Predictors of Nonseroconversion after SARS-CoV-2 Infection.

Not all persons recovering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection develop SARS-CoV-2-specific antibodies. We show that nonseroconversion is associated with younger age and higher reverse transcription PCR cycle threshold values and identify SARS-CoV-2 viral loads in the nasopharynx as a major correlate of the systemic antibody response.

A study of disparities in access to genetic care pre- and post-pandemic.

We aimed to explore the delivery of pediatric genetic care before and during the COVID-19 pandemic and assess if disparities in care existed or emerged. We retrospectively reviewed the electronic medical record for patients 18 years old or younger seen in the Division of Pediatric Genetics between September 2019-March 2020 and April-October 2020. Outcomes included time between referral and new visit, recommendation and completion of genetic testing and/or follow-up visit within 6 months, and telemedicine versus in-person format. Outcomes were compared pre- and post-COVID-19 emergence across ethnicity, race, age, health insurance, socioeconomic status (SES), and use of medical interpretation services. Three hundred thirteen total records were reviewed with comparable demographics between cohorts. Cohort 2 had shorter times between referral and new visit, greater telemedicine utilization, and a greater proportion of testing completed. Younger patients tended to have shorter times between referral and initial visit. In Cohort 1, those with Medicaid insurance or no coverage had longer referral-initial visit times. In Cohort 2, there were differences in testing recommendation based on age. For all outcomes, no disparities were observed across ethnicity, race, SES, or use of medical interpretation services. This study characterizes the impact of the pandemic on pediatric genetics care delivery at our center and may have wider implications.

Changes in Short-term, Long-term, and Preventive Care Delivery in US Office-Based and Telemedicine Visits During the COVID-19 Pandemic.

Importance: While the COVID-19 pandemic has been associated with some substitution of telemedicine for office-based care in the US, to our knowledge, little is known regarding the pandemic's association with the clinical content of ambulatory care. Objective: To characterize changes in the clinical content of ambulatory care among office-based vs telemedicine encounters in the US before vs during the COVID-19 pandemic. Design Settings and Participants: This analysis of serial cross-sectional data from the IQVIA National Disease and Therapeutic Index was a 2-stage, stratified nationally representative audit of outpatient care in the US from January 1, 2018, through December 31, 2020. The National Disease and Therapeutic Index generates approximately 33 617 quarterly visits that are projected to 306.7 million national visits based on the survey design. Main Outcomes and Measures: (1) Prevalence of common diagnoses and (2) mix of long-term, short-term, and preventive care. Results: The mean (SD) number of projected quarterly, in-person, office-based visits was 282.1 (1.4) million in 2018 and 284.7 (10.3) in 2019 before declining to 250.8 million in quarter 1 of 2020 and 147.8 million in quarter 2 of 2020 and then increasing moderately to 181.5 million in quarter 3 of 2020 and 180.2 million in quarter 4 of 2020. The mean (SD) number of telemedicine visits was 2.8 (0.4) million in 2018 and 3.0 (0.1) million in 2019 before increasing to 8.6 million in quarter 1 of 2020 and 72.2 million in quarter 2 of 2020 and then declining notably to 43.8 million in quarter 3 of 2020 and 44.2 million in quarter 4 of 2020. Office-based care during the second through fourth quarters of 2020 involved 58.0% long-term, 23.0% short-term, and 25.6% preventive care. In contrast to office-based care, 4 of the top 10 diagnoses that were treated by telemedicine during 2020 were for psychiatric or behavioral conditions: depression, attention deficit/hyperactivity, anxiety, and bipolar disorders. Throughout this period, approximately half of office-based visits and nearly two-thirds of telemedicine visits were for established rather than new patients. Conclusions and Relevance: This cross-sectional study's findings suggest that while telemedicine rapidly increased early during course of the COVID-19 pandemic, its use declined modestly since then. In contrast to office-based care, telemedicine was more commonly used for established patients and substantially greater delivery of psychiatric or behavioral treatments rather than preventive care.

Social Determinants Predict Poor Exercise Self-Efficacy Outcomes in Cardiac Rehabilitation

Background: Building confidence to exercise regularly (exercise self-efficacy) in the face of constraints is a key goal of cardiac rehabilitation (CR) because these beliefs are predictors of sustained exercise behaviours. This study identifies patient subgroups at risk of poor self-efficacy to enable targeting and tailoring of CR interventions. Methods: Patients with coronary heart disease at four CR sites in Australia completed the Exercise Self-Efficacy Scale at CR entry and completion (6-8 weeks). A General Linear Model was used to identify independent predictors of least change in exercise self-efficacy. Data collection included COVID-19 pandemic time, so delivery mode (in-person versus remote) was included in the analyses. Results: Patients (n=194) had a mean age of 65.9 (SD 10.5) years, 81% were males. The majority (80%) were married/partnered, 76% were White, and 24% were from an ethnic minority background. Patients received CR in-person (47%) or remote-delivered (54%). At CR entry, the mean exercise self-efficacy score was 24.9 (SD 6.0) of potential 30 points, which improved significantly by completion (p=0.027). Independent predictors of least improvements in exercise self-efficacy were being an ethnic minority (β= -2.96, 95%CI -4.90, -1.02), not having a spouse/partner (β=-2.42, 95% CI -4.49, -0.35), attending in-person CR (β= -1.75, 95%CI -3.39, -0.12), and having higher exercise self-efficacy at entry (β= -0.37, 95%CI -0.51, -0.23). Conclusions: Confidence to exercise improves in CR programs. Assessing exercise self-efficacy at CR entry is recommended to ensure interventions can be tailored for patients’ needs. The relative lesser increase in confidence in ethnic minorities and solo patients should be explored.

Predictors of poor exercise self-efficacy improvements after cardiac rehabilitation

Background/Introduction: Building confidence to exercise regularly (exercise self-efficacy (ESE)) in the face of constraints and barriers, is a key goal of cardiac rehabilitation (CR) because such self-efficacy beliefs are predictors of sustained exercise behaviours. Therefore, identifying patient subgroups at risk of poor ESE enables tailoring of CR and appropriate targeting of support interventions. Purpose: To identify independent predictors of poor ESE and poor improvements in ESE in CR participants. Methods: The study used a prospective observational cohort design and recruited patients with coronary heart disease at CR entry across four sites in Metropolitan Sydney, Australia (2019-2020). Data were also compared for traditional in-person and remote-delivered CR during COVID-19 pandemic restrictions. The Exercise Self Efficacy Scale was used to measure ESE at CR entry and completion, and General Linear Models were used for analyses. Results: Participants (n=194) had a mean age of 65.94 (SD 10.46) years, with 80.9% males;and 80.0% were married or partnered, with 23.6% from an ethnic minority background. Referral diagnosis included elective percutaneous coronary intervention (PCI) (40.2%), coronary artery bypass surgery (26.3%), and myocardial infarction with or without PCI (33.5%). At CR entry, the mean ESE score was 24.93 (SD 5.99) points, which improved significantly by completion (p=.027). The GLM of ESE change (Adjusted R2=.247) identified that predictors of less change in ESE scores by CR completion included ethnic minorities (β=2.96, p=.003), not having a spouse or an intimate partner (β=-2.42, p=.023), and attending in-person CR (β=1.75, p=.036). Having higher ESE scores at entry was also associated with less ESE change on completion, such that for every point increase in ESE at entry, there was a reduction of .37 points in change (p<.001). These variables were also the same predictors of poor ESE at CR completion. Conclusions: Confidence to exercise improves in CR, and screening for ESE at CR entry enables identification of patients at-risk of poor improvements. Tailoring of interventions to provide appropriate support such as extending CR should be considered for patients from ethnic minorities and those who are single/widowed. Exploring the reasons for differences in outcomes from in-person and remote-delivered CR using appropriate methods should be the focus of future research.

A Comparative Utility Score for Digital Health Tools.

Digital health tools (DHT) are increasingly poised to change healthcare delivery given the Coronavirus Disease 2019 (COVID-19) pandemic and the drive to telehealth. Establishing the potential utility of a given DHT could aid in identifying how it could be best used and further opportunities for healthcare improvement. We propose a metric, a Utility Factor Score, which quantifies the benefits of a DHT by explicitly defining adherence and linking it directly to satisfaction and health goals met. To provide data for how the comparative utility score can or should work, we illustrate in detail the application of our metrics across four DHTs with two simulated users. The Utility Factor Score can potentially facilitate integration of DHTs into various healthcare settings and should be evaluated within a clinical study.

Comprehensive mapping of SARS-CoV-2 peptide epitopes for development of a highly sensitive serological test for total and neutralizing antibodies.

Quantification of the anti-SARS-CoV-2 antibody response has proven to be a prominent diagnostic tool during the COVID-19 pandemic. Antibody measurements have aided in the determination of humoral protection following infection or vaccination and will likely be essential for predicting the prevalence of population level immunity over the next several years. Despite widespread use, current tests remain limited in part, because antibody capture is accomplished through the use of complete spike and nucleocapsid proteins that contain significant regions of overlap with common circulating coronaviruses. To address this limitation, a unique epitope display platform utilizing monovalent display and protease-driven capture of peptide epitopes was used to select high affinity peptides. A single round of selection using this strategy with COVID-19 positive patient plasma samples revealed surprising differences and specific patterns in the antigenicity of SARS-CoV-2 proteins, especially the spike protein. Putative epitopes were assayed for specificity with convalescent and control samples, and the individual binding kinetics of peptides were also determined. A subset of prioritized peptides was used to develop an antibody diagnostic assay that showed low cross reactivity while detecting 37% more positive antibody cases than a gold standard FDA EUA test. Finally, a subset of peptides were compared with serum neutralization activity to establish a 2 peptide assay that strongly correlates with neutralization. Together, these data demonstrate a novel phage display method that is capable of comprehensively and rapidly mapping patient viral antibody responses and selecting high affinity public epitopes for the diagnosis of humoral immunity.

Improvement in patient activation measure (PAM) is seen following a focused framework of education in a newly diagnosed inflammatory bowel disease cohort

Introduction: Inflammatory bowel disease (IBD) is a lifelong relapsingremitting condition. Education is one aspect of high quality care that empowers patients with knowledge, skills and confidence to manage their disease. Patient Activation Measure (PAM)1 is an objective tool designed to assess patient empowerment. A high PAM is associated with better clinical outcomes in chronic conditions including IBD.2 We aimed to measure the effect of education on PAM scores for newly diagnosed IBD patients over 12 months. Aims & Methods: A New Diagnosis of IBD clinic (NDC) was set-up whereby patients had a 45 minute consultation delivered jointly by an IBD physician, and nurse specialist. The topics covered were the natural history of IBD, triggers to relapse, self-management of mild relapses, and signposting to reliable information sources. PAM is a tool consisting of 13 questions, which generates a score from 1 (poor activation) to 4 (high activation). A patient with PAM score of ≥3 is considered 'activated'. 2 PAM scores were taken prior to NDC (T1), immediately following NDC (T2) and 12 months later (T3). The primary outcome was the proportion of activated patients at 12 months. A change in PAM score by ≥1 was a secondary outcome. Data on age, gender, ethnicity, smoking, IBD sub-type, and baseline disease activity were collected. An amendment to assess patient activation due to the COVID-19 pandemic was made. Data was collected on change in employment due to COVID-19, and/or having PCR proven COVID-19, and the use of healthcare resources. Median (IQR) and mean (±SD) described continuous variables. Unpaired and paired categorical variables were compared with Fischer's test and McNemar's test respectively. Results: 54 patients attended the NDC;38 completed the study (20 male);16 were lost to follow-up (LFU) and thus only had a baseline score recorded, and were excluded from 12 month analysis. Median age was 42(range 18-83) years. 24 patients had ulcerative colitis, 10 Crohn's disease, and 4 had IBD-unclassified. 25 had active disease at baseline. The mean time from symptom onset to NDC attendance was 3.26 (±2.89) months. At T1, the median PAM score for the 38 patients was 3 (IQR 2) in contrast to 1 (IQR 1) for the LFU group. 24 (63%) had a PAM score ≥3 (activated) at T1, and T2. 14 patients were PAM <3 (non-activated) at T1 of whom 8 (57%) had an increase PAM by ≥1 at T2, (p=0.0133). From this non-activated patient cohort at T1, 9/14 patients (64%) had an improved PAM at T3. At T3, 23/38 (60%) had a PAM score ≥3;11/38(29%) had an improvement in PAM of ≥1 and13/38 (34%) patients had no change. PAM score changes were independent of disease activity, age, gender, ethnicity or smoking. The COVID affected group included 6 patients with PCR proven COVID infection (1 death) and 9/38 patients with a change in employment due to COVID. This group was labelled the COVID group. 5/15 patients in the COVID group had a PAM score ≤2 at T1;an improvement in PAM by ≥1 was seen at T3 in all 5 cases. 6/9 (67%) activated patients in the COVID group at T1 in maintained activation at T3. 19/24 patients in the non-COVID group made use of healthcare resources compared to 8/14 in the COVID group (p=0.0027). Conclusion: Patient activation at baseline was sustained at 12 months. There was an improvement in PAM of ≥1 immediately after attendance at the NDC. This improvement is independent of the patient demographics, or disease status. The COVID-19 pandemic was not associated with a worsening in PAM, or an increase in demand on healthcare resources.

Personal Protective Equipment Adherence of Pediatric Resuscitation Team Members During the COVID-19 Pandemic.

STUDY OBJECTIVE: During the COVID-19 pandemic, health care workers have had the highest risk of infection among essential workers. Although personal protective equipment (PPE) use is associated with lower infection rates, appropriate use of PPE has been variable among health care workers, even in settings with COVID-19 patients. We aimed to evaluate the patterns of PPE adherence during emergency department resuscitations that included aerosol-generating procedures. METHODS: We conducted a retrospective, video-based review of pediatric resuscitations involving one or more aerosol-generating procedures during the first 3 months of the COVID-19 pandemic in the United States (March to June 2020). Recommended adherence (complete, inadequate, absent) with 5 PPE items (headwear, eyewear, masks, gowns, gloves) and the duration of potential exposure were evaluated for individuals in the room after aerosol-generating procedure initiation. RESULTS: Among the 345 health care workers observed during 19 resuscitations, 306 (88.7%) were nonadherent (inadequate or absent adherence) with the recommended use of at least 1 PPE type at some time during the resuscitation, 23 (6.7%) of whom had no PPE. One hundred and forty health care workers (40.6%) altered or removed at least 1 type of PPE during the event. The aggregate time in the resuscitation room for health care workers across all events was 118.7 hours. During this time, providers had either absent or inadequate eyewear for 46.4 hours (39.1%) and absent or inadequate masks for 35.2 hours (29.7%). CONCLUSION: Full adherence with recommended PPE use was limited in a setting at increased risk for SARS-CoV-2 virus aerosolization. In addition to ensuring appropriate donning, approaches are needed for ensuring ongoing adherence with PPE recommendations during exposure.

Multiplex serological assay for establishing serological profiles of polymorphic, closely related peptide antigens.

Profiling of serological responses to establish the landscape of antibody specificities in individuals exposed to pathogens or vaccines is crucial for (a) revealing humoral immune correlates of protection; (b) uncovering markers of pathogen exposure; and (c) identifying antigens and epitopes associated with disease vs. protection. Establishing the antigenic profile of serological responses requires either expensive microarrays or labor- and time-intensive ELISA assays. Multiplex assay platforms are increasingly being evaluated for their usefulness for high-throughput testing of sera or plasma. The methodology described here utilizes a plate-based assay that allows the simultaneous detection of up to ten antigens per well in a 96 well format using an electrochemiluminescence immunoassay (ECLIA).•The newly developed protocol outlines high-throughput profiling of serological responses using a multiplex testing platform with subsequent computational analysis.•The protocol is a modification of the basic assay development manual from the manufacturer of the MESO QuickPlex SQ 120 instrument (MSD, Gaithersburg, MD) and can be used for synthetic peptides as well as full length proteins.•The protocol can be applied to map serological responses to pathogens or pathogen-derived antigens to establish serological profiles in search for biomarkers or immune correlates.

Convalescent plasma-mediated resolution of COVID-19 in a patient with humoral immunodeficiency.

Convalescent plasma (CP) is widely used to treat COVID-19, but without formal evidence of efficacy. Here, we report the beneficial effects of CP in a severely ill COVID-19 patient with prolonged pneumonia and advanced chronic lymphocytic leukemia (CLL), who was unable to generate an antiviral antibody response of her own. On day 33 after becoming symptomatic, the patient received CP containing high-titer (ID50 > 5,000) neutralizing antibodies (NAbs), defervesced, and improved clinically within 48 h and was discharged on day 37. Hence, when present in sufficient quantities, NAbs to SARS-CoV-2 have clinical benefit even if administered relatively late in the disease course. However, analysis of additional CP units revealed widely varying NAb titers, with many recipients exhibiting endogenous NAb responses far exceeding those of the administered units. To obtain the full therapeutic benefits of CP immunotherapy, it will thus be important to determine the neutralizing activity in both CP units and transfusion candidates.

Use and Content of Primary Care Office-Based vs Telemedicine Care Visits During the COVID-19 Pandemic in the US.

Importance: Little is known about the association between the coronavirus disease 2019 (COVID-19) pandemic and the level and content of primary care delivery in the US. Objective: To quantify national changes in the volume, type, and content of primary care delivered during the COVID-19 pandemic, especially with regard to office-based vs telemedicine encounters. Design, Setting, and Participants: Analysis of serial cross-sectional data from the IQVIA National Disease and Therapeutic Index, a 2-stage, stratified nationally representative audit of outpatient care in the US from the first calendar quarter (Q1) of 2018 to the second calendar quarter (Q2) of 2020. Main Outcomes and Measures: Visit type (office-based or telemedicine), overall and stratified by patient population and geographic region; assessment of blood pressure or cholesterol measurement; and initiation or continuation of prescription medications. Results: In the 8 calendar quarters between January 1, 2018, and December 31, 2019, between 122.4 million (95% CI, 117.3-127.5 million) and 130.3 million (95% CI, 124.7-135.9 million) quarterly primary care visits occurred in the US (mean, 125.8 million; 95% CI, 121.7-129.9 million), most of which were office-based (92.9%). In 2020, the total number of encounters decreased to 117.9 million (95% CI, 112.6-123.2 million) in Q1 and 99.3 million (95% CI, 94.9-103.8 million) in Q2, a decrease of 21.4% (27.0 million visits) from the average of Q2 levels during 2018 and 2019. Office-based visits decreased 50.2% (59.1 million visits) in Q2 of 2020 compared with Q2 2018-2019, while telemedicine visits increased from 1.1% of total Q2 2018-2019 visits (1.4 million quarterly visits) to 4.1% in Q1 of 2020 (4.8 million visits) and 35.3% in Q2 of 2020 (35.0 million visits). Decreases occurred in blood pressure level assessment (50.1% decrease, 44.4 million visits) and cholesterol level assessment (36.9% decrease, 10.2 million visits) in Q2 of 2020 compared with Q2 2018-2019 levels, and assessment was less common during telemedicine than during office-based visits (9.6% vs 69.7% for blood pressure; P < .001; 13.5% vs 21.6% for cholesterol; P < .001). New medication visits in Q2 of 2020 decreased by 26.0% (14.1 million visits) from Q2 2018-2019 levels. Telemedicine adoption occurred at similar rates among White individuals and Black individuals (19.3% vs 20.5% of patient visits, respectively, in Q1/Q2 of 2020), varied by region (low of 15.1% of visits [East North Central region], high of 26.8% of visits [Pacific region]), and was not correlated with regional COVID-19 burden. Conclusions and Relevance: The COVID-19 pandemic has been associated with changes in the structure of primary care delivery, with the content of telemedicine visits differing from that of office-based encounters.

Head and neck oncology during the COVID-19 pandemic: Reconsidering traditional treatment paradigms in light of new surgical and other multilevel risks.

The COVID-19 pandemic demands reassessment of head and neck oncology treatment paradigms. Head and neck cancer (HNC) patients are generally at high-risk for COVID-19 infection and severe adverse outcomes. Further, there are new, multilevel COVID-19-specific risks to patients, surgeons, health care workers (HCWs), institutions and society. Urgent guidance in the delivery of safe, quality head and neck oncologic care is needed. Novel barriers to safe HNC surgery include: (1) imperfect presurgical screening for COVID-19; (2) prolonged SARS-CoV-2 aerosolization; (3) occurrence of multiple, potentially lengthy, aerosol generating procedures (AGPs) within a single surgery; (4) potential incompatibility of enhanced personal protective equipment (PPE) with routine operative equipment; (5) existential or anticipated PPE shortages. Additionally, novel, COVID-19-specific multilevel risks to HNC patients, HCWs and institutions, and society include: use of immunosuppressive therapy, nosocomial COVID-19 transmission, institutional COVID-19 outbreaks, and, at some locations, societal resource deficiencies requiring health care rationing. Traditional head and neck oncology doctrines require reassessment given the extraordinary COVID-19-specific risks of surgery. Emergent, comprehensive management of these novel, multilevel surgical risks are needed. Until these risks are managed, we temporarily favor nonsurgical therapy over surgery for most mucosal squamous cell carcinomas, wherein surgery and nonsurgical therapy are both first-line options. Where surgery is traditionally preferred, we recommend multidisciplinary evaluation of multilevel surgical-risks, discussion of possible alternative nonsurgical therapies and shared-decision-making with the patient. Where surgery remains indicated, we recommend judicious preoperative planning and development of COVID-19-specific perioperative protocols to maximize the safety and quality of surgical and oncologic care.