COVID-19 and practice transformation: Building an office-based opioid treatment program in a family medicine residency practice.

INTRODUCTION: This brief report describes how a family medicine residency practice (FMRP) leveraged a resident-led quality improvement project and a grant-funded Addiction Integrated Care Team (AICT) to initiate an office-based opioid treatment (OBOT) program to provide medications for opioid use disorder during the COVID-19 pandemic. METHOD: In 2020, the practice experienced four disruptors that shifted motivation for practice development: (a) The COVID-19 pandemic demanded rapid change in primary care processes/staffing, including pivoting to telehealth/remote practice. (b) The practice's transition to a federally qualified community health center model meant a shift in organizational priorities that required offering OBOT services. (c) External grant resources became available through the AICT program to support practice core for OBOT, and 10 implementation strategies were utilized. (d) A resident champion implemented an OBOT quality improvement project. RESULTS: These efforts resulted in the practice offering the OBOT program and 18 patients receiving OBOT from January 2020 to February 2021, with 10 of 18 patients engaged for 12 months or longer. Further, the cumulative adoption and reach from January 2020 through September 2022 was 15 faculty and 14 residents becoming prescribers and 101 patients served within the OBOT program, respectively. DISCUSSION: FMRPs striving for significant practice transformation, such as implementing an OBOT program during a pandemic, may benefit from synergistic guidance and resources including established theory, strategies from the implementation science literature, and resident-led quality improvement efforts. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Impact of Virtual Interviews on Recruitment and Implicit Bias.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic accelerated virtual residency interview adoption. The impact of virtual interviews on program directors' (PD) National Residency Matching Program (NRMP) Match satisfaction, their future interview plans, and their perceptions about virtual interviews' influence on bias are unknown. We report the results of a survey of family medicine (FM) PDs about these topics after mandatory virtual interviews in 2020-2021. METHODS: A national survey of all FM PDs was conducted in April 2021 (n=619). The response rate was 46.37% (n=287). Questions asked whether PDs conducted virtual interviews, as well as PDs' general perceptions of virtual interviews' impact on administrative burden, diversity and bias; PD's ability to communicate program culture and assess applicants' alignment with program values; PD's satisfaction with Match results; and plans for interview structure postpandemic. RESULTS: Two hundred forty-four (93.1%) respondents performed only virtual interviews; 83.9% (n=220) conducting virtual interviews were satisfied with Match results, with no difference between programs with all virtual interviews vs others (OR 1.2, P=.994). PDs who communicated program values and involved residents in virtual interviews experienced higher Match satisfaction (OR 7.6, P<.001; OR 4.21, P=.001). PDs concerned about virtual interviews increasing bias against minorities before 2020 were still concerned after (OR 8.81, P<.001) and had lower Match satisfaction (OR 0.24, P=.001). CONCLUSIONS: Most FM PDs conducted entirely virtual interviews in 2020 and were satisfied with the Match. Interview processes including residents and conveying residency culture increased Match satisfaction. PDs are concerned about bias in virtual interviews, but more investigation about bias is needed.

TeenCovidLife: a resource to understand the impact of the COVID-19 pandemic on adolescents in Scotland.

TeenCovidLife is part of Generation Scotland's CovidLife projects, a set of longitudinal observational studies designed to assess the psychosocial and health impacts of the COVID-19 pandemic. TeenCovidLife focused on how adolescents in Scotland were coping during the pandemic. As of September 2021, Generation Scotland had conducted three TeenCovidLife surveys. Participants from previous surveys were invited to participate in the next, meaning the age ranges shifted over time. TeenCovidLife Survey 1 consists of data from 5,543 young people age 12 to 17, collected from 22 May to 5 July 2020, during the first school closures period in Scotland. TeenCovidLife Survey 2 consists of data from 2,245 young people aged 12 to 18, collected from 18 August to 14 October 2020, when the initial lockdown measures were beginning to ease, and schools reopened in Scotland. TeenCovidLife Survey 3 consists of data from 597 young people age 12 to 19, collected from 12 May to 27 June 2021, a year after the first survey, after the schools returned following the second lockdown in 2021. A total of 316 participants took part in all three surveys. TeenCovidLife collected data on general health and well-being, as well as topics specific to COVID-19, such as adherence to COVID-19 health guidance, feelings about school closures, and the impact of exam cancellations. Limited work has examined the impact of the COVID-19 pandemic on young people. TeenCovidLife provides relevant and timely data to assess the impact of the pandemic on young people in Scotland. The dataset is available under authorised access from Generation Scotland; see the Generation Scotland website for more information.

TeenCovidLife: a resource to understand the impact of the COVID-19 pandemic on adolescents in Scotland [version 2;peer review: 2 approved]

TeenCovidLife is part of Generation Scotland’s CovidLife projects, a set of longitudinal observational studies designed to assess the psychosocial and health impacts of the COVID-19 pandemic. TeenCovidLife focused on how adolescents in Scotland were coping during the pandemic. As of September 2021, Generation Scotland had conducted three TeenCovidLife surveys. Participants from previous surveys were invited to participate in the next, meaning the age ranges shifted over time. TeenCovidLife Survey 1 consists of data from 5,543 young people age 12 to 17, collected from 22 May to 5 July 2020, during the first school closures period in Scotland. TeenCovidLife Survey 2 consists of data from 2,245 young people aged 12 to 18, collected from 18 August to 14 October 2020, when the initial lockdown measures were beginning to ease, and schools reopened in Scotland. TeenCovidLife Survey 3 consists of data from 597 young people age 12 to 19, collected from 12 May to 27 June 2021, a year after the first survey, after the schools returned following the second lockdown in 2021. A total of 316 participants took part in all three surveys. TeenCovidLife collected data on general health and well-being, as well as topics specific to COVID-19, such as adherence to COVID-19 health guidance, feelings about school closures, and the impact of exam cancellations. Limited work has examined the impact of the COVID-19 pandemic on young people. TeenCovidLife provides relevant and timely data to assess the impact of the pandemic on young people in Scotland. The dataset is available under authorised access from Generation Scotland;see the Generation Scotland website for more information.

SARS-CoV-2 vaccination diversifies the CD4+ spike-reactive T cell repertoire in patients with prior SARS-CoV-2 infection.

BACKGROUND: COVID-19 mRNA vaccines elicit strong T and B cell responses to the SARS-CoV-2 spike glycoprotein in both SARS-CoV-2 naïve and experienced patients. However, it is unknown whether the post-vaccine CD4+ T cell responses seen in patients with a history of COVID-19 are due to restimulation of T cell clonotypes that were first activated during natural infection or if they are the result of new clones activated by the vaccine. METHODS: To address this question, we analyzed the SARS-CoV-2 spike glycoprotein-specific CD4+ T cell receptor repertoire before and after vaccination in 10 COVID-19 convalescent patients and 4 SARS-CoV-2 naïve healthy donor vaccine recipients. We used the viral Functional Expansion of Specific T cells (ViraFEST) assay to quantitatively identify specific SARS-CoV-2 and common cold coronavirus CD4+ T cell clonotypes post COVID-19 disease resolution and post mRNA SARS-CoV-2 vaccination. FINDINGS: We found that while some preexisting T cell receptor clonotypes persisted, the post-vaccine repertoire consisted mainly of vaccine-induced clones and was largely distinct from the repertoire induced by natural infection. Vaccination-induced clones led to an overall maintenance of the total number of SARS-CoV-2 reactive clonotypes over time through expansion of novel clonotypes only stimulated through vaccination. Additionally, we demonstrated that the vaccine preferentially induces T cells that are only specific for SARS-CoV-2 antigens, rather than T cells that cross-recognize SARS-CoV-2/common cold coronaviruses. INTERPRETATION: These data demonstrate that SARS-CoV-2 vaccination in patients with prior SARS-CoV-2 infection induces a new antigen-specific repertoire and sheds light on the differential immune responses induced by vaccination versus natural infection. FUNDING: Bloomberg∼Kimmel Institute for Cancer Immunotherapy, The Johns Hopkins University, The Bill and Melinda Gates Foundation, NCI U54CA260492, NIH.

A deep dive into testing and management of COVID-19 for Australian high performance and professional sport. (Special Issue: COVID19 - moving forward.)

The purpose of testing for any communicable disease is to support clinicians in the diagnosis and management of individual patients and to describe transmission dynamics. The novel coronavirus is formally named SARS-CoV-2 and the clinical disease state resulting from an infection is known as COVID-19. Control of the COVID-19 pandemic requires clinicians, epidemiologists, and public health officials to utilise the most comprehensive, accurate and timely information available to manage the rapidly evolving COVID-19 environment. High performance sport is a unique context that may look towards comprehensive testing as a means of risk mitigation. Characteristics of the common testing options are discussed including the circumstances where additional testing may be of benefit and considerations for the associated risks. Finally, a review of the available technology that could be considered for use by medical staff at the point of care (PoC) in a high-performance sporting context is included.

Social Networks Shape Beliefs and Behavior: Evidence from Social Distancing During the COVID-19 Pandemic

We show that social network exposure to COVID-19 cases shapes individuals’ beliefs and behaviors concerning the coronavirus. We use de-identified data from Facebook to document that individuals with friends in areas with worse COVID-19 outbreaks reduce their mobility more than otherwise similar individuals with friends in less affected areas. The effects are quantitatively large and long-lasting: a one standard deviation increase in friend-exposure to COVID-19 cases in March 2020 results in a 1.2 percentage point increase in the probability of staying home on a given day through at least the end of May 2020. As the pandemic progresses—and the characteristics of individuals with the highest friend-exposure vary— changes in friend-exposure continue to drive changes in social distancing behavior, ruling out many unobserved effects as drivers of our results. We also show that individuals with higher friend-exposure to COVID-19 are more likely to publicly post in support of social distancing measures and less likely to be members of groups advocating to "reopen" the economy. These findings suggest that friends can influence individuals’ beliefs about the risks of the disease and thereby induce them to engage in mitigating public health behavior.

Usefulness of Mobile Electrocardiographic Devices to Reduce Urgent Healthcare Visits.

Mobile electrocardiogram (mECG) devices are being used increasingly, supplying recordings to providers and providing automatic rhythm interpretation. Given the intermittent nature of certain cardiac arrhythmias, mECGs allow instant access to a recording device. In the current COVID-19 pandemic, efforts to limit in-person patient interactions and avoid overwhelming emergency and inpatient services would add value. Our goal was to evaluate whether a mECG device would reduce healthcare utilization overall, particularly those of urgent nature. We identified a cohort of KardiaMobile (AliveCor, USA) mECG users and compared their healthcare utilization 1 year prior to obtaining the device and 1 year after. One hundred and twenty-eight patients were studied (mean age 64, 47% female). Mean duration of follow-up pre-intervention was 9.8 months. One hundred and twenty-three of 128 individuals completed post-intervention follow-up. Patients were less likely to have cardiac monitors ordered (30 vs 6; p <0.01), outpatient office visits (525 vs 382; p <0.01), cardiac-specific ED visits (51 vs 30; p <0.01), arrhythmia related ED visits (45 vs 20; p <0.01), and unplanned arrhythmia admissions (34 vs 11; p <0.01) in the year after obtaining a KardiaMobile device compared to the year prior to obtaining the device. Mobile technology is available for heart rhythm monitoring and can give feedback to the user. This study showed a reduction of in-person, healthcare utilization with mECG device use. In conclusion, this strategy would be expected to decrease the risk of exposure to patients and providers and would avoid overwhelming emergency and inpatient services.

Functional characterization of CD4+ T cell receptors crossreactive for SARS-CoV-2 and endemic coronaviruses.

BACKGROUNDRecent studies have reported T cell immunity to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in unexposed donors, possibly due to crossrecognition by T cells specific for common cold coronaviruses (CCCs). True T cell crossreactivity, defined as the recognition by a single TCR of more than one distinct peptide-MHC ligand, has never been shown in the context of SARS-CoV-2.METHODSWe used the viral functional expansion of specific T cells (ViraFEST) platform to identify T cell responses crossreactive for the spike (S) glycoproteins of SARS-CoV-2 and CCCs at the T cell receptor (TCR) clonotype level in convalescent COVID-19 patients (CCPs) and SARS-CoV-2-unexposed donors. Confirmation of SARS-CoV-2/CCC crossreactivity and assessments of functional avidity were performed using a TCR cloning and transfection system.RESULTSMemory CD4+ T cell clonotypes that crossrecognized the S proteins of SARS-CoV-2 and at least one other CCC were detected in 65% of CCPs and unexposed donors. Several of these TCRs were shared among multiple donors. Crossreactive T cells demonstrated significantly impaired SARS-CoV-2-specific proliferation in vitro relative to monospecific CD4+ T cells, which was consistent with lower functional avidity of their TCRs for SARS-CoV-2 relative to CCC.CONCLUSIONSOur data confirm, for what we believe is the first time, the existence of unique memory CD4+ T cell clonotypes crossrecognizing SARS-CoV-2 and CCCs. The lower avidity of crossreactive TCRs for SARS-CoV-2 may be the result of antigenic imprinting, such that preexisting CCC-specific memory T cells have reduced expansive capacity upon SARS-CoV-2 infection. Further studies are needed to determine how these crossreactive T cell responses affect clinical outcomes in COVID-19 patients.FUNDINGNIH funding (U54CA260492, P30CA006973, P41EB028239, R01AI153349, R01AI145435-A1, R21AI149760, and U19A1088791) was provided by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the National Institute of Biomedical Imaging and Bioengineering. The Bloomberg~Kimmel Institute for Cancer Immunotherapy, The Johns Hopkins University Provost, and The Bill and Melinda Gates Foundation provided funding for this study.

Face covering adherence is positively associated with better mental health and wellbeing: a longitudinal analysis of the CovidLife surveys (preprint)

Face masks or coverings are effective at reducing airborne infection rates, yet pandemic mitigation measures, including wearing face coverings, have been suggested to contribute to reductions in quality of life and poorer mental health. Longitudinal analyses of more than 11,000 participants across the UK found no association between lower adherence to face covering guidelines and poorer mental health. The opposite appears to be true. Even after controlling for behavioral, social, and psychological confounds, including measures of pre-pandemic mental health, individuals who wore face coverings "most of the time" or "always" had better mental health and wellbeing than those who did not. These results suggest that wearing face coverings more often will not negatively impact mental health.

Discovery of drugs to treat cytokine storm-induced cardiac dysfunction using human cardiac organoids (preprint)

SARS-CoV2 infection leads to cardiac injury and dysfunction in 20-30% of hospitalized patients1 and higher rates of mortality in patients with pre-existing cardiovascular disease2,3. Inflammatory factors released as part of the cytokine storm are thought to play a critical role in cardiac dysfunction in severe COVID-19 patients4. Here we use human cardiac organoids combined with high sensitivity phosphoproteomics and single nuclei RNA sequencing to identify inflammatory targets inducing cardiac dysfunction. This state-of-the-art pipeline allowed rapid deconvolution of mechanisms and identification of putative therapeutics. We identify a novel interferon-{gamma} driven BRD4 (bromodomain protein 4)-fibrosis/iNOS axis as a key intracellular mediator of inflammation-induced cardiac dysfunction. This axis is therapeutically targetable using BRD4 inhibitors, which promoted full recovery of function in human cardiac organoids and prevented severe inflammation and death in a cytokine-storm mouse model. The BRD inhibitor INCB054329 was the most efficacious, and is a prime candidate for drug repurposing to attenuate cardiac dysfunction and improve COVID-19 mortality in humans.

Dynamics of the N-terminal domain of SARS-CoV-2 nucleocapsid protein drives dsRNA melting in a counterintuitive tweezer-like mechanism (preprint)

The N protein of betacoronaviruses is responsible for nucleocapsid assembly and other essential regulatory functions. Its N-terminal domain (NTD) interacts and melts the double-stranded transcriptional regulatory sequences (dsTRS), regulating the discontinuous subgenome transcription process. Here, we used molecular dynamics (MD) simulations to study the binding of SARS-CoV-2 N-NTD to non-specific (NS) and TRS dsRNAs. We probed dsRNAs Watson and Crick (WC) base-pairing over 25 replicas of 100 ns MD simulations, showing that only one N-NTD of dimeric N is enough to destabilize dsRNAs, initiating melting. N-NTD dsRNA destabilizing activity was more efficient for dsTRS than dsNS. N-NTD dynamics, especially a tweezer-like motion of {beta}2-{beta}3 and * 2-{beta}5 loops, played a key role in WC base-pairing destabilization. Based on experimental information available in the literature, we constructed kinetics models for N-NTD-mediated dsRNA melting. Our results support a 1:1 stoichiometry (N-NTD:dsRNA), matching MD simulations and raising different possibilities for N-NTD action: (i) two N-NTDs of dimeric N would act independently, increasing efficiency; (ii) two N-NTDs of dimeric N would bind to two different RNA sites, bridging distant regions of the genome; and (iii) monomeric N would be active, opening up the possibility of a regulatory dissociation event.

An hACE2 peptide mimic blocks SARS-CoV-2 Pulmonary Cell Infection (preprint)

In the light of the recent accumulated knowledge on SARS-CoV-2 and its mode of human cells invasion, the binding of viral spike glycoprotein to human Angiotensin Converting Enzyme 2 (hACE2) receptor plays a central role in cell entry. We designed a series of peptides mimicking the N-terminal helix of hACE2 protein which contains most of the contacting residues at the binding site and have a high helical folding propensity in aqueous solution. Our best peptide mimic binds to the virus spike protein with high affinity and is able to block SARS-CoV-2 human pulmonary cell infection with an inhibitory concentration (IC50) in the nanomolar range. This first in class blocking peptide mimic represents a powerful tool that might be used in prophylactic and therapeutic approaches to fight the coronavirus disease 2019 (COVID-19). In BriefHelical peptide mimicking H1 helix of hACE2 and composed of only natural amino acids binds to SARS-CoV-2 spike protein with high affinity and blocks human pulmonary cells infection with IC50 in the nM range. HighlightsA peptide mimic of hACE2 designed from H1 helix and composed of only natural amino acids show high helical folding propensity in aqueous media. This peptide mimic binds to virus spike RBD with high affinity (sub-nM range). This peptide mimic blocks SARS-CoV-2 pulmonary cells infection with an IC50 in the nM range. This peptide mimic is devoid of toxicity on pulmonary cells.

A negative feedback model to explain regulation of SARS-CoV-2 replication and transcription (preprint)

BackgroundCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a preliminary understanding of the replication and transcription mechanisms of SARS-CoV-2 has recently emerged, their regulation remains unclear. ResultsBased on reanalysis of public data, we propose a negative feedback model to explain the regulation of replication and transcription in--but not limited to--SARS-CoV-2. The key step leading to new discoveries was the identification of the cleavage sites of nsp15--an RNA uridylate-specific endoribonuclease, encoded by CoVs. According to this model, nsp15 regulates the synthesis of subgenomic RNAs (sgRNAs) and genomic RNAs (gRNAs) by cleaving transcription regulatory sequences in the body. The expression level of nsp15 determines the relative proportions of sgRNAs and gRNAs, which in turn change the expression level of nps15 to reach equilibrium between the replication and transcription of CoVs. ConclusionsThe replication and transcription of CoVs are regulated by a negative feedback mechanism that influences the persistence of CoVs in hosts. Our findings enrich fundamental knowledge in the field of gene expression and its regulation, and provide new clues for future studies. One important clue is that nsp15 may be an important and ideal target for the development of drugs (e.g. uridine derivatives) against CoVs.

Excess registered deaths in England and Wales during the COVID-19 pandemic, March 2020 to May 2020 (preprint)

Official counts of COVID-19 deaths have been criticized for potentially including people who did not die of COVID-19 but merely died with COVID-19. I address that critique by fitting a generalized additive model to weekly counts of all deaths registered in England and Wales during the 2010s. The model produces baseline rates of death registrations expected without the COVID-19 pandemic, and comparing those baselines to recent counts of registered deaths exposes the emergence of excess deaths late in March 2020. By April's end, England and Wales registered 45,300 $\pm$ 3200 excess deaths of adults aged 45+. Through 22 May, the last day of available all-deaths data, 56,600 $\pm$ 4400 were registered (about 53% of which were of men). Both the ONS's corresponding count of 43,205 death certificates which mention COVID-19, and the Department of Health and Social Care's count of 33,671 deaths, are appreciably less, implying that their counting methods have underestimated, not overestimated, the pandemic's true death toll. If underreporting rates have held steady during May, about 59,000 direct and indirect COVID-19 deaths might have been registered through the end of May but not yet publicly reported in full.