Associations between SARS-CoV-2 Infection or COVID-19 Vaccination and Human Milk Composition: A Multi-Omics Approach (preprint)

The risk of contracting SARS-CoV-2 via human milk-feeding is virtually non-existent. Adverse effects of COVID-19 vaccination for lactating individuals are not different from the general population, and no evidence has been found that their infants exhibit adverse effects. Yet, there remains substantial hesitation among this population globally regarding the safety of these vaccines. Herein we aimed to determine if compositional changes in milk occur following infection or vaccination, including any evidence of vaccine components. Using an extensive multi-omics approach, we found that compared to unvaccinated individuals SARS-CoV-2 infection was associated with significant compositional differences in 67 proteins, 385 lipids, and 13 metabolites. In contrast, COVID-19 vaccination was not associated with any changes in lipids or metabolites, although it was associated with changes in 13 or fewer proteins. Compositional changes in milk differed by vaccine. Changes following vaccination were greatest after 1-6 hours for the mRNA-based Moderna vaccine (8 changed proteins), 3 days for the mRNA-based Pfizer (4 changed proteins), and adenovirus-based Johnson and Johnson (13 changed proteins) vaccines. Proteins that changed after both natural infection and Johnson and Johnson vaccine were associated mainly with systemic inflammatory responses. In addition, no vaccine components were detected in any milk sample. Together, our data provide evidence of only minimal changes in milk composition due to COVID-19 vaccination, with much greater changes after natural SARS-CoV-2 infection.

High-affinity binding to the SARS-CoV-2 spike trimer by a nanostructured, trivalent protein-DNA synthetic antibody (preprint)

Multivalency enables nanostructures to bind molecular targets with high affinity. Although antibodies can be generated against a wide range of antigens, their shape and size cannot be tuned to match a given target. DNA nanotechnology provides an attractive approach for designing customized multivalent scaffolds due to the addressability and programmability of the nanostructure shape and size. Here, we design a nanoscale synthetic antibody ("nano-synbody") based on a three-helix bundle DNA nanostructure with one, two, or three identical arms terminating in a mini-binder protein that targets the SARS-CoV-2 spike protein. The nano-synbody was designed to match the valence and distance between the three receptor binding domains (RBDs) in the spike trimer, in order to enhance affinity. The protein-DNA nano-synbody shows tight binding to the wild-type, Delta, and several Omicron variants of the SARS-CoV-2 spike trimer, with affinity increasing as the number of arms increases from one to three. The effectiveness of the nano-synbody was also verified using a pseudovirus neutralization assay, with the three-arm nanostructure inhibiting two Omicron variants against which the structures with only one or two arms are ineffective. The structure of the three-arm nano-synbody bound to the Omicron variant spike trimer was solved by negative-stain transmission electron microscopy reconstruction, and shows the protein-DNA nanostructure with all three arms attached to the RBD domains, confirming the intended trivalent attachment. The ability to tune the size and shape of the nano-synbody, as well as its potential ability to attach two or more different binding ligands, will enable the high-affinity targeting of a range of proteins not possible with traditional antibodies.

The development and validation of a dashboard prototype for real-time suicide mortality data.

Introduction/Aim: Data visualisation is key to informing data-driven decision-making, yet this is an underexplored area of suicide surveillance. By way of enhancing a real-time suicide surveillance system model, an interactive dashboard prototype has been developed to facilitate emerging cluster detection, risk profiling and trend observation, as well as to establish a formal data sharing connection with key stakeholders via an intuitive interface. Materials and Methods: Individual-level demographic and circumstantial data on cases of confirmed suicide and open verdicts meeting the criteria for suicide in County Cork 2008-2017 were analysed to validate the model. The retrospective and prospective space-time scan statistics based on a discrete Poisson model were employed via the R software environment using the "rsatscan" and "shiny" packages to conduct the space-time cluster analysis and deliver the mapping and graphic components encompassing the dashboard interface. Results: Using the best-fit parameters, the retrospective scan statistic returned several emerging non-significant clusters detected during the 10-year period, while the prospective approach demonstrated the predictive ability of the model. The outputs of the investigations are visually displayed using a geographical map of the identified clusters and a timeline of cluster occurrence. Discussion: The challenges of designing and implementing visualizations for suspected suicide data are presented through a discussion of the development of the dashboard prototype and the potential it holds for supporting real-time decision-making. Conclusions: The results demonstrate that integration of a cluster detection approach involving geo-visualisation techniques, space-time scan statistics and predictive modelling would facilitate prospective early detection of emerging clusters, at-risk populations, and locations of concern. The prototype demonstrates real-world applicability as a proactive monitoring tool for timely action in suicide prevention by facilitating informed planning and preparedness to respond to emerging suicide clusters and other concerning trends.

Effects of older adults' social identification on psychological flourishing and exercise program adherence.

BACKGROUND: With the onset of the COVID-19 pandemic, many exercise programs moved online. The purpose of this study was to examine the extent to which older adults' social identification with other exercise program members contributed to their psychological flourishing and exercise program adherence. METHODS: The study represented a secondary analysis of data derived from the Seniors COVID-19 Pandemic and Exercise (SCOPE) Trial, in which older adults were randomized to a waitlist control condition or one of two online (personal v group) exercise programs. Only data from participants in the trial intervention conditions (N = 162; Mage = 73.52 years; SD = 5.61) were utilized in this secondary analysis. We assessed psychological flourishing and social identification at baseline and every two weeks, as well as program adherence over each 2-week block, for 12 weeks. RESULTS: Based on stepwise multilevel modeling the results revealed that older adults' social identification with others in their respective exercise program had a direct effect on psychological flourishing (ΔR2Unique Marginal = 0.063, p < .001) and program adherence (ΔR2Unique Marginal = 0.014, p = .03). CONCLUSIONS: The results highlight the value of bolstering older adults' social identification with others in an online exercise program to support adherence and well-being.

Researching COVID to enhance recovery (RECOVER) adult study protocol: Rationale, objectives and design (preprint)

Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. Methods: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged [≥]18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. Discussion: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.

Effects of triple combination therapy on quality of life and psychosocial outcomes: A longitudinal study

Background: Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator triple combination therapy (TCT) is available to approximately 85% of the U.S. CF population. Clinical trials of TCT demonstrate numerous improvements in physical health and healthrelated quality of life (HRQoL), but fewstudies have examined the effects of TCTon mental health and psychosocial outcomes, and little is known about whether gains in HRQoL are sustained over time.We aimed to describe the HRQoL and psychosocial outcomes of people with CF (PwCF) initiating TCT and explored changes in these outcomes up to 1 year after starting TCT. Method(s): This longitudinal study enrolled PwCF aged 14 and older who were followed at a large, combined pediatric and adult CF center. Questionnaires were administered within 6 months of initiating TCT (baseline) and 3, 6, and 12 months later. Study self-report measures evaluated were HRQoL (Cystic Fibrosis Questionnaire-Revised;CFQ-R), optimism, self-efficacy, medication-related beliefs (Medication Beliefs Questionnaire;MBQ), perceived social stigma of illness, and body image. Data were also collected from medical charts on measures of health and mental health screening. Four open-ended questionswere included at each timepoint to elicit qualitative data on experiences starting TCT. Longitudinal data were analyzed using linear mixed-effects models for repeated measures. Result(s): Sixty-three adults and adolescents with CF completed the full set of surveys at baseline. Mean participant age was 30.0 +/- 14.2. Fifty-four percent identified as female, 43% as male, and 2% as nonbinary. Seventyfour percent had private insurance. Mean percentage predicted forced expiratory volume in 1 second (FEV1pp) at baseline was 76.0 +/- 24.1%, and mean body mass index (BMI) was 22.9 +/- 3.1 kg/m2. At 12 months, mean FEV1pp was 80.8 +/- 21.9%, and mean BMI was 24.5 +/- 4.1 kg/m2. On standard measures used in CF mental health screening, mean baseline Patient Health Questionnaire (PHQ-9) score was 3.4 +/- 3.5, and mean General Anxiety Disorder score was 3.4 +/- 3.7. Mean PHQ-9 (3.5 +/- 4.0) and GAD-7 (3.4 +/- 3.7) scores at 12 months were similar to baseline. We found no statistically significant differences between the survey time points in participants' physical, respiratory, or emotional functioning on the CFQ-R, but there was a significant change in social functioning ( p < 0.001). There was no statistically significant change over time in optimism or selfefficacy, but there was a significant difference in CF medication beliefs between the four survey time points ( p = 0.008 for MBQ Importance subscale), with a decrease in perceived importance from baseline to 12 months. Conclusion(s): Whereas lung function and BMI increased in our sample by 12 months, similar improvementswere not seen in standard mental health outcomes. There was no change over time in physical, respiratory, or emotional functioning, optimism, or self-efficacy. Only CFQ-R social functioning had changed by 12 months, perhaps reflecting decreased COVID-related social isolation. There was also a change in medicationrelated beliefs, with a decrease in perceived importance of taking CF medications at 12 months. Future directions include conducting qualitative analyses of open-ended questions and further examining data on social stigma, motivation to take medications, and body image, as well as examining relationships between outcome variables and baseline FEV1 and BMICopyright © 2022, European Cystic Fibrosis Society. All rights reserved

Video Calls as a Replacement for Family Visits During Lockdowns in Aged Care: Interview Study With Family Members.

BACKGROUND: Lockdowns have been used to prevent the spread of transmissible illnesses such as influenza, norovirus, and COVID-19 in care homes. However, lockdowns deny care home residents supplemental care and the socioemotional enrichment that comes from seeing family members. Video calling has the potential to enable ongoing contact between residents and family members during lockdowns. However, video calls can be considered by some as a poor substitute for in-person visits. It is important to understand family members' experiences with video calling during lockdowns to ensure the effective use of this technology in the future. OBJECTIVE: This study aimed to understand how family members use video calls to communicate with relatives living in aged care during lockdowns. We focused on experiences during the COVID-19 pandemic, which involved extensive lockdowns in aged care homes. METHODS: We conducted semistructured interviews with 18 adults who had been using video calls with relatives living in aged care during pandemic lockdowns. The interviews focused on how participants had been using video calls, what benefits they gained from video-based interactions, and what challenges they encountered when using the technology. We analyzed the data using the 6-phase reflexive approach to thematic analysis by Braun and Clarke. RESULTS: We developed 4 themes through our analysis. Theme 1 interprets video calling as a medium for the continuation of care during lockdowns. Using video calls, family members were able to provide social enrichment for residents and engaged in health monitoring to uphold residents' welfare. Theme 2 highlights how video calling extended care by supporting frequent contact, transmitting nonverbal cues that were essential for communication, and negating the need for face masks. Theme 3 interprets organizational issues such as the lack of technology and staff time as impediments to the continuation of familial care through video. Finally, theme 4 highlights the need for 2-way communication, interpreting residents' unfamiliarity with video calling and their health conditions as further barriers to the continuation of care. CONCLUSIONS: This study suggests that, during restrictions arising from the COVID-19 pandemic, video calls became a medium for enabling family members to continue participating in the care of their relatives. The use of video calls to continue care illustrates their value for families during times of mandatory lockdown and supports the use of video to complement face-to-face visits at other times. However, better support is needed for video calling in aged care homes. This study also revealed a need for video calling systems that are designed for the aged care context.

Cardiac injury in children with COVID-19.

BACKGROUND: There is little known about the spectrum of cardiac injury in acute COVID-19 infection in children. METHODS: A single-centre, retrospective chart analysis was performed. The protocol was deemed IRB exempt. All patients under the age of 21 years admitted from 20 March, 2020 to 22 June, 2021 for acute symptomatic COVID-19 infection or clinical suspicion of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 were included. Past medical history, lab findings, echocardiogram and electrocardiogram/telemetry findings, and clinical outcomes were reviewed. RESULTS: Sixty-six patients with MIS-C and 178 with acute COVID-19 were reviewed. Patients with MIS-C had more cardiac testing than those with acute COVID-19. Inflammatory markers were more likely elevated, and function was more likely abnormal on echocardiogram in those with MIS-C with testing performed. Among patients with MIS-C, 17% had evidence of coronary dilation versus 0% in the acute COVID-19 group. One (0.6%) patient with acute COVID-19 had clinically significant electrocardiogram or telemetry findings, and this was in the setting of prior arrhythmias and CHD. Four (6%) patients with MIS-C had clinically significant findings on electrocardiogram or telemetry. Among patients with acute COVID-19, extracorporeal membrane oxygenation support was required in 0.6% of patients with acute COVID-19, and there was a 2.8% mortality. There were no deaths in the setting of MIS-C. CONCLUSIONS: Patients with acute COVID-19 and clinical suspicion of cardiac injury had a lower incidence of abnormal laboratory findings, ventricular dysfunction, or significant arrhythmia than those with MIS-C.

Trauma-Informed Supervision and Related Predictors of Burnout and Secondary Traumatic Stress Among Prelicensed Counsellors During the COVID-19 Pandemic.

In the current study, we examined individual factors, organizational factors, COVID-19 anxiety, and trauma-informed supervision as predictors of prelicensed counsellor burnout and secondary traumatic stress (STS). In a sample of 282 prelicensed counsellors, we conducted two hierarchical regression analyses for counsellor burnout and STS. The variables of interest accounted for 38% of the variance in counsellor burnout and 32% of the variance in counsellor STS. In the model of counsellor burnout, statistically significant variables included age, caseload, setting, COVID-19 anxiety, and trauma-informed supervision. For STS, statistically significant predictor variables were age, caseload, COVID-19 anxiety, and trauma-informed supervision. Implications of the findings for prelicensed counsellors, supervisors, and counselling researchers are discussed.

E-scooter use continues to rev up fracture diagnoses and hospital admissions compared to other modes of transportation.

Introduction: The COVID-19 pandemic was associated with an increase in popularity of e-scooter usage and a rise in e-scooter related injuries. Recent studies have elucidated trends within e-scooter injuries but there are few epidemiological studies that evaluate injury rates amongst multiple modes of transportation. This study seeks to investigate trends of e-scooter orthopedic fracture injuries compared to other traditional methods of transportation using a national database. Methods: The National Electronic Injury Surveillance System (NEISS) database was queried between 2014 and 2020 for patients who were injured after usage of e-scooters, bicycles, or all-terrain vehicles. Primary analysis included patients with a diagnosis of fracture and utilized univariate/multivariate models to evaluate risk of hospital admission. Secondary analysis included all isolated patients to evaluate the odds of fracture development amongst modes of transportation. Results: A total of 70,719 patients with injuries associated with e-scooter, bicycle, or all-terrain vehicle use were isolated. 15997 (22.6%) of these patients had a fracture diagnosis. Both e-scooters and all-terrain vehicles reported increased odds of fracture-related injury and direct hospitalization when compared to bicycles. E-scooter users reported a greater odds of both associated fracture (OR 1.25; 95%CI 1.03-1.51; p = 0.024) and hospital admission (OR: 2.01; 95%CI: 1.26-3.21; p = 0.003) in 2020 compared to 2014-2015. Discussion: E-scooter related orthopedic injuries and hospital admissions had the largest incidence rate increase compared to bicycle and all-terrain vehicles between 2014 and 2020. E-scooter fractures were most commonly located in the lower leg in 2014-2017, the wrist in 2018-2019, and the upper trunk in 2020. In comparison, bicycle and all-terrain vehicle fractures was most commonly shoulder and upper trunk within the study period. Further research will help to promote further understanding of the e-scooter health care burden and in prevention of these injuries. Level of evidence: 3.

Three-Month Symptom Profiles Among Symptomatic Adults With Positive and Negative Severe Acute Respiratory Syndrome Coronavirus 2 Tests: A Prospective Cohort Study From the INSPIRE Group.

BACKGROUND: Long-term symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are a major concern, yet their prevalence is poorly understood. METHODS: We conducted a prospective cohort study comparing adults with SARS-CoV-2 infection (coronavirus disease-positive [COVID+]) with adults who tested negative (COVID-), enrolled within 28 days of a Food and Drug Administration (FDA)-approved SARS-CoV-2 test result for active symptoms. Sociodemographic characteristics, symptoms of SARS-CoV-2 infection (assessed with the Centers for Disease Control and Prevention [CDC] Person Under Investigation Symptom List), and symptoms of post-infectious syndromes (ie, fatigue, sleep quality, muscle/joint pains, unrefreshing sleep, and dizziness/fainting, assessed with CDC Short Symptom Screener for myalgic encephalomyelitis/chronic fatigue syndrome) were assessed at baseline and 3 months via electronic surveys sent via text or email. RESULTS: Among the first 1000 participants, 722 were COVID+ and 278 were COVID-. Mean age was 41.5 (SD 15.2); 66.3% were female, 13.4% were Black, and 15.3% were Hispanic. At baseline, SARS-CoV-2 symptoms were more common in the COVID+ group than the COVID- group. At 3 months, SARS-CoV-2 symptoms declined in both groups, although were more prevalent in the COVID+ group: upper respiratory symptoms/head/eyes/ears/nose/throat (HEENT; 37.3% vs 20.9%), constitutional (28.8% vs 19.4%), musculoskeletal (19.5% vs 14.7%), pulmonary (17.6% vs 12.2%), cardiovascular (10.0% vs 7.2%), and gastrointestinal (8.7% vs 8.3%); only 50.2% and 73.3% reported no symptoms at all. Symptoms of post-infectious syndromes were similarly prevalent among the COVID+ and COVID- groups at 3 months. CONCLUSIONS: Approximately half of COVID+ participants, as compared with one-quarter of COVID- participants, had at least 1 SARS-CoV-2 symptom at 3 months, highlighting the need for future work to distinguish long COVID. CLINICAL TRIALS REGISTRATION: NCT04610515.

Severe Fatigue and Persistent Symptoms at 3 Months Following Severe Acute Respiratory Syndrome Coronavirus 2 Infections During the Pre-Delta, Delta, and Omicron Time Periods: A Multicenter Prospective Cohort Study.

BACKGROUND: Most research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants focuses on initial symptomatology with limited longer-term data. We characterized prevalences of prolonged symptoms 3 months post-SARS-CoV-2 infection across 3 variant time-periods (pre-Delta, Delta, and Omicron). METHODS: This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, organ system-based symptoms, and ≥3 symptoms across variants among participants with a positive ("COVID-positive") or negative SARS-CoV-2 test ("COVID-negative") at 3 months after SARS-CoV-2 testing. Variant periods were defined by dates with ≥50% dominant strain. We performed multivariable logistic regression modeling to estimate independent effects of variants adjusting for sociodemographics, baseline health, and vaccine status. RESULTS: The study included 2402 COVID-positive and 821 COVID-negative participants. Among COVID-positives, 463 (19.3%) were pre-Delta, 1198 (49.9%) Delta, and 741 (30.8%) Omicron. The pre-Delta COVID-positive cohort exhibited more prolonged severe fatigue (16.7% vs 11.5% vs 12.3%; P = .017) and presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; P < .001) compared with the Delta and Omicron cohorts. No differences were seen in the COVID-negatives across time-periods. In multivariable models adjusted for vaccination, severe fatigue and odds of having ≥3 symptoms were no longer significant across variants. CONCLUSIONS: Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during pre-Delta than with Delta and Omicron; however, these differences were no longer significant after adjusting for vaccination status, suggesting a beneficial effect of vaccination on risk of long-term symptoms. Clinical Trials Registration. NCT04610515.

Case studies in adaptation: centring equity in global health education during the COVID-19 pandemic and beyond.

The COVID-19 pandemic disrupted all aspects of life globally and laid bare the pervasive inequities in access to education, employment, healthcare and economic security in both high-resource and low-resource settings. The global health field's brittle attempts of addressing global health inequities, through efforts that in some cases have evoked the colonialist forces implicated in shaping these disparities, have been further challenged by the pandemic. COVID-19 has forced global health leaders to reimagine their field through innovation such as shifting the application of global health to a local focus, collaborating with community organisations and exploring virtual education technologies. We present four case studies illustrating this promising movement towards a more sustainable, ethical and equitable model of global health education practice.Case 1: trainees from the Massachusetts General Hospital Center for Global Health partnered with the Board of Health of Holyoke, a majority Latinx city with high poverty levels, to respond to the COVID-19 pandemic through research and intervention. Case 2: Prevencasa, a community health organisation in Tijuana, Mexico, providing healthcare to local underserved communities, shifted its focus from hosting international trainees to developing a multidisciplinary training programme for Mexican healthcare professionals. Case 3: the Johns Hopkins Global Health Leadership Program adapted its curriculum into a hybrid online and in-person migrant health and human rights elective, collaborating with local organisations. Case 4: a US-based and a Latin American-based organisation collaborated to create a longitudinal, virtual urogynaecology training programme with hybrid simulation practice to increase accessibility of procedural-based training.

Effectiveness of COVID-19 mRNA Vaccines in Preventing COVID-19-Associated Outpatient Visits and Hospitalizations Among American Indian and Alaska Native Persons, January-November 2021: A Test-Negative Case-Control Analysis Using Surveillance Data.

Background: Despite the disproportionate morbidity and mortality experienced by American Indian and Alaska Native (AI/AN) persons during the coronavirus disease 2019 (COVID-19) pandemic, few studies have reported vaccine effectiveness (VE) estimates among these communities. Methods: We conducted a test-negative case-control analysis among AI/AN persons aged ≥12 years presenting for care from January 1, 2021, through November 30, 2021, to evaluate the effectiveness of mRNA COVID-19 vaccines against COVID-19-associated outpatient visits and hospitalizations. Cases and controls were patients with ≥1 symptom consistent with COVID-19-like illness; cases were defined as those test-positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and controls were defined as those test-negative for SARS-CoV-2. We used unconditional multivariable logistic regression to estimate VE, defined as 1 minus the adjusted odds ratio for vaccination among cases vs controls. Results: The analysis included 207 cases and 267 test-negative controls. Forty-four percent of cases and 78% of controls received 2 doses of either BNT162b2 or mRNA-1273 vaccine. VE point estimates for 2 doses of mRNA vaccine were higher for hospitalized participants (94.6%; 95% CI, 88.0-97.6) than outpatient participants (86.5%; 95% CI, 63.0-95.0), but confidence intervals overlapped. Conclusions: Among AI/AN persons, mRNA COVID-19 vaccines were highly effective in preventing COVID-associated outpatient visits and hospitalizations. Maintaining high vaccine coverage, including booster doses, will reduce the burden of disease in this population.

Disruption of National Cancer Database Data Models in the First Year of the COVID-19 Pandemic.

Importance: Each year, the National Cancer Database (NCDB) collects and analyzes data used in reports to support research, quality measures, and Commission on Cancer program accreditation. Because data models used to generate these reports have been historically stable, year-to-year variances have been attributed to changes within the cancer program rather than data modeling. Cancer submissions in 2020 were anticipated to be significantly different from prior years because of the COVID-19 pandemic. This study involved a validation analysis of the variances in observed to expected 2020 NCDB cancer data in comparison with 2019 and 2018. Observations: The NCDB captured a total of 1 223 221 overall cancer cases in 2020, a decrease of 14.4% (Δ = -206 099) compared with 2019. The early months of the COVID-19 pandemic (March-May 2020) coincided with a nadir of cancer cases in April 2020 that did not recover to overall prepandemic levels through the remainder of 2020. In the early months of the COVID-19 pandemic, the proportion of early-stage disease decreased sharply overall, while the proportion of late-stage disease increased. However, differences in observed to expected stage distribution in 2020 varied by primary disease site. Statistically significant differences in the overall observed to expected proportions of race and ethnicity, sex, insurance type, geographic location, education, and income were identified, but consistent patterns were not evident. Conclusions and Relevance: Historically stable NCDB data models used for research, administrative, and quality improvement purposes were disrupted during the first year of the COVID-19 pandemic. NCDB data users will need to carefully interpret disease- and program-specific findings for years to come to account for pandemic year aberrations when running models that include 2020.

The Early Effects of the COVID-19 Pandemic on Pediatric Resident Education: A National Assessment.

PURPOSE: Residency programs must ensure resident competence for independent practice. The COVID-19 pandemic disrupted healthcare delivery, impacting pediatric residencies. This study examines the impact on pediatric resident education. METHODS: The authors conducted a mixed methods national survey of pediatric residency program directors (PDs) from May- July 2020. Data analysis included descriptive statistics, χ2, Wilcox rank sum tests. Multivariable modeling identified factors associated with resident preparation for more senior roles. Thematic analysis was performed on open-ended questions about PD COVID-19 pandemic recommendations to peers, Accreditation Council for Graduate Medical Education and American Board of Pediatrics. RESULTS: Response rate was 55% (110/199). PDs reported the COVID-19 pandemic negatively affected inpatient (n= 86, 78.2%), and outpatient education (n=104, 94.5%), procedural competence (n=64; 58.2%), and resident preparation for more senior roles (n= 50, 45.5%). In bivariate analyses, increasingly negative impacts on inpatient and outpatient education were associated with an increasingly negative impact on resident preparation for more senior roles (p=0.03, p=0.008), these relationships held true in multivariable analysis. Qualitative analysis identified 4 themes from PD recommendations: 1) Clear communication from governing bodies and other leaders; 2) Flexibility within programs and from governing bodies; 3) Clinical exposure is key for competency development; 4) Online platforms are important for education, communication, and support. CONCLUSIONS: The COVID-19 pandemic negatively impacted inpatient and outpatient education. When these were more negatively impacted, resident preparation for more senior roles was worse. Highlighting the importance of competency based medical education to tailor experiences ensuring each resident is competent for independent practice. WHAT'S NEW: The COVID-19 pandemic negatively impacted inpatient and outpatient clinical education which negatively impacted resident preparation for more senior roles. This highlights the importance of competency based medical education to ensure each graduating resident is competent for independent practice.

Tuaimenal A, a Meroterpene from the Irish Deep-Sea Soft Coral Duva florida, Displays Inhibition of the SARS-CoV-2 3CLpro Enzyme.

Cold water benthic environments are a prolific source of structurally diverse molecules with a range of bioactivities against human disease. Specimens of a previously chemically unexplored soft coral, Duva florida, were collected during a deep-sea cruise that sampled marine invertebrates along the Irish continental margin in 2018. Tuaimenal A (1), a cyclized merosesquiterpenoid representing a new carbon scaffold with a highly substituted chromene core, was discovered through exploration of the soft coral secondary metabolome via NMR-guided fractionation. The absolute configuration was determined through vibrational circular dichroism. Functional biochemical assays and in silico docking experiments found tuaimenal A selectively inhibits the viral main protease (3CLpro) of SARS-CoV-2.