Synergistic effect of elevated glucose levels with SARS-CoV-2 spike protein induced NOX-dependent ROS production in endothelial cells.

BACKGROUND: Diabetic patients infected with coronavirus disease 2019 (COVID-19) often have a higher probability of organ failure and mortality. The potential cellular mechanisms through which blood glucose exacerbates tissue damage due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still unclear. METHODS AND RESULTS: We cultured endothelial cells within differing glucose mediums with an increasing concentration gradient of SARS-CoV-2 Spike protein (S protein). S protein can cause the reduction of ACE2 and TMPRSS2, and activation of NOX2 and NOX4. A high glucose medium was shown to aggravate the decrease of ACE2 and activation of NOX2 and NOX4 in cultured cells, but had no effect on TMPRSS2. S protein mediated activation of the ACE2-NOX axis induced oxidative stress and apoptosis within endothelial cells, leading to cellular dysfunction via the reduction of NO and tight junction proteins which may collectively be exacerbated by elevated glucose. In addition, the glucose variability model demonstrated activation of the ACE2-NOX axis in a similar manner observed in the high glucose model in vitro. CONCLUSIONS: Our present study provides evidence for a mechanism through which hyperglycemia aggravates endothelial cell injury resulting from S protein mediated activation of the ACE2-NOX axis. Our research thus highlights the importance of strict monitoring and control of blood glucose levels within the context of COVID-19 treatment to potentially improve clinical outcomes.

Emergency department visits in Connecticut for survivors of sexual assault before and during the COVID-19 pandemic.

STUDY OBJECTIVE: We evaluate the impact of the COVID-19 pandemic on care for survivors of sexual assault in three urban Emergency Departments (ED) in the United States. METHODS: A retrospective chart review was conducted on patients who presented after sexual assault to three EDs during 6-month intervals before and during the COVID-19 pandemic. We excluded individuals <18 years old. We performed a structured chart review to ascertain demographics, ED treatments, and adherence to guidelines for care of sexual assault survivors. RESULTS: Of 105 patients who received care after a sexual assault, 57 presented during the COVID-19 pandemic. The majority were female, White/Caucasian, and presented within 120 h of sexual assault. There was an increase in ED presentations for sexual assault during the pandemic. While there was no difference in medical care, there were fewer sexual assault advocates called during the pandemic. In addition, there was an increase in non-White survivors in the first 3 months of the pandemic that did not remain at 6 months. CONCLUSION: The care of survivors in the ED was disrupted by the COVID-19 pandemic. While medical care remained similar, fewer calls to sexual assault advocates, a key component of ED and long-term care of survivors, demonstrate a disruption in their care.

The University of Colorado Virtual Physical Examination for Spine Surgeons: A Preliminary Study.

As coronavirus disease 2019 (COVID-19) reached pandemic status, in-person orthopedic clinics across the United States were forced to close as many states adopted stay-at-home orders. Previously, the use of telemedicine in orthopedic practices was minimal for a variety of reasons, one being the inability to perform a physical examination in a specialty reliant on direct patient contact for diagnosis and treatment. A prospective cohort of 52 patients consented to participate in a novel virtual physical examination protocol during routine telemedicine visits at a large, tertiary orthopedic spine practice. Participants were asked to perform a series of carefully designed physical maneuvers using readily available household objects to allow their provider to better assess sensory and motor function in the tele-medicine setting. Patients were then asked to complete a short satisfaction survey. In total, 52 patients completed the physical examination and survey. Males and females were distributed evenly among the cohort at 50%. The mean age was 52.1±15.5 years. The average score for ease of understanding the examination (1=easiest, 5=hardest) was 1.1, while the average score for ease of performance was 1.5. Most participants (97.56%) felt their provider was better able to understand their condition using the virtual examination findings. This study highlights the utility of a virtual physical examination for assessment of spine patients in the telemedicine setting. Furthermore, this study illustrates the ease with which such an examination can be implemented and performed to improve patient evaluation and satisfaction. [Orthopedics. 2022;45(1):e7-e10.].

Educational Setting and SARS-CoV-2 Transmission Among Children With Multisystem Inflammatory Syndrome: A French National Surveillance System.

Background: Multisystem inflammatory syndrome in children (MIS-C) is the most severe form associated with SARS-CoV-2 infection in children. To reduce the spread of SARS-CoV-2 at the population level, educational setting closure have been implemented in many countries. However, the direct benefit of school closure on the MIS-C burden remains to be explored. We aimed to assess the role of educational settings in SARS-CoV-2 transmission among children with MIS-C. Methods: We conducted a French national prospective surveillance of MIS-C, coordinated by Public Health France, from April 2020 to March 2021. During this period, we included all children with MIS-C fulfilling the WHO definition who were reported to Public Health France. For each child, we traced the source of SARS-CoV-2 transmission. The main outcome was the proportion of children with MIS-C, with educational setting-related SARS-CoV-2 infection, during the period of school opening. Results: We included 142 children fulfilling WHO criteria for MIS-C: 104 (70%) cases occurred during school opening periods. In total, 62/104 children (60%, 95%CI [50; 69]) had been contaminated by a household contact and 5/104 in educational settings (5%, 95%CI [2; 11]). Among children with MIS-C occurring during school closure periods, the proportion of household transmission remained similar (66%, 25/38). Conclusion: Children with MIS-C were mainly infected by SARS-CoV-2 within their family environment, and the educational setting played a marginal role in this transmission. This suggests that mitigating school attendance may not reduce substantially the burden of MIS-C.

Polarization and Public Health: Partisan Differences in Social Distancing during the Coronavirus Pandemic

We study partisan differences in Americans’ response to the COVID-19 pandemic. Political leaders and media outlets on the right and left have sent divergent messages about the severity of the crisis, which could impact the extent to which Republicans and Democrats engage in social distancing and other efforts to reduce disease transmission. We develop a simple model of a pandemic response with heterogeneous agents that clarifies the causes and consequences of heterogeneous responses. We use location data from a large sample of smartphones to show that areas with more Republicans engaged in less social distancing, controlling for other factors including public policies, population density, and local COVID cases and deaths. We then present new survey evidence of significant gaps at the individual level between Republicans and Democrats in self-reported social distancing, beliefs about personal COVID risk, and beliefs about the future severity of the pandemic.

Civil Liberties in Times of Crisis

Major crises—from terrorist attacks to outbreaks of disease—bring the trade-off between individual civil liberties and national security or well-being into sharp relief. In this paper, we study to what extent individual preferences for protecting rights and civil liberties are elastic to health insecurity. We design and conduct representative surveys involving approximately 550,000 responses across 15 countries, including China and the United States, during many months of the COVID-19 pandemic, from March 2020 until January 2021. We document significant heterogeneity across countries and demographic groups in willingness to sacrifice rights for public welfare. Citizens disadvantaged by income, education, or race are less willing to sacrifice rights than their more advantaged peers in every country, as are those with prior experience in communist regimes. Leveraging naturally-occurring variation as well as experimental approaches, we estimate that a one standard deviation increase in health security concerns increases willingness to sacrifice civil liberties by approximately 72%-92% of the difference between the average Chinese and U.S. citizen. Stated preferences correlate with observed behavior including demand for tracing apps, donations, and petitions.

Fall of Community-Acquired Pneumonia in Children following COVID-19 Non-Pharmaceutical Interventions: A Time Series Analysis.

Non-pharmaceutical interventions (NPIs) were implemented to reduce the spread of coronavirus disease 2019 (COVID-19). A first national lockdown was decided in France on the 17 March 2020. These measures had an impact on other viral and non-viral infectious diseases. We aimed to assess this impact on community-acquired pneumonia (CAP) in children. We performed a quasi-experimental interrupted time series analysis. We used data from a French prospective surveillance system of six pediatric emergency departments (PEDs). All visits from 1 January 2017 to 31 December 2020 were included. Pre-intervention period was before 17 March 2020 and post-intervention period was after 18 March 2020. We estimated the impact on the weekly number of visits for CAP and CAP admission using quasi-Poisson regression modeling. A total of 981,782 PEDs visits were analyzed; among them, 8318 visits were associated with CAP, and 1774 of these were followed by a hospital admission. A major decrease was observed for CAP visits (-79.7% 95% CI [-84.3; -73.8]; p < 0.0001), and CAP admission (-71.3% 95 CI [-78.8; -61.1]; p < 0.0001). We observed a dramatic decrease of CAP in children following NPIs implementation. Further studies are required to assess the long-term impact of these measures.

Using community-based participatory research methods to inform care for patients experiencing homelessness: An opportunity for resident education on health care disparities.

People experiencing homelessness (PEH) suffer higher burdens of chronic illnesses, have higher rates of emergency medicine (ED) use and hospitalization, and ultimately are at increased risk for premature death compared to housed counterparts. Structural racism contributes to a disproportionate burden of homelessness among people of color. PEH experience not only significant medical concerns but also complex social needs that need to be addressed concurrently for effective healing, issues that have been magnified by the COVID-19 pandemic. As health disparities and structural racism intersect among PEH, it is critically important to develop PEH-centered interventions to improve care and health outcomes as part of an effort to dismantle racism. One opportunity to address these disparities in care for PEH is through training ED physicians on methods for identifying and intervening on the unique needs of vulnerable patient groups. The Accreditation Council for Graduate Medical Education has outlined health quality pathways in the clinical learning environment to address health disparities. Community-based participatory research (CBPR) is particularly well suited for this scenario as it allows experiential learning for trainees to work with and understand a diverse group of stakeholders, to deepen their knowledge of local health disparities, and to lead research and measure outcomes of interventions to tackle health disparities. In this paper, we highlight the utility of CBPR in fostering experiential learning for EM residents on tackling health disparities and the importance of community collaboration in trainee-led interventions for comprehensive ED care.

P41. The University of Colorado virtual physical exam for spine surgeons: A preliminary study

BACKGROUND CONTEXT As COVID-19 reached pandemic status, in-person orthopedic clinics across the United States were forced to close as many states adopted stay-at-home orders. Previously, the use of telemedicine in orthopedic practices was minimal for a variety of reasons, one being the inability to perform a physical exam in a specialty reliant on direct patient contact for diagnosis and treatment. PURPOSE To evaluate the administration of a novel virtual physical exam for evaluation of spine patients in the telehealth setting. STUDY DESIGN/SETTING Prospective consecutive cohort at a large academic spine center. METHODS A prospective cohort of 52 patients consented to participating in a novel virtual physical exam protocol during routine telemedicine visits at a large, tertiary orthopedic spine practice. Participants were asked to perform a series of carefully designed physical maneuvers using readily available household objects to allow their provider to better assess sensory and motor function in the telemedicine setting. Patients were then asked to complete a short satisfaction survey. RESULTS In total, 52 patients completed the physical exam and survey. Males and females were distributed evenly among the cohort at 50%. The average age was 52.1 +/- 15.5 years. The average score for ease of understanding the exam (1 = easiest, 5 = hardest) was 1.1 while the average score for ease of performance was 1.5. There were 97.56% of participants who felt their provider was better able to understand their condition using the virtual exam findings. CONCLUSIONS This study highlights the utility of a virtual physical exam for assessment of spine patients in the telemedicine setting. Furthermore, this study illustrates the ease with which such an exam can implemented and performed to improve patient evaluation and satisfaction. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown. Objective: To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. Design, Setting, and Participants: Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021. Exposures: IVIG and methylprednisolone vs IVIG alone. Main Outcomes and Measures: The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1. Results: Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P = .004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]). Conclusions and Relevance: Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.

Coronavirus Disease 2019 Pandemic: Impact Caused by School Closure and National Lockdown on Pediatric Visits and Admissions for Viral and Nonviral Infections-a Time Series Analysis.

A time series analysis of 871 543 pediatric emergency visits revealed that the coronavirus disease 2019 (COVID-19) lockdown and school closures were associated with a significant decrease in infectious diseases disseminated through airborne or fecal-oral transmission: common cold, gastroenteritis, bronchiolitis, and acute otitis. No change was found for urinary tract infections.

Massively multiplexed nucleic acid detection with Cas13.

The great majority of globally circulating pathogens go undetected, undermining patient care and hindering outbreak preparedness and response. To enable routine surveillance and comprehensive diagnostic applications, there is a need for detection technologies that can scale to test many samples1-3 while simultaneously testing for many pathogens4-6. Here, we develop Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic acids (CARMEN), a platform for scalable, multiplexed pathogen detection. In the CARMEN platform, nanolitre droplets containing CRISPR-based nucleic acid detection reagents7 self-organize in a microwell array8 to pair with droplets of amplified samples, testing each sample against each CRISPR RNA (crRNA) in replicate. The combination of CARMEN and Cas13 detection (CARMEN-Cas13) enables robust testing of more than 4,500 crRNA-target pairs on a single array. Using CARMEN-Cas13, we developed a multiplexed assay that simultaneously differentiates all 169 human-associated viruses with at least 10 published genome sequences and rapidly incorporated an additional crRNA to detect the causative agent of the 2020 COVID-19 pandemic. CARMEN-Cas13 further enables comprehensive subtyping of influenza A strains and multiplexed identification of dozens of HIV drug-resistance mutations. The intrinsic multiplexing and throughput capabilities of CARMEN make it practical to scale, as miniaturization decreases reagent cost per test by more than 300-fold. Scalable, highly multiplexed CRISPR-based nucleic acid detection shifts diagnostic and surveillance efforts from targeted testing of high-priority samples to comprehensive testing of large sample sets, greatly benefiting patients and public health9-11.

Factors Associated With Severe SARS-CoV-2 Infection.

BACKGROUND: Initial reports on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children suggested that very young age and comorbidities may increase risk of severe evolution, but these findings remained to be confirmed. We aimed to analyze the clinical spectrum of hospitalized pediatric SARS-CoV-2 infection and predictors of severe disease evolution. METHODS: We conducted a French national prospective surveillance of children hospitalized with SARS-CoV-2 infection. We included all children with confirmed SARS-CoV-2 infection in 60 hospitals during February 15 to June 1, 2020. The main outcome was the proportion of children with severe disease, defined by hemodynamic or ventilatory (invasive or not) support requirement. RESULTS: We included 397 hospitalized children with SARS-CoV-2 infection. We identified several clinical patterns, ranging from paucisymptomatic children, admitted for surveillance, to lower respiratory tract infection or multisystem inflammatory syndrome in children. Children <90 days old accounted for 37% of cases (145 of 397), but only 4 (3%) had severe disease. Excluding children with multisystem inflammatory syndrome in children (n = 29) and hospitalized for a diagnosis not related to SARS-CoV-2 (n = 62), 23 of 306 (11%) children had severe disease, including 6 deaths. Factors independently associated with severity were age ≥10 years (odds ratio [OR] = 3.4, 95% confidence interval: 1.1-10.3), hypoxemia (OR = 8.9 [2.6-29.7]), C-reactive protein level ≥80 mg/L (OR = 6.6 [1.4-27.5]). CONCLUSIONS: In contrast with preliminary reports, young age was not an independent factor associated with severe SARS-CoV-2 infection, and children <90 days old were at the lowest risk of severe disease evolution. This may help physicians to better identify risk of severe disease progression in children.

Utilization and Results of Repeat SARS-CoV-2 RT-PCR Testing in a Presumptive Low Prevalence Population.

INTRODUCTION: Early reports have raised concerns regarding the clinical sensitivity of nasopharyngeal SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) testing for patients with COVID-19 symptoms, which has led to requests for repeat testing at our institution. However, to our knowledge, there are no reports to date of the utilization or results of repeat testing to help guide this practice. METHODS: The authors searched the institutional laboratory information system for consecutive patients who were tested for SARS-CoV-2 by RT-PCR of a nasopharyngeal specimen over a 1-month period. Characteristics and results of patients who received a single or multiple tests were documented and analyzed. RESULTS: Six thousand three (6003) tests were performed on 5757 patients; 272 (4.7%) patients were positive based on their initial test results. Two hundred thirty-six (4%) patients were tested more than once, with 226 (96%) tested twice. The largest proportion of these patients (n=160, 71%) were those who had an initial negative test followed by a repeat test for persistent symptoms. This group included all 7 patients who had discordant positive results on their second test; the result concordance rate within this group was 96%. CONCLUSION: In a population of patients with a low positive rate for SARS-CoV-2 by nasopharyngeal RT-PCR testing, repeat nasopharyngeal testing of negative patients who have persistent symptoms still yields a negative result in 96% of the cases.

Polarization and public health: Partisan differences in social distancing during the coronavirus pandemic.

We study partisan differences in Americans' response to the COVID-19 pandemic. Political leaders and media outlets on the right and left have sent divergent messages about the severity of the crisis, which could impact the extent to which Republicans and Democrats engage in social distancing and other efforts to reduce disease transmission. We develop a simple model of a pandemic response with heterogeneous agents that clarifies the causes and consequences of heterogeneous responses. We use location data from a large sample of smartphones to show that areas with more Republicans engaged in less social distancing, controlling for other factors including public policies, population density, and local COVID cases and deaths. We then present new survey evidence of significant gaps at the individual level between Republicans and Democrats in self-reported social distancing, beliefs about personal COVID risk, and beliefs about the future severity of the pandemic.

Disparities in Coronavirus 2019 Reported Incidence, Knowledge, and Behavior Among US Adults.

Importance: Data from the coronavirus disease 2019 (COVID-19) pandemic in the US show large differences in hospitalizations and mortality across race and geography. However, there are limited data on health information, beliefs, and behaviors that might indicate different exposure to risk. Objective: To determine the association of sociodemographic characteristics with reported incidence, knowledge, and behavior regarding COVID-19 among US adults. Design, Setting, and Participants: A US national survey study was conducted from March 29 to April 13, 2020, to measure differences in knowledge, beliefs, and behavior about COVID-19. The survey oversampled COVID-19 hotspot areas. The survey was conducted electronically. The criteria for inclusion were age 18 years or older and residence in the US. Data analysis was performed in April 2020. Main Outcomes and Measures: The main outcomes were incidence, knowledge, and behaviors related to COVID-19 as measured by survey response. Results: The survey included 5198 individuals (mean [SD] age, 48 [18] years; 2336 men [45%]; 3759 white [72%], 830 [16%] African American, and 609 [12%] Hispanic). The largest differences in COVID-19-related knowledge and behaviors were associated with race/ethnicity, sex, and age, with African American participants, men, and people younger than 55 years showing less knowledge than other groups. African American respondents were 3.5 percentage points (95% CI, 1.5 to 5.5 percentage points; P = .001) more likely than white respondents to report being infected with COVID-19, as were men compared with women (3.2 percentage points; 95% CI, 2.0 to 4.4 percentage points; P < .001). Knowing someone who tested positive for COVID-19 was more common among African American respondents (7.2 percentage points; 95% CI, 3.4 to 10.9 percentage points; P < .001), people younger than 30 years (11.6 percentage points; 95% CI, 7.5 to 15.7 percentage points; P < .001), and people with higher incomes (coefficient on earning ≥$100 000, 12.3 percentage points; 95% CI, 8.7 to 15.8 percentage points; P < .001). Knowledge of potential fomite spread was lower among African American respondents (-9.4 percentage points; 95% CI, -13.1 to -5.7 percentage points; P < .001), Hispanic respondents (-4.8 percentage points; 95% CI, -8.9 to -0.77 percentage points; P = .02), and people younger than 30 years (-10.3 percentage points; 95% CI, -14.1 to -6.5 percentage points; P < .001). Similar gaps were found with respect to knowledge of COVID-19 symptoms and preventive behaviors. Conclusions and Relevance: In this survey study of US adults, there were gaps in reported incidence of COVID-19 and knowledge regarding its spread and symptoms and social distancing behavior. More effort is needed to increase accurate information and encourage appropriate behaviors among minority communities, men, and younger people.

Clinical Evaluation and Utilization of Multiple Molecular In Vitro Diagnostic Assays for the Detection of SARS-CoV-2.

OBJECTIVES: To evaluate the clinical performance of 3 molecular assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We used 184 nasopharyngeal swab specimens to compare Abbott ID NOW COVID-19 (Abbott ID NOW), DiaSorin Molecular Simplexa COVID-19 Direct (DiaSorin Simplexa), and Roche cobas 6800 SARS-CoV-2 (Roche cobas) assays. In a separate analysis, 3 specimens (nasopharyngeal, oropharyngeal, and nasal) were collected from 182 unique patients presenting to the emergency department with suspicion of coronavirus disease 2019 and were tested utilizing Abbott ID NOW. To further characterize each assay, relative limits of detection were evaluated utilizing positive nasopharyngeal patient samples. RESULTS: The positive percent agreement was 91% (95% confidence interval [CI], 0.76-0.97) for Abbott ID NOW and 100% (95% CI, 0.90-1.00) for DiaSorin Simplexa and Roche cobas. The negative percent agreement was 100% (95% CI, 0.98-1.00) for all 3 assays. All swab types tested with the Abbott assay produced concordant results. Polymerase chain reaction assays had approximately 10 to 100 times lower limits of detection than Abbott ID NOW. CONCLUSIONS: Based on these evaluations, a multiplatform testing approach is proposed, depending on patient population and assay sensitivity, to address testing needs during a public health emergency.