Olfactory Training Impacts Olfactory Dysfunction Induced by COVID-19: A Pilot Study.

INTRODUCTION: Olfactory dysfunction is one of the main symptoms of COVID-19 and may last beyond resolution of the infection. The most promising intervention for post-viral olfactory dysfunction is olfactory training (OT), which involves exposing the olfactory system to a range of odors daily. This approach is thought of promoting the regeneration of olfactory receptor cells, but its effectiveness in patients with post-COVID-19 olfactory dysfunction has yet to be confirmed. METHODS: This double-blind randomized pilot study compared the effectiveness of OT versus placebo in the treatment of post-COVID-19 olfactory dysfunction. Twenty-five participants were recruited in each group. OT protocol consisted of sniffing 4 scents (rose, orange, clove, and eucalyptus) for 5 min twice daily for 12 weeks. Olfactory function was assessed before and after the training using (1) a validated odor identification test (UPSIT-40) and (2) a 10-point visual analog scale; we further assessed the presence of (3) parosmia. RESULTS: While we did not observe any effect of OT on olfactory test scores, we observed a significant improvement of subjective olfactory function in the intervention group, while no such effect was observed in the placebo group. Finally, the frequency of parosmia was significantly lower in the intervention group. CONCLUSIONS: This study highlights an increase in subjective but not objective olfactory function when performing OT for 12 weeks. Further, parosmia seems to be positively affected by OT. These results may serve as a starting point for larger scale studies to assess the efficacy of OT for treatment of post-COVID-19 olfactory dysfunction.

Removing systemic barriers to equity, diversity, and inclusion: Report of the 2019 Plant Science Research Network workshop "Inclusivity in the Plant Sciences".

A future in which scientific discoveries are valued and trusted by the general public cannot be achieved without greater inclusion and participation of diverse communities. To envision a path towards this future, in January 2019 a diverse group of researchers, educators, students, and administrators gathered to hear and share personal perspectives on equity, diversity, and inclusion (EDI) in the plant sciences. From these broad perspectives, the group developed strategies and identified tactics to facilitate and support EDI within and beyond the plant science community. The workshop leveraged scenario planning and the richness of its participants to develop recommendations aimed at promoting systemic change at the institutional level through the actions of scientific societies, universities, and individuals and through new funding models to support research and training. While these initiatives were formulated specifically for the plant science community, they can also serve as a model to advance EDI in other disciplines. The proposed actions are thematically broad, integrating into discovery, applied and translational science, requiring and embracing multidisciplinarity, and giving voice to previously unheard perspectives. We offer a vision of barrier-free access to participation in science, and a plant science community that reflects the diversity of our rapidly changing nation, and supports and invests in the training and well-being of all its members. The relevance and robustness of our recommendations has been tested by dramatic and global events since the workshop. The time to act upon them is now.

Telemedicine catches on: changes in the utilization of telemedicine services during the COVID-19 pandemic.

OBJECTIVES: To determine the degree of telemedicine expansion overall and across patient subpopulations and diagnoses. We hypothesized that telemedicine visits would increase substantially due to the need for continuity of care despite the disruptive effects of COVID-19. STUDY DESIGN: A retrospective study of health insurance claims for telemedicine visits from January 1, 2018, through March 10, 2020 (prepandemic period), and March 11, 2020, through October 31, 2020 (pandemic period). METHODS: We analyzed claims from 1,589,777 telemedicine visits that were submitted to Independence Blue Cross (Independence) from telemedicine-only providers and providers who traditionally deliver care in person. The primary exposure was the combination of individual behavior changes, state stay-at-home orders, and the Independence expansion of billing policies for telemedicine. The comparison population consisted of telemedicine visits in the prepandemic period. RESULTS: Telemedicine increased rapidly from a mean (SD) of 773 (155) weekly visits in prepandemic 2020 to 45,632 (19,937) weekly visits in the pandemic period. During the pandemic period, a greater proportion of telemedicine users were older, had Medicare Advantage insurance plans, had existing chronic conditions, or resided in predominantly non-Hispanic Black or African American Census tracts compared with during the prepandemic period. A significant increase in telemedicine claims containing a mental health-related diagnosis was observed. CONCLUSIONS: Telemedicine expanded rapidly during the COVID-19 pandemic across a broad range of clinical conditions and demographics. Although levels declined later in 2020, telemedicine utilization remained markedly higher than 2019 and 2018 levels. Trends suggest that telemedicine will likely play a key role in postpandemic care delivery.

UME-to-GME PandEMonium in COVID-19: Large-Scale Implementation of a Virtual ACGME Milestone-Based Curriculum for Senior Medical Students Matched Into Emergency Medicine.

BACKGROUND: The COVID-19 pandemic displaced newly matched emergency medicine "pre-interns" from in-person educational experiences at the end of medical school. This called for novel remote teaching modalities. OBJECTIVE: This study assesses effectiveness of a multisite Accreditation Council for Graduate Medical Education (ACGME) sub-competency-based curricular implementation on Slack during the first wave of the COVID-19 pandemic in the United States. METHODS: Emergency medicine residency programs were recruited via national organization listservs. Programs designated instructors to manage communications and teaching for the senior medical students who had matched to their programs (pre-interns) in spring/summer 2020. Pre- and post-surveys of trainees and instructors assessed perceived preparedness for residency, perceived effectiveness of common virtual educational modalities, and concern for the pandemic's effects on medical education utilizing a Likert scale of 1 (very unconcerned) to 5 (very concerned). Data were analyzed using descriptive statistics and the t test. RESULTS: Of 276 possible residency programs, 28 enrolled. Of 324 possible pre-interns, 297 (91.7%) completed pre-surveys in April/May and 249 (76.9%) completed post-surveys in June/July. The median weeks since performing a physical examination was 8 (IQR 7-12), since attending in-person didactics was 10 (IQR 8-15) and of rotation displacement was 4 (IQR 2-6). Perceived preparedness increased both overall and for 14 of 21 ACGME Milestone topics taught. Instructors reported higher mean concern (4.32, 95% CI 4.23-4.41) than pre-interns (2.88, 95% CI 2.74-3.02) regarding the pandemic's negative effects on medical education. CONCLUSIONS: Pre-interns reported improvements in residency preparedness after participating in this ACGME sub-competency-based curriculum on Slack.

The Impact of the Non-essential Business Closure Policy on Covid-19 Infection Rates

In response to the Covid-19 pandemic, many localities instituted non-essential business closure orders, keeping individuals categorized as essential workers at the frontlines while sending their non-essential counterparts home. We examine the extent to which being designated as an essential or non-essential worker impacts one’s risk of being Covid-positive following the non-essential business closure order in Pennsylvania. We also assess the intrahousehold transmission risk experienced by their cohabiting family members and roommates. Using a difference-in-differences framework, we estimate that workers designated as essential have a 55% higher likelihood of being positive for Covid-19 than those classified as non-essential;in other words, non-essential workers experience a protective effect. While members of the health care and social assistance subsector contribute significantly to this overall effect, it is not completely driven by them. We also find evidence of intrahousehold transmission that differs in intensity by essential status. Dependents cohabiting with an essential worker have a 17% higher likelihood of being Covid-positive compared to those cohabiting with a non-essential worker. Roommates cohabiting with an essential worker experience a 38% increase in likelihood of being Covid-positive. Analysis of households with a Covid-positive member suggests that intrahousehold transmission is an important mechanism

Cowpea Mosaic Virus Nanoparticle Vaccine Candidates Displaying Peptide Epitopes Can Neutralize the Severe Acute Respiratory Syndrome Coronavirus.

The development of vaccines against coronaviruses has focused on the spike (S) protein, which is required for the recognition of host-cell receptors and thus elicits neutralizing antibodies. Targeting conserved epitopes on the S protein offers the potential for pan-beta-coronavirus vaccines that could prevent future pandemics. We displayed five B-cell epitopes, originally identified in the convalescent sera from recovered severe acute respiratory syndrome (SARS) patients, on the surface of the cowpea mosaic virus (CPMV) and evaluated these formulations as vaccines. Prime-boost immunization of mice with three of these candidate vaccines, CPMV-988, CPMV-1173, and CPMV-1209, elicited high antibody titers that neutralized the severe acute respiratory syndrome coronavirus (SARS-CoV) in vitro and showed an early Th1-biased profile (2-4 weeks) transitioning to a slightly Th2-biased profile just after the second boost (6 weeks). A pentavalent slow-release implant comprising all five peptides displayed on the CPMV elicited anti-S protein and epitope-specific antibody titers, albeit at a lower magnitude compared to the soluble formulations. While the CPMV remained intact when released from the PLGA implants, processing results in loss of RNA, which acts as an adjuvant. Loss of RNA may be a reason for the lower efficacy of the implants. Finally, although the three epitopes (988, 1173, and 1209) that were found to be neutralizing the SARS-CoV were 100% identical to the SARS-CoV-2, none of the vaccine candidates neutralized the SARS-CoV-2 in vitro suggesting differences in the natural epitope perhaps caused by conformational changes or the presence of N-linked glycans. While a cross-protective vaccine candidate was not developed, a multivalent SARS vaccine was developed. The technology discussed here is a versatile vaccination platform that can be pivoted toward other diseases and applications that are not limited to infectious diseases.

Trivalent Subunit Vaccine Candidates for COVID-19 and Their Delivery Devices.

The COVID-19 pandemic highlights the need for platform technologies enabling rapid development of vaccines for emerging viral diseases. The current vaccines target the SARS-CoV-2 spike (S) protein and thus far have shown tremendous efficacy. However, the need for cold-chain distribution, a prime-boost administration schedule, and the emergence of variants of concern (VOCs) call for diligence in novel SARS-CoV-2 vaccine approaches. We studied 13 peptide epitopes from SARS-CoV-2 and identified three neutralizing epitopes that are highly conserved among the VOCs. Monovalent and trivalent COVID-19 vaccine candidates were formulated by chemical conjugation of the peptide epitopes to cowpea mosaic virus (CPMV) nanoparticles and virus-like particles (VLPs) derived from bacteriophage Qß. Efficacy of this approach was validated first using soluble vaccine candidates as solo or trivalent mixtures and subcutaneous prime-boost injection. The high thermal stability of our vaccine candidates allowed for formulation into single-dose injectable slow-release polymer implants, manufactured by melt extrusion, as well as microneedle (MN) patches, obtained through casting into micromolds, for prime-boost self-administration. Immunization of mice yielded high titers of antibodies against the target epitope and S protein, and data confirms that antibodies block receptor binding and neutralize SARS-CoV and SARS-CoV-2 against infection of human cells. We present a nanotechnology vaccine platform that is stable outside the cold-chain and can be formulated into delivery devices enabling single administration or self-administration. CPMV or Qß VLPs could be stockpiled, and epitopes exchanged to target new mutants or emergent diseases as the need arises.

The impact of the non-essential business closure policy on Covid-19 infection rates.

In response to the Covid-19 pandemic, many localities instituted non-essential business closure orders, keeping individuals categorized as essential workers at the frontlines while sending their non-essential counterparts home. We examine the extent to which being designated as an essential or non-essential worker impacts one's risk of being Covid-positive following the non-essential business closure order in Pennsylvania. We also assess the intrahousehold transmission risk experienced by their cohabiting family members and roommates. Using a difference-in-differences framework, we estimate that workers designated as essential have a 55% higher likelihood of being positive for Covid-19 than those classified as non-essential; in other words, non-essential workers experience a protective effect. While members of the health care and social assistance subsector contribute significantly to this overall effect, it is not completely driven by them. We also find evidence of intrahousehold transmission that differs in intensity by essential status. Dependents cohabiting with an essential worker have a 17% higher likelihood of being Covid-positive compared to those cohabiting with a non-essential worker. Roommates cohabiting with an essential worker experience a 38% increase in likelihood of being Covid-positive. Analysis of households with a Covid-positive member suggests that intrahousehold transmission is an important mechanism driving these effects.

Characteristics of Nursing Homes by COVID-19 Cases Among Staff: March to August 2020.

OBJECTIVE: To measure the association between nursing home (NH) characteristics and Coronavirus Disease 2019 (COVID-19) prevalence among NH staff. DESIGN: Retrospective cross-sectional study. SETTING AND PARTICIPANTS: Centers for Disease Control and Prevention COVID-19 database for US NHs between March and August 2020, linked to NH facility characteristics (LTCFocus database) and local COVID-19 prevalence (USA Facts). METHODS: We estimated the associations between NH characteristics, local infection rates, and other regional characteristics and COVID-19 cases among NH staff (nursing staff, clinical staff, aides, and other facility personnel) measured per 100 beds, controlling for the hospital referral regions in which NHs were located to account for local infection control practices and other unobserved characteristics. RESULTS: Of the 11,858 NHs in our sample, 78.6% reported at least 1 staff case of COVID-19. After accounting for local COVID-19 prevalence, NHs in the highest quartile of confirmed resident cases (413.5 to 920.0 cases per 1000 residents) reported 18.9 more staff cases per 100 beds compared with NHs that had no resident cases. Large NHs (150 or more beds) reported 2.6 fewer staff cases per 100 beds compared with small NHs (<50 beds) and for-profit NHs reported 0.8 fewer staff cases per 100 beds compared with nonprofit NHs. Higher occupancy and more direct-care hours per day were associated with more staff cases (0.4 more cases per 100 beds for a 10% increase in occupancy, and 0.7 more cases per 100 beds for an increase in direct-care staffing of 1 hour per resident day, respectively). Estimates associated with resident demographics, payer mix, or regional socioeconomic characteristics were not statistically significant. CONCLUSIONS AND IMPLICATIONS: These findings highlight the urgent need to support facilities with emergency resources such as back-up staff and protocols to reduce resident density within the facility, which may help stem outbreaks.

Disruptions in preventive care: Mammograms during the COVID-19 pandemic.

OBJECTIVE: To measure the extent to which the provision of mammograms was impacted by the COVID-19 pandemic and surrounding guidelines. DATA SOURCES: De-identified summary data derived from medical claims and eligibility files were provided by Independence Blue Cross for women receiving mammograms. STUDY DESIGN: We used a difference-in-differences approach to characterize the change in mammograms performed over time and a queueing formula to estimate the time to clear the queue of missed mammograms. DATA COLLECTION: We used data from the first 30 weeks of each year from 2018 to 2020. PRINCIPAL FINDINGS: Over the 20 weeks following March 11, 2020, the volume of screening mammograms and diagnostic mammograms fell by 58% and 38% of expected levels, on average. Lowest volumes were observed in week 15 (April 8 to 14), when screening and diagnostic mammograms fell by 99% and 74%, respectively. Volumes began to rebound in week 19 (May), with diagnostic mammograms reaching levels to similar to previous years' and screening mammograms remaining 14% below expectations. We estimate it will take a minimum of 22 weeks to clear the queue of missed mammograms in our study sample. CONCLUSIONS: The provision of mammograms has been significantly disrupted due to the COVID-19 pandemic.

Social Media Bridges the Training Gap Between Match Day and Internship With ACGME Milestone-based Clinical Case Curriculum.

OBJECTIVES: The objective was to bridge the relative educational gap for newly matched emergency medicine preinterns between Match Day and the start of internship by implementing an Accreditation Council for Graduate Medical Education Milestone (ACGME)-based virtual case curriculum over the social media platform Slack. METHODS: We designed a Milestone-based curriculum of 10 emergency department clinical cases and used Slack to implement it. An instructor was appointed for each participating institution to lead the discussion and encourage collaboration among preinterns. Pre- and postcurriculum surveys utilized 20 statements adapted from the eight applicable Milestones to measure the evolution of preintern self-reported perceived preparedness (PP) as well as actual clinical knowledge (CK) performance on a case-based examination. RESULTS: A total of 11 institutions collaborated and 151 preinterns were contacted, 127 of whom participated. After participating in the Slack intern curriculum (SIC), preinterns reported significant improvements in PP regarding multiple Milestone topics. They also showed improved CK regarding the airway management Milestone based on examination performance. CONCLUSIONS: Implementation of our SIC may ease the difficult transition between medical school and internship for emergency medicine preinterns. Residency leadership and medical school faculty will benefit from knowledge of preintern PP, specifically of their perceived strengths and weaknesses, because this information can guide curricular focus at the end of medical school and beginning of internship. Limitations of this study include variable participation and a high attrition rate. Further studies will address the utility of such a virtual curriculum for preinterns and for rotating medical students who have been displaced from clinical rotations during the novel coronavirus pandemic.

COVID-19 vaccine development and a potential nanomaterial path forward.

The COVID-19 pandemic has infected millions of people with no clear signs of abatement owing to the high prevalence, long incubation period and lack of established treatments or vaccines. Vaccines are the most promising solution to mitigate new viral strains. The genome sequence and protein structure of the 2019-novel coronavirus (nCoV or SARS-CoV-2) were made available in record time, allowing the development of inactivated or attenuated viral vaccines along with subunit vaccines for prophylaxis and treatment. Nanotechnology benefits modern vaccine design since nanomaterials are ideal for antigen delivery, as adjuvants, and as mimics of viral structures. In fact, the first vaccine candidate launched into clinical trials is an mRNA vaccine delivered via lipid nanoparticles. To eradicate pandemics, present and future, a successful vaccine platform must enable rapid discovery, scalable manufacturing and global distribution. Here, we review current approaches to COVID-19 vaccine development and highlight the role of nanotechnology and advanced manufacturing.

Long-Term Care, Residential Facilities, and COVID-19: An Overview of Federal and State Policy Responses.

The COVID-19 pandemic has disproportionately affected residents and staff at long-term care (LTC) and other residential facilities in the United States. The high morbidity and mortality at these facilities has been attributed to a combination of a particularly vulnerable population and a lack of resources to mitigate the risk. During the first wave of the pandemic, the federal and state governments received urgent calls for help from LTC and residential care facilities; between March and early June of 2020, policymakers responded with dozens of regulatory and policy changes. In this article, we provide an overview of these responses by first summarizing federal regulatory changes and then reviewing state-level executive orders. The policy and regulatory changes implemented at the federal and state levels can be categorized into the following 4 classes: (1) preventing virus transmission, which includes policies relating to visitation restrictions, personal protective equipment guidance, and testing requirements; (2) expanding facilities' capacities, which includes both the expansion of physical space for isolation purposes and the expansion of workforce to combat COVID-19; (3) relaxing administrative requirements, which includes measures enacted to shift the attention of caretakers and administrators from administrative requirements to residents' care; and (4) reporting COVID-19 data, which includes the reporting of cases and deaths to residents, families, and administrative bodies (such as state health departments). These policies represent a snapshot of the initial efforts to mitigate damage inflicted by the pandemic. Looking ahead, empirical evaluation of the consequences of these policies-including potential unintended effects-is urgently needed. The recent availability of publicly reported COVID-19 LTC data can be used to inform the development of evidence-based regulations, though there are concerns of reporting inaccuracies. Importantly, these data should also be used to systematically identify hot spots and help direct resources to struggling facilities.