Future Pandemics Research Articles

Higher Affinity Enables More Accurate Detection of SARS-CoV-2 in Human Saliva Using Aptamer-Based Litmus Test.

Many aptamers have been generated by systematic evolution of ligands by exponential enrichment (SELEX) to recognize spike proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2&ek), some of which have been engineered into dimeric and trimeric versions for enhanced affinity for diagnostic applications. However, no studies have been conducted to compare the utilities of monomeric, dimeric and trimeric aptamers in diagnostic assays with real clinical samples to answer the question of what levels of affinity an aptamer must have for accurate clinical diagnostics. Herein, we carried out a comparative study with two monomeric aptamers MSA1 and MSA5, one dimeric aptamer and two homotrimeric aptamers constructed with MSA1 and MSA5, with affinity varying by 1000-fold. Using a colorimetric sandwich assay to analyze 48 human saliva samples, we found that the trimeric aptamer assay (Kd≈10 pM) can identify the SARS-CoV-2 infection much more accurately than the dimeric aptamer assay (Kd≈100 pM) and monomeric aptamer assay (Kd≈10,000 pM). Based on the experimental data, we theoretically predict the levels of affinity an aptamer needs to possess to achieve 80-100 % sensitivity and 100 % specificity. The findings from this study highlight the need for deriving very high affinity aptamers to enable highly accurate detection of viral infection for future pandemics.

Biothermodynamic analysis of the Dengue virus: Empirical formulas, biosynthesis reactions and thermodynamic properties of antigen-receptor binding and biosynthesis

After the experience with the COVID-19 pandemic, WHO has issued a warning about the possible causes of future pandemics. One such causative agent is the Dengue virus. Until now, we have had information mostly on biological properties of the Dengue virus and very little information about its chemical and thermodynamic properties. To be better prepared for a potential Dengue pandemic, the goal of this paper is to chemically and thermodynamically characterize the Dengue virus, as well as to describe the biophysical basis of the virus-host interactions of the Dengue virus. To that goal, the empirical formula was determined, as well as biosynthesis reactions and thermodynamic properties of antigen-receptor binding and thermodynamic properties of biosynthesis and multiplication of the Dengue virus. A model was developed of virus-host interactions between the Dengue virus and its host tissues, based on nonequilibrium thermodynamics.

Higher Affinity Enables More Accurate Detection of SARS‐CoV‐2 in Human Saliva Using Aptamer‐Based Litmus Test

AbstractMany aptamers have been generated by systematic evolution of ligands by exponential enrichment (SELEX) to recognize spike proteins of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2&ek), some of which have been engineered into dimeric and trimeric versions for enhanced affinity for diagnostic applications. However, no studies have been conducted to compare the utilities of monomeric, dimeric and trimeric aptamers in diagnostic assays with real clinical samples to answer the question of what levels of affinity an aptamer must have for accurate clinical diagnostics. Herein, we carried out a comparative study with two monomeric aptamers MSA1 and MSA5, one dimeric aptamer and two homotrimeric aptamers constructed with MSA1 and MSA5, with affinity varying by 1000‐fold. Using a colorimetric sandwich assay to analyze 48 human saliva samples, we found that the trimeric aptamer assay (Kd≈10 pM) can identify the SARS‐CoV‐2 infection much more accurately than the dimeric aptamer assay (Kd≈100 pM) and monomeric aptamer assay (Kd≈10,000 pM). Based on the experimental data, we theoretically predict the levels of affinity an aptamer needs to possess to achieve 80–100 % sensitivity and 100 % specificity. The findings from this study highlight the need for deriving very high affinity aptamers to enable highly accurate detection of viral infection for future pandemics.

Cost of COVID-19 vaccine delivery in nine States in Nigeria via the U.S. Government Initiative for Global Vaccine Access

BackgroundIn 2022, the U.S. Centers for Disease Control and Prevention collaborated with implementing partners, African Field Epidemiology Network and Sydani Group, to support COVID-19 vaccination efforts in Nigeria. To characterize the costs of COVID-19 vaccination, this study evaluated financial costs per dose for activities implemented to support the intensification campaign for COVID-19 vaccination.MethodsThis retrospective evaluation collected secondary data from existing expenditure and programmatic records on resource utilization to roll out COVID-19 vaccination during 2022. The study included incremental financial costs of the activities implemented to support an intensification campaign for COVID-19 vaccination across nine states and six administrative levels in Nigeria from the perspective of the external donor (U.S. Government). Costs for vaccines and injection supplies, transport of vaccines, and any economic costs, including government in-kind contributions, were not included. All costs were converted from Nigerian Naira to 2022 U.S. Dollars (US$).ResultsThe estimated financial delivery cost of the COVID-19 vaccination intensification campaign was US$0.84 per dose (total expenditure of US$6.29 million to administer 7,461,971 doses). Most of the financial resources were used for fieldwork activities (86%), followed by monitoring and supervision activities (8%), coordination activities (5%), and training-related activities (1%). Labor (58%) and travel (37%) were the resource inputs that accounted for the majority of the cost, while shares of other resource inputs were marginal (1% for each). Most labor costs (79%) were spent on payments for mass vaccination campaign teams, including pay-for-performance incentives. By administrative level, the largest share of costs (46%) was for pay-for-performance incentives at the community, health facility, or campus levels combined, followed by local government area level (24%), community level only (15%), state level (9%), national level (3%), campus level only (1%), and health facility level only (< 1%).ConclusionsFindings from the evaluation can help to inform resources needed for vaccination activities to respond to future outbreaks and pandemics in resource-limited settings, particularly to reach new target populations not regularly included in routine childhood immunization delivery.

Financial impact of pandemics on pension sustainability: an application for Spain

AbstractEpidemiologists are warning that the next pandemic is almost around the corner. As we have seen during the COVID-19 pandemic, the death toll was at the highest for over 60th, transforming the population pyramids. In times of pandemics, two effects on sustainability of the pay-as-you-go (PAYG) pension scheme go in different directions: the increase in old-age mortality (leading to a decrease in pension spending) and the increase in unemployment (leading to a decline in income from contributions). In this paper, we investigate the long-term effects of pandemics on the financial sustainability of PAYG pension schemes, taking into account changes in both mortality and unemployment factors. Using functional data analysis we develop projections of population pyramids and allow for anticipated mortality jumps as a result of future pandemics. An application is carried out using mortality and fertility data from Spain. Given some plausible assumptions, our findings indicate, firstly, that the financial sustainability of the Spanish pension system is compromised. Secondly, in the event of a pandemic, we observe that financial sustainability is primarily driven by the mortality effect—resulting in a decrease in pension expenditure—while the impact of unemployment is almost negligible.

Oxoammonium salts exert antiviral effects against coronavirus via denaturation of their spike proteins

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2) infection has forced social changes worldwide. Development of potent antiviral agents is necessary to prevent future pandemics. Titanium oxide, a photocatalyst, is a long-acting antiviral agent; however, its effects are weakened in the dark. Therefore, new antiviral substances that can be used in the dark are needed. Two types of nitroxyl radicals, 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) and 2-azaadamantane N-oxyl (AZADO), are commonly used as oxidation catalysts utilizing oxygen in the air as the terminal oxidant. Therefore, in this study, we aimed to evaluate the potential of these radicals as antiviral compounds with sustained activity even in the dark. We evaluated the antiviral effects of oxoammonium salts corresponding to TEMPO and AZADO (TEMPO-Oxo and AZADO-Oxo, respectively), which are the active forms of nitroxyl radicals in oxidation reactions. TEMPO-Oxo and AZADO-Oxo inhibited the binding of SARS-CoV2 spike protein receptor-binding domain (S-RBD) to angiotensin-converting enzyme 2. Notably, AZADO-Oxo exhibited a 10-fold stronger inhibitory effect than TEMPO-Oxo. TEMPO-Oxo and AZADO-Oxo also denatured S-RBD; however, effects of AZADO-Oxo were 10-fold stronger than those of TEMPO-Oxo and did not change in the dark. Some S-RBD peptides treated with AZADO-Oxo were cleaved at the N-terminal side of tyrosine residues. TEMPO-Oxo and AZADO-Oxo exhibited concentration-dependent antiviral effects against feline coronavirus. In conclusion, active forms of the nitroxyl radicals, TEMPO-Oxo and AZADO-Oxo, exerted antiviral effects by denaturing S-RBD, regardless of the presence or absence of light, suggesting their potential as novel antiviral agents.

Exploring differences in perceived barriers and facilitators to COVID-19 vaccine uptake and testing intention by vaccination status and testing hesitancy among rural Latino communities in Southwest Florida

ABSTRACT Background: Identifying factors impacting vaccination and testing for COVID-19 is crucial to reduce health disparities, especially for rural/agricultural, low access and high poverty Latino communities disproportionately affected by the pandemic. This study examined differences in perceived barriers and facilitators (such as values, beliefs, and concerns) to COVID-19 vaccine uptake and testing intention by vaccination status and testing hesitancy among rural Latino community members in Southwest Florida. Methods: Rural Latino community members (N = 493) completed a cross-sectional survey in Spanish (86.0%) or English (14.0%) on perceived COVID-19 vaccine/testing barriers and facilitators, as well as demographics, mental health, medical history, health perceptions, and health literacy. Results: At the time of the survey, approximately 43% of participants were unvaccinated and 46.4% were testing hesitant. Significantly more vaccinated participants acknowledged keeping their family (d = .25), community (d = .27), and themselves (d = .22) safe as facilitators to vaccination (ps < .001). Among the unvaccinated participants, the most common concerns for getting vaccinated were side effects (d = −.53) and lack of knowledge about how the vaccine works (d = −.35, ps < .001). Testing hesitant participants reported concerns including not knowing where to get tested (d = −.25, p = 0.01) and less confidence in a positive test result (d = −.40, p < 0.001). Doctors and faith leaders were ranked as the most trusted information sources across groups. In logistic regression models, vaccination was linked to age, gender, education, and protecting others, while concerns about needles and side effects reduced odds; testing was driven by education, anxiety, hope, and safety concerns. Conclusion: Promoting family and community safety may be effective facilitators influencing vaccine and testing intention in rural Latino communities. Enhanced education by trusted information sources, such as doctors and faith leaders may alleviate associated concerns. Our findings may inform actions for future pandemics. Further studies should determine the generalizability of our findings across other rural migrant communities and other vaccines.

COVID-19 Deaths and Minority Health Social Vulnerability, in the U.S., January 1, 2020 through June 24, 2023.

Health disparities, leading to worse health outcomes such as elevated COVID-19 mortality rates, are rooted in social and structural factors. These disparities notably impact individuals from lower socioeconomic backgrounds and more socially vulnerable areas. We analyzed the relationship between COVID-19 deaths and social vulnerability using the Minority Health Social Vulnerability Index (MHSVI). COVID-19 death data in the U.S. was obtained from the Centers for Disease Control and Prevention (CDC) National Center for Health Statistics, where COVID-19 deaths were defined using the ICD-10 code U07.1. MHSVI composite scores were calculated for 3089 U.S. counties and categorized into social vulnerability quartiles, where values ranged from 0 (lowest vulnerability) to 1 (highest vulnerability). Negative binomial regression was employed to determine death rate ratios for each quartile within each theme. Finally, a multivariate negative binomial regression including all MHSVI sub-themes, excluding the overall index ranking, was used to assess the association between each theme and COVID-19 death rates independently. There were 1,134,272 COVID-19 deaths from January 1, 2020 through June 24, 2023. Adjusted rate ratios for COVID-19 deaths in the overall index ranking were 1.06 (95% CI 0.99-1.13), 1.14 (95% CI 1.06-1.22), and 1.41 (95% CI 1.31-1.52) for the second, third and fourth quartiles, respectively. Sub-themes of socioeconomic status (SES), household characteristics (HC), racial and ethnic minority status (REMS), housing type and transportation (HTT), and medical vulnerability (MV) revealed increasing death rates in higher vulnerability quartiles. The healthcare infrastructure and access (HIA) theme had decreasing death rate ratios of 0.74 (95% CI 0.71-0.78), 0.59 (95% CI 0.56-0.62), and 0.42 (95% CI 0.39-0.44) for the second, third, and fourth quartiles, respectively. Finally, the multivariate analysis showed that the HC, HTT, HIA, and MV themes were associated with COVID-19 deaths (P < 0.05). Counties that were identified as more socially vulnerable experienced higher death rates from COVID-19. These areas may need additional public health and social support during future pandemics.

The Moderating Role of Proposed External Incentives on COVID-19 Vaccination Intentions in an Emerging Economy Context

The COVID-19 pandemic has highlighted the critical need for widespread vaccination to combat the spread of the virus and protect public health. This study aims to investigate the factors that influence COVID-19 vaccination intentions and examine the moderating role of proposed external incentives in an emerging economy context. Specifically, the study explores the impact of attitude, subjective norms (SN) and perceived behavioural (PB) control on vaccination intentions and examines how external incentives interact with these factors to strengthen vaccination intentions. Data was collected through 318 structured self-report questionnaires administered to individuals. The collected data underwent statistical analysis using partial least squares structural equation modelling (PLS-SEM) with SmartPLS 3.0. The analysis fulfilled all the necessary assumptions and criteria for data quality and model robustness. The findings indicate that attitude, SN and PB control significantly influence individuals’ intentions to get vaccinated against COVID-19. However, the main contribution of this study lies in its revelation that proposed external incentives positively impact the relationship between attitude and vaccination intentions. This suggests that external factors, such as monetary and non-monetary incentives, play a crucial role in attracting individuals towards preventive vaccination. The findings hold practical implications for policymakers and medical service providers, as they highlight the importance of external incentives in positively influencing vaccination intentions. These insights can aid in designing effective strategies to encourage vaccine uptake and reduce the likelihood of future pandemics.

Building resilience of the Ghanaian healthcare system: Lessons from a global health stage: Preparedness for the next pandemic: A scoping review

Background The coronavirus disease (COVID-19) pandemic has underscored the need for resilient health systems. However, Ghana does not seem to achieve commensurate results, suggesting potential gaps in critical interventions. This study examines these gaps by drawing on global experiences to guide Ghana's preparedness for future emergencies. Methods A scoping review based on the synthesis of published journal articles and grey literature was used to gather relevant evidence to address the study’s objective. Peer-reviewed literature searches were conducted in databases, including Medline, Scopus, and Health Sources, supplemented by searches on organizational websites to identify grey literature. We adopted the Organization for Economic Co-operation and Development (OECD) framework to explore how health systems responded to the COVID-19 pandemic globally and draw lessons for strengthening Ghana's health system resilience. We analyzed policy responses in three main areas: pandemic preparedness, crisis management, and response and recovery. Results Ten strategies emerged from the study as critical in strengthening health system resilience against future pandemics. These strategies include whole-of-government engagement, financing for preparedness, community engagement and trust, robust surveillance systems, emergency medical care, diverse workforce development, digital health integration, critical health infrastructure, well-planned commodities/products, and social capital. Each strategy plays a vital role in enhancing preparedness, response, and recovery efforts, highlighting the multifaceted approach needed to mitigate the impact of future pandemics on health systems. Conclusions The identified strategies align with the attributes of a resilient healthcare system. By adopting these strategies, Ghana can build a resilient healthcare system that effectively addresses future challenges, guided by global insights and experiences.

Pandemic perspectives from detained youth during COVID-19: Bridging the knowledge gap for future safeguards.

Despite the worsening health disparities among youth in detention during the COVID-19 pandemic, there has been minimal exploration into the pandemic experiences of detained youth and opportunities for pandemic mitigation. This paper analyzes the perspectives of youth in detention on the pandemic, including the effect of the pandemic on their detention experience and their perceptions about COVID-19 vaccination. The study used purposive sampling to recruit 16 participants (aged 14-17 years) from two juvenile detention centers in the urban Midwest. We conducted semi-structured interviews and analyzed verbatim transcripts using a hybrid deductive-inductive approach and thematic analysis. Four themes emerged: 1) personal experience influenced youth perceptions of pandemic severity and risk; 2) distrust and misconceptions contributed to youth vaccine hesitancy or refusal; 3) desired opportunities and parental opinion motivated youth to get the COVID-19 vaccine; and 4) pandemic mitigation strategies negatively impacted youths' detention center experience. Study findings identify opportunities for detention centers to minimize the negative impacts of pandemic mitigation strategies on youth in detention, expand vaccination knowledge and uptake, and build trust to positively impact the health and wellbeing of detained youth currently and during future pandemics.

Responding to COVID-19: an exploration of EU country responses and directions for further research.

During COVID-19, scientists advising policymakers were forced to deal with high uncertainty and risks in an environment of unknowns. Evidence on which policies and measures were effective in responding to the pandemic remains underdeveloped to answer the key question 'what worked and why?'. This study aims to provide a basis for studies to go further to answer this critical question, by starting to look efficacy or how countries ensured that health services remained available and what measures were enacted to protect and treat their populations and workers. We applied a three-phase sequential mixed methods design. In phase one, we started with a qualitative content analysis of the EU Country Profile reports to retrieve and analyse data on COVID-19 responses taken by 29 countries in the European region. Phase two is the step of data transformation, converting qualitative data into numerical codes that can be statistically analysed, which are then used in a quantitative cross-national comparative analysis that comprises phase three. The quantifying process resulted in a numerical indicator to measure the 'response efficacy' of the 29 countries, which is used in phase three's association of the response measure with country performance indicators that were derived from European Centre for Disease Control (ECDC) COVID-19 case and death rate data. Through comparing the frequency of COVID-19 measures taken, we found that many countries in the European region undertook similar actions but with differing effects. The cross-national analysis revealed an expected relationship: a lower COVID-19 response efficacy appeared to be related to a higher case and death rates. Still, marked variation for countries with similar response efficacy indicators was found, signalling that the combination and sequence of implementation of COVID-19 responses is possibly just as important as their efficacy in terms of which response measures were implemented. Many European countries employed similar COVID-19 measures but still had a wide variation in their case and death rates. To unravel the question 'what worked and why?', we suggest directions from which more refined research can be designed that will eventually contribute to mitigate the impact of future pandemics and to be better prepared for their economic and human burden.

One Health Index applied to countries in South America.

The One Health concept has proposed an integrated and unified approach aiming for health balance and enhancement by recognizing the interdependence of human, animal, and environmental health. The COVID-19 pandemic has pushed global One Health initiatives and policy improvement toward preventive measures for future pandemics, particularly of zoonotic origin. Such a scenario may be particularly relevant for South America, which is considered highly vulnerable due to its natural biodiversity superposed to socioeconomic and environmental issues, demanding effective methods and indicators for proper One Health strategies and goals that are aligned with macroregional contexts. Accordingly, the present study aimed to assess the One Health Index (OHI) in South American countries, along with potential interactions with socioeconomic indicators. The results obtained using clustering analysis and permutational multivariate analysis of variance (PERMANOVA) have revealed a positive association between the OHI and the Human Development Index (HDI) but not with gross domestic product (GDP). Although South American countries with political stability, robust investment in health, and progressive policies have shown a higher OHI, better environmental health is not associated with better human and animal health. In addition, although the Amazon biome- spanning 9 of the 12 South American countries-has positively impacted environmental health, this benefit contrasts with the rudimentary local human health systems, highlighting the complexity of One Health within the South American context. The lack of stronger indicators for animal health was also considered an important weak point for a true OHI assessment. Nonetheless, countries with more developed livestock have presented better animal health, which may not reflect an overall animal health indicator, as companion and wildlife animal health indicators were not available. Although lower (within-country) scale analysis such as states and metropolitan areas may better shape internal differences, the study herein has clearly shown One Health inequalities and challenges among South American countries. Equally important, forests and other natural areas in developing countries, particularly the Amazon, should receive incentives to promote sustainable economic growth. This approach would help prevent sacrificing environmental health for the benefit of human and livestock animal health.

Innovative packaging design enhances vaccine accessibility for developing countries

Innovative packaging design enhances vaccine accessibility for developing countries Unither Pharmaceuticals is dedicated to innovating and expanding capacity to provide equitable vaccine accessibility in developing countries and enhance preparedness for future pandemics. Here, they explain how the Euroject® device can support their goals.The SARS-CoV-2 pandemic has had a devastating impact worldwide, causing seven million deaths and infecting more than 775 million people. (1) Despite the rapid development and approval of vaccines, their distribution faced significant hurdles due to shortages of consumables like glass vials. To prepare for ‘Disease X’, a term coined by governments to describe an unknown pathogen that could emerge and cause an epidemic or pandemic, many steps have been taken to increase preparedness. In this context, Blow-Fill-Seal (BFS) technology has emerged as a game-changing solution, particularly for developing countries, owing to its efficient and scalable packaging design.

Deep learning on chest X-ray and computed tomography scans for detection of COVID-19 as a part of a network-centric digital health stack for future pandemics

Developing a reliable rapid screening protocol for highly infectious diseases like COVID-19 is of paramount interest since it facilitates the isolation of infected patients from the rest of the population. Reverse-transcription polymerase chain reaction (RT-PCR) test is presently the most widely accepted gold-standard test to detect COVID-19. In this method, the RNA of the virus is duplicated by a process called reverse transcription to form DNA for facilitating the copying process. Fluorescent dye is attached to the viral genetic material and copied billions of times through the process called polymerase chain reaction. Enhanced fluorescence is used to identify the presence of genetic material of the virus. These tests are time-consuming and have significant false negatives, i.e., a person with COVID-19 might be categorized as not having the virus. Large-scale RT-PCR testing has its own share of problems such as logistics, availability and affordability in underdeveloped nations, and reliability of the test results. Machine learning algorithms can act as a cheaper supplementary/alternative diagnostic tool for the testing process. In the current study, using publicly available chest X-ray image datasets, different convolutional neural network (CNN)-based models were developed for efficient identification of COVID-19 infected patients, and their efficacies were compared. Key innovations in training the CNNs are discussed. Our results indicate that EfficientNet, SeResNext, and ResNet are best at classifying normal, pneumonia and COVID-19 cases, respectively. The ResNet architecture with transfer learning performed best at detecting COVID-19 with an accuracy of 94%, a rate far superior to that in the RT-PCR test, which is typically in the range of 70 &amp;ndash; 80%. This is particularly attractive as an additional noninvasive protocol since such technology-augmented detection is likely to help in reducing the psychological refractory period due to COVID-19 infections. Toward the healthy lung initiative in the post-COVID-19 era, we propose close coupling of the present diagnostic protocols with digital approaches to ensure more reliable personal care within the ambit of large-scale pandemic control mechanisms. Such integration with emerging technological tools can create a benchmark for the first line of defense against future global pandemics.

Can COVID-19 infection be considered an occupational disease or injury? Analysis to fill up regulatory gaps.

Although the pandemic is nearing its end, the question of whether COVID-19 infection will be considered a work-related or occupational disease remains a legal issue. Therefore, this study aims to provide clarification on this matter. Since the International Labour Organization (ILO) serves as the primary authority on work-related matters, this study is focused on analyzing the ILO's policies regarding the acknowledgment of COVID-19 infections as occupational diseases. It also investigates how States can recognize COVID-19 as such a disease while delving into the connection between the disease or injury and the occupation itself. This study utilizes a doctrinal methodology, focusing on legal research. This approach employs an applied (expository) research method and discusses the topic from a professional constituency perspective, as proposed by Arthurs in 1983. The findings indicate that the ILO does not explicitly mention the pandemic or COVID-19 infection as an occupational disease in its list. However, it does include "infectious-related diseases" or "work that carries a particular risk of contamination" as occupational or work-related diseases, which can logically be interpreted as encompassing COVID-19 infection as an occupational or work-related disease. As the ILO sets guiding principles for its member States, this study recommends that the ILO should establish clear and comprehensive guidelines for member States to recognize COVID-19 infections or any future pandemics as occupational diseases. This study will serve as a valuable resource for policymakers who intend to enact or amend national legislation to align with the ILO. Furthermore, it will assist relevant stakeholders in taking necessary actions based on the study's findings.

Cell-based high-content approach for SARS-CoV-2 neutralization identifies unique monoclonal antibodies and PI3K pathway inhibitors.

The sudden rise of the SARS-CoV-2 virus and the delay in the development of effective therapeutics to mitigate it made evident a need for ways to screen for compounds that can block infection and prevent further pathogenesis and spread. Yet, identifying effective drugs efficacious against viral infection and replication with minimal toxicity for the patient can be difficult. Monoclonal antibodies were shown to be effective, yet as the SARS-CoV-2 mutated, these antibodies became ineffective. Small molecule antivirals were identified using pseudovirus constructs to recapitulate infection in non-human cells, such as Vero E6 cells. However, the impact was limited due to poor translation of these compounds in the clinical setting. This is partly due to the lack of similarity of screening platforms to the in vivo physiology of the patient and partly because drugs effective in vitro showed dose-limiting toxicities. In this study, we performed two high-throughput screens in human lung adenocarcinoma cells with authentic SARS-CoV-2 virus to identify both monoclonal antibodies that neutralize the virus and clinically useful kinase inhibitors to block the virus and prioritize minimal host toxicity. Using high-content imaging combined with single-cell and multidimensional analysis, we identified antibodies and kinase inhibitors that reduce virus infection without affecting the host. Our screening technique uncovered novel antibodies and overlooked kinase inhibitors (i.e. PIK3i, mTORi, multiple RTKi) that could be effective against SARS-CoV-2 virus. Further characterization of these molecules will streamline the repurposing of compounds for the treatment of future pandemics and uncover novel mechanisms viruses use to hijack and infect host cells.

Drug Repurposing Using Computational Tools and Preventive Strategies for COVID-19 and Future Pandemics

Coronavirus disease-19 (COVID-19) was declared a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that targets the lower respiratory tract in human species. Since the target receptor molecule is angiotensin-converting enzyme 2 (ACE2), which is highly expressed on the cell lining of the respiratory tract, the virus is responsible for causing acute respiratory distress syndrome (ARDS). Computational tools such as artificial intelligence, machine learning and deep learning-based platforms are used for drug repurposing, identification, and selection of target molecules that can be used for vaccine development and antiviral drug production. Computer-aided drug designing, molecular docking and homology modelling are some of the most widely used in silico models for drug discovery against COVID-19. It is important to take preventive measures to control the spread of the virus. The present review focuses on the computational tools used for recognising the target molecules for vaccine production, the transmission networks of COVID-19 and the long-term strategies to prevent future pandemics such as COVID-19.

Rural community pharmacists' willingness to receive, administer, and recommend COVID-19 vaccines after the First U.S. vaccine rollout

IntroductionVaccines remain the cornerstone for prevention of COVID-19. Particularly in rural areas, community pharmacists are among the most accessible healthcare professionals. Their advocacy for immunization can help overcome patients' vaccine hesitancy and close the disparity gap between rural and urban regions. This study explored factors influencing the willingness to recommend and administer COVID-19 vaccines among rural community pharmacists after the first U.S. vaccine rollout. MethodsA convenience sample of rural community pharmacists completed a selfadministered, validated paper/online survey (n = 86, 23.4% response rate). Measures included COVID-19 vaccination status, perceived benefits of offering COVID-19 immunization services at the pharmacy, and willingness to recommend and administer COVID-19 vaccines. Descriptive, bivariate, and multivariate statistics were used to analyze potential nonresponse bias, survey responses, and associations between variables as appropriate. Alpha was set at 0.05. ResultsThe proportion of pharmacists who were vaccinated against COVID-19 was 79.1%. Over 75% of participants were in favor of recommending COVID-19 immunizations to eligible family members and patients and almost 85% agreed that they would administer COVID-19 vaccines to their patients. Most pharmacists perceived COVID-19 immunization services to be beneficial, such as attracting more patients into the pharmacy (81.2%), increasing pharmacy revenue (75.3%), and enhancing relationships with local clinics/public health agencies (74.1%). COVID-19 vaccination status and the perceived benefit of offering immunization services at the pharmacy were significantly associated with pharmacists' willingness to recommend and administer COVID-19 vaccines. ConclusionThe relatively high rates of COVID-19 vaccination uptake and the strong willingness of rural community pharmacists to recommend and administer COVID-19 vaccines, after the first national vaccine rollout, were encouraging. The findings underscore the importance of engaging rural community pharmacists in efforts to prepare for and respond to future pandemics and public health crises.

Burden of SARS-CoV-2 infection prior to vaccine eligibility among immunocompromised children aged 1-11years at a pediatric tertiary referral hospital in Toronto, Canada.

SARS-CoV-2 seroprevalence reflects the efficacy of pandemic infection prevention and control measures. We performed anti-spike IgG serological testing on residual sera of children 1-11years old at a tertiary care referral center between October and November 2021. Immunocompromised patients had the highest SARS-CoV-2 seroprevalence, at 40.5%, compared to 19.3% in non-immunocompromised patients. Targeted infection prevention and public health interventions are warranted for pediatric immunocompromised patients in future pandemics.