The recency and geographical origins of the bat viruses ancestral to SARS-CoV and SARS-CoV-2 (preprint)

The emergence of SARS-CoV in 2002 and SARS-CoV-2 in 2019 has led to increased sampling of related sarbecoviruses circulating primarily in horseshoe bats. These viruses undergo frequent recombination and exhibit spatial structuring across Asia. Employing recombination-aware phylogenetic inference on bat sarbecoviruses, we find that the closest-inferred bat virus ancestors of SARS-CoV and SARS-CoV-2 existed just ~1-3 years prior to their emergence in humans. Phylogeographic analyses examining the movement of related sarbecoviruses demonstrate that they traveled at similar rates to their horseshoe bat hosts and have been circulating for thousands of years in Asia. The closest-inferred bat virus ancestor of SARS-CoV likely circulated in western China, and that of SARS-CoV-2 likely circulated in a region comprising southwest China and northern Laos, both a substantial distance from where they emerged. This distance and recency indicate that the direct ancestors of SARS-CoV and SARS-CoV-2 could not have reached their respective sites of emergence via the bat reservoir alone. Our recombination-aware dating and phylogeographic analyses reveal a more accurate inference of evolutionary history than performing only whole-genome or single gene analyses. These results can guide future sampling efforts and demonstrate that viral genomic fragments extremely closely related to SARS-CoV and SARS-CoV-2 were circulating in horseshoe bats, confirming their importance as the reservoir species for SARS viruses.

Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is lethal in 88% of patients1, yet harbours mutation-derived T cell neoantigens that are suitable for vaccines 2,3. Here in a phase I trial of adjuvant autogene cevumeran, an individualized neoantigen vaccine based on uridine mRNA-lipoplex nanoparticles, we synthesized mRNA neoantigen vaccines in real time from surgically resected PDAC tumours. After surgery, we sequentially administered atezolizumab (an anti-PD-L1 immunotherapy), autogene cevumeran (a maximum of 20 neoantigens per patient) and a modified version of a four-drug chemotherapy regimen (mFOLFIRINOX, comprising folinic acid, fluorouracil, irinotecan and oxaliplatin). The end points included vaccine-induced neoantigen-specific T cells by high-threshold assays, 18-month recurrence-free survival and oncologic feasibility. We treated 16 patients with atezolizumab and autogene cevumeran, then 15 patients with mFOLFIRINOX. Autogene cevumeran was administered within 3 days of benchmarked times, was tolerable and induced de novo high-magnitude neoantigen-specific T cells in 8 out of 16 patients, with half targeting more than one vaccine neoantigen. Using a new mathematical strategy to track T cell clones (CloneTrack) and functional assays, we found that vaccine-expanded T cells comprised up to 10% of all blood T cells, re-expanded with a vaccine booster and included long-lived polyfunctional neoantigen-specific effector CD8+ T cells. At 18-month median follow-up, patients with vaccine-expanded T cells (responders) had a longer median recurrence-free survival (not reached) compared with patients without vaccine-expanded T cells (non-responders; 13.4 months, P = 0.003). Differences in the immune fitness of the patients did not confound this correlation, as responders and non-responders mounted equivalent immunity to a concurrent unrelated mRNA vaccine against SARS-CoV-2. Thus, adjuvant atezolizumab, autogene cevumeran and mFOLFIRINOX induces substantial T cell activity that may correlate with delayed PDAC recurrence.

Predictors of Death, Survival, Need for Intubation, and Need for Oxygen Support Among Admitted COVID-19 Patients of the Veterans Affairs Greater Los Angeles Healthcare System.

INTRODUCTION: While risk factors for severe COVID-19 infections have been well explored among the public, population-specific studies for the U.S. Veteran community are limited in the literature. By performing a comprehensive analysis of the demographics, comorbidities, and symptomatology of a population of COVID-19 positive Veterans Affairs (VA) patients, we aim to uncover predictors of death, survival, need for intubation, and need for nasal cannula oxygen support among this understudied community. MATERIALS AND METHODS: A retrospective review was conducted of 124 COVID-19 Veteran patients who were admitted from March to October 2020 to the VA Greater Los Angeles Healthcare System (IRB#2020-000272). Chi-square and Fisher's exact tests were employed to assess differences in baseline demographic and clinical variables between Veterans who survived COVID-19 versus those who succumbed to COVID-19 illness. Multivariate logistic regression and Cox regression analyses were employed to assess predictors of outcome variables, including death, survival, need for intubation, and need for oxygen support (via nasal cannula). Covariates included a wide range of demographic, comorbidity-related, symptom-related, and summary index variables. RESULTS: Our study population consisted of primarily senior (average age was 73) Caucasian and African American (52.5% and 40.7%, respectively) Veterans. Bivariate analyses indicated that need for intubation was significantly associated with mortality (P = 0.002). Multivariate analyses revealed that age (P < 0.001, adjusted odds ratio (OR) = 1.16), dyspnea (P = 0.015, OR = 7.73), anorexia (P = 0.022, OR = 16.55), initial disease severity as classified by WHO (P = 0.031, OR = 4.55), and having more than one of the three most common comorbidities (hypertension, diabetes, and cardiac disease) and symptoms (cough, fever, and dyspnea) among our sample (P = 0.009; OR = 19.07) were independent predictors of death. Furthermore, age (P < 0.001, hazard ratio (HR) = 1.14), cerebrovascular disease (P = 0.022, HR = 3.76), dyspnea (P < 0.001, HR = 7.71), anorexia (P < 0.001, HR = 16.75), and initial disease severity as classified by WHO (P = 0.025, HR = 3.30) were independent predictors of poor survival. Finally, dyspnea reliably predicted need for intubation (P = 0.019; OR = 29.65). CONCLUSIONS: Several independent predictors of death, survival, and need for intubation were identified. These risk factors may provide guidelines for risk-stratifying Veterans upon admission to VA hospitals. Additional investigations of COVID-19 prognosis should be conducted on the larger U.S. Veteran population to confirm our findings and add to the current body of literature.

Personality, Defenses, Mentalization, and Epistemic Trust Related to Covid-19 Containment Strategies: A Psychodynamic Perspective

Introduction: The COVID-19 pandemic has considerably influenced all the domains of people's lives worldwide, determining a high increase in overall psychological distress and several clinical conditions. The study attempted to shed light on the relationship between strategies adopted to manage the pandemic, vaccine hesitancy, and distinct features of personality and mental functioning. Method(s): The sample consisted of 367 Italian individuals (68.1% women, 31.9% men;M age=37, SD=12.79) who completed an online survey including an instrument assessing four response styles to the pandemic and lockdown(s) (RSPL;Tanzilli et al., 2021), the Personality Inventory for DSM-5-Brief Form (PID-BF;Krueger et al., 2013), the Defense Mechanisms Rating Scales-Self-Report-30 (DMRS-SR-30;Di Giuseppe et al., 2020, 2014), the Reflective Functioning Questionnaire (RFQ;Fonagy et al., 2016), and the Epistemic Trust, Mistrust, Credulity Questionnaire (ETMCQ;Campbell et al., 2021). Result(s): Maladaptive response patterns to pandemic restrictions were related to dysfunctional personality traits, immature defense mechanisms, poor mentalization, and epistemic mistrust or credulity. Moreover, more severe levels of personality pathology was predictive of an extraverted-maladaptive response style to health emergency through the full mediation of low overall defensive functioning, poor certainty of others' mental states, and high epistemic credulity. Conclusion(s): Recognizing and understanding dysfunctional psychological pathways associated with individuals' difficulties in dealing with the pandemic are crucial for developing tailored mental health interventions and promoting best practices in healthcare services.

Long-term high-dose immunoglobulin successfully treats Long COVID patients with pulmonary, neurologic, and cardiologic symptoms.

Introduction: Long COVID is the overarching name for a wide variety of disorders that may follow the diagnosis of acute SARS-COVID-19 infection and persist for weeks to many months. Nearly every organ system may be affected. Methods: We report nine patients suffering with Long COVID for 101 to 547 days. All exhibited significant perturbations of their immune systems, but only one was known to be immunodeficient prior to the studies directed at evaluating them for possible treatment. Neurological and cardiac symptoms were most common. Based on this data and other evidence suggesting autoimmune reactivity, we planned to treat them for 3 months with long-term high-dose immunoglobulin therapy. If there was evidence of benefit at 3 months, the regimen was continued. Results: The patients' ages ranged from 34 to 79 years-with five male and four female patients, respectively. All nine patients exhibited significant immune perturbations prior to treatment. One patient declined this treatment, and insurance support was not approved for two others. The other six have been treated, and all have had a significant to remarkable clinical benefit. Conclusion: Long-term high-dose immunoglobulin therapy is an effective therapeutic option for treating patients with Long COVID.

COVID-19 Vaccination Status and Capsular Contracture Following Prosthetic Breast Reconstruction: A Retrospective, Multicenter Nested Case-Control Study.

BACKGROUND: Capsular contracture (CC) is a common long-term complication following prosthetic-based breast reconstruction (PBBR). Seven cases of CC following mRNA vaccination for coronavirus 2019 (COVID-19) are reported in the literature. OBJECTIVES: We sought to determine whether receiving the COVID-19 vaccine was associated with CC development following PBBR. METHODS: A retrospective, multicenter nested case-control study was performed from January 2014-July 2022 of adult female patients who underwent PBBR with acellular dermal matrix placement. Cases of CC were selected if no adjuvant radiation was received and they presented for follow-up between December of 2020-July 2022. Controls included patients who met inclusion criteria but who did not experience CC in either breast. Patient demographics, breast cancer characteristics, reconstructive surgery details, postoperative complications, and COVID-19 exposure details were analyzed and correlated with CC development. RESULTS: Of a total of 230 patients (393 breasts) who received PBBR, 85 patients (135 breasts) met inclusion criteria; of which, 12 patients (19 breasts) developed CC and 73 patients (116 breasts) did not. At the time of median follow up of 18.1 months (n = 85, IQR: 12.2, 33.6), we observed no statistically significant differences between the short- or long-term complications in cases or controls. There were no significant differences in COVID-19 vaccination status, number of vaccine doses, or vaccination type between cases and controls. Vaccination status was not associated with greater odds of CC development (Odds Ratio: 1.44, 95% Confidence Interval: 0.42 to 5.37, p > 0.05). CONCLUSIONS: Direct association between CC and COVID-19 vaccination is difficult to prove. Given the known risk of severe COVID-19 infection among immunocompromised patients, those with breast cancer who undergo PBBR should be properly counseled on the benefits and risks of vaccination.

Are we hunting bats to extinction? Worldwide patterns of hunting risk in bats are driven by species ecology and regional economics

Bats are routinely neglected in conservation, often regarded as uncharismatic and constantly maligned despite their provision of economic and ecosystem services. Yet many species are threatened, and while the loss of roosting and foraging habitat has been explored, the impacts of hunting on species survival are less well understood. Here, we analysed the hunting risk of 1320 bat species (of 1400 known) from around the world and explored the association between ecological traits and socioeconomic variables. Globally, at least 19 % of species are threatened by hunting. Large-bodied bats with narrow distributions are at increased risk of hunting, particularly in tropical regions. Multiple threats, such as habitat loss and modification, are likely to exacerbate the pressures experienced by hunted species. Furthermore, accessibility to bat habitats and low-income drive bat hunting in developing countries. With the global economic recession and the need for economic recovery following the pandemic, hunters may rely more on wildlife for subsistence and pose a threat to both biodiversity and public health. Achieving the balance between economics and conserving biodiversity is challenging due to socioeconomic factors, and the complex interplay of different forms of threat. Therefore, interventions to reduce bat hunting activities should include greater investment to facilitate sustainable livelihood development in the rural economy, and elevating public knowledge about bat ecosystem services, and their potential role in the transmission of zoonotic diseases.

'Self-Management Intervention through Lifestyle Education for Kidney health' (the SMILE-K study): protocol for a single-blind longitudinal randomised controlled trial with nested pilot study.

INTRODUCTION: Many people living with chronic kidney disease (CKD) are expected to self-manage their condition. Patient activation is the term given to describe the knowledge, skills and confidence a person has in managing their own health and is closely related to the engagement in preventive health behaviours. Self-management interventions have the potential to improve remote disease management and health outcomes. We are testing an evidence-based and theory-based digital self-management structured 10-week programme developed for peoples with CKD called 'My Kidneys & Me'. The primary aim of the study (Self-Management Intervention through Lifestyle Education for Kidney health (SMILE-K)) is to assess the effect on patient activation levels. METHODS AND ANALYSIS: A single-blind randomised controlled trial (RCT) with a nested pilot study will assess the feasibility of the intervention and study design before continuation to a full RCT. Individuals aged 18 years or older, with established CKD stage 3-4 (eGFR of 15-59 mL/min/1.73 m2) will be recruited through both primary and secondary care pathways. Participants will be randomised into two groups: intervention group (receive My Kidneys & Me in addition to usual care) and control group (usual care). The primary outcome of the nested pilot study is feasibility and the primary outcome of the full RCT is the Patient Activation Measu (PAM-13). The full RCT will assess the effect of the programme on online self-reported outcomes which will be assessed at baseline, after 10 weeks, and then after 20 weeks in both groups. A total sample size of N=432 participants are required based on a 2:1 randomisation. A substudy will measure physiological changes (eg, muscle mass, physical function) and patient experience (qualitative semi-structured interviews). ETHICS AND DISSEMINATION: This study was fully approved by the Research Ethics Committee-Leicester South on the 19 November 2020 (reference: 17/EM/0357). All participants are required to provide informed consent obtained online. The results are expected to be published in scientific journals and presented at clinical research conferences. This is protocol version 1.0 dated 27 January 2021. TRIAL REGISTRATION NUMBER: ISRCTN18314195.

EXPERIENCES OF DIRECTORS OF NURSING IN RESIDENTIAL CARE OF OLDER PEOPLE DURING COVID 19

Background: COVID-19 was a global public health crisis and deaths in the over 65 age group represented a disproportionate number of deaths in older people. In particular, nursing homes experienced clusters of infection and high mortality rates. This paper discusses experiences of care homes’ Directors of Nursing/Persons in Charge (DoN) in their preparedness, management and control of care during COVID-19. Methods: A mixed methods approach was used (survey- n=122) and semi-structured interviews (n=20) were conducted with DoNs in private and voluntary older person care homes in the Republic of Ireland. Survey data was analysed using descriptive and inferential statistics. Interviews were analysed using Braun & Clarke's thematic analysis. Results: DoNs demonstrated an initial challenge in protecting residents from infection and also managing infection outbreak. However, over time they experienced more effectiveness in managing infection prevention and control as demanded at the level of a pandemic. Fifty percent of respondents experienced an infection outbreak and the data does not demonstrate any significant difference in preparedness and management in care homes which had outbreaks and those who had no outbreaks. Other challenges were related to financial sustainability of their facility while 47% of DoNs were either actively seeking other work, or thinking of leaving their post. In the interviews, the DoNs spoke of persistent concerns with the well-being of the staff and residents and a constant worry about meeting regulatory requirements and ensuring adequate staff cover for residents care needs. Moreover, the DoNs spoke of the difficulties when the media sensationalized poor care leading to a reduction of public confidence in the sector. Conclusion: The DoNs were under constant alert and although had acclimatized to high level of infection control and prevention and managing emerging issues, the strain of the pandemic remained evident. Recommendations are given related to care homes and related to system level management for future public health crisis.

Myotis fimbriatus Virome, a Window to Virus Diversity and Evolution in the Genus Myotis.

Significant efforts have been made to characterize viral diversity in bats from China. Many of these studies were prospective and focused mainly on Rhinolophus bats that could be related to zoonotic events. However, other species of bats that are part of ecosystems identified as virus diversity hotspots have not been studied in-depth. We analyzed the virome of a group of Myotis fimbriatus bats collected from the Yunnan Province during 2020. The virome of M. fimbriatus revealed the presence of families of pathogenic viruses such as Coronavirus, Astrovirus, Mastadenovirus, and Picornavirus, among others. The viral sequences identified in M. fimbriatus were characterized by significant divergence from other known viral sequences of bat origin. Complex phylogenetic landscapes implying a tendency of co-specificity and relationships with viruses from other mammals characterize these groups. The most prevalent and abundant virus in M. fimbriatus individuals was an alphacoronavirus. The genome of this virus shows evidence of recombination and is likely the product of ancestral host-switch. The close phylogenetic and ecological relationship of some species of the Myotis genus in China may have played an important role in the emergence of this alphacoronavirus.

External Validation of Deep Learning Algorithms for Radiologic Diagnosis: A Systematic Review.

Purpose: To assess generalizability of published deep learning (DL) algorithms for radiologic diagnosis. Materials and Methods: In this systematic review, the PubMed database was searched for peer-reviewed studies of DL algorithms for image-based radiologic diagnosis that included external validation, published from January 1, 2015, through April 1, 2021. Studies using nonimaging features or incorporating non-DL methods for feature extraction or classification were excluded. Two reviewers independently evaluated studies for inclusion, and any discrepancies were resolved by consensus. Internal and external performance measures and pertinent study characteristics were extracted, and relationships among these data were examined using nonparametric statistics. Results: Eighty-three studies reporting 86 algorithms were included. The vast majority (70 of 86, 81%) reported at least some decrease in external performance compared with internal performance, with nearly half (42 of 86, 49%) reporting at least a modest decrease (≥0.05 on the unit scale) and nearly a quarter (21 of 86, 24%) reporting a substantial decrease (≥0.10 on the unit scale). No study characteristics were found to be associated with the difference between internal and external performance. Conclusion: Among published external validation studies of DL algorithms for image-based radiologic diagnosis, the vast majority demonstrated diminished algorithm performance on the external dataset, with some reporting a substantial performance decrease.Keywords: Meta-Analysis, Computer Applications-Detection/Diagnosis, Neural Networks, Computer Applications-General (Informatics), Epidemiology, Technology Assessment, Diagnosis, Informatics Supplemental material is available for this article. © RSNA, 2022.

Functional Improvement Trajectories After Surgery (FIT After Surgery) study: protocol for a multicentre prospective cohort study to evaluate significant new disability after major surgery in older adults.

INTRODUCTION: Older adults prioritise surviving surgery, but also preservation of their functional status and quality of life. Current approaches to measure postoperative recovery, which focus on death, complications and length of hospitalisation, may miss key relevant domains. We propose that postoperative disability is an important patient-centred outcome to measure intermediate-to-long recovery after major surgery in older adults. METHODS AND ANALYSIS: The Functional Improvement Trajectories After Surgery (FIT After Surgery) study is a multicentre cohort study of 2000 older adults (≥65 years) having major non-cardiac surgery. Its objectives are to characterise the incidence, trajectories, risk factors and impact of new significant disability after non-cardiac surgery. Disability is assessed using WHO Disability Assessment Schedule (WHODAS) 2.0 instrument and participants' level-of-care needs. Disability assessments occur before surgery, and at 1, 3, 6, 9 and 12 months after surgery. The primary outcome is significantly worse WHODAS score or death at 6 months after surgery. Secondary outcomes are (1) significantly worse WHODAS score or death at 1 year after surgery, (2) increased care needs or death at 6 months after surgery and (3) increased care needs or death at 1 year after surgery. We will use multivariable logistic regression models to determine the association of preoperative characteristics and surgery type with outcomes, joint modelling to characterise longitudinal time trends in WHODAS scores over 12 months after surgery, and longitudinal latent class mixture models to identify clusters following similar trajectories of disability. ETHICS AND DISSEMINATION: The FIT After Surgery study has received research ethics board approval at all sites. Recruitment began in December 2019 but was placed on hold in March 2020 because of the COVID-19 pandemic. Recruitment was gradually restarted in October 2020, with 1-year follow-up expected to finish in 2023. Publication of the primary results is anticipated to occur in 2024.

Outcome in patients undergoing postponed elective surgery during the COVID-19 pandemic (TRACE II): study protocol for a multicentre prospective observational study.

INTRODUCTION: During the COVID-19 pandemic many non-acute elective surgeries were cancelled or postponed around the world. This has created an opportunity to study the effect of delayed surgery on health conditions prior to surgery and postsurgical outcomes in patients with postponed elective surgery. The control group of the Routine Postsurgical Anesthesia Visit to Improve Patient Outcome (TRACE I) study, conducted between 2016 and 2019, will serve as a control cohort. METHODS AND ANALYSIS: TRACE II is an observational, multicentre, prospective cohort study among surgical patients with postponed surgery due to COVID-19 in academic and non-academic hospitals in the Netherlands. We aim to include 2500 adult patients. The primary outcome will be the 30-day incidence of major postoperative complications. Secondary outcome measures include the 30-day incidence of minor postoperative complications, 1 year mortality, length of stay (in hospital, medium care and intensive care), quality of recovery 30 days after surgery and postoperative quality of life up to 1 year following surgery. Multivariable logistic mixed-effects regression analysis with a random intercept for hospital will be used to test group differences on the primary outcome. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Institutional Review Board of Maastricht University Medical Centre+ and Amsterdam UMC. Findings will be presented at national and international conferences, as well as published in peer-reviewed scientific journals, with a preference for open access journals. Data will be made publicly available after publication of the main results. TRIAL REGISTRATION NUMBER: NL8841.

Peptide microarrays coupled to machine learning reveal individual epitopes from human antibody responses with neutralizing capabilities against SARS-CoV-2.

The coronavirus SARS-CoV-2 is the causative agent for the disease COVID-19. To capture the IgA, IgG, and IgM antibody response of patients infected with SARS-CoV-2 at individual epitope resolution, we constructed planar microarrays of 648 overlapping peptides that cover the four major structural proteins S(pike), N(ucleocapsid), M(embrane), and E(nvelope). The arrays were incubated with sera of 67 SARS-CoV-2 positive and 22 negative control samples. Specific responses to SARS-CoV-2 were detectable, and nine peptides were associated with a more severe course of the disease. A random forest model disclosed that antibody binding to 21 peptides, mostly localized in the S protein, was associated with higher neutralization values in cellular anti-SARS-CoV-2 assays. For antibodies addressing the N-terminus of M, or peptides close to the fusion region of S, protective effects were proven by antibody depletion and neutralization assays. The study pinpoints unusual viral binding epitopes that might be suited as vaccine candidates.

Management of post-COVID-19 olfactory dysfunction.

Purpose of Review: Olfactory dysfunction is a frequent complication of SARS-CoV-2 infection. This review presents the current literature regarding the management of post-COVID-19 olfactory dysfunction (PCOD). Recent Findings: A systematic review of the literature using the PubMed/MEDLINE, EMBASE, and Cochrane databases for the following keywords, "Covid-19," "SARS-CoV-2," "anosmia," "olfactory," "treatment," and "management" was performed. While most cases of post-COVID-19 olfactory dysfunction resolve spontaneously within 2 weeks of symptom onset, patients with symptoms that persist past 2 weeks require medical management. The intervention with the greatest degree of supporting evidence is olfactory training, wherein patients are repeatedly exposed to potent olfactory stimuli. To date, no large-scale randomized clinical trials exist that examine the efficacy of pharmacologic therapies for PCOD. Limited clinical trials and prospective controlled trials suggest intranasal corticosteroids and oral corticosteroids may alleviate symptoms. Summary: Olfactory training should be initiated as soon as possible for patients with PCOD. Patients may benefit from a limited intranasal or oral corticosteroid course. Further research on effective pharmacologic therapies for PCOD is required to manage the growing number of patients with this condition.

Melatonin use and occurrence of respiratory illnesses

IMPACT: Melatonin use could alleviate virus-induced respiratory illnesses. OBJECTIVES/GOALS: Melatonin was identified as a potential repurposable drug in the fight against SARS Cov-2. Its ability to attenuate some virus inoculation effects raises the question whether melatonin use could alleviate virus-induced respiratory illness. Here we evaluated the occurrence of respiratory conditions in melatonin users and non-users surveyed. METHODS/STUDY POPULATION: Records from the Medical Panels Expenditure Survey (MEPS) database made available by the Agency for Healthcare Research and Quality were used to evaluate whether melatonin may be associated with reduced viral respiratory disease burden. First, all subjects reporting melatonin use (1996-2017) were collected along with records for all subjects reporting respiratory diseases as identified by consolidated ICD-9/10 codes. Second, all diagnosis codes were retrieved for all individuals identified in the first step. In total there were 201,490 occurrences of the specified conditions among 180,468 unique individuals. The relative risk of specific respiratory disease occurrence was computed for melatonin users and non-users. Population estimates for melatonin use were also determined. RESULTS/ANTICIPATED RESULTS: Among 221 melatonin users, 132 had at least one respiratory illness. Among the 180,468 total subjects reporting at least one respiratory condition, melatonin use was associated with a lower rate of the common cold, pharyngitis, strep throat, scarlet fever, and sinusitis. Furthermore, melatonin was associated with a significantly reduced risk of common cold (RR 0.760, CI 0.587-0.985) and sinusitis (RR 0.407, CI 0.186-0.890). Due to low subject counts, the reduced risk observed for scarlet fever and strep throat was not considered significant. Melatonin users had a higher relative risk of allergic rhinitis (RR 1.393, CI 1.043-1.862) and asthma (RR 2.166, CI 1.672-2.806), probably due to melatonin active prescribing in these patients as sleep aid. DISCUSSION/SIGNIFICANCE OF FINDINGS: Although melatonin showed a lower relative risk of certain viral respiratory conditions, the low melatonin user numbers and their heterogeneous distribution over the time interval led to highly variable population estimates. Yet, our data suggests that melatonin may alleviate viral respiratory illness and deserves further investigation.

The impact of COVID-19 on ophthalmology resident surgical experience: a retrospective cross-sectional analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused significant disruption to in-office and surgical procedures in the field of ophthalmology. The magnitude of the impact of the pandemic on surgical training among ophthalmology residents is not known. This study aims to quantify changes in average case logs among United States (U.S.) ophthalmology residency graduates prior to and during the COVID-19 pandemic. METHODS: Retrospective, cross-sectional analysis of aggregate, national data on case logs of U.S. ophthalmology residency graduates from 2012 to 2020. The yearly percent change in the average number of procedures performed in the Accreditation Council for Graduate Medical Education (ACGME) ophthalmology resident case logs were analyzed using linear regression on log-transformed dependent variables. The average percent change from 2019 to 2020 was compared to the average yearly percent change from 2012 to 2019 for procedures performed as the primary surgeon, and primary surgeon and surgical assistant (S + A), as well as procedures for which there are ACGME minimum graduating numbers. RESULTS: Across all procedures and roles, average case logs in 2020 were lower than the averages in 2019. While average total cases logged as primary surgeon increased yearly by 3.2% (95% CI: 2.7, 3.8%, p < 0.001) from 2012 to 2019, total primary surgeon case logs decreased by 11.2% from 2019 to 2020. Cataract (-22.0%) and keratorefractive (-21.1%) surgery experienced the greatest percent decrease in average primary surgeon cases logged from 2019 to 2020. Average total cases logged as S + A experienced an average yearly increase by 1.2% (95% CI: 0.9,1.6%, p < 0.001) prior to 2020, but decreased by 9.6% from 2019 to 2020. For ACGME minimum requirements, similar changes were observed. Specifically, the average case logs in YAG, SLT, filtering (glaucoma), and intravitreal injections had been increasing significantly prior to 2020 (p < 0.05 for all) but decreased in 2020. CONCLUSIONS: These findings demonstrate the vulnerability of ophthalmology residency programs to a significant interruption in surgical volume. There is a critical need for development of competency-based, rather than volume-based, requirements to evaluate readiness for independent practice.

Summary of COVID-19 Vaccine-Related Reports in the Vaccine Adverse Event Reporting System.

Identification of the severe acute respiratory syndrome coronavirus 2 in humans toward the end of 2019 triggered a rapid, intensive effort to develop a vaccine. Among the first three COVID-19 vaccines granted emergency use authorization by the U. S. Food and Drug Administration (FDA) were two mRNA vaccines, never used on a large scale in humans, and one replication-incompetent human adenovirus vector vaccine. Since the beginning of the vaccination efforts in December 2020, almost 220,000 adverse events (AEs) have been reported through the Vaccine Adverse Event Reporting System, a reporting platform administered jointly by the FDA and the Centers for Disease Control to monitor vaccine-related AEs. We queried this database twice (04/23/21 and 05/14/21) and identified the AE reports with valid manufacturer-specific lot numbers (n = 76,336), a subset representing 33.54% of the total reported AEs. Using vaccine and demographic characteristics at the time of each query date, a model was generated to predict significant AEs, such as death. Our regression analysis revealed that the average age (IRR 1.08) and the number of doses administered in an assisted living facility (IRR 1.01) were significantly associated with the number of deaths observed in each lot, whereas the proportion of remaining vaccine shelf-life (IRR 1.30) and the vaccine manufacturer (IRR 1.09) were not. Studies such as this one are vital, as one of the best answers to vaccine hesitancy is reliable data confirming that the available COVID-19 vaccines are safe and not associated with a significantly higher risk of AEs than vaccines for other conditions.