Identifying parent anxiety and family distress of critically ill children in response to changes in hospital visitation policies during the COVID-19 pandemic

This research study describes parent anxiety and family distress among three study groups of varying restrictions in parent presence for children in the PICU during a pandemic. A retrospective study was conducted to describe differences in parent anxiety and family distress for parents of children hospitalized before and during the COVID-19 pandemic. Participants fell into three study groups based on the dates of the child's hospital stay and the level of parent and family presence or restriction they experienced. Participants were asked to complete a survey that included basic demographic information along with utilization of the GAD-7 and FDI measures. The data were assessed using descriptive statistics, Fisher's exact test, and the Kruskal-Wallis test. A total of 82 parents of children hospitalized during the specified times in the PICU participated. There was a statistically significant difference among the three cohorts in diagnoses (respiratory, cardiovascular, and medical-surgical), p ≤0.001. A larger percentage of children of the study participants were hospitalized with respiratory illnesses (62.5%) in the unrestricted study group when compared to the other study groups with higher patient acuity. There was also a statistical significance among the three study groups regarding whether the second parent was able to visit the child during the PICU admission (p = 0.007). Our study suggests that restricting parent and visitor presence does not increase parent anxiety or family distress during a child's admission to the PICU. The literature widely supports that having a critically ill child is undoubtedly stressful for parents and families, but the most significant causation for the anxiety and stress remains unknown and is likely multifactorial. Parents who experienced rigid restrictions in parent and visitor presence did not have increased anxiety. Other impactful variables such as a child's mortality risk and the uncertainty of outcome may have impacted anxiety for parents whose children were critically ill. Further research is needed to understand which stressors are most significant, during a critically ill child's hospitalization, from a parent's perspective. Limiting staff and patient exposure to persons who may have contagious illness (restricting parent and family presence) may not in itself lead to increased anxiety and distress for parents and families. This study may provide context for careful development of hospital visitation policies to ensure balance between patient and family centered care and protection from infectious disease. • A child's admission to a pediatric intensive care unit (PICU) is one of the most stressful and anxiety-provoking situations for parents. • Restricting parent presence interrupts the social and emotional relationship and offers less time for bonding.. • Coronavirus-19 (COVID-19) forced hospitals to make abrupt changes to existing visitation policies. • This research provides context for support of careful development and implementation of hospital visitation policies.

Predictive capacity of COVID-19-related risk beliefs on weight management behaviors on a commercial weight loss program and speed of COVID-19 vaccination uptake: prospective cohort study.

BACKGROUND: Recent work has shown that obesity may be a risk factor for severe COVID-19. However, it is unclear to what extent individuals have heard or believe this risk factor information, and how these beliefs may predict their preventive behaviors (e.g., weight management behaviors or COVID-19 preventive behaviors). Previous work has primarily looked at overall risk likelihood perceptions (i.e., not about obesity as a risk factor) within general populations of varying weight and concentrated on COVID-19-related preventive behaviors. Therefore, this prospective cohort study explored whether beliefs about obesity as a risk factor and overall risk likelihood perceptions predicted weight management and COVID-19 preventive behaviors over the next 16 weeks in individuals with obesity or overweight. METHODS: Participants were 393 individuals in the US who joined a commercial weight management program in January, 2021. We leveraged the mobile program's automatic measurement of real-time engagement in weight management behaviors (e.g., steps taken), while surveys measured risk beliefs at baseline as well as when individuals received COVID-19 vaccination doses (asked monthly) over the next 16 weeks. Mixed effects models predicted engagement and weight loss each week for 16 weeks, while ordinal logistic regression models predicted the month that individuals got vaccinated against COVID-19. RESULTS: We found that belief in obesity as a risk factor at baseline significantly predicted greater engagement (e.g., steps taken, foods logged) in program-measured weight management behaviors over the next 16 weeks in models adjusted for baseline BMI, age, gender, and local vaccination rates (minimally adjusted) and in models additionally adjusted for demographic factors. Belief in obesity as a risk factor at baseline also significantly predicted speed of COVID-19 vaccination uptake in minimally adjusted models but not when demographic factors were taken into account. Exposure to obesity risk factor information at baseline predicted greater engagement over 16 weeks in minimally adjusted models. CONCLUSIONS: The results highlight the potential utility of effective education to increase individuals' belief in obesity risk factor information and ultimately promote engagement or faster vaccination. Future research should investigate to what extent the results generalize to other populations.

Identifying parent anxiety and family distress of critically ill children in response to changes in hospital visitation policies during the COVID-19 pandemic

Purpose This research study describes parent anxiety and family distress among three study groups of varying restrictions in parent presence for children in the PICU during a pandemic. Design and methods A retrospective study was conducted to describe differences in parent anxiety and family distress for parents of children hospitalized before and during the COVID-19 pandemic. Participants fell into three study groups based on the dates of the child's hospital stay and the level of parent and family presence or restriction they experienced. Participants were asked to complete a survey that included basic demographic information along with utilization of the GAD-7 and FDI measures. The data were assessed using descriptive statistics, Fisher's exact test, and the Kruskal-Wallis test. Results A total of 82 parents of children hospitalized during the specified times in the PICU participated. There was a statistically significant difference among the three cohorts in diagnoses (respiratory, cardiovascular, and medical-surgical), p ≤0.001. A larger percentage of children of the study participants were hospitalized with respiratory illnesses (62.5%) in the unrestricted study group when compared to the other study groups with higher patient acuity. There was also a statistical significance among the three study groups regarding whether the second parent was able to visit the child during the PICU admission (p = 0.007). Conclusions Our study suggests that restricting parent and visitor presence does not increase parent anxiety or family distress during a child's admission to the PICU. The literature widely supports that having a critically ill child is undoubtedly stressful for parents and families, but the most significant causation for the anxiety and stress remains unknown and is likely multifactorial. Clinical and research implications Parents who experienced rigid restrictions in parent and visitor presence did not have increased anxiety. Other impactful variables such as a child's mortality risk and the uncertainty of outcome may have impacted anxiety for parents whose children were critically ill. Further research is needed to understand which stressors are most significant, during a critically ill child's hospitalization, from a parent's perspective. Limiting staff and patient exposure to persons who may have contagious illness (restricting parent and family presence) may not in itself lead to increased anxiety and distress for parents and families. This study may provide context for careful development of hospital visitation policies to ensure balance between patient and family centered care and protection from infectious disease.

Natural Polyphenols, 1,2,3,4,6-O-Pentagalloyglucose and Proanthocyanidins, as Broad-Spectrum Anticoronaviral Inhibitors Targeting Mpro and RdRp of SARS-CoV-2.

The natural plant dietary polyphenols 1,2,3,4,6-O-Pentagalloylglucose (PGG) and proanthocyanidin (PAC) have potent antioxidant activity and a variety of pharmacological activities, including antiviral activity. In this study, we examined the inhibitory effect of PGG and PAC on SARS-CoV-2 virus infection, and elucidated its mode of action. PGG and PAC have dose-dependent inhibitory activity against SARS-CoV-2 infection in Vero cells. PGG has a lower IC50 (15.02 ± 0.75 µM) than PAC (25.90 ± 0.81 µM), suggesting that PGG has better inhibitory activity against SARS-CoV-2 than PAC. The PGG and PAC inhibit similar Mpro activities in a protease activity assay, with IC50 values of 25-26 µM. The effects of PGG and PAC on the activity of the other essential SARS-CoV-2 viral protein, RdRp, were analyzed using a cell-based activity assay system. The activity of RdRp is inhibited by PGG and PAC, and PGG has a lower IC50 (5.098 ± 1.089 µM) than PAC (21.022 ± 1.202 µM), which is consistent with their inhibitory capacity of SARS-CoV-2 infection. PGG and PAC also inhibit infection by SARS-CoV and MERS-CoV. These data indicate that PGG and PAC may be candidate broad-spectrum anticoronaviral therapeutic agents, simultaneously targeting the Mpro and RdRp proteins of SARS-CoV-2.

Natural Polyphenols, 1,2,3,4,6-O-Pentagalloyglucose and Proanthocyanidins, as Broad-Spectrum Anticoronaviral Inhibitors Targeting Mpro and RdRp of SARS-CoV-2

The natural plant dietary polyphenols 1,2,3,4,6-O-Pentagalloylglucose (PGG) and proanthocyanidin (PAC) have potent antioxidant activity and a variety of pharmacological activities, including antiviral activity. In this study, we examined the inhibitory effect of PGG and PAC on SARS-CoV-2 virus infection, and elucidated its mode of action. PGG and PAC have dose-dependent inhibitory activity against SARS-CoV-2 infection in Vero cells. PGG has a lower IC50 (15.02 ±0.75 μM) than PAC (25.90 ±0.81 μM), suggesting that PGG has better inhibitory activity against SARS-CoV-2 than PAC. The PGG and PAC inhibit similar Mpro activities in a protease activity assay, with IC50 values of 25–26 μM. The effects of PGG and PAC on the activity of the other essential SARS-CoV-2 viral protein, RdRp, were analyzed using a cell-based activity assay system. The activity of RdRp is inhibited by PGG and PAC, and PGG has a lower IC50 (5.098 ±1.089 μM) than PAC (21.022 ±1.202 μM), which is consistent with their inhibitory capacity of SARS-CoV-2 infection. PGG and PAC also inhibit infection by SARS-CoV and MERS-CoV. These data indicate that PGG and PAC may be candidate broad-spectrum anticoronaviral therapeutic agents, simultaneously targeting the Mpro and RdRp proteins of SARS-CoV-2.

Inhibition of ACE2‐Spike Interaction by an ACE2 Binder Suppresses SARS‐CoV‐2 Entry

The emergence of SARS‐CoV‐2 variants is a significant concern in developing effective therapeutics and vaccines in the middle of the ongoing COVID‐19 pandemic. Here, we have identified a novel small molecule that inhibited the interactions between SARS‐CoV‐2 spike RBDs and ACE2 by modulating ACE2 without impairing its enzymatic activity necessary for normal physiological functions. Furthermore, the identified compounds suppressed viral infection in cultured cells by inhibiting the entry of ancestral and variant SARS‐CoV‐2. Our study suggests that targeting ACE2 could be a novel therapeutic strategy to inhibit SARS‐CoV‐2 entry into host cells and prevent the development of COVID‐19. [ FROM AUTHOR] Copyright of Angewandte Chemie is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Anticoronaviral Activity of the Natural Phloroglucinols, Dryocrassin ABBA and Filixic Acid ABA from the Rhizome of Dryopteris crassirhizoma by Targeting the Main Protease of SARS-CoV-2.

The rhizome of Dryopteris crassirhizoma Nakai. (Dryopteridaceae) has been used in traditional medicine in East Asia and has recently been reported to have anticancer, anti-inflammation, and antibacterial activity as well as antiviral activity. Natural phloroglucinols from D. crassirhizoma, dryocrassin ABBA and filixic acid ABA were reported to inhibit influenza virus infection with an inhibitory activity on neuraminidase. In this study, we found that dryocrassin ABBA and filixic acid ABA have an inhibitory activity against the main protease of SARS-CoV-2. Therefore, dryocrassin ABBA and filixic acid ABA exhibited inhibitory activity against SARS-CoV-2 infection in Vero cells dose-dependently using the immunofluorescence-based antiviral assays. Moreover, these compounds inhibited SARS-CoV and MERS-CoV infection, suggesting their broad-spectrum anticoronaviral activity. In addition, a 5-day repeated-dose toxicity study of dryocrassin ABBA and filixic acid ABA suggested that an approximately lethal dose of these compounds in mice was >10 mg/kg. Pharmacokinetic studies of dryocrassin ABBA showed good microsomal stability, low hERG inhibition, and low CYP450 inhibition. In vivo pharmacokinetic properties of dryocrassin ABBA showed a long half-life (5.5-12.6 h) and high plasma exposure (AUC 19.3-65 µg·h/mL). Therefore, dryocrassin ABBA has therapeutic potential against emerging coronavirus infections, including COVID-19.

Exploring the Effects of the COVID-19 Pandemic on the Children and Families Cared for by Pediatric-Focused Advanced Practice Registered Nurses.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has significantly affected children and families. The study purpose was to better understand the perceptions of pediatric-focused advanced practice registered nurses (P-APRNs) on the impact of COVID-19 on patients and practice. METHOD: A 25-item electronic survey including Likert scales, multiple choice , and open-ended questions was sent by e-mail to electronic mailing list of the National Association of Pediatric Nurse Practitioners. RESULTS: Responses (N = 109) reflect the magnitude of challenges affecting child physical health, mental health, parental stress, and social determinants of health. P-APRNs expect greater refusal of the COVID-19 vaccine compared with other vaccines. Telehealth use continues at an increased rate and greater resources are needed to support clinical practice. DISCUSSION: The COVID-19 pandemic has transformed the lives of children, families, and P-APRN practice. These findings reflect challenges and opportunities moving forward. P-APRNs are well-prepared to lead change to support better and more equitable outcomes for all.

Harnessing stress granule formation by small molecules to inhibit the cellular replication of SARS-CoV-2.

We identified small-molecule enhancers of cellular stress granules by observing molecular crowding of proteins and RNAs in a time-dependent manner. Hit molecules sensitized the IRF3-mediated antiviral mechanism in the presence of poly(I:C) and inhibited the replication of SARS-CoV-2 by inducing stress granule formation. Thus, modulating multimolecular crowding can be a promising strategy against SARS-CoV-2.

Broad Spectrum Antiviral Properties of Cardiotonic Steroids Used as Potential Therapeutics for Emerging Coronavirus Infections.

Cardiotonic steroids are steroid-like natural compounds known to inhibit Na+/K+-ATPase pumps. To develop a broad-spectrum antiviral drug against the emerging coronavirus infection, this study assessed the antiviral properties of these compounds. The activity of seven types of cardiotonic steroids against the MERS-CoV, SARS-CoV, and SARS-CoV-2 coronavirus varieties was analyzed using immunofluorescence antiviral assay in virus-infected cells. Bufalin, cinobufagin, and telocinobufagin showed high anti-MERS-CoV activities (IC50, 0.017~0.027 µM); bufalin showed the most potent anti-SARS-CoV and SARS-CoV-2 activity (IC50, 0.016~0.019 µM); cinobufotalin and resibufogenin showed comparatively low anti-coronavirus activity (IC50, 0.231~1.612 µM). Differentially expressed genes in Calu3 cells treated with cinobufagin, telocinobufagin, or bufalin, which had high antiviral activity during MERS-CoV infection were analyzed using QuantSeq 3' mRNA-Seq analysis and data showed similar gene expression patterns. Furthermore, the intraperitoneal administration of 10 mg/kg/day bufalin, cinobufagin, or digitoxin induced 100% death after 1, 2, and 4 days in 5-day repeated dose toxicity studies and it indicated that bufalin had the strongest toxicity. Pharmacokinetic studies suggested that telocinobufagin, which had high anti-coronavirus activity and low toxicity, had better microsomal stability, lower CYP inhibition, and better oral bioavailability than cinobufagin. Therefore, telocinobufagin might be the most promising cardiotonic steroid as a therapeutic for emerging coronavirus infections, including COVID-19.

TMPRSS2 and RNA-Dependent RNA Polymerase Are Effective Targets of Therapeutic Intervention for Treatment of COVID-19 Caused by SARS-CoV-2 Variants (B.1.1.7 and B.1.351).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative agent of the coronavirus disease 2019 (COVID-19) pandemic, and the development of therapeutic interventions is urgently needed. So far, monoclonal antibodies and drug repositioning are the main methods for drug development, and this effort was partially successful. Since the beginning of the COVID-19 pandemic, the emergence of SARS-CoV-2 variants has been reported in many parts of the world, and the main concern is whether the current vaccines and therapeutics are still effective against these variant viruses. Viral entry and viral RNA-dependent RNA polymerase (RdRp) are the main targets of current drug development; therefore, the inhibitory effects of transmembrane serine protease 2 (TMPRSS2) and RdRp inhibitors were compared among the early SARS-CoV-2 isolate (lineage A) and the two recent variants (lineage B.1.1.7 and lineage B.1.351) identified in the United Kingdom and South Africa, respectively. Our in vitro analysis of viral replication showed that the drugs targeting TMPRSS2 and RdRp are equally effective against the two variants of concern. IMPORTANCE The COVID-19 pandemic is causing unprecedented global problems in both public health and human society. While some vaccines and monoclonal antibodies were successfully developed very quickly and are currently being used, numerous variants of the causative SARS-CoV-2 are emerging and threatening the efficacy of vaccines and monoclonal antibodies. In order to respond to this challenge, we assessed antiviral efficacy of small-molecule inhibitors that are being developed for treatment of COVID-19 and found that they are still very effective against the SARS-CoV-2 variants. Since most small-molecule inhibitors target viral or host factors other than the mutated sequence of the viral spike protein, they are expected to be potent control measures against the COVID-19 pandemic.

Virtual Experience of Perioperative Patients: Walking in the Patients' Shoes Using Virtual Reality and Blended Learning.

PURPOSE: This study examined the significance, nature, and structure of the virtual experience of perioperative patients as undergone by nursing students during their practical training through VR and blended learning. METHODS: Data were collected through a focus group interview (FGI) of 21 nursing student participants from November 2019 to December 2019 and analyzed through Colaizzi's phenomenological method. RESULTS: Seven theme clusters were organized that described nursing students' experiences. They are "placed in a passive position," "facing the limits of communication," "thinking of developing and improving competency as a nurse," "recognizing the importance of interacting with their patients", "learning vividly through experience", "engaging in a new type of participatory learning", and "designing nursing knowledge." CONCLUSION: Patient-centered care can be achieved in the nursing school curriculum through "patient experiences." Additionally, the feedback from research participants who have "become keenly aware of the need for patient experiences" shows that empathizing with the "patient experience" is an essential quality to acquire by prospective medical professionals before they are introduced to the nursing field. We suggest future studies that expand on nursing students' patient experience in various teaching methods and curriculums.

Comparison of Digital PCR and Quantitative PCR with Various SARS-CoV-2 Primer-Probe Sets.

The World Health Organization (WHO) has declared the coronavirus disease 2019 (COVID-19) as an international health emergency. Current diagnostic tests are based on the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) method, which is the gold standard test that involves the amplification of viral RNA. However, the RT-qPCR assay has limitations in terms of sensitivity and quantification. In this study, we tested both qPCR and droplet digital PCR (ddPCR) to detect low amounts of viral RNA. The cycle threshold (CT) of the viral RNA by RT-PCR significantly varied according to the sequences of the primer and probe sets with in vitro transcript (IVT) RNA or viral RNA as templates, whereas the copy number of the viral RNA by ddPCR was effectively quantified with IVT RNA, cultured viral RNA, and RNA from clinical samples. Furthermore, the clinical samples were assayed via both methods, and the sensitivity of the ddPCR was determined to be equal to or more than that of the RT-qPCR. However, the ddPCR assay is more suitable for determining the copy number of reference materials. These findings suggest that the qPCR assay with the ddPCR defined reference materials could be used as a highly sensitive and compatible diagnostic method for viral RNA detection.

Lycorine, a non-nucleoside RNA dependent RNA polymerase inhibitor, as potential treatment for emerging coronavirus infections.

BACKGROUND: Highly effective novel treatments need to be developed to suppress emerging coronavirus (CoV) infections such as COVID-19. The RNA dependent RNA polymerase (RdRp) among the viral proteins is known as an effective antiviral target. Lycorine is a phenanthridine Amaryllidaceae alkaloid isolated from the bulbs of Lycoris radiata (L'Hér.) Herb. and has various pharmacological bioactivities including antiviral function. PURPOSE: We investigated the direct-inhibiting action of lycorine on CoV's RdRp, as potential treatment for emerging CoV infections. METHODS: We examined the inhibitory effect of lycorine on MERS-CoV, SARS-CoV, and SARS-CoV-2 infections, and then quantitatively measured the inhibitory effect of lycorine on MERS-CoV RdRp activity using a cell-based reporter assay. Finally, we performed the docking simulation with lycorine and SARS-CoV-2 RdRp. RESULTS: Lycorine efficiently inhibited these CoVs with IC50 values of 2.123 ± 0.053, 1.021 ± 0.025, and 0.878 ± 0.022 µM, respectively, comparable with anti-CoV effects of remdesivir. Lycorine directly inhibited MERS-CoV RdRp activity with an IC50 of 1.406 ± 0.260 µM, compared with remdesivir's IC50 value of 6.335 ± 0.731 µM. In addition, docking simulation showed that lycorine interacts with SARS-CoV-2 RdRp at the Asp623, Asn691, and Ser759 residues through hydrogen bonding, at which the binding affinities of lycorine (-6.2 kcal/mol) were higher than those of remdesivir (-4.7 kcal/mol). CONCLUSIONS: Lycorine is a potent non-nucleoside direct-acting antiviral against emerging coronavirus infections and acts by inhibiting viral RdRp activity; therefore, lycorine may be a candidate against the current COVID-19 pandemic.

Antiviral activity against Middle East Respiratory Syndrome coronavirus by Montelukast, an anti-asthma drug.

Middle East Respiratory Syndrome (MERS) is a respiratory disease caused by a coronavirus (MERS-CoV). Since its emergence in 2012, nosocomial amplifications have led to its high epidemic potential and mortality rate of 34.5%. To date, there is an unmet need for vaccines and specific therapeutics for this disease. Available treatments are either supportive medications in use for other diseases or those lacking specificity requiring higher doses. The viral infection mode is initiated by the attachment of the viral spike glycoprotein to the human Dipeptidyl Peptidase IV (DPP4). Our attempts to screen antivirals against MERS led us to identify montelukast sodium hydrate (MSH), an FDA-approved anti-asthma drug, as an agent attenuating MERS-CoV infection. We showed that MSH directly binds to MERS-CoV-Receptor-Binding Domain (RBD) and inhibits its molecular interaction with DPP4 in a dose-dependent manner. Our cell-based inhibition assays using MERS pseudovirions demonstrated that viral infection was significantly inhibited by MSH and was further validated using infectious MERS-CoV culture. Thus, we propose MSH as a potential candidate for therapeutic developments against MERS-CoV infections.

Identification of 4-anilino-6-aminoquinazoline derivatives as potential MERS-CoV inhibitors.

New therapies for treating coronaviruses are urgently needed. A series of 4-anilino-6-aminoquinazoline derivatives were synthesized and evaluated to show high anti-MERS-CoV activities. N4-(3-Chloro-4-fluorophenyl)-N6-(3-methoxybenzyl)quinazoline-4,6-diamine (1) has been identified in a random screen as a hit compound for inhibiting MERS-CoV infection. Throughout optimization process, compound 20 was found to exhibit high inhibitory effect (IC50 = 0.157 µM, SI = 25) with no cytotoxicity and moderate in vivo PK properties.

Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs.

Drug repositioning is the only feasible option to immediately address the COVID-19 global challenge. We screened a panel of 48 FDA-approved drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which were preselected by an assay of SARS-CoV. We identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low 50% inhibitory concentrations (IC50s), and in particular, two FDA-approved drugs-niclosamide and ciclesonide-were notable in some respects.