. A booster was given at 5 months after the second dose using either 10 or 15 μg of BNT162b2. Immunogenicity following…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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