Disparities in COVID-19 Related Outcomes in the United States By Race and Ethnicity: An Umbrella Review of Meta-Analyses

Objectives: Meta-analyses have investigated associations between race and ethnicity and COVID-19 outcomes. However, there is uncertainty about these associations' existence, magnitude, and level of evidence. We, therefore, aimed to synthesize, quantify, and grade the strength of evidence of race and ethnicity and COVID-19 outcomes in the US. Method(s): In this umbrella review, we searched four databases (Pubmed, Embase, the Cochrane Database of Systematic Reviews, and Epistemonikos) from database inception to April 2022. The methodological quality of each meta-analysis was assessed using the Assessment of Multiple Systematic Reviews, version 2 (AMSTAR-2). The strength of evidence of the associations between race and ethnicity with outcomes was ranked according to established criteria as convincing, highly suggestive, suggestive, weak, or non-significant. The study protocol was registered with PROSPERO, CRD42022336805 Results: Of 880 records screened, we selected seven meta-analyses for evidence synthesis, with 42 associations examined. Overall, 10 of 42 associations were statistically significant (p <= 0.05). Two associations were highly suggestive, two were suggestive, and two were weak, whereas the remaining 32 associations were non-significant. The risk of COVID-19 infection was higher in Black individuals compared to White individuals (risk ratio, 2.08, 95% Confidence Interval (CI), 1.60-2.71), which was supported by highly suggestive evidence;with the conservative estimates from the sensitivity analyses, this association remained suggestive. Among those infected with COVID-19, Hispanic individuals had a higher risk of COVID-19 hospitalization than non-Hispanic White individuals (odds ratio, 2.08, 95% CI, 1.60-2.70) with highly suggestive evidence which remained after sensitivity analyses. Conclusion(s): Individuals of Black and Hispanic groups had a higher risk of COVID-19 infection and hospitalization. These associations of race and ethnicity and COVID-19 outcomes existed more obviously in the pre-hospitalization stage. More consideration should be given in this stage for addressing health inequity.Copyright © 2023

SARS-CoV-2 Nsp13 Catalytic Efficiency is Regulated by ATP: Mg2+ Stoichiometry and Functional Cooperativity Among Nsp13 Molecules

Coronavirus disease 19 (COVID-19) is a highly contagious and lethal disease caused by the SARS-CoV-2 positive-strand RNA virus. Nonstructural protein 13 (Nsp13) is the highly conserved ATPase/helicase required for replication of the SARS-CoV-2 genome which allows for the infection and transmission of COVID-19. We biochemically characterized the purified recombinant SARS-CoV-2 Nsp13 helicase protein expressed using a eukaryotic cell-based system and characterized its catalytic functions, focusing on optimization of its reaction conditions and assessment of functional cooperativity among Nsp13 molecules during unwinding of duplex RNA substrates. These studies allowed us to carefully determine the optimal reaction conditions for binding and unwinding various nucleic acid substrates. Previously, ATP concentration was suggested to be an important factor for optimal helicase activity by recombinant SARS-CoV-1 Nsp13. Apart from a single study conducted using fixed concentrations of ATP, the importance of the essential divalent cation for Nsp13 helicase activity had not been examined. Given the importance of the divalent metal ion cofactor for ATP hydrolysis and helicase activity, we assessed if the molar ratio of ATP to Mg2+ was important for optimal SARS-CoV-2 Nsp13 RNA helicase activity. We determined that Nsp13 RNA helicase activity was dependent on ATP and Mg2+ concentrations with an optimum of 1 mM Mg2+ and 2 mM ATP. Next, we examined Nsp13 helicase activity as a function of equimolar ATP:Mg2+ ratio and determined that helicase activity decreased as the equimolar concentration increased, especially above 5 mM. We determined that Nsp13 catalytic functions are sensitive to Mg2+ concentration suggesting a regulatory mechanism for ATP hydrolysis, duplex unwinding, and protein remodeling, processes that are implicated in SARS-CoV-2 replication and proofreading to ensure RNA synthesis fidelity. Evidence is presented that excess Mg2+ impairs Nsp13 helicase activity by dual mechanisms involving both allostery and ionic strength. In addition, using single-turnover reaction conditions, Nsp13 unwound partial duplex RNA substrates of increasing doublestranded regions (16-30 base pairs) with similar kinetic efficiency, suggesting the enzyme unwinds processively in this range under optimal reaction conditions. Furthermore, we determined that Nsp13 displayed sigmoidal behavior for helicase activity as a function of enzyme concentration, suggesting that functional cooperativity and oligomerization are important for optimal activity. The observed functional cooperativity of Nsp13 protomers suggests the essential coronavirus RNA helicase has roles in RNA processing events beyond its currently understood involvement in the SARS-CoV-2 replication-transcription complex (RTC), in which it was suggested that only one of the two Nsp13 subunits has a catalytic function, whereas the other has only a structural role in complex stability. Altogether, the intimate regulation of Nsp13 RNA helicase by divalent cation and protein oligomerization suggests drug targets for modulation of enzymatic activity that may prove useful for the development of novel anti-coronavirus therapeutic strategies. This work was supported by the Intramural Training Program, National Institute on Aging (NIA), NIH, and a Special COVID-19 Grant from the Office of the Scientific Director, NIA, NIH.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

COVID crisis, austerity and the ‘Left Behind' city: Exploring poverty and destitution in Stoke-on-Trent

Whilst the COVID-19 pandemic and ‘cost of living' crisis revealed and intensified the United Kingdom's (UK) socio-spatial inequalities, these crises did not emerge into a vacuum. Long-term trends of deindustrialisation and austerity have meant many places particularly the former industrial areas across the North and Midlands have been ‘left behind'. The current crises have exposed the structural fault-lines created by austerity across 2010/20 especially comprising significant cuts to welfare and local government services, with the outcome being sizable parts of the UK's post-industrial landscape experiencing poverty and destitution. In this paper, we focus upon deindustrialised Stoke-on-Trent in the North Midlands of England. Enduring long-term deindustrialisation and suffering from austerity, the article draws on qualitative and quantitative data to outline how the city contains a panoply of embedded structural problems including low-paid jobs, welfare retrenchment, poverty and destitution. Given it is a possibility that austerity will be reimposed after the next UK general election in December 2024, the paper concludes by briefly discussing the implications of these structural problems for UK government policy, indicating the urgent need for alternative policies to adequately address structural issues in places like Stoke. © The Author(s) 2023.

The SARS-CoV-2 Nsp13 Helicase Required for Coronavirus Replication Interacts with Structured Nucleic Acids in a Strand-Specific Manner and Catalyzes a Novel Protein-RNA Remodeling Activity Implicated in the Proofreading Mechanism of the Replication-Transc

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded, positive-sense RNA virus responsible for COVID-19, requires a set of virally encoded nonstructural proteins that compose a replication-transcription complex (RTC) to replicate its 30 kilobase genome. One such nonstructural protein within the RTC is Nsp13, a highly conserved molecular motor ATPase/helicase. Upon purification of the recombinant SARS-CoV-2 Nsp13 protein expressed using a eukaryotic cell-based system, we biochemically characterized the enzyme by examining its catalytic functions, nucleic acid substrate specificity, and putative protein-nucleic acid remodeling activity. We determined that Nsp13 preferentially interacts with single-stranded (ss) DNA compared to ssRNA during loading to unwind with greater efficiency a partial duplex helicase substrate. The binding affinity of Nsp13 to nucleic acid was confirmed through electrophoretic mobility shift assays (EMSA) by determining that Nsp13 binds to DNA substrates with significantly greater efficiency than RNA. These results demonstrate strand-specific interactions of SARS-CoV-2 Nsp13 that dictate its ability to load and unwind structured nucleic acid substrates. We next determined that Nsp13 catalyzed unwinding of double-stranded (ds) RNA forked duplexes on substrates containing a backbone disruption (neutrally charged polyglycol linker (PGL)) was strongly inhibited when the PGL was positioned in the 5' ssRNA overhang, suggesting an unwinding mechanism in which Nsp13 is strictly sensitive to perturbation of the translocating strand sugar-phosphate backbone integrity. Furthermore, we demonstrated for the first time the ability of the coronavirus Nsp13 helicase to disrupt a high-affinity nucleic acid-protein interaction, i.e., a streptavidin tetramer bound to biotinylated RNA or DNA substrate, in a uni-directional manner and with a preferential displacement of the streptavidin complex from biotinylated ssDNA versus ssRNA. In contrast to the poorly hydrolysable ATP-gamma-S or non-hydrolysable AMP-PNP, ATP supports Nsp13-catalyzed disruption of the nucleic acidprotein complex, suggesting that nucleotide binding by Nsp13 is not sufficient for protein-RNA disruption and the chemical energy of nucleoside triphosphate hydrolysis is required to fuel remodeling of protein bound to RNA or DNA. Our results build upon structural studies of the SARS-CoV-2 RTC in which it was suggested that Nsp13 pushes the RNA polymerase (Nsp12) backward on the template RNA strand. Experimental evidence from our studies demonstrate that Nsp13 helicase efficiently remodels a large high affinity protein-RNA complex in a manner dependent on its intrinsic ATP hydrolysis function. We proposed that this novel biochemical activity of Nsp13 is relevant to its role in SARS-CoV-2 RNA processing functions and replication. It was proposed that Nsp13 facilitates proofreading during coronavirus replication when a mismatched base is inadvertently incorporated into the SARS-CoV-2 genome during replication to reposition the RTC so that the proofreading nuclease complex (Nsp14-Nsp10) can gain access and remove the nascently synthesized nucleotide to ensure polymerase fidelity. Our findings implicate a direct catalytic role of Nsp13 in protein-RNA remodeling during coronavirus genome replication beyond its duplex strand separation or structural stabilization of the RTC, yielding new insight into the proofreading mechanism. This work was supported by the Intramural Training Program, National Institute on Aging (NIA), NIH, and a Special COVID-19 Grant from the Office of the Scientific Director, NIA, NIH.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Employment and mental health among UK ex-service personnel during the initial period of the COVID-19 pandemic

Introduction: The COVID-19 pandemic has interrupted participation in the labour force and may have affected mental health, both directly through the effects of illness and isolation and indirectly through negative effects on employment. Former military personnel may be at particular risk as a result of both additional exposure to risk factors for poor mental health and barriers to labour market participation raised by the transition from military to civilian working environments. This article examines furlough and unemployment as a result of the COVID-19 pandemic among UK working-age ex-service personnel and its associations with poor mental health. Methods: Participants from an existing cohort study of Iraq- and Afghanistan-era UK Armed Forces personnel were invited to provide information on employment before the COVID-19 pandemic and how it has changed since the pandemic. Mental health was measured using the General Health Questionnaire and compared with data collected pre-pandemic. Results: Although Veteran unemployment is not higher than civilian unemployment (4.7% and 4.8%, respectively, in September 2020), it rose during the pandemic from a lower level (1.3%). Part-time and self-employed Veterans were more likely than full-time employees to experience furlough or unemployment. A negative impact on employment was associated with the onset of new mental ill health. Discussion: Employment of ex-service personnel was more negatively affected by the COVID-19 pandemic, possibly because ex-service personnel are mostly men, and men were more affected in the UK general population. This employment instability has negative consequences for mental health that are not mitigated by furlough. LAY SUMMARYThis article examines how employment status changed for working-age UK ex-military personnel in the early period of the COVID-19 pandemic and how this relates to their mental health. Overall, the unemployment rate among ex-military personnel was not worse than that in the general population;however, because ex-military personnel generally have a lower unemployment rate than the general population, this suggests they were worse hit by the pandemic. Part-time and self-employed personnel were more likely to experience negative changes to their employment situation. Both becoming unemployed and being furloughed were correlated with negative changes in mental health. However, it should be noted that the mental health data used for this comparison predate the onset of the pandemic;hence, other factors related to both change in employment status and change in mental health could be the cause of this apparent relationship.

Volunteering behaviours among UK military Veterans during the COVID-19 pandemic and associations with health and well-being

LAY SUMMARYThe COVID-19 pandemic influenced ways in which individuals volunteered and created barriers for participation because of differing restrictions. The research assessing how Veterans volunteer is limited, but there may be aspects of military culture that encourage service to others. The authors investigated volunteering among UK Veterans during the COVID-19 pandemic and what factors made Veterans more or less likely to volunteer. The study found that 60% of Veterans had volunteered in the past 12 months, a level similar to that among the UK general population. Overall, Veterans volunteered more often through formal organizations rather than on an informal basis, such as helping individuals such as neighbours. However, in relative terms, levels of formal volunteering decreased and levels of informal volunteering increased during the pandemic. Veterans were more likely to volunteer if they were officers or to increase volunteering if they felt lonely. Veterans who reduced volunteering were more likely to have mental health problems. Understanding volunteering among Veterans may open up more opportunities for participation. Introduction: The COVID-19 pandemic facilitated new methods of and motivations for volunteering and created barriers to participation through social restrictions and lockdowns. The research assessing the volunteering behaviours of ex-service personnel (Veterans) is limited;however, as a group they may be more likely to volunteer because of aspects of military culture that encourage pro-social behaviours. The authors investigated levels of formal and informal volunteering among UK Veterans during the pandemic, factors associated with volunteering, and whether the pandemic affected Veterans' volunteering behaviours. Methods: An additional wave of data was collected from a longitudinal cohort study of the UK Armed Forces through an online survey conducted from June to September 2020. Participants were included if they had left the armed forces after regular service and were living in the United Kingdom. Invitation emails were sent to 3,547 Veterans, with a 44% response rate (N = 1,562). Results: Overall, 60% of Veterans reported volunteering in the past 12 months. Of those who volunteered, 41% reported formal volunteering, and 44% reported informal volunteering. Veterans reported reducing formal volunteering because of the pandemic (45%), but they also reported increasing informal volunteering (66%). Discussion: During the pandemic, UK Veterans volunteered at a level similar to the UK general population. They reported higher levels of formal volunteering and lower levels of informal volunteering compared with the UK general population. Understanding who among Veterans is likely to engage in volunteering could support future strategies to engage volunteers and open more opportunities for participation.

Can't Touch This: Rethinking Public Technology in a COVID-19 Era

What do pedestrian crossings, ATMs, elevators and ticket machines have in common? These are just a few of the ubiquitous yet essential elements of public-space infrastructure that rely on physical buttons or touchscreens;common interactions that, until recently, were considered perfectly safe to perform. This work investigates how we might integrate touchless technologies into public-space infrastructure in order to minimise physical interaction with shared devices in light of the ongoing COVID-19 pandemic. Drawing on an ethnographic exploration into how public utilities are being used, adapted or avoided, we developed and evaluated a suite of technology probes that can be either retrofitted into, or replace, these services. In-situ community deployments of our probes demonstrate strong uptake and provide insight into how hands-free technologies can be adapted and utilised for the public domain;and, in turn, used to inform the future of walk-up-and use public technologies.

Is Treating Post-Menopausal Women With Symptomatic Hand Osteoarthritis With Hormone Replacement Therapy Feasible?: Results From The Hope-E Randomised, Placebo-Controlled Feasibility Study

Purpose: Hand osteoarthritis (OA) is more common in women. Hand OA incidence increases further in females around the age of 50, the typical age of menopause. Estrogen-deficient states are associated with increased musculoskeletal pain and inflammation and with increased rates of symptomatic OA. Estrogen replacement and selective estrogen receptor modulators (SERMs) can improve pain and structure in some pre-clinical models of OA associated with estrogen loss, and in exploratory analysis from hormone replacement therapy (HRT) trials. However, no randomised clinical trials (RCTs) of HRT had been performed in symptomatic OA populations, specifically hand OA. By carrying out a RCT feasibility study of a form of HRT (conjugated estrogens (CE)-bazedoxifene) in post-menopausal women with painful hand OA, we set out to determine the feasibility and acceptability of this. We also aimed to generate proof-of concept data on likely outcomes, calculate a sample size and refine methods for a full trial. Method(s): We recruited females aged 40-65 years and 1-10 years after final menstrual period with definite hand OA and >=2 painful hand joints across three primary/secondary care sites and from the community. Medical exclusions included those typical for clinical HRT use. Design was parallel group, double-blind 1:1 randomisation of CE-bazedoxifene or placebo, taken orally once daily for 24 weeks, then tapering for 4 weeks before study end at Week 28. Primary feasibility outcomes were rates of eligible participant identification, recruitment, randomisation, retention, compliance, and likelihood of unblinding. Adverse events (AEs) were collected. Secondary clinical outcomes included the anticipated primary outcome in a full trial of mean hand pain over 14 days prior to each visit, scored on a 0-10 numerical rating scale (NRS) where 10 is worst pain possible, as well as hand function, appearance and menopause symptoms. Progression criteria to a full RCT were: (i) recruitment >=30 participants across all sites in 18 months (or proportionate to time open);(ii) a drop-out rate of <=30% of randomised individuals;and (iii) acceptability to the majority of participants, including acceptable AE rates. All clinical outcomes were analysed on an intention-to-treat basis. Though not powered to detect a treatment difference, change and treatment effects (the difference in the outcome between the two groups) were indicated with 95% CIs, with all models adjusted for clinical subtype of painful hand joint, study site, and baseline values. The sample size for a full trial was estimated using the standard deviation (SD) of week 24 mean hand pain. Result(s): Due to the COVID-19 pandemic, the recruitment window was reduced to 12-15 months. From May 2019 to December 2020, 434 enquiries/referrals were received. Of 96 telephone pre-screens, 35 individuals were potentially eligible and of these, 33 gave consent to participate. Of the remaining, 250/401 (62%) were ineligible, whilst 55/401 (14%) chose not to proceed, with the most common reason being not wanting to take HRT. 28/35 (80% (95%CI 63%,92%)) eligible participants were randomised to study medication. All 28 participants completed all follow-ups with high compliance (100% active, 13/14[93%] placebo) and outcome measure completeness (100%, mean hand pain). All three AE-related treatment withdrawals were on placebo when unblinded. No serious AEs occurred. Participants/investigators were well blinded (participant blinding index 0.50[95%CI 0.25 to 0.75]). All three prespecified progression criteria were therefore met for a full trial. The treatment effect difference over 24 weeks in mean hand pain between active and placebo was -0.71 (95% CI -2.20 to 0.78) (Fig 1A). During tapering/stopping medication, mean hand pain increased by 1.31 points in the active arm compared with 0.17 in the placebo arm, indicating a possible effect of cessation of medication (Fig 1A). Furthermore, 6/13 (46%) participants in the active group reported worsening pain at week 28 compared with week 24, but only 2/12 (17%) were worse on withdrawing placebo (Fig 1B). The sample size for a full trial was estimated as 296 (based on MCID 0.8 on NRS, SD 2.0, 90% power, 10% drop-out, alpha 5%). Conclusion(s): This first study of a RCT of HRT for painful hand OA met its progression criteria, indicating that a full trial of an HRT in this population is feasible and acceptable. Although not powered to detect an effect, there was a trend towards improvement in hand pain on treatment and worsening of hand pain on tapering in the active arm only. This adds to proof-of-concept data in this area, justifying more work.ISRCTN12196200. Funded by Research for Patient Benefit programme, National Institute for Health Research (UK) PB-PG-0416-20023 [Formula presented]Copyright © 2023

CRIRES+on sky at the ESO Very Large Telescope: Observing the Universe at infrared wavelengths and high spectral resolution

The CRyogenic InfraRed Echelle Spectrograph (CRIRES) Upgrade project CRIRES+ extended the capabilities of CRIRES. It transformed this VLT instrument into a cross-dispersed spectrograph to increase the wavelength range that is covered simultaneously by up to a factor of ten. In addition, a new detector focal plane array of three Hawaii 2RG detectors with a 5.3 μm cutoff wavelength replaced the existing detectors. Amongst many other improvements, a new spectropolarimetric unit was added and the calibration system has been enhanced. The instrument was installed at the VLT on Unit Telescope 3 at the beginning of 2020 and successfully commissioned and verified for science operations during 2021, partly remotely from Europe due to the COVID-19 pandemic. The instrument was subsequently offered to the community from October 2021 onwards. This article describes the performance and capabilities of the upgraded instrument and presents on sky results. © 2023 The Author(s).

A natural language processing system for national COVID-19 surveillance in the US Department of Veterans Affairs

Timely and accurate accounting of positive cases has been an important part of the response to the COVID-19 pandemic. While most positive cases within Veterans Affairs (VA) are identified through structured laboratory results, some patients are tested or diagnosed outside VA so their clinical status is documented only in free-text narratives. We developed a Natural Language Processing pipeline for identifying positively diagnosed COVID-19 patients and deployed this system to accelerate chart review. As part of the VA national response to COVID-19, this process identified 6,360 positive cases which did not have corresponding laboratory data. These cases accounted for 36.1% of total confirmed positive cases in VA to date. With available data, performance of the system is estimated as 82.4% precision and 94.2% recall. A public-facing implementation is released as open source and available to the community. © ACL 2020.All right reserved.

Hospitalizations for acute bronchiolitis in infants after relaxation of COVID-19 mitigation strategies in Brazil

Background: The coronavirus disease 2019 (COVID-19) pandemic led to daycare and school closures and children staying home for several months. The season of the respiratory viruses have been significantly changed. Aims and objectives: This study aims to assess the course of acute bronchiolitis in Brazil during the 2020-2021 season and compare them with the previous seasons. Method(s): Data from hospitalizations of acute bronchiolitis in infants <1 year were obtained from the Brazilian Public Health database for the period between 2016 and 2021. These data were also analyzed by Brazilian macroregions. The absolute and relative reductions were calculated by analyzing the yearly subsets: 2016-2019 vs 2020, 2016- 2019 vs 2021 and 2020 vs 2021. Result(s): A statiscally significant reduction was observed between 2016-2019 vs 2020, -76% (incidence rate ratio [IRR], 0.23 [95% confidence interval {CI},. 21-.25]) while a significant increase was observed between 2020 vs 2021 +55% (IRR, 0.44 [95% CI,. 40-.48]). Conclusion(s): More than a year into the COVID-19 pandemic, intensified infection control measures have controlled most viral respiratory infections in Brazil. From March to June 2021, however, an increasing number of hospitalizations for acute bronchiolitis were reported in Brazil. This resurgence have probably resulted from restarting social activities for children.

A review of South African sugarcane production in the 2021/22 season: climate, production and economics

This paper characterises South African sugarcane production for the 2021/22 milling season, from an agricultural perspective, to enable the industry to evaluate recent production strategies, and to identify priorities for improved efficiency. The industry's cane and sugar production during the 2021/22 season was 17.2 and 1.84 million tons, respectively. These figures show a marked drop of 5.6% for cane and 8.7% for sugar, when compared to the production figures for the 2020/21 season. The estimated industry average cane yield and quality also decreased slightly, compared to the previous season, but the main reason the drop in cane and sugar production was the limited milling capacity at several mills in KwaZulu-Natal. The civil unrest in July 2021 exacerbated the situation, causing disruptions to harvest and mill operations, as well as the subsequent closure of mills in parts of KwaZulu-Natal. The area harvested decreased considerably from an estimated 254 028 ha in 2020/21 to 241 030 ha in 2021/22 while estimated carry-over cane area increased from 24 029 ha to 32 476 ha over the same period. Rainfall was generally well above the long-term mean and well-distributed in most areas, while irrigation water supply also improved remarkably, compared to 2020 supply. Low temperatures and reduced sunshine duration caused yield reduction in the northern irrigated areas, but most rainfed areas experienced yield improvements when compared to 2020/21, because of the good rainfall. The Midlands region experienced severe frost damage during the winter of 2021, which had a negative impact on cane yield and quality. The Sugar Industry Value Chain Master Plan continued to help stabilise local sugar demand as well as reduce imports and exports at low world market prices, which all contributed to a 6% increase in the Recoverable Value (RV) price. This improved profitability for both largeand small-scale growers. COVID-19 had no noteworthy impact on sugarcane production.

36. Adolescent Mental Health and Big Tech: Investigating Policy Avenues to Regulate Harmful Social Media Algorithms

Purpose: Adolescents are using social media now more than ever, especially given the ongoing COVID-19 pandemic. A growing body of research demonstrates longitudinal associations between social media use and poor mental health outcomes among adolescents, including anxiety, suicidality, depression, poor body image, and eating disorders. One driving factor in the role of social media on mental health concerns is social media platforms' use of algorithms, which drive increasingly extreme content to vulnerable youth users over time;however, little is known about what specific policy action could be taken, and on what legal basis, to prevent the harms caused by social media to adolescents. The purpose of this study was to inform the development of practical, evidence-based policy strategies to regulate social media platforms' use of algorithms. Methods: We assembled a team of adolescent health researchers and legal scholars specializing in First Amendment law. Two separate narrative reviews were conducted to inform the legal research and summarize the evidence of the harms of social media on adolescents' (1) neurodevelopment (e.g., cognitive control, reward processing, neuronal activity);and (2) mental health (e.g., eating disorders, depression, cyberbullying). Legal scholars conducted reviews of federal and state legal precedent, with a focus on First Amendment rulings, to investigate avenues for the regulation of social media platforms' use of algorithms. Finally, the adolescent health and legal research teams conducted virtual consultations with stakeholders in business regulation, technology, and federal and state government, including state lawmakers and attorneys general, to inform the findings. Results: The findings of the narrative reviews highlight the significant harm posed to adolescents by social media algorithmic practices. Rigorous studies find that social media use poses negative effects for mental health (e.g., body dissatisfaction, anxiety, depression) among youth who exhibit high use in early adolescence, frequently use image-based platforms, and who are girls. Normal processes of brain development in mid adolescence may heighten vulnerability to exaggerated emotional responses to platform algorithmic practices, such as feeds that are tailored to user behavior and content that becomes increasingly extreme the longer a session continues. These harms provide justification for legal approaches to regulate social media platform practices and protect adolescent mental health. Furthermore, our legal research indicates that states rather than the federal government are more able and likely to adopt innovative and effective legal strategies that could survive constitutional scrutiny (i.e., the First Amendment). One policy innovation that holds the most promise to protect adolescent mental health would be for states to compel social media companies to conduct algorithm risk audits by objective third parties and publicly disclose the results. Algorithm risk audits are a promising avenue to mitigate the harms caused to adolescent mental health resulting from social media platform algorithms. Conclusions: Our legal analysis has generated viable policy recommendations and actions that state lawmakers and attorneys general can take to protect adolescents from the harms of dangerous social media algorithms. Sources of Support: This study was funded by the Becca Schmill Foundation.

‘Everybody is sick and there won't be a cure': The Power of Privileging U.S. Student Voices through COVID-19 Drawings

The COVID-19 pandemic and the subsequent lockdown was particularly challenging for elementary students who experienced disruptions in almost all aspects of their daily activities. Our study addressed a dearth of U.S. studies documenting the adverse effects the pandemic created and continues to have for children by analyzing their drawings. This study was conducted post-lockdown after students resumed normal school operations. The Mosaic Approach framed this case study research that was conducted using drawings created by sixteen students in grades prekindergarten through fifth grade (ages 4 to 10 years old). Students drew what came to mind when thinking of COVID-19. We conducted a content analysis of the data and determined four dominant themes: (1) symptoms related to COVID-19, (2) evidence of psychological or emotional responses, (3) health and safety precautions, and (4) depictions of the virus cell. We assert children's drawings as a useful tool for educators to create opportunities to connect with students and potentially reduce their anxieties about issues, including those beyond the pandemic. This will be of interest to educators who may not have considered the power of children's drawings as a means to provide voice about current issues. It will also add to the global knowledge base about children's perceptions of COVID-19 and the resulting lockdown. © 2022 Published by KURA Education & Publish-ing.

QEEG Individualized Protocols for the Treatment of Alcohol Use Disorder

Throughout United States history, alcohol use disorder (AUD) continues to be a national health concern. Within the last few years, pandemic stressors may also increase the potential for relapse in individuals struggling with AUD (Da et al., 2020). Medical professionals are imploring helping professionals to stay aware of this rising concern and to enhance AUD treatment options. Whereas treatments such as psychotherapy and pharmacology can be efficacious for AUD, there are also limitations to these types of interventions. AUD affects brain wave activity;while the prior mentioned treatments do not directly target brain activity, one treatment that does is neuron feed back. Neurofeed back is well documented for helping individuals with AUD, and other addiction concerns, to reach an enhanced state of regulation (Sokhadze et al., 2008). After IRB approval and participant recruitment, my supervisor and I created qEEG individualized protocols while also considering Peniston and Kulkosky's (1989, 1990) seminal neuron feed back studies that recommend certain brain wave parameters for AUD protocols. In addition, we also referred to the Scott-Kaiser modification (Scott & Kaiser, 1998) of the Peniston Protocol. The Peniston Protocol uses alpha/theta training and seeks to reduce states of stress and anxiety, while the Scott-Kaiser modification (e.g., SMR-beta modulation) aims to reduce impulsivity tendencies by remedying cognitive issues (Dousset et al., 2020). Participants were asked to complete pre and post qEEG and heart rate variability (HRV) measures along with self-report assessments of pre, post, and follow-up measures of the Alcohol Use Disorders Identification Test (AUDIT;Saunders et al., 1993), and repeated measures of a craving desire assessment after every neuron feed back session. Also, participants were asked to attend twice-weekly neuron feedback sessions for 6 weeks or at least twelve 10- to 25-minute sessions. University student clinicians and neuron feedback clinicians administered the neuron feedback sessions. Due to the pandemic and subsequent limiting factors (i.e., COVID concerns or lack of money for transportation), participants were allowed remote neuron feedback. Only one participant asked to utilize remote services. The primary purpose of this study was to determine if qEEG individualized neuron feedback protocols helped participants regulate their brain activity and reduce AUD cravings. Secondary purposes included comparing physiological data to self-report data and exploring neuron feedback session-to-session changes with a single-subject approach. This poster presentation will include pre and post qEEG z-score comparisons from NeuroGuide and pre and post HRV comparisons from BioTrace. Further, I will explore individual changes over time according to participants' neuron feedback protocols using single-case research design methods and participants' individual craving desire changes. The presentation will also entail implications for future research..

The Host Response to SARS-CoV-2 Infection Differs by Age

Background. Infection with SARS-CoV-2 and the resulting host immune response has been primarily characterized in middle and older aged populations due to a higher incidence of symptoms in these age groups. Due to reduced severity of disease, children were poorly studied and assumed to be less frequently infected compared to older age groups. We measured the viral load and adaptive immune response across the age-spectrum to define the age-dependent viral and host responses. Methods. From March 2020-March 2022, we enrolled individuals across the age spectrum who presented to U.S. military medical treatment facilities with COVID-19-like symptoms. In this longitudinal cohort study, demographic and clinical data were collected in addition to nasopharyngeal swabs and peripheral blood. Magnitude of viral RNA was measured by quantitative PCR (qPCR) from nasopharyngeal samples and SARS-CoV-2-specific IgG antibodies were measured from blood with multiplex microsphere immunoassays. Results. 4,768 SARS-CoV-2 positive participants were enrolled, among whom 42, 64, 89, 380, 948 and 245 individuals were in age brackets 0-4y, 5-11y, 12-17y, 18-44, 45-64y, and >65y, respectively. Viral load as measured by qPCR was determined to be similar across age groups within the first week post symptom onset. The magnitude of the IgG antibody response against the spike protein was also compared across age groups at early and convalescent time points and was higher in those over the age of 65 years. Conclusion. Early viral load during acute infection did not correlate with age in individuals who experienced COVID-19. These findings diverge from other respiratory viruses, such as respiratory syncytial virus and influenza where children tend to have higher viral loads. In contrast, the magnitude of the antibody response against the spike protein correlated with older age at acute and convalescent time points. Together our data suggest that the host response against SAR-CoV-2 differs with age and is not associated with the acute viral load. Defining age-dependent immunity against SARS-CoV-2 has the potential to identify key immunologic responses that can be used to optimize treatment and vaccine strategies.

Precision phenotyping of 'long COVID' through machine learning

Background. Characterizing, diagnosing, and caring for 'long COVID' patients has proven to be challenging due to heterogenous symptoms and broad definitions of these post-acute sequelae. Here, we take a machine learning approach to identify discrete clusters of long COVID symptoms which may define specific long COVID phenotypes. Figure 1: (A) Principal component analysis followed by K-means clustering identified three groups of participants. (B) Heatmap depicting three distinct clusters (high values are in red and low value are in blue);Cluster 1 exhibits sensory symptoms (e.g., loss of smell and/or taste), Cluster 2 exhibits fatigue and difficulty thinking (e.g., changes in ability to think) symptoms, and Cluster 3 exhibits difficulty breathing and exercise intolerance symptoms. (C) Clinical and demographic characteristics of 97 military health system beneficiaries by identified clusters Methods. The Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) study is a longitudinal COVID-19 cohort study with data and biospecimens collected from 10 military treatment facilities and online recruitment. Demographic and clinical characteristics were collected using case report forms and surveys completed at enrollment and at 1, 3, 6, 9, and 12 months. For this analysis, we identified those who reported any moderate to severe persistent symptoms on surveys collected 6-months post-COVID-19 symptom onset. Using the survey responses, we applied principal component analysis (PCA) followed by unsupervised machine learning clustering algorithm K-means to identify groups with distinct clusters of symptoms. Results. Of 1299 subjects with 6-month survey responses, 97 (7.47%) reported moderate to severe persistent symptoms. Among these subjects, three clusters were identified using PCA (Figure 1A). Cluster 1 is characterized by sensory symptoms (loss of taste and/or smell), Cluster 2 by fatigue and difficulty thinking, and Cluster 3 by difficulty breathing and exercise intolerance (Figure 1B). More than half of these subjects (57%) were female, 64% were 18-44 years old, and 64% had no comorbidities at enrollment (Figure 1C). Those in the sensory symptom cluster were all outpatients at the time of initial COVID-19 presentation (p < 0.01). The difficulty breathing and exercise intolerance symptom-clusters had a higher proportion of older participants (Age group >= 45-64) with more comorbidities (CCI >= 1-2). Conclusion. We identified three distinct 'long COVID' phenotypes among those with moderate to severe COVID-19 symptoms at 6-months post-symptom onset. With further validation and characterization, this framework may allow more precise classification of long COVID cases, and potentially improve the diagnosis, prognosis, and treatment of post- infectious sequelae.

Correlates of Omicron SARS-CoV-2 viral load: diagnostic and clinical implications

Background. Omicron SARS-CoV-2 infections are associated with less frequent olfactory sensory loss and a predominance of pharyngitis symptoms compared to prior variants, with proposed diagnostic implications. We examined whether such symptomology predicts a higher RNA abundance in the oropharynx. We further investigated how age, symptom-day, vaccination history and clinical severity correlate with viral load to inform clinical prognostication and transmission modeling. Methods. The EPICC study is a longitudinal cohort of COVID-19 cases enrolled through U.S military medical treatment facilities. Demographic and clinical characteristics were measured with interviews and surveys. Nasopharyngeal (NP), oropharyngeal (OP) and nasal swabs (NS) were collected for SARS-CoV-2 qPCR and sequence genotyping. Multivariable linear regression models were fit to estimate the effect of anatomical site on SARS-CoV-2 RNA abundance (a proxy for viral load), adjusting for sampling time, vaccine history and host age. Results. We analyzed 77 sequence-confirmed Omicron cases;no BA.2 cases were detected. The median age was 38.8 years. 81.8% were vaccinated and 15.6% cases were hospitalized. 80.0%, 21.8%, and 65.5% reported nasal congestion, loss of smell or taste, and sore throat, respectively. The median RNA abundance was lowest in OP swabs (p < 0.001) (Fig 1). Linear regression confirmed that OP sampling was associated with lower viral load (p < 0.001). We further noted that greater age and symptom-day were independent correlates of viral load (Table 1). By bivariate analysis there was a trend toward lower RNA abundance in vaccinated subjects (p = 0.35). RNA abundance (at any site) was substantially higher in hospitalized (10634 N2 genome equivalents [GE]/reaction) versus outpatient cases (1419 N1 GE/reaction) but this was not statistically significant (p = 0.26). Conclusion. We noted prevalent sore throat symptoms and infrequent sensory loss in Omicron cases. Despite this, viral load was highest in NP/NS collected swabs as has been noted in prior variants. We note an age correlation with RNA abundance, and provide a viral load decay rate which may be useful for transmission modeling. Vaccination and clinical severity may also correlate with Omicron viral load, as noted with prior SARS-CoV-2 variants.