Healthcare worker intentions to receive a COVID-19 vaccine and reasons for hesitancy: A survey of 16,158 health system employees on the eve of vaccine distribution -

Healthcare workers (HCWs) have been recommended to receive first priority for limited COVID-19 vaccines. They have also been identified as potential ambassadors of COVID-19 vaccine acceptance, helping to ensure that sufficient members of a hesitant public accept COVID-19 vaccines to achieve population immunity. Yet HCWs themselves have shown vaccine hesitancy in other contexts and the few prior surveys of U.S. HCW intentions to receive a COVID-19 vaccine report acceptance rates of only 28% to 34%. However, it is unknown whether HCW acceptance remains low following mid-November announcements of the efficacy of the first COVID-19 vaccines and the issuance of two emergency use authorizations (EUA) in December. We report the results of a December 2020 survey (N = 16,158; response rate 61%) administered by a large Pennsylvania health system to determine the intentions of its employees to receive a vaccine when it is offered to them. In a mixed sample of individuals serving in patient-facing and other roles, 55% would decide to receive a COVID-19 vaccine when offered, 16.4% would not, and 28.5% reported being undecided. The distribution of responses varied little across hospital campuses, between those in patient-facing roles and other HCWs, or by area or department of work. The higher rate of COVID-19 vaccine acceptance we observe may reflect the framing and timing of our survey. Among hesitant respondents, an overwhelming majority (90.3%) reported concerns about unknown risks and insufficient data. Other commonly reported concerns included known side effects (57.4%) and wanting to wait until they see how it goes with others (44.4%). We observed a substantial increase in self-reported intent to receive a COVID-19 vaccine after an FDA advisory committee voted to recommend an EUA. Among respondents who completed the survey after that point in time, 79% intend to receive a COVID-19 vaccine (n = 1155). Although only suggestive, this trend offers hope that rates of COVID-19 vaccine acceptance may be higher among HCWs and, perhaps, the general public than more hypothetical survey results have indicated.

🖺 Full Text HTML: Healthcare worker intentions to receive a COVID-19 vaccine and reasons for hesitancy: A survey of 16,158 health system employees on the eve of vaccine distribution

Glycyrrhizin effectively neutralizes SARS-CoV-2 in vitro by inhibiting the viral main protease -

The newly emerged coronavirus, which was designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 disease. High effective and well-tolerated medication for hospitalized and non-hospitalized patients is urgently needed. Traditional herbal medicine substances were discussed as promising candidates for the complementary treatment of viral diseases and recently suggested for the treatment of COVID-19. In the present study, we investigated aqueous licorice root extract for its neutralizing activity against SARS-CoV-2 in vitro, identified the active compound glycyrrhizin and uncovered the respective mechanism of viral neutralization. We demonstrated that glycyrrhizin, the primary active ingredient of the licorice root, potently neutralizes SARS-CoV-2 by inhibiting the viral main protease. Our experiments highlight glycyrrhizin as a potential antiviral compound that should be further investigated for the treatment of COVID-19.

🖺 Full Text HTML: Glycyrrhizin effectively neutralizes SARS-CoV-2 in vitro by inhibiting the viral main protease

Mental health among pregnant women during the pandemic in Sweden, a mixed methods approach using data from the Mom2B mobile application for research -

Public health emergencies such as the coronavirus (SARS-CoV-2) pandemic have significant impact on mental health, and have been shown to impact on already prevalent affective disorders during and after pregnancy. The aim of this study was to utilize modern tools to assess depressive and anxiety symptoms, as well as wellbeing and life changes in pregnant women during the pandemic in Sweden, where no lockdown has been in place. Data from the Mom2B, a national ongoing mobile application-based study of pregnant and newly-delivered women were utilized. Participants (n= 1345) filled out self-report screeners of depression, anxiety and wellbeing. Questions about COVID symptoms and effects on life and health care were added from March 2020. Movement data was collected using the phone9s GPS sensor. Mood scores were compared with throughout the months of 2020 and to the levels of a previous collected material. Highest levels of depression and anxiety were evident in April and October 2020. Symptoms were higher among those feeling socially isolated, but not for those infected or with symptomatic family members. Wellbeing and mobility were strongly positively correlated and were lowest in April. Women reported on cancelled healthcare appointments and worry about their partners being absent from the delivery. The Mom2B application enabled gathering information at a national level in real-time as the pandemic has been evolving. Levels of perinatal affective symptoms and low wellbeing were elevated compared with previous years as well as with months with fewer cases of SARS-Cov-2. Similar applications can help healthcare providers and governmental bodies to in real time monitor high-risk groups during crises, as well as to adjust measures and the support offered.

🖺 Full Text HTML: Mental health among pregnant women during the pandemic in Sweden, a mixed methods approach using data from the Mom2B mobile application for research

The impact of the first UK Covid-19 lockdown on carers and people living with low prevalence dementia: results from the Rare Dementia Support survey -

Introduction The public health measures imposed to contain Covid-19 during the first UK lockdown resulted in significant changes in the provision of community support and care for people with dementia. People with low prevalence and young-onset dementias often experience non-memory, behavioural or neuropsychiatric symptoms that require specialised support. Objective We explored the impact of the first Covid-19 lockdown on people living with low prevalence and young-onset dementia and their carers in the UK. Method An online survey, including eleven questions about the impact of the lockdown on both the person with dementia and their family caregivers was conducted. Participants were people living with dementia and caregivers who are members of the UK national-reach organisation Rare Dementia Support. Results 184 carers and 24 people with dementia completed the survey. People with dementia experienced worsening of cognitive symptoms (70%), ability to do things (62%) and well-being (57%) according to their carers. Carers also reported a reduction in the support received for caring (55%). 93% of carers of people living in care homes reported a reduction in their ability to provide care. 26% of carers reported changes in the medication of the person with dementia during the lockdown. 74% of people with dementia reported decreased ability to connect with people socially. Conclusions People with dementia experienced a worsening of dementia symptoms, removal of support and increased difficulty to connect with other people socially during the 1st wave of Covid-19. Carers encountered barriers to both receiving and providing support and a decline in their own mental health and well-being.

🖺 Full Text HTML: The impact of the first UK Covid-19 lockdown on carers and people living with low prevalence dementia: results from the Rare Dementia Support survey

SARS-CoV-2-Specific Antibody Profiles Distinguish Patients with Moderate from Severe COVID-19 -

The production of SARS-CoV-2-specific neutralizing antibodies is widely considered as a key mechanism for COVID-19 resolution and protection. However, beyond their protective function, antibodies to SARS-CoV-2 may also participate in disease pathogenesis. To explore the potential relationship between virus-specific humoral responses and COVID-19 immunopathology, we measured serum antibody classes and subclasses to the receptor-binding domain of the SARS-CoV-2 spike protein and the nucleoprotein in a cohort of hospitalized COVID-19 patients with moderate to severe disease. We found that RBD-specific IgG1 and IgG3 dominated the humoral response to SARS-CoV-2, were more abundant in severe patients, and positively correlated with several clinical parameters of inflammation. In contrast, a virus-specific IgA2 response skewed toward RBD rather than NP associated with a more favorable clinical course. Interestingly, RBD-dominant IgA2 responses were mostly detected in patients with gastrointestinal symptoms, suggesting the possible involvement of intrinsically tolerogenic gut immune pathways in the attenuation of virus-induced inflammation and disease resolution.

🖺 Full Text HTML: SARS-CoV-2-Specific Antibody Profiles Distinguish Patients with Moderate from Severe COVID-19

Effects of obesity on serum levels of SARS-CoV-2-specific antibodies in COVID-19 patients -

SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus-2), cause of COVID-19 (Coronavirus Disease of 2019), represents a significant risk to people living with pre-existing conditions associated with exacerbated inflammatory responses and consequent dysfunctional immunity. In this paper, we have evaluated the effects of obesity, a condition associated with chronic systemic inflammation, on the secretion of SARS-CoV-2-specific IgG antibodies in the blood of COVID-19 patients. Results have shown that SARS-CoV-2 IgG antibodies are negatively associated with Body Mass Index (BMI) in COVID-19 obese patients, as expected based on the known effects of obesity on humoral immunity. Antibodies in COVID-19 obese patients are also negatively associated with serum levels of pro-inflammatory and metabolic markers of inflammaging and pulmonary inflammation, such as SAA (serum amyloid A protein), CRP (C-reactive protein) and ferritin, but positively associated with NEFA (nonesterified fatty acids). These results altogether could help to identify an inflammatory signature with strong predictive value for immune dysfunction that could be targeted to improve humoral immunity in individuals with obesity as well as with other chronic inflammatory conditions.

🖺 Full Text HTML: Effects of obesity on serum levels of SARS-CoV-2-specific antibodies in COVID-19 patients

Failure to replicate the association of rare loss-of-function variants in type I IFN immunity genes with severe COVID-19 -

A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,934 COVID-19 cases (713 with severe and 1,221 with mild disease) and 15,251 ancestry-matched population controls across four independent COVID-19 biobanks. We then tested if rare pLOF variants in these 13 genes were associated with severe COVID-19. We identified only one rare pLOF mutation across these genes amongst 713 cases with severe COVID-19 and observed no enrichment of pLOFs in severe cases compared to population controls or mild COVID-19 cases. We find no evidence of association of rare loss-of-function variants in the proposed 13 candidate genes with severe COVID-19 outcomes.

🖺 Full Text HTML: Failure to replicate the association of rare loss-of-function variants in type I IFN immunity genes with severe COVID-19

Genetic correlations between COVID-19 and a variety of diseases and other medically relevant traits -

We analyzed GWAS results released by COVID-19 Host Genetics Initiative, UK biobank and GWAS Catalog to explore the genetic overlap between COVID-19 and a broad spectrum of traits and diseases. We validate previously reported medical conditions and risk factors based on epidemiological studies, including but not limited to hypertension, type 2 diabetes and obesity. We also report novel traits associated with COVID-19, which have not been previously reported from epidemiological data, such as opioid use and educational attainment. Taken together, this study extends our understanding of the genetic basis of COVID-19, and provides target traits for further epidemiological studies.

🖺 Full Text HTML: Genetic correlations between COVID-19 and a variety of diseases and other medically relevant traits

Public adherence to governmental recommendations regarding quarantine and testing for COVID-19 in two Norwegian cohorts -

Background Combatting the COVID-19 pandemic relies at present on non-pharmacological interventions. Governments are using various approaches from general advice to full lockdown. There is a need to describe and understand adherence to public health actions. Methods Participants from two ongoing cohorts, the Norwegian Mother, Father and Child Cohort Study (MoBa) and The Norwegian Influenza Pregnancy Cohort (NorFlu), answered questionnaires every 14 days since March 2020. From the summer of 2020, testing for presence of SARS-CoV-2 became easily available. Recommendations were that respiratory symptoms should lead to testing, and that confirmed or suspected COVID-19 should be followed by quarantine. We estimated the adherence to these guidelines in responses from cohort participants in the period August to October 2020. Results Less than 40% of men who were ill and less than 45% of women who were ill, tested themselves for SARS-CoV-2 during the same 14-day periods. Among subjects tested for COVID-19, about 53% of men and 59% of women reported quarantine. For subjects with a confirmed or suspected COVID-19 diagnosis, the proportions quarantined were 65% for men and 72% for women. Conclusions Public adherence to governmental recommendations regarding testing and quarantine were lower than expected in a country with high trust in government. This leaves considerable room for improvement in adherence, possibly reducing the need for more restrictive interventions.

🖺 Full Text HTML: Public adherence to governmental recommendations regarding quarantine and testing for COVID-19 in two Norwegian cohorts

Forecasting daily confirmed COVID-19 cases in Algeria using ARIMA models -

ABSTRACT Coronavirus disease has become a worldwide threat affecting almost every country in the world. The aim of this study is to identify the COVID-19 cases (positive, recovery and death) in Algeria using the Double Exponential Smoothing Method and an Autoregressive Integrated Moving Average (ARIMA) model for forecasting the COVID-19 cases. The data for this study were obtained from March 21st, 2020 to November 26th, 2020. The daily Algerian COVID-19 confirmed cases were sourced from The Ministry of Health, Population and Hospital Reform of Algeria. Based on the results of PACF, ACF, and estimated parameters of the ARIMA model in the COVID-19 case in Algeria following the ARIMA model (0,1,1). Observed cases during the forecast period were accurately predicted and were placed within the prediction intervals generated by the fitted model. This study shows that ARIMA models with optimally selected covariates are useful tools for monitoring and predicting trends of COVID-19 cases in Algeria. Keywords: COVID-19, Time series, Double Exponential Smoothing, ARIMA; forecast, Algeria.

🖺 Full Text HTML: Forecasting daily confirmed COVID-19 cases in Algeria using ARIMA models

An expedited approach towards the rationale design of non-covalent SARS-CoV-2 main protease inhibitors with in vitro antiviral activity -

The main protease (Mpro) of SARS-CoV-2 is a validated antiviral drug target. Several Mpro inhibitors have been reported with potent enzymatic inhibition and cellular antiviral activity, including GC376, boceprevir, calpain inhibitors II and XII, each containing a reactive warhead that covalently modifies the catalytic Cys145. In this study, we report an expedited drug discovery approach by coupling structure-based design and Ugi four-component (Ugi-4CR) reaction methodology to the design of non-covalent Mpro inhibitors. The most potent compound 23R had cellular antiviral activity similar to covalent inhibitors such as GC376. Our designs were guided by overlaying the structure of SARS-CoV Mpro + ML188 (R), a non-covalent inhibitor derived from Ug-4CR, with the X-ray crystal structures of SARS-CoV-2 Mpro + calpain inhibitor XII/GC376/UAWJ247. Binding site analysis suggests a strategy of extending the P2 and P3 substitutions in ML188 (R) to achieve optimal shape complementary with SARS-CoV-2 Mpro. Lead optimization led to the discovery of 23R, which inhibits SARS-CoV-2 Mpro and SARS-CoV-2 viral replication with an IC50 of 0.31 microM and EC50 of 1.27 microM, respectively. The binding and specificity of 23R to SARS-CoV-2 Mpro were confirmed in a thermal shift assay and native mass spectrometry assay. The co-crystal structure of SARS-CoV-2 Mpro with 23R revealed the P2 biphenyl fits snuggly into the S2 pocket and the benzyl group in the -methylbenzyl faces towards the core of the enzyme, occupying a previously unexplored binding site located in between the S2 and S4 pockets. Overall, this study revealed the most potent non-covalent SARS-CoV-2 Mpro inhibitors reported to date and a novel binding pocket that can be explored for Mpro inhibitor design.

🖺 Full Text HTML: An expedited approach towards the rationale design of non-covalent SARS-CoV-2 main protease inhibitors with in vitro antiviral activity

Sterilizing immunity against SARS-CoV-2 in hamsters conferred by a novel recombinant subunit vaccine -

A safe and effective SARS-CoV-2 vaccine is essential to avert the on-going COVID-19 pandemic. Here, we developed a subunit vaccine, which is comprised of CHO-expressed spike ectodomain protein (StriFK) and nitrogen bisphosphonates-modified zinc-aluminum hybrid adjuvant (FH002C). This vaccine candidate rapidly elicited the robust humoral response, Th1/Th2 balanced helper CD4 T cell and CD8 T cell immune response in animal models. In mice, hamsters, and non-human primates, 2-shot and 3-shot immunization of StriFK-FH002C generated 28- to 38-fold and 47- to 269-fold higher neutralizing antibody titers than the human COVID-19 convalescent plasmas, respectively. More importantly, the StriFK-FH002C immunization conferred sterilizing immunity to prevent SARS-CoV-2 infection and transmission, which also protected animals from virus-induced weight loss, COVID-19-like symptoms, and pneumonia in hamsters. Vaccine-induced neutralizing and cell-based receptor-blocking antibody titers correlated well with protective efficacy in hamsters, suggesting vaccine-elicited protection is immune-associated. The StriFK-FH002C provided a promising SARS-CoV-2 vaccine candidate for further clinical evaluation.

🖺 Full Text HTML: Sterilizing immunity against SARS-CoV-2 in hamsters conferred by a novel recombinant subunit vaccine

A comprehensive transcriptome analysis reveals broader but weaker host response of SARS-CoV-2 than SARS-CoV -

COVID-19, which has resulted a worldwide health crisis with more than 74.9 million confirmed cases worldwide by December 2020, is caused by a newly emerging coronavirus identified and named SARS-CoV-2 in February in Wuhan, China. Experiences in defeating SARS, which infested during 2002-2003, can be used in treating the new disease. However, comparative genomics and epidemiology studies have shown much difference between SARS-CoV and SARS-CoV-2, which underlies the different clinical features and therapies in between those two diseases. Further studies comparing transcriptomes infected by these two viruses to uncover the differences in host responses would be necessary. Here we conducted a comprehensive transcriptome analysis of SARS-CoV and SARS-CoV-2-infected human cell lines, including Caco-2, Calu-3, H1299. Clustering analysis and expression of ACE2 show that SARS-CoV-2 has broader but weaker infection, where the largest discrepancy occurs in the epithelial lung cancer cell, Calu-3. SARS-CoV-2 genes also show less tissue specificity than SARS-CoV genes. Furthermore, we detected more general but moderate immune responses in SARS-CoV-2 infected transcriptomes by comparing weighted gene co-expression networks and modules. Our results suggest a different immune therapy and treatment scheme for COVID-19 patients than the ones used on SARS patients. The wider but weaker permissiveness and host responses of virus infection may also imply a long-term existence of SARS-CoV-2 among human populations.

🖺 Full Text HTML: A comprehensive transcriptome analysis reveals broader but weaker host response of SARS-CoV-2 than SARS-CoV

The polybasic cleavage site in the SARS-CoV-2 spike modulates viral sensitivity to Type I IFN and IFITM2 -

The cellular entry of severe acute respiratory syndrome-associated coronaviruses types 1 and 2 (SARS-CoV-1 and -2) requires sequential protease processing of the viral spike glycoprotein (S). The presence of a polybasic cleavage site in SARS-CoV-2 S at the S1/S2 boundary has been suggested to be a factor in the increased transmissibility of SARS-CoV-2 compared to SARS-CoV-1 by facilitating maturation of the S precursor by furin-like proteases in the producer cells rather than endosomal cathepsins in the target. We investigate the relevance of the polybasic cleavage site in the route of entry of SARS-CoV-2 and the consequences this has for sensitivity to interferons, and more specifically, the IFN-induced transmembrane (IFITM) protein family that inhibit entry of diverse enveloped viruses. We found that SARS-CoV-2 is restricted predominantly by IFITM2 and the degree of this restriction is governed by route of viral entry. Removal of the cleavage site in the spike protein renders SARS-CoV-2 entry highly pH- and cathepsin-dependent in late endosomes where, like SARS-CoV-1 S, it is more sensitive to IFITM2 restriction. Furthermore, we find that potent inhibition of SARS-CoV-2 replication by type I but not type II IFNs is alleviated by targeted depletion of IFITM2 expression. We propose that the polybasic cleavage site allows SARS-CoV-2 to mediate viral entry in a pH-independent manner, in part to mitigate against IFITM-mediated restriction and promote replication and transmission. This suggests therapeutic strategies that target furin-mediated cleavage of SARS-CoV-2 S may reduce viral replication through the activity of type I IFNs.

🖺 Full Text HTML: The polybasic cleavage site in the SARS-CoV-2 spike modulates viral sensitivity to Type I IFN and IFITM2

The challenges of the coming mass vaccination and exit strategy in prevention and control of COVID-19, a modelling study -

With success in the development of COVID-19 vaccines, it is urgent and challenging to analyse how the coming large-scale vaccination in the population and the growing public desire of relaxation of non-pharmaceutical interventions (NPIs) interact to impact the prevention and control of the COVID-19 pandemic. Using mathematical models, we focus on two aspects: 1) how the vaccination program should be designed to balance the dynamic exit of NPIs; 2) how much the vaccination coverage is needed to avoid a second wave of the epidemics when the NPIs exit in stages. We address this issue globally, and take six countries--China, Brazil, Indonesia, Russia, UK, and US-in our case study. We showed that a dynamic vaccination program in three stages can be an effective approach to balance the dynamic exit of the NPIs in terms of mitigating the epidemics. The vaccination rates and the accumulative vaccination coverage in these countries are estimated by fitting the model to the real data. We observed that the required effective vaccination coverages are greatly different to balance the dynamic exit of NPIs in these countries, providing a quantitative criterion for the requirement of an integrative package of NPIs. We predicted the epidemics under different vaccination rates for these countries, and showed that the vaccination can significantly decrease the peak value of a future wave. Furthermore, we found that a lower vaccination coverage can result in a subsequent wave once the NPIs exit. Therefore, there is a critical (minimum) vaccination coverage, depending on effectiveness of NPIs to avoid a subsequent wave. We estimated the critical vaccination coverages for China, Brazil, and Indonesia under different scenarios. In conclusion, we quantitatively showed that the dynamic vaccination program can be the effective approach to supplement or even eventually replace NPIs in mitigating the epidemics and avoiding future waves, and we suggest that country level-based exit strategies of the NPIs should be considered, according to the possible quarantine rate and testing ability, and the accessibility, affordability and efficiency of the vaccines.

🖺 Full Text HTML: The challenges of the coming mass vaccination and exit strategy in prevention and control of COVID-19, a modelling study

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