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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>The RNA demethylase FTO controls m6A marking on SARS-CoV-2 and classifies COVID-19 severity in patients</strong> -
<div>
The RNA modification N6-methyladenosine (m6A) plays a key role in the life cycles of several RNA viruses. Whether this applies to SARS-CoV-2 and whether m6A affects the outcome of COVID-19 disease is still poorly explored. Here we report that the RNA demethylase FTO strongly affects both m6A marking of SARS-CoV-2 and COVID-19 severity. By m6A profiling of SARS-CoV-2, we confirmed in infected cultured cells and showed for the first time in vivo in hamsters that the regions encoding TRS_L and the nucleocapsid protein are multiply marked by m6A, preferentially within RRACH motifs that are specific to {beta}-coronaviruses and well conserved across SARS-CoV-2 variants. In cells, downregulation of the m6A demethylase FTO, occurring upon SARS-CoV-2 infection, increased m6A marking of SARS-CoV-2 RNA and slightly promoted viral replication. In COVID-19 patients, a negative correlation was found between FTO expression and both SARS-CoV-2 expression and disease severity. FTO emerged as a classifier of disease severity and hence a potential stratifier of COVID-19 patients.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.27.497749v1" target="_blank">The RNA demethylase FTO controls m6A marking on SARS-CoV-2 and classifies COVID-19 severity in patients</a>
</div></li>
<li><strong>Roadkill in a time of pandemic: the analysis of wildlife-vehicle collisions reveals the differential impact of COVID-19 lockdown over mammal assemblages</strong> -
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Collisions with vehicles are a major anthropogenic cause of mortality for wildlife, with conservation and evolutionary implications. Due to the COVID-19 pandemic, many countries worldwide enforced lockdowns which importantly reduced traffic, and therefore had unprecedented consequences for global wildlife populations. We modeled how the two lockdown periods in spring and autumn 2020 influenced wildlife-vehicle collisions in Slovenia (central Europe), by comparing long-term (for the period 20102020) and high-quality time series data on road mortality of seven mammalian species: European roe deer (n = 53,259), red fox (n = 9,889), European badger (n = 5,170), brown hare (n = 5,050), stone marten (n = 4,267), wild boar (n = 1,188), and red deer (n = 1,088). We decomposed 20102019 data through autoregressive Bayesian Generalized Additive Models, and then we compared 2020 data to forecasts, aiming to estimate anomalies in number of collisions during both lockdown periods. During the spring lockdown (16 March 30 April 2020), we observed far less collisions than in the 20102019 average as well as in 2020 forecasts, for roe deer and badger. In the autumnal lockdown (20 October 31 December 2020), we observed significantly less collisions for roe deer and wild boar. Traffic reduction in both lockdown periods had a major impact on roe deer, which in autumn and spring 2020 experienced 270330 less road-related mortality cases than expected. COVID-19 lockdown reduced traffic-related mortality for the majority of studied species. In some species, this decrease reached a magnitude of biological significance, which can have long-term repercussions on both evolution and management. Obviously, large-scale sanitary policies, imposing a reduction to human mobility, can have large-scale impacts on wildlife. As pandemics may increase in the next decades, we encourage further research exploring the consequences of their enforcement over global change and wildlife conservation and evolution.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://ecoevorxiv.org/p3zft/" target="_blank">Roadkill in a time of pandemic: the analysis of wildlife-vehicle collisions reveals the differential impact of COVID-19 lockdown over mammal assemblages</a>
</div></li>
<li><strong>A Siege on Positive Ageing: Experiences of identity threat and coping among Older Adults during COVID-19 pandemic</strong> -
<div>
Older adults face significant challenges in regards to the various stereotypes associated with ageing, which have consequences for their mental health and wellbeing. The COVID-19 pandemic has heightened these age-based stereotypes due to older adults proportionally higher vulnerability to the virus. The present research explored how the pandemic has exacerbated the challenges of ageing by impacting on the social identities of older adults and how these challenges have been met. Eleven focus groups were conducted with 32 UK older adults from a range of household compositions. Guided by the social identity approach, a thematic analysis found that participants faced a number of recognisable stereotype threats: loss of opportunities to enact meaningful identities, loss of autonomy and loss of usefulness. Despite these threats, we also found participants used identity management strategies and mobilised existing or new social identities to give and receive of support and to retain a meaningful and purposeful life. The implications of this research are that governments and those supporting older adults can attend to the negative psychology impact of protective policies and know that fostering group connections can be a source of pandemic resilience.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/pufd5/" target="_blank">A Siege on Positive Ageing: Experiences of identity threat and coping among Older Adults during COVID-19 pandemic</a>
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<li><strong>Coupling Wastewater-Based Epidemiological Surveillance and Modelling of SARS-COV-2/COVID-19: Practical Applications at the Public Health Agency of Canada</strong> -
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Wastewater-based surveillance (WBS) of SARS-CoV-2 offers a complementary tool for clinical surveillance to detect and monitor Coronavirus Disease 2019 (COVID-19). Since both symptomatic and asymptomatic individuals infected with SARS-CoV-2 can shed the virus through the fecal route, WBS has the potential to measure community prevalence of COVID-19 without restrictions from healthcare-seeking behaviors and clinical testing capacity. During the Omicron wave, the limited capacity of clinical testing to identify COVID-19 cases in many jurisdictions highlighted the utility of WBS to estimate disease prevalence and inform public health strategies. However, there is a plethora of in-sewage, environmental and laboratory factors that can influence WBS outputs. The implementation of WBS therefore requires a comprehensive framework to outline an analysis pipeline that accounts for these complex and nuanced factors. This article reviews the framework of the national WBS conducted at the Public Health Agency of Canada to present WBS methods used in Canada to track and monitor SARS-CoV-2. In particular, we focus on five Canadian cities - Vancouver, Edmonton, Toronto, Montreal and Halifax - whose wastewater signals are analyzed by a mathematical model to provide case forecasts and reproduction number estimates. This work provides insights on approaches to implement WBS at the national scale in an accurate and efficient manner. Importantly, the national WBS system has implications beyond COVID-19, as a similar framework can be applied to monitor other infectious disease pathogens or antimicrobial resistance in the community.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.26.22276912v1" target="_blank">Coupling Wastewater-Based Epidemiological Surveillance and Modelling of SARS-COV-2/COVID-19: Practical Applications at the Public Health Agency of Canada</a>
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<li><strong>Predicting Hand, Foot, and Mouth Disease in Japan Using Google Trends: Infodemiology Study</strong> -
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Objectives: We aimed to predict the number of hand, foot, and mouth disease (HFMD) infections before and during the COVID-19 pandemic using Internet search data. Methods: We obtained actual HFMD cases from the National Institute of Infectious Disease and Internet search data using Google Trends between 2004 and 2021 in Japan. We calculated the Pearson correlation coefficients between actual HFMD cases and the search topic “HFMD” from 2004 to 2021. We conducted a cross-correlation analysis between the actual HFMD cases and 43 HFMD-related search terms before and during the pandemic. We identified the most significant predictors of HFMD infection using stepwise multiple linear regression. Results: We found that actual HFMD cases and Internet search volume peaked around July in most years, except for 2020 and 2021. The search topic “HFMD” presented a strong correlation with actual HFMD cases, but the correlation was weaker in 2004, 2008, and 2020. Results from stepwise multiple linear regression exhibited that the search terms “infect,” “daycare,” “vomit,” “HFMD,” “eczema,” “pain,” and “high fever were the most significant predictors before the pandemic, while”infect," “enterovirus,” “herpangina,” “kindergarten,” “myocarditis,” “HFMD,” “contact infection,” “blister,” “high fever” “dermatology,” and “plantar” were the most significant predictors during the pandemic. Conclusions: The predictors for HFMD infections before and during the COVID-19 pandemic were different. The awareness of HFMD infection in Japan may improved during the COVID-19 pandemic. Continuous monitoring is important to promote public health and prevent resurgence. Public interest reflected in information-seeking behavior can be helpful for public health surveillance.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.26.22276919v1" target="_blank">Predicting Hand, Foot, and Mouth Disease in Japan Using Google Trends: Infodemiology Study</a>
</div></li>
<li><strong>Analysis of 16S rRNA gene sequence of nasopharyngeal exudate from healthy donors reveals changes in key microbial communities associated with aging</strong> -
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Background: Functional or compositional perturbations of the microbiome can occur at different sites of the body and this dysbiosis has been linked to various diseases. Changes in the nasopharyngeal microbiome are associated to patient susceptibility to multiple viral infections, including COVID-19, supporting the idea that the nasopharynx may be playing an important role in health and disease. Most studies on the nasopharyngeal microbiome have focused on a specific component in the lifespan, such as infanthood or the elderly, or have other limitations such as low sample sizes. Therefore, detailed studies analyzing the age- and sex-associated changes in the nasopharyngeal microbiome of healthy people across their whole life are essential to understand the relevance of the nasopharynx in the pathogenesis of multiple diseases, particularly viral infections such as COVID-19. Results: 120 nasopharyngeal samples from healthy subjects of all ages and both sexes were analyzed by 16s rRNA sequencing. Nasopharyngeal bacterial alpha diversity did not vary in any case between age or sex groups. Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were the predominant phyla in all the age groups, with several sex-associated differences probably due to the different levels of sex hormones between both sexes. Acinetobacter, Brevundimonas, Dolosigranulum, Finegoldia, Haemophilus, Leptotrichia, Moraxella, Peptoniphilus, Pseudomonas, Rothia, and Staphylococcus were the only 11 bacterial genera that presented significant age-associated differences. Other bacterial genera such as Anaerococcus, Burkholderia, Campylobacter, Delftia, Prevotella, Neisseria, Propionibacterium, Streptococcus, Ralstonia, Sphingomonas, and Corynebacterium appeared in the population with a very high frequency, suggesting that their presence might be biologically relevant. Conclusions: In contrast to other anatomical areas such as the gut, bacterial diversity in the nasopharynx of healthy subjects remains very stable and resistant to perturbations throughout the whole life and in both sexes. Age-associated changes in taxonomic composition were observed at phylum, family, and genus levels, as well as several sex-associated changes probably due to the different levels of sex hormones present in both sexes at certain ages. Our results provide a complete and valuable dataset that will be useful for future research aiming for studying the relationship between changes in the nasopharyngeal microbiome and susceptibility to or severity of multiple diseases, including COVID-19.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.26.22276913v1" target="_blank">Analysis of 16S rRNA gene sequence of nasopharyngeal exudate from healthy donors reveals changes in key microbial communities associated with aging</a>
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<li><strong>An Economic Evaluation of a virtual Covid Ward in Leicester, Leicestershire, and Rutland</strong> -
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Objective The objective of this study was to demonstrate the impact of a virtual Covid 19 ward on NHS resource use. Methods Different methods were used to derive comparators for the observational data on acute length of stay versus the actual lengths of stay of 310 patients on acute wards and differences estimated. The resource use associated with delivering care in the virtual ward were collected on an ongoing basis. Results The virtual ward delivered estimated health care system savings of 1,103 bed days, 529,719 UK Pounds in net financial savings across two key groups of patients; those who had been on oxygen and required weaning off it while within the virtual ward and those not requiring oxygen therapy with less severe acute Covid disease. The costs of the intervention were 9.7% of the estimated gross savings and the mean net saving per patient was 1,709 UK pounds in the base case without including the savings associated with a likely reduction in re-admissions. The 30-day re-admission rate was 2.9%, which was substantially beneath alternative comparative data. The mean cost of the intervention was 184.38 UK pounds per patient. Conclusion The virtual ward delivered significant financial savings in both groups of patients, did so with a high degree of confidence, whilst doing so at a very low absolute and relative cost.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.27.22276736v1" target="_blank">An Economic Evaluation of a virtual Covid Ward in Leicester, Leicestershire, and Rutland</a>
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<li><strong>Strong correlations between the binding antibodies against wild type and neutralizing antibodies against omicron BA.1 and BA.2 variants of SARS-CoV-2 in individuals following booster (third dose) vaccination</strong> -
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This study examined the neutralizing activity and receptor binding domain (RBD) antibody levels against wild-type and omicron BA.1 and BA.2 variants in individuals who received three doses of COVID-19 vaccination. The relationship between the SARS-CoV-2 RBD antibody against wild-type and live virus neutralizing antibody titers against omicron BA.1 and BA.2 variants was examined. In total, 310 sera samples from individuals after booster vaccination (third dose) vaccination were tested for specific IgG wild-type SARS-CoV-2 RBD and the omicron BA.1 surrogate virus neutralization test (sVNT). The live virus neutralization assay against omicron BA.1 and BA.2 was performed using the foci-reduction neutralization test (FRNT50). The anti-RBD IgG strongly correlated with FRNT50 titers against BA.1 and BA.2. Non-linear regression showed that anti-RBD IgG with ≥148 BAU/mL and ≥138 BAU/mL were related to detectable FRNT50 titers (≥1:20) against BA.1 and BA.2, respectively. A moderate correlation was observed between the sVNT and FRNT50 titers. At detectable FRNT50 titers (≥1:20), the predicted sVNT for BA.1 and BA.2 were ≥10.57% and ≥11.52%, respectively. The study identified anti-RBD IgG and sVNT levels that predict detectable neutralizing antibodies against omicron variants. Assessment and monitoring of protective immunity support vaccine policies and will help identify optimal timing for booster vaccination.
</p>
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.27.22276959v1" target="_blank">Strong correlations between the binding antibodies against wild type and neutralizing antibodies against omicron BA.1 and BA.2 variants of SARS-CoV-2 in individuals following booster (third dose) vaccination</a>
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<li><strong>Telemedicine Use Among People with HIV in 2021: The Hybrid-Care Environment</strong> -
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Background: Telemedicine use for the care of people with HIV (PWH) was widely expanded during the COVID-19 pandemic. During 2021, as on-site care was re-introduced, care was delivered through a mixture of in-person and telemedicine. We studied how different patient populations used telemedicine in this hybrid-care environment. Methods: Using observational data from patients enrolled in the Johns Hopkins HIV Clinical Cohort, we analyzed all in-person and telemedicine HIV primary care visits completed in an HIV clinic from January 1st, 2021 to December 30th, 2021. We used log-binomial regression models to investigate the association between patient characteristics and the probability of completing a telemedicine versus in-person visit. A secondary analysis of telemedicine visits investigated the probably of completing a video versus telephone visit. Results: A total of 5,518 visits were completed by 1,884 patients; 4,282 (77.6%) visits were in-person, 800 (14.5%) by phone, and 436 (7.9%) by video. The relative risk (RR) of completing telemedicine vs. in-person visits was 0.65 (95% Confidence Interval (CI): 0.47, 0.91) for patients age 65+ vs. age 20-39; 0.84 (95% CI: 0.72, 0.98) for males vs. females; 0.81 (95% CI: 0.66, 0.99) for Black vs. white patients; 0.62 (95% CI: 0.49, 0.79) for patients in the highest vs. lowest quartile of Area Deprivation Index; and 1.52 (95% CI: 1.26, 1.84) for patients &gt;15 miles vs. &lt;5 miles from clinic. Conclusions: In the second year of the pandemic, overall in-person care was utilized more than telemedicine, and significant differences persist across subgroups in telemedicine uptake.
</p>
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.27.22276960v1" target="_blank">Telemedicine Use Among People with HIV in 2021: The Hybrid-Care Environment</a>
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<li><strong>Within-hotel transmission of SARS-CoV-2 during on-arrival quarantine in Hong Kong</strong> -
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Background: On-arrival quarantine has been one of the primary measures used to prevent the introduction of COVID-19 into Hong Kong since the start of the pandemic. Most on-arrival quarantines have been done in hotels, with the duration of quarantine and testing frequency during quarantine varying throughout the pandemic for various reasons. However, hotels are not necessarily designed with infection control in mind. We aimed to study the potential risk of transmission between persons in on-arrival quarantine. Methods: We examined data on each laboratory-confirmed COVID-19 case identified in on-arrival quarantine in a hotel in Hong Kong between 1 May 2020 and 31 January 2022. We sequenced the full genomes of viruses from cases that overlapped with other confirmed cases in terms of the hotel of stay, date of arrival and date of testing positive. A combination of epidemiological information and sequence information was then used to identify probable transmission events. Findings: Among 221 imported cases that overlapped with other quarantined cases, phylogenetic analysis identified eight suspected clusters comprising 20 cases in total. Only three of these clusters had been recognised as hotel transmission events. Interpretation: We have identified potential occurrences of COVID-19 transmission within hotel quarantine in Hong Kong demonstrating the underlying low but non-zero risk associated with sequestering arrivals within hotels. In future pandemics, on-arrival quarantine in hotels could be used to delay the introduction of infection, but the construction of purpose-built facilities for on-arrival quarantine might be necessary to minimize importation risk.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.25.22276894v1" target="_blank">Within-hotel transmission of SARS-CoV-2 during on-arrival quarantine in Hong Kong</a>
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<li><strong>Non-Adherence of PLWHA in taking Antiretroviral during the COVID-19 pandemic in West Sumatra, Indonesia: Qualitative analysis</strong> -
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Abstract Introduction: COVID-19 pandemic condition affects the adherence of PLWHA in taking antiretroviral drugs. People with Lost to Follow-up (LTFU) were an average of 26 %, The feared impact is the high mortality rate and decreased productivity, visits of PLWHA patients to M Jamil Hospital come from all regions in West Sumatra to the southern provinces of Jambi and Bengkulu. This study aimed to determine factors that influence patient non-Adherence during the COVID-19 pandemic. Method: This study was conducted by exploring the experiences of patients and health workers by observing adherence to taking antiretroviral, 34 informant: 25 patients, 5 NGOs, and 4 health workers, The data were collected from September 6th to October 9th 2021, Analysis data using N VIVO 12. Results: Patients in taking medication during the COVID-19 pandemic were feeling bored, most of the patient lived was so far, so patients often asked for help from NGOs to take medication. Forgetfulness, busyness, and fear of being exposed to COVID-19. Then, the economic factor, due to the large number of layoffs, and the absence of BPJS insurance affects compliance, while the factors of stigma, stress, feeling well are slightly expressed by patients. It turns out that the Covid-19 condition affects patients to come for treatment to the hospital. In addition to drug side effects, dizziness, nausea, and vomiting also affect medication adherence. The role of NGOs in providing information and education as well as motivating and taking medication during the COVID-19 condition is very important. Conclusion: The most common causes of non-compliance from loss to follow-up during the COVID-19 pandemic are; bored, far from home, forgetful, and economic factors for fear of covid-19. Most of the side effects of drugs are dizziness, and nausea and vomiting so that the role of NGOs is important in helping patients take medication.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.26.22276906v1" target="_blank">Non-Adherence of PLWHA in taking Antiretroviral during the COVID-19 pandemic in West Sumatra, Indonesia: Qualitative analysis</a>
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<li><strong>Digitalization impacts the COVID-19 pandemic and the stringency of government measures</strong> -
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COVID-19 poses a significant burden on populations worldwide. Although the pandemic has accelerated digital transformation, little is known about digitalization9s influence on pandemic developments. Using the Digital Adoption Index (DAI), we examined the effects of digitalization on early COVID-19 cases, deaths, and stringency indices (SI) of government measures. Gradient Tree Boosting pinpointed essential features, such as populations9 smoker fraction, age, poverty, and DAI. Then, regression analyses indicated that higher DAI was associated with significant declines in new cases ( β =-362.25/pm; p&lt;0.001) and deaths ( β =-5.53/pm; p&lt;0.001) months after the peak. Over the entire range, higher DAI was associated with higher mean SI ( β =4.86; p&lt;0.01). Interestingly, however, in countries with high DAI &gt;0.68, the correlation inverted ( β =-55.26; p&lt;0.05). Finally, a scoping review identified 70 publications providing valuable arguments for our findings. Thus, digitalization is evident for handling current and future pandemics but can also facilitate stronger government actions restricting individual freedom.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.27.22276377v1" target="_blank">Digitalization impacts the COVID-19 pandemic and the stringency of government measures</a>
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<li><strong>Population genomic insights into the evolution of the SARS-CoV-2 Omicron variant</strong> -
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A thorough understanding of the patterns of population subdivision of a pathogen can prevent disease spread. For SARS-CoV-2, the availability of millions of genomes makes this task analytically challenging. Our study used population genomic methods and identified subtle subdivisions within the Omicron variant, in addition to that captured by the Pango lineage. Further, some of the identified clusters of the Omicron variant revealed statistically significant signatures of selection or expansion revealing the role of microevolutionary processes in the spread of the virus. These are crucial information for policy makers as preventive measures can be designed to mitigate further spread based on a holistic understanding of the variability of the virus and evolutionary processes aiding its spread.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.27.22276933v1" target="_blank">Population genomic insights into the evolution of the SARS-CoV-2 Omicron variant</a>
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<li><strong>The burden of respiratory conditions in the emergency department of Muhimbili National Hospital in Tanzania in the first two years of the COVID-19 pandemic</strong> -
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Background Globally, respiratory diseases cause 10 million deaths every year. With the COVID19 pandemic, the burden of respiratory illness increased and led to significant morbidity and mortality in both high- and low-income countries. This study assessed the burden and trend of respiratory conditions among patients presenting to the emergency department of Muhimbili National Hospital in Tanzania and compared with national COVID-19 data to determine if this knowledge may be useful for the surveillance of disease outbreaks in settings of limited specific diagnostic testing. Methods The study used routinely collected data from the electronic information system in the Emergency Medical Department (EMD) of Muhimbili National Hospital in Tanzania. All patients presenting to the EMD in a 2-year period, 2020 and 2021 with respiratory conditions were included. Descriptive statistics and graphical visualizations were used to describe the burden of respiratory conditions and the trends over time and to compare to national Tanzanian COVID-19 data during the same period. Results One in every four patients who presented to the EMD of the Muhimbili National Hospital had a respiratory condition 1039 patients per month. Of the 24,942 patients, 52% were males, and the median age (IQR) was 34.7 (21.7, 53.7) years. The most common respiratory diagnoses were pneumonia (52%), upper respiratory tract infections (31%), asthma (4.8%) and suspected COVID-19 (2.5%). There were four peaks of respiratory conditions coinciding with the four waves in the national COVID-19 data. Conclusions There is a high burden of respiratory conditions among patients presenting to the EMD of Muhimbili National Hospital. The trend shows four peaks of respiratory conditions in 2020-2021 seen to coincide with the four waves in the national COVID-19 data. Real-time hospital-based surveillance tools may be useful for early detection of respiratory disease outbreaks and other public health emergencies in settings with limited diagnostic testing.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.06.26.22276861v1" target="_blank">The burden of respiratory conditions in the emergency department of Muhimbili National Hospital in Tanzania in the first two years of the COVID-19 pandemic</a>
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<li><strong>Antiviral T-cell Biofactory platform for SARS-CoV-2</strong> -
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Vaccines help reduce new infections, but interventions that can prevent the disease from transitioning to a severe stage are rather limited. Dysregulated IFN kinetics are mostly exploited by pathogenic viruses, including SARS-CoV-2. The clinical benefits of systemically infused IFN are, unfortunately, mired by undesired side effects. To address this situation, we engineered a T cell to synthesize interferons (IFNs) as antiviral proteins upon recognizing the virus envelop protein of SARS-CoV-2, i.e., anti-SARS T-cell Biofactory. The T-cell Biofactory, capable of regulating the IFN expression with spatiotemporal resolution within the infected tissues, can mitigate these concerns. In this work, we determined the prophylactic and therapeutic effects of the type-I and type-III IFNs produced from the T cell Biofactory against SARS-CoV-2 infection in host cells and investigated the expression profiles of ensuing IFN-stimulated genes (ISGs). To enable the translation of T cell Biofactory as an effective antiviral countermeasure, we also investigated an irradiation dose that renders the T-cell Biofactory non-proliferative and thus non-oncogenic. The ongoing public health crisis motivated us to direct the T cell Biofactory technology to target SARS-CoV-2. The T-cell Biofactory, based on T cells engineered with chimeric antigen receptors (CAR T cells), is a platform technology that can be rapidly re-engineered and become available for targeting any new pathogen.
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<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.06.26.497669v1" target="_blank">Antiviral T-cell Biofactory platform for SARS-CoV-2</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunobridging Study of COVID-19 Protein Subunit Recombinant Vaccine</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: COVID-19 Protein Subunit Recombinant Vaccine;   Biological: Active Comparator<br/><b>Sponsors</b>:   PT Bio Farma;   Faculty of Medicine, Universitas Indonesia, Jakarta;   Faculty of Medicine, Diponegoro University, Semarang;   Faculty of Medicine, Universitas Andalas, Padang;   Faculty of Medicine, Universitas Hassanudin, Makassar<br/><b>Recruiting</b></p></li>
<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 SARS-CoV-2 Variant (COVID-19 Omicron) mRNA Vaccine (Phase 1)</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: ABO1009-DP<br/><b>Sponsor</b>:   Suzhou Abogen Biosciences Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Discussing COVID-19 Vaccines in Private Facebook Groups</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Behavioral: Gist messages on COVID-19 vaccination;   Behavioral: COVID-19 vaccine information<br/><b>Sponsor</b>:   George Washington University<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety Study of One Booster Dose of Trivalent COVID-19 Vaccine (Vero Cell), Inactivated</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Trivalent COVID-19 Vaccine (Vero Cell), Inactivated, Prototype Strain, Delta Strain and Omicron Strain;   Biological: COVID-19 Vaccine (Vero Cell), Inactivated<br/><b>Sponsors</b>:   Sinovac Biotech (Colombia) S.A.S.;   Sinovac Life Sciences Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Home-Based Exercise Tele-Rehabilitation After COVID-19</strong> - <b>Condition</b>:   Post SARS-CoV2 (COVID-19)<br/><b>Intervention</b>:   Other: Tele-exercise<br/><b>Sponsors</b>:   VA Office of Research and Development;   Baltimore Veterans Affairs Medical Center;   Salem Veterans Affairs Medical Center<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IMM-BCP-01 in Mild to Moderate COVID-19</strong> - <b>Conditions</b>:   SARS-CoV2 Infection;   COVID-19<br/><b>Interventions</b>:   Drug: IMM-BCP-01;   Drug: Placebo<br/><b>Sponsors</b>:   Immunome, Inc.;   United States Department of Defense<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mesenchymal Stromal Cells for the Treatment of Patients With COVID-19.</strong> - <b>Conditions</b>:   COVID-19 Pneumonia;   COVID-19<br/><b>Interventions</b>:   Biological: Mesenchymal stem cell;   Other: Placebo<br/><b>Sponsors</b>:   Paulo Brofman;   Conselho Nacional de Desenvolvimento Científico e Tecnológico<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Olfactory Training in COVID-19 Associated Loss of Smell</strong> - <b>Conditions</b>:   COVID-19;   Hyposmia<br/><b>Intervention</b>:   Device: Sniffin sticks Duftquartett<br/><b>Sponsor</b>:   Medical University Innsbruck<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Psychological Impact of Medical Evacuations on Families of Patients Admitted to Intensive Care Unit for Severe COVID-19</strong> - <b>Conditions</b>:   COVID-19;   Stress Disorders, Post-Traumatic<br/><b>Interventions</b>:   Other: Revised Impact of Event Scale;   Other: Hospital Anxiety and Depression scale;   Other: 36-Item Short Form Survey;   Other: satisfaction survey;   Other: semi-directed interview with trusted person on the general experience of the patients medical evacuation;   Other: semi-directed interview with trusted person on the general experience of hospitalization in intensive care<br/><b>Sponsor</b>:   Centre Hospitalier Metropole Savoie<br/><b>Completed</b></p></li>
<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 COVID-19 on Platelet Mitochondrial Bioenergetic, Antioxidants and Oxidative Stress in Infertile Men.</strong> - <b>Conditions</b>:   Infertility, Male;   COVID-19<br/><b>Intervention</b>:   Other: diagnostic test and sperm analysis<br/><b>Sponsors</b>:   Comenius University;   GYN-FIV<br/><b>Active, not recruiting</b></p></li>
<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 Immunogenicity and Safety of MVC-COV1901 Vaccine Compared With AZD1222</strong> - <b>Condition</b>:   COVID-19 Vaccine<br/><b>Interventions</b>:   Biological: MVC-COV1901;   Biological: AZD1222<br/><b>Sponsor</b>:   Medigen Vaccine Biologics Corp.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ACE2 Chewing Gum on SARS-CoV-2 Viral Load (COVID 19)</strong> - <b>Condition</b>:   SARS-CoV-2<br/><b>Interventions</b>:   Drug: ACE2 Chewing Gum;   Other: Placebo Chewing Gum<br/><b>Sponsor</b>:   University of Pennsylvania<br/><b>Not yet recruiting</b></p></li>
<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 Vaccine Uptake Trial</strong> - <b>Conditions</b>:   Vaccination Refusal;   COVID-19<br/><b>Interventions</b>:   Other: Short Message Service (SMS) + Website Link Strategy;   Other: Phone Call with Peer Strategy<br/><b>Sponsor</b>:   Washington University School of Medicine<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Laser Therapy on Tension-type Cephalea and Orofacial Pain in Post-covid-19 Patients</strong> - <b>Conditions</b>:   Tension-Type Headache;   Orofacial Pain;   COVID-19<br/><b>Intervention</b>:   Radiation: Photobimodulation<br/><b>Sponsor</b>:   University of Nove de Julho<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cardiovascular Autonomic and Immune Mechanism of Post COVID-19 Tachycardia Syndrome</strong> - <b>Conditions</b>:   Post-acute COVID-19 Syndrome;   Postural Tachycardia Syndrome (POTS);   Long COVID;   SARS CoV 2 Infection<br/><b>Interventions</b>:   Diagnostic Test: Determine the inflammatory and immune profile of post-COVID-19 POTS patients;   Diagnostic Test: Measurement of PNS activity by HRV (Heart rate Variation);   Diagnostic Test: Autonomic Symptoms assessment<br/><b>Sponsors</b>:   Vanderbilt University Medical Center;   American Heart Association<br/><b>Recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Analysis of Interaction between odorant receptors and flexible spike of SARS CoV-2- key to loss of smell</strong> - The vaccine development for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is primarily focused on structure of the spike (S) protein. The heavy glycosylation of S with flexible hinges at stalk shields from antibodies. The flexible nature of hinges may be one of the important factors which are responsible for binding the odorant receptor of those neurons which are responsible for the loss of smell in patients with COVID-19 infection. In this study strong and stable bond formation…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ongoing positive selection drives the evolution of SARS-CoV-2 genomes</strong> - SARS-CoV-2 is a new RNA virus affecting humans and spreads extensively through world populations since its first outbreak in December, 2019. Whether the transmissibility and pathogenicity of SARS-CoV-2 in humans after zoonotic transfer are actively evolving, and driven by adaptation to the new host and environments is still under debate. Understanding the evolutionary mechanism underlying epidemiological and pathological characteristics of COVID-19 is essential for predicting the epidemic trend,…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Assessment of disinfectant efficacy in reducing microbial growth</strong> - The incidence of hospital- and community-acquired infections has been dramatically increased worldwide. Accordingly, hands hygiene and the use of disinfectants have been increased leading to the expansion in hand sanitizers production to meet public demand. This study was conducted to assess the efficiency of common disinfectants in the market of Riyadh, Saudi Arabia in inhibiting the microbial growth during the time of Coronavirus disease 2019 (COVID-19) pandemic. Five bacterial strains of…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Apixaban, an orally available anticoagulant, inhibits SARS-CoV-2 replication and its major protease in a non-competitive way</strong> - No abstract</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An engineered 5-helix bundle derived from SARS-CoV-2 S2 pre-binds sarbecoviral spike at both serological- and endosomal-pH to inhibit virus entry</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related sarbecoviruses enter host cells by receptor-recognition and membrane-fusion. An indispensable step in fusion is the formation of 6-helix bundle by viral spike heptad repeats 1 and 2 (HR1 and HR2). Here, we report the construction of 5-helix bundle (5HB) proteins for virus infection inhibition. The optimal construct inhibits SARS-CoV-2 pseudovirus entry with sub-micromolar IC50. Unlike HR2-based peptides that cannot bind…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Development of an efficient reproducible cell-cell transmission assay for rapid quantification of SARS-CoV-2 Spike interaction with hACE2</strong> - Efficient quantitative assays for measurement of viral replication and infectivity are indispensable to future endeavors to develop prophylactic or therapeutic antiviral drugs or vaccines against SARS-CoV-2. We developed a SARS-CoV-2 cell-cell transmission assay that provides a rapid and quantitative readout to assess SARS-CoV-2 Spike hACE2 interaction in the absence of pseudotyped particles or live virus. We established two well-behaved stable cell lines, which demonstrated a remarkable…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Heparanase Is a Putative Mediator of Endothelial Glycocalyx Damage in COVID-19 - A Proof-of-Concept Study</strong> - Coronavirus disease 2019 (COVID-19) is a systemic disease associated with injury (thinning) of the endothelial glycocalyx (eGC), a protective layer on the vascular endothelium. The aim of this translational study was to investigate the role of the eGC-degrading enzyme heparanase (HPSE), which is known to play a central role in the destruction of the eGC in bacterial sepsis. Excess activity of HPSE in plasma from COVID-19 patients correlated with several markers of eGC damage and perfused…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Neutrophil Extracellular Traps, Sepsis and COVID-19 - A Tripod Stand</strong> - The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic. Majority of COVID-19 patients have mild disease but about 20% of COVID-19 patients progress to severe disease. These patients end up in the intensive care unit (ICU) with clinical manifestations of acute respiratory distress syndrome (ARDS) and sepsis. The formation of neutrophil extracellular traps (NETs) has also been associated with severe…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunosuppressant Treatment in Rheumatic Musculoskeletal Diseases Does Not Inhibit Elicitation of Humoral Response to SARS-CoV-2 Infection and Preserves Effector Immune Cell Populations</strong> - COVID-19 has proven to be particularly serious and life-threatening for patients presenting with pre-existing pathologies. Patients affected by rheumatic musculoskeletal disease (RMD) are likely to have impaired immune responses against SARS-CoV-2 infection due to their compromised immune system and the prolonged use of disease-modifying anti-rheumatic drugs (DMARDs), which include conventional synthetic (cs) DMARDs or biologic and targeted synthetic (b/ts) DMARDs. To provide an integrated…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Seroprevalence of Anti-S1-RBD Antibodies in Pre-pandemic and Pandemic Subjects From Hail Region, KSA</strong> - CONCLUSION: Antibody levels increased in samples collected during the pandemic, even though these subjects were not clinically COVID-19 positive. A small number of pre-pandemic subjects showed serum antibodies, suggesting prior exposure to other coronaviruses in the region. With dwindling neutralizing antibody levels and reduced vaccine efficacy against newer variants, it remains crucial to develop better assays for surveillance, management, and future research.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 infects an <em>in vitro</em> model of the human developing pancreas through endocytosis</strong> - Recent studies showed that SARS-CoV-2 can infect adult human pancreas and trigger pancreatic damage. Here, using human fetal pancreas samples and 3D differentiation of human pluripotent cells into pancreatic endocrine cells, we determined that SARS-CoV-2 receptors ACE2, TMPRSS2 and NRP1 are expressed in precursors of insulin-producing pancreatic β-cells, rendering them permissive to SARS-CoV-2 infection. We also show that SARS-CoV-2 enters and undergoes efficient replication in human multipotent…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A review of the effects of ATP and hydroxychloroquine on the phase separation of the SARS-CoV-2 nucleocapsid protein</strong> - SARS-CoV-2 is the coronavirus causing the ongoing pandemic with &gt; 460 millions of infections and &gt; 6 millions of deaths. SARS-CoV-2 nucleocapsid (N) is the only structural protein which plays essential roles in almost all key steps of the viral life cycle with its diverse functions depending on liquid-liquid phase separation (LLPS) driven by interacting with various nucleic acids. The 419-residue N protein is highly conserved in all variants including delta and omicron, and composed of both…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phytochemistry, biological activities and in silico molecular docking studies of <em>Oxalis pes-caprae</em> L. compounds against SARS-CoV-2</strong> - Phytochemicals are directly involved in therapeutic treatment or precursors to synthesize useful drugs. The current study was aimed to evaluate the phytocompounds and their biopotentials using methanolic and n-hexane extracts of various parts of Oxalis pes-caprae. For the phytochemical analysis, standard procedures were used, whereas Aluminum Chloride reagent and Follin-ciocalteau reagent methods were used to determine total flavonoid and phenolic contents. Radical scavenging DPPH,…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Interaction of 5-[4-(<em>N</em>-Methyl-1,3-benzimidazol-2-yl)phenyl]-10,15,20-tri-(<em>N</em>-methyl-3-pyridyl)porphyrin Triiodide with SARS-CoV-2 Spike Protein</strong> - The results of experimental studies of the interaction of the S-protein with a monohetaryl-substituted porphyrin containing a benzimidazole residue are presented. It has been revealed that the S-protein forms high-affinity complexes with the specified porphyrin. The porphyrin binding by the SARS-CoV-2 S-protein has proceeded stepwise; at the first stage, the driving force of the complexation is electrostatic interaction between the surface negatively charged regions of the protein and cationic…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Human miRNAs to Identify Potential Regions of SARS-CoV-2</strong> - It is two years now but the world is still struggling against COVID-19 due to the havoc created by the SARS-CoV-2 virus and its multiple variants. Considering this perspective, in this work, we have hypothesized a new approach in order to identify potential regions in SARS-CoV-2 similar to the human miRNAs. Thus, they may have similar consequences as caused by the human miRNAs in human body. Therefore, the same way by which human miRNAs are inhibited can be applied for such potential regions of…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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