COVID-19 booster vaccination uptake and infection breakthrough amongst health care workers in Wales: A national prospective cohort study br

Background: From September 2021, Health Care Workers (HCWs) in Wales began eceiving a COVID-19 booster vaccination. This is the first dose beyond the primary vaccination schedule. Given the emergence o. new variants, vaccine waning vaccine, and increasing vaccination hesitancy, there is a need to understand booster vaccine uptake and subsequent breakthrough in this high-risk population. Methods: We conducted a prospective, national-scale, observational cohort study of HCWs in Wales using anonymised, linked data from the SAIL Databank. We analysed uptake of COVID-19 booster vaccinations from September 2021 to Februari 2022, with comparisons against uptake of the initial primary vaccination schedule. We also analysed booster breakthrough, in the form of PCR-confirmed SARS-Cov-2 infection, comparing to the second primarJ dose. Cox proportional hazard models were used to estimate associations for vaccination uptake and breakthrough regarding staff roles, socio-demographics, household composition, and other factors. Results: We derived a cohort of 73,030 HCWs living in Wales (78% female, 60% 18-49 years old). Uptake was quickest amongst HCWs aged 60 + years old (aHR 2.54, 95%Cl 2.45-2.63), compared with those aged 18-29. Asian HCWs had quicker uptake (aHR 1.18, 95%Cl 1.14-1.22), whilst Black HCWs had slower uptake (aHR 0.67, 95%Cl 0.61-0.74), compared to white HCWs. HCWs residing in the least deprived areas were slightly quicker to have received a booster dose (aHR 1.12, 95%Cl 1.09-1.15), compared with those in the most deprived areas. Strongest associations with breakthrough infections were found for those living with children (aHR 1.52, 95%Cl 1.41-1.63), compared to two-adult only households. HCWs aged 60+ years old were less likely to get breakthrough infections, compared to those aged 18-29 (aHR 0.42,<br />95%CI 0.38-0.47). Conclusion: Vaccination uptake was consistently lower among black HCWs, as well as those from deprived areas. Whilst breakthrough infections were highest in households with children. creativecommons.org/licenses/by/4.0/).<br />(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license

Diverging Ozone Trends Above Western North America: Boundary Layer Decreases Versus Free Tropospheric Increases

This study has produced an improved percentile and seasonal (median) trend estimate of free tropospheric ozone above western North America (WNA), through a data fusion of ozonesonde, lidar, commercial aircraft, and field campaign measurements. Our method combines heterogeneous data sets according to the consensus data characteristics and inherent uncertainty in order to produce our best fused product. In response to different data collection environments (in situ or ground‐based), we investigate the ozone variability based on a wide range of percentiles, which is preferable for trend detection due to tropospheric ozone's high degree of heteroscedasticity (i.e., inconsistent trends and variability between different ozone percentiles). We then compare the ozone trends and variability above the California sub‐domain to the full WNA region for better understanding of the correlations between different regional scales. In California, the 1995–2021 percentile (from the 5th to 95th) and seasonal trends are clearly positive in terms of high signal‐to‐noise ratios. The magnitude of the trends is generally weaker over WNA compared to California, but reliable positive trends can still be found between the 10th and 70th percentiles, as well as winter and summer, whereas autumn shows a negative trend over the same period. In addition, dozens of rural surface sites across the region are selected to represent the boundary layer variability. In contrast to increasing free tropospheric ozone, we find overall strong negative surface trends since 1995, with the greatest divergence found in summer. Throughout the analysis implications of the COVID‐19 economic downturn on ozone variability are discussed.Alternate :Plain Language SummaryFree tropospheric ozone above western North America has increased since the mid‐1990s. Despite an observed drop of ozone in 2020 due to the COVID‐19 economic downturn, this observation‐based study shows the overall free tropospheric ozone trends have not been offset and continued to increase over 1995–2021, mainly driven by strong positive trends in winter and summer. In combination with the strong negative trends observed at rural surface sites over the same period, this study adds to the growing body of evidence that surface trends are frequently disconnected from the general increases observed in the free troposphere.

A long road to recovery? Reduced quality of life, impaired functional status and the lived experience of Long COVID patients, a cohort analysis

Introduction: One in ten people will develop symptoms of Long COVID (LC) following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite widely reported symptomology, the impact upon quality of life (QoL) and functional status (FS) is not well documented. Accordingly, we conducted a cohort observation to determine the impact of LC on QoL and FS that also captured the lived experience. Method(s): Fifty-six patients (n=41 female, mean age 51+/-10 years) with confirmed history of COVID-19 were recruited from LC clinics in the United Kingdom and completed a 16-week cohort observation (five face-to-face visits and biweekly telephone consultations). QoL was assessed via the EQ-5D-5L and FS via the post-COVID functional status scale (PCFS) and the six-minute walk test (6MWT). Symptom profile and lived experience was captured via selfreport diaries and analysed via thematic analysis. Result(s): QoL across all domains was 2.5+/-0.6 AU at baseline and unchanged at 16-weeks (2.4+/-0.9, P=0.12). PCFS was improved at 16-weeks (2.1 +/-1.1 AU) when compared to baseline (2.7+/-0.4 AU, P=0.02) but highlighted impaired FS. 6MWT was 322+/-133 M at baseline and improved at 16 weeks (430+/-150 meters, P<0.01) but was lower than normative data for healthy age matched controls. Patients recorded 2,197 references to symptoms profile (66% coverage), highlighting broad and cyclical symptoms that impacted QoL (30% coverage) and physical and mental wellbeing. Conclusion(s): LC patients exhibit severely impacted QoL and FS that demonstrates little change over 16 weeks. Research must inform treatment and support to address symptomology and restore QoL and FS.

T cell phenotypes in COVID-19 - a living review.

COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients' long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation.

Antibody Correlates of Protection for COVID-19 Convalescent Plasma Associated with Reduced Outpatient Hospitalizations (preprint)

SARS-CoV-2 antibody levels associated with reduced hospitalization risk remain undefined. Our outpatient COVID-19 convalescent plasma (CCP), placebo-controlled trial observed SARS-CoV-2 antibody levels decreasing 22-fold from matched donor units into post-transfusion seronegative recipients. Unvaccinated recipients were jointly stratified by a) early or late transfusion (< 5 or >5 days from symptom onset) and b) high or low post-transfusion SARS-CoV-2 antibody levels (< or > geometric mean). Early treatment with high post-transfusion antibody levels reduced hospitalization risk-0/102 (0%) compared to all other CCP recipients-17/370 (4.6%; Fisher exact-p-0.03) and to all control plasma recipients-35/461 (7.6%; Fisher exact p-0.001). A similar donor upper/lower half antibody level and early late transfusion stratified analyses indicated significant hospital risk reduction. Pre-transfusion nasal viral loads were similar in CCP and control recipients regardless of hospitalization outcome. Therapeutic CCP should comprise the upper 30% of donor antibody levels to provide effective outpatient use for immunocompromised and immunocompetent outpatients.

Early Treatment, Inflammation and Post-COVID Conditions (preprint)

ABSTRACT Background: Post-COVID conditions (PCC) are common and have significant morbidity. Risk factors for PCC include advancing age, female sex, obesity, and diabetes mellitus. Little is known about early treatment, inflammation, and PCC. Methods: Among 883 individuals with confirmed SARS-CoV-2 infection participating in a randomized trial of CCP vs. control plasma with available biospecimens and symptom data, the association between early COVID treatment, cytokine levels and PCC was evaluated. Cytokine and chemokine levels were assessed at baseline, day 14 and day 90 using a multiplexed sandwich immuosassay (Mesoscale Discovery). Presence of any self-reported PCC symptoms was assessed at day 90. Associations between COVID treatment, cytokine levels and PCC were examined using multivariate logistic regression models. Results: One-third of the 882 participants had day 90 PCC symptoms, with fatigue (14.5%) and loss of smell (14.5%) being most common. Cytokine levels decreased from baseline to day 90. In a multivariable analysis including diabetes, body mass index, race, and vaccine status, female sex (adjusted odds ratio[AOR]=2.70[1.93-3.81]), older age (AOR=1.32[1.17-1.50]), and elevated baseline levels of IL-6 (AOR=1.59[1.02-2.47]) were associated with development of PCC. There was a trend for decreased PCC in those with early CCP treatment (<5 days after symptom onset) compared to late CCP treatment. Conclusion: Increased IL-6 levels were associated with the development of PCC and there was a trend for decreased PCC with early CCP treatment in this predominately unvaccinated population. Future treatment studies should evaluate the effect of early treatment and anti-IL-6 therapies on PCC development.

Pancreas and islet transplantation in the United Kingdom during the COVID-19 era

Introduction: WHO declared a pandemic of COVID-19 in March 2020. This study analyses the impact of COVID-19 on beta-cell replacement therapy in the UK. Method(s): Pancreas and islet donation and transplant activity in the period March 2020/2021 was compared with the same period the previous year. Result(s): 2,180 patients had a functioning graft during March 2020/2021. 5.8%(n=126) tested positive for COVID-19 and two died (1%). In this period there was a 43% reduction in solid organ donors n=1,615, compared with the previous year, n=2,840. Of the 625 solid organ donors with a pancreas offered, 32% had the pancreas retrieved compared with 51% the previous period. 97 whole pancreas and islet transplants were performed in the UK down 54% from the prior period. Of the 84 pancreas transplant recipients;four tested positive for COVID-19 but none died, and two grafts failed within the first week from vascular thrombosis (neither were COVID-19 positive). Of the 13 SIK and islet alone transplant recipients, two tested positive for COVID-19 but neither died. Of these SIK transplants, one is known to have failed within a month and this is equivalent to that seen in the previous time period. To our knowledge, no patient receiving beta cell replacement therapy died of COVID during the first year of the pandemic despite immunosuppression. Conclusion(s): In the UK, pancreas, and islet transplantation have continued during the pandemic at a lower rate. Outcomes following transplantation within the COVID era are, so far, similar to those in the period prior. Take-home message: Outcomes following transplantation within the COVID era are, so far, similar to those in the period prior.

Reduced respiratory muscle strength, lung function, and functional status and symptomology in patients referred to Long COVID clinics, an observational cohort analysis

IntroductionOne in ten people will develop Long COVID (LC) following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite broad-ranging and episodic symptomology, there are no data that demonstrate changes in functional status (FS), respiratory muscle strength and lung function over time. We conducted a sixteen-week cohort observation of LC patients to determine changes in FS, respiratory muscle strength and lung function.MethodSixty-six patients (n=48 females, mean age 51 ± 10 years, n=8 hospitalised, mean time post-infection 6.2 ± 1.8 months) were recruited from LC clinics in the United Kingdom (CPMS ID: 52331). Patients completed five face-to-face visits (day 0, 28, 56, 84 and 110 ± 3 days) and bi-weekly telephone consultations (day 14, 42, 70 and 98 ± 3 days). FS was assessed via the post-COVID functional status scale (PCFS) and the six-minute walk test (6MWT). Maximum inspiratory (MIP) and expiratory (MEP) respiratory muscle pressure and lung function (forced vital capacity (FVC) and forced expired volume in one second (FEV1) were assessed during face-to-face visits according to published standards.ResultsPCFS was 2.7 ± 0.4 AU, P=0.02 at baseline and improved at 16-weeks (2.1 ±1.1 AU) and still highlighted impaired FS. 6MWT was 322 ± 133 meters at baseline and improved at 16 weeks (430 ± 150 meters, P<0.01) but remained lower than normative values for healthy age-matched controls. MIP was 77 ± 21 cmH2O at baseline (86% predicted) and was unchanged post 16 weeks (88 ± 25 cmH2O, 92% predicted, P>0.05). Baseline MEP was 115 ± 41 cmH2O (96% and was unchanged post-16-weeks (119 ± 48 cmH2O, 92% predicted, P>0.05). Lung function data were below predicted values and unchanged over 16 weeks (baseline FVC: 3.10 ± 0.53 L.s-1, 72% predicted, post 16 weeks: 3.16 ± 0.34 L.s-1, 73% predicted, P>0.05 and baseline FEV1: 2.68 ± 0.39 L.s-1, 85% predicted, post 16 weeks: 2.75 ± 0.36 L.s-1, 85% predicted).ConclusionLC patients demonstrate reduced respiratory muscle strength and lung function which could be associated with reduced FS and should be addressed via specific rehabilitation approaches.Please refer to page A216 for declarations of interest related to this .

HOSPICE EDUCATION LEARNING PARTNERSHIP - HELP IN THE TIME OF COVID-19

St Christopher's Hospice and Greenwich and Bexley Community Hospice established HELP in 2019 to respond to the learning needs of end-of-life care professionals in South East London. This already successful partnership was mobilised during the pandemic to meet the demands of the clinicians asthey dealt with the significant increase in people dying from COVID-19 and this poster explores the themes that emerged by undertaking this work. Initially a whole scale digital pivot was required as the pandemic hit: moving all existing education activity online utilising tools such as Zoom for live teaching and providing asynchronous, self-study opportunities using an online learning platform to ensure professionals could continue to be upskilled during this time. An innovative example of this was the development of a fully asynchronous product on Nurse Verification of Expected Death, a clinical need that grew exponentially during this time. The HELP team provided two bespoke webinar series, which responded to clinical needs and was developed in collaboration with a range of clinicians who were able to provide case studies and examples to secure the learning. The first webinar series in April 2020 focused on two distinct areas, supporting GPs and supporting colleagues in care homes. The team provided weekly care homes webinars and additional ECHO sessions for them. The positive feedback received resulted in further consultation to design the second wave webinar series in November which was open to all professionals in the region and included topics continuing the conversation around wellbeing along with the opportunity to contextualise dying during COVID-19 and highlighting the value of joint working during this difficult time. This poster explores this range of activities that were undertaken during the pandemic and focuses specifically on the values that underpin the approach including the need to be responsive and flexible, collaborative, current and contextspecific in the design of these learning opportunities.

Post-acute COVID syndrome (long COVID): What should radiographers know and the potential impact for imaging services.

OBJECTIVES: The COVID-19 pandemic caused an unprecedented health crisis resulting in over 6 million deaths worldwide, a figure, which continues to grow. In addition to the excess mortality, there are individuals who recovered from the acute stages, but suffered long-term changes in their health post COVID-19, commonly referred to as long COVID. It is estimated there are currently 1.8 million long COVID sufferers by May 2022 in the UK alone. The aim of this narrative literature review is to explore the signs, symptoms and diagnosis of long COVID and the potential impact on imaging services. KEY FINDINGS: Long COVID is estimated to occur in 9.5% of those with two doses of vaccination and 14.6% if those with a single dose or no vaccination. Long COVID is defined by ongoing symptoms lasting for 12 or more weeks post acute infection. Symptoms are associated with reductions in the quality of daily life and may involve multisystem manifestations or present as a single symptom. CONCLUSION: The full impact of long COVID on imaging services is yet to be realised, but there is likely to be significant increased demand for imaging, particularly in CT for the assessment of lung disease. Educators will need to include aspects related to long COVID pathophysiology and imaging presentations in curricula, underpinned by the rapidly evolving evidence base. IMPLICATIONS FOR PRACTICE: Symptoms relating to long COVID are likely to become a common reason for imaging, with a particular burden on Computed Tomography services. Planning, education and updating protocols in line with a rapidly emerging evidence base is going to be essential.

Differential antibody production by symptomatology in SARS-CoV-2 convalescent individuals.

The association between COVID-19 symptoms and antibody responses against SARS-CoV-2 is poorly characterized. We analyzed antibody levels in individuals with known SARS-CoV-2 infection to identify potential antibody-symptom associations. Convalescent plasma from 216 SARS-CoV-2 RNA+ individuals with symptomatology information were tested for the presence of IgG to the spike S1 subunit (Euroimmun ELISA), IgG to receptor binding domain (RBD, CoronaCHEK rapid test), and for IgG, IgA, and IgM to nucleocapsid (N, Bio-Rad ELISA). Logistic regression was used to estimate the odds of having a COVID-19 symptom from the antibody response, adjusting for sex and age. Cough strongly associated with antibodies against S1 (adjusted odds ratio [aOR] = 5.33; 95% CI from 1.51 to 18.86) and RBD (aOR = 4.36; CI 1.49, 12.78). In contrast, sore throat significantly associated with the absence of antibodies to S1 and N (aOR = 0.25; CI 0.08, 0.80 and aOR = 0.31; 0.11, 0.91). Similarly, lack of symptoms associated with the absence of antibodies to N and RBD (aOR = 0.16; CI 0.03, 0.97 and aOR = 0.16; CI 0.03, 1.01). Cough appeared to be correlated with a seropositive result, suggesting that SARS-CoV-2 infected individuals exhibiting lower respiratory symptoms generate a robust antibody response. Conversely, those without symptoms or limited to a sore throat while infected with SARS-CoV-2 were likely to lack a detectable antibody response. These findings strongly support the notion that severity of infection correlates with robust antibody response.

DEVELOPMENT of A HIGH-THROUGHPUT NGS WORKFLOW for SARS-CoV-2 WHOLE-GENOME SEQUENCING

Background: Monitoring new mutations in SARS-CoV-2 is crucial for identifying diagnostic and therapeutic targets and important insights to achieve a more effective COVID-19 control strategy. Next-generation sequencing (NGS) has been widely used for whole-genome sequencing of SARS-CoV-2. However, NGS methods may be limited by the complexity of workflow, which limits scalability. Here, we address this limitation by designing a workflow optimized for high-throughput studies. Methods: We utilized modified ARTIC network v3 primers for SARS-CoV-2 whole-genome amplification. Similar to a previously reported tailed PCR approach, libraries were prepared by a 2-step PCR method but optimized to improve amplicon balance, integrate robotic liquid handlers, and minimize amplicon dropout for viral genomes harboring primer-binding site mutation(s). Sequencing was performed on the Illumina NovaSeq 6000 and the Illumina MiSeq. An in-house analysis pipeline utilized the BWA aligner and iVar software. Assay precision was assessed with unique clinical samples. Assay sensitivity was assessed with serial dilutions of clinical samples. Robustness was assessed by sequencing samples and controls on the NovaSeq from multiple prior ARTIC v3 runs. Results: Intra-assay (n=188) and inter-assay (n=168) precision at the amino acid substitution level was 99.8% and 99.5%, respectively. Over 98.2% (111/113) of samples with a cycle threshold (Ct) <28 yielded a near-complete (≥97%) consensus sequence, and 98.7% (147/149) of samples with a Ct <30 yielded ≥90% consensus coverage. 2,688 samples and controls were sequenced in a single NovaSeq run yielding a 94.3% (2,416/2,562) sample pass rate. The optimized workflow gave more complete SARS-CoV-2 genome consensus sequences for most viral clades than the original ARTIC v3 workflow (Table). From over 65,000 clinical samples sequenced in 2021, we observed clade and lineage prevalence in-line with those documented by the CDC in 2021, including the Alpha clade that peaked at 65.3% in May, and the Delta clade that attained near-100% prevalence in September. Conclusion: We present an optimized workflow to process up to 2,688 samples in a single NovaSeq 6000 run without compromising sensitivity or robustness and with fewer amplicon dropout events compared to the standard ARTIC protocol. We additionally report results for over 65,000 SARS-CoV-2 clinical specimens collected in the United States between January and September of 2021, as part of an ongoing national genomics surveillance effort.

Impact of the COVID‐19 Economic Downturn on Tropospheric Ozone Trends: An Uncertainty Weighted Data Synthesis for Quantifying Regional Anomalies Above Western North America and Europe

This study quantifies the association between the COVID‐19 economic downturn and 2020 tropospheric ozone anomalies above Europe and western North America, and their impact on long‐term trends. Anomaly detection for an atmospheric time series is usually carried out by identifying potentially aberrant data points relative to climatological values. However, detecting ozone anomalies from sparsely sampled ozonesonde profiles (once per week at most sites) is challenging due to ozone's high temporal variability. We first demonstrate the challenges for summarizing regional trends based on independent time series from multiple nearby ozone profiling stations. We then propose a novel regional‐scale anomaly detection framework based on generalized additive mixed models, which accounts for the sampling frequency and inherent data uncertainty associated with each vertical profile data set, measured by ozonesondes, lidar or commercial aircraft. This method produces a long‐term monthly time series with high vertical resolution that reports ozone anomalies from the surface to the middle‐stratosphere under a unified framework, which can be used to quantify the regional‐scale ozone anomalies during the COVID‐19 economic downturn. By incorporating extensive commercial aircraft data and frequently sampled ozonesonde profiles above Europe, we show that the complex interannual variability of ozone can be adequately captured by our modeling approach. The results show that free tropospheric ozone negative anomalies in 2020 are the most profound since the benchmark year of 1994 for both Europe and western North America, and positive trends over 1994–2019 are diminished in both regions by the 2020 anomalies. Key Points 2020 is the only year that both Europe and western North America show strong negative tropospheric ozone anomalies since 1994 Positive free tropospheric ozone trends above Europe and western North America since 1994 are diminished by the 2020 anomalies Data integration of multiple time series provides a better understanding of ozone variability compared to individual records

Mental health of people with multiple sclerosis during the COVID-19 outbreak: A prospective cohort and cross-sectional case-control study of the UK MS Register.

BACKGROUND: People with MS (pwMS) have had higher rates of anxiety and depression than the general population before the COVID-19 pandemic, placing them at higher risk of experiencing poor psychological wellbeing during the pandemic. OBJECTIVE: To assess mental health and its social/lifestyle determinants in pwMS during the first wave of the outbreak in the United Kingdom. METHODS: This is a community-based, prospective longitudinal cohort and cross-sectional case-control online questionnaire study. It includes 2010 pwMS from the UK MS Register and 380 people without MS. RESULTS: The Hospital Anxiety and Depression Scale scores of pwMS for anxiety and depression during the outbreak did not change from the previous year. PwMS were more likely to have anxiety (using General Anxiety Disorder-7) and/or depression (using Patient Health Questionnaire-9) than controls during the outbreak (OR: 2.14, 95% CI: 1.58-2.91). PwMS felt lonelier (OR: 1.37, 95% CI: 1.04-1.80) reported worse social support (OR: 1.90, 95% CI: 1.18-3.07) and reported worsened exercise habits (OR: 1.65, 95% CI: 1.18-2.32) during the outbreak than controls. CONCLUSION: Early in the pandemic, pwMS remained at higher risk of experiencing anxiety and depression than the general population. It is important that multidisciplinary teams improve their support for the wellbeing of pwMS, who are vulnerable to the negative effects of the pandemic on their lifestyle and social support.

Neutrophilia, lymphopenia and myeloid dysfunction: a living review of the quantitative changes to innate and adaptive immune cells which define COVID-19 pathology.

Destabilization of balanced immune cell numbers and frequencies is a common feature of viral infections. This occurs due to, and further enhances, viral immune evasion and survival. Since the discovery of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), which manifests in coronavirus disease 2019 (COVID-19), a great number of studies have described the association between this virus and pathologically increased or decreased immune cell counts. In this review, we consider the absolute and relative changes to innate and adaptive immune cell numbers, in COVID-19. In severe disease particularly, neutrophils are increased, which can lead to inflammation and tissue damage. Dysregulation of other granulocytes, basophils and eosinophils represents an unusual COVID-19 phenomenon. Contrastingly, the impact on the different types of monocytes leans more strongly to an altered phenotype, e.g. HLA-DR expression, rather than numerical changes. However, it is the adaptive immune response that bears the most profound impact of SARS-CoV-2 infection. T cell lymphopenia correlates with increased risk of intensive care unit admission and death; therefore, this parameter is particularly important for clinical decision-making. Mild and severe diseases differ in the rate of immune cell counts returning to normal levels post disease. Tracking the recovery trajectories of various immune cell counts may also have implications for long-term COVID-19 monitoring. This review represents a snapshot of our current knowledge, showing that much has been achieved in a short period of time. Alterations in counts of distinct immune cells represent an accessible metric to inform patient care decisions or predict disease outcomes.

Orthopedic Surgery in Ambulatory Surgery Centers During the COVID-19 Pandemic: Low Incidence of Infection Among Patients, Surgeons, and Staff.

Background and objective The coronavirus disease 2019 (COVID-19) pandemic has presented tremendous challenges to the healthcare systems worldwide. Consequently, ambulatory surgery centers (ASCs) have been forced to find new and innovative ways to function safely and maintain operations. We conducted a study at a large United States (US) private orthopedic surgery practice, where a universal screening policy and testing protocol for COVID-19 was implemented for patients and ASC personnel including surgeons, in order to examine the incidence of COVID-19 in patients scheduled for orthopedic surgery in ASC settings as well as the incidence among the surgeons and ASC personnel. Methods The universal screening protocol was implemented in the ASCs of the facility during the early stage of the pandemic for an eight-month period from April 28, 2020, to December 31, 2020. All ASC personnel including surgeons had their symptoms tracked daily and were rapid-tested every two weeks. All patients were screened and tested before they entered the ASC. Results A total of 70 out of 12,115 patients and 41 out of 642 ASC personnel tested positive for COVID-19, resulting in infection rates of 0.6% and 6.4%, respectively. Individual symptoms, age, the American Society of Anesthesiologists (ASA) scores, and comorbidities were documented, and no single factor was found to be common among positive (+) tests. Conclusions The implementation of universal screening and symptom-reporting procedures was associated with a very low rate of infections among ASC patients, staff, and surgeons, and it offers a reproducible framework for other facilities to continue to provide orthopedic outpatient operations in ASC settings during the ongoing iterations of the COVID-19 pandemic.

Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Seroprevalence in Decedents Undergoing Forensic Postmortem Examination: Feasibility for Real-Time Pandemic Surveillance.

Background: Population-based seroprevalence studies offer comprehensive characterization of coronavirus disease 2019 (COVID-19) spread, but barriers exist and marginalized populations may not be captured. We assessed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody seroprevalence among decedents in Maryland over 6 months in 2020. Methods: Data were collected on decedents undergoing forensic postmortem examination in Maryland from 24 May through 30 November 2020 from whom a blood specimen could be collected. Those with available blood specimens were tested with the CoronaCHEK lateral flow antibody assay. We assessed monthly seroprevalence compared to the statewide estimated number of cases and proportion of positive test results (testing positivity). We used Poisson regression with robust variance to estimate adjusted prevalence ratios (aPRs) with 95% confidence intervals (CIs) for associations of demographic characteristics, homelessness, and manner of death with SARS-CoV-2 antibodies. Results: Among 1906 decedents, 305 (16%) were positive for SARS-CoV-2 antibodies. Monthly seroprevalence increased from 11% to 22% over time and was consistently higher than state-level estimates of testing positivity. Hispanic ethnicity was associated with 2- to 3.2-fold higher seropositivity (P < .05) irrespective of sex. Deaths due to motor vehicle crash were associated with 62% increased seropositivity (aPR, 1.62 [95% CI, 1.15-2.28]) vs natural manner of death. Though seroprevalence was lower in decedents of illicit drug overdose vs nonoverdose in early months, this shifted, and seroprevalence was comparable by November 2020. Conclusions: Decedents undergoing forensic postmortem examination, especially those dying due to motor vehicle trauma, may be a sentinel population for COVID-19 spread in the general population and merits exploration in other states/regions.

Differential antibody production by symptomatology in SARS-CoV-2 convalescent individuals (preprint)

The association between COVID-19 symptoms and antibody responses against SARS-CoV-2 is poorly characterized. We analyzed antibody levels in individuals with known SARS-CoV-2 infection to identify potential antibody-symptom associations. Convalescent plasma from 216 SARS-CoV-2 RNA+ individuals with symptomatology information were tested for the presence of IgG to the spike S1 subunit (Euroimmun ELISA), IgG to receptor binding domain (RBD, CoronaCHEK rapid test), and for IgG, IgA, and IgM to nucleocapsid (N, Bio-Rad ELISA). Logistic regression was used to estimate the odds of having a COVID-19 symptom from the antibody response, adjusting for sex and age. Cough strongly associated with antibodies against S1 (adjusted odds ratio [aOR]= 5.33; 95% CI from 1.51 to 18.86) and RBD (aOR=4.36; CI 1.49, 12.78). In contrast, sore throat significantly associated with the absence of antibodies to S1 and N (aOR=0.25; CI 0.08, 0.80 and aOR=0.31; 0.11, 0.91). Similarly, lack of symptoms associated with the absence of antibodies to N and RBD (aOR=0.16; CI 0.03, 0.97 and aOR=0.16; CI 0.03, 1.01). Cough appeared to be correlated with a seropositive result, suggesting that SARS-CoV-2 infected individuals exhibiting lower respiratory symptoms generate a robust antibody response. Conversely, those without symptoms or limited to a sore throat while infected with SARS-CoV-2 were likely to lack a detectable antibody response. These findings strongly support the notion that severity of infection correlates with robust antibody response.

Evaluating student attitudes and learning at remote collegiate soil judging events

As with many aspects of teaching, the COVID-19 pandemic forced soil judging teams to attempt new strategies towards achieving student learning outcomes. Soil judging Regions IV and V hosted remote regional contests in October 2020 in place of traditional, in-person contests typically held each fall. We conducted pre- and post-contest surveys to assess student learning outcomes, attitudes, and reflections on the remote contest experience compared to past, in-person contest experiences. We received 108 total responses from students who participated in the Region IV and Region V remote soil judging contests (>80% response rate). In self-reported learning outcomes, there were no significant gains post-contest and there were minimal differences between students in Regions IV and V. Female students, students with more soil judging experience, and students who had taken more soil science courses agreed more strongly that soil science is important, that they planned to pursue careers in soil science, and that they gained important skills from soil judging. Finally, students who previously participated in contests reported that they gained more knowledge and enjoyed in-person contests more than the remote contests held in Fall 2020. Thus, while it is possible to replicate some aspects of the soil judging experience in a remote contest, other aspects that are critical to student engagement are lost when teams are unable to gather at the contest location and examine soils in the field. © 2021 The Authors. Natural Sciences Education published by Wiley Periodicals LLC on behalf of American Society of Agronomy

Fitness, a UK Myeloma Research Alliance (UK-MRA) Frailty-Adjusted Therapy Study, Supports the Feasibility of Recruiting Frail Newly Diagnosed Myeloma Patients to Large Clinical Trials

Background Although the median age of patients with newly diagnosed multiple myeloma (MM) is 70-74 years, recruitment of frail older patients to clinical trials is poor. The International Myeloma Working Group (IMWG) frailty score predicts survival, adverse events and treatment tolerability using age, the Katz Activity of Daily Living, the Lawton Instrumental Activity of Daily Living, and the Charlson Comorbidity Index, rather than age alone. Despite IMWG score prognostic biomarker capability, to date no evidence exists of its predictive biomarker potential. The UK-MRA Myeloma Risk Profile (MRP) has also been shown in both clinical trial and real-world populations to be a prognostic biomarker in transplant ineligible patients but prospective comparisons of the two scores have not been previously conducted. Study Design/Methods The FiTNEss trial (Myeloma XIV, NCT03720041, Figure 1A) is a UK-MRA phase III, multi-centre, randomised controlled trial for newly diagnosed MM patients not suitable for stem cell transplant. The primary objectives are 1) to compare early treatment cessation (<60 days from randomisation) between patients randomised to standard (reactive) and frailty-adjusted (adaptive, based on IMWG score) induction therapy delivery with the triplet ixazomib, lenalidomide and dexamethasone (IRd) 2) to compare progression free survival for maintenance lenalidomide plus placebo (R) and lenalidomide plus ixazomib (IR). The FiTNEss trial is designed as an all-comers study with few exclusion criteria other than necessary for safety including some haematological and biochemical parameters, but there is no exclusion based on renal function. Patients with grade 2 or greater baseline peripheral neuropathy, current systemic infection or recent surgery or other cancer are excluded. Here we report the demographics for the first patients recruited, including IMWG frailty assessments and MRP to demonstrate the feasibility of recruiting frail patients to randomised phase III clinical trials. Results The FiTNEss trial opened on 04/08/2020 during the second wave of the COVID-19 pandemic in the UK. At the time of data cut off (14/07/2021) recruitment is active at 84 sites, with 180 patients randomised. Baseline characteristics for the randomised patients are shown in Figure 1B. The median age of patients is 77 years (range 64, 93) with 36.1% aged 76-80 and 26.1% over 80. In keeping with the older patient population 26.6% have an ECOG performance status of 2 or 3 and 31.7% ISS stage III. The IMWG frailty classification at baseline is FIT 43/180 (23.9%), UNFIT 53/180 (29.4%) and FRAIL 84/180 (46.7%). The effect of using age groups on the definition of patient frailty was explored. The IMWG frailty score defines all patients over 80 as FRAIL whilst an age of 76-80 contributes one point to the score. An analysis of patients' frailty was repeated with the contribution of age removed. For those aged over 80 years (n=47, 100% FRAIL) we found that 20 (42.6%) would have been re-classified as FIT and 18 (38.3%) as UNFIT, with only 9 (19.2%) retaining the FRAIL category. For those aged 76-80 (n=65, 53.8% UNFIT, 46.2% FRAIL) all 35 patients previously classified as UNFIT became FIT (53.8%) whilst 19 (29.2%) classed as FRAIL became UNFIT with 11 (16.9%) remaining FRAIL. The MRP classification, using age as a continuous variable, was Low-risk 45/180 (25.0%), Medium-risk 46/180 (25.6%), High-risk 75/180 (41.7%) and not available for 14/180 (7.8%) patients. Concordance between the IMWG frailty score and the MRP occurred in 48.9% of patients (88/180). 37.2% of FIT patients were classified as MRP Low-risk, 32.1% of UNFIT patients as MRP Medium-risk and 65.5% of FRAIL patients as MRP High-risk. Discussion The FiTNEss trial demonstrates the feasibility of recruiting older, less fit patients to clinical trials. Recruitment of patients classified as FRAIL was very high despite the COVID pandemic, likely due to the all-oral nature of the regimen under investigation enabling patients to avoid attendance at hospital day units for treatment and associa ed exposure risk. In the population recruited to date we found age to be a key contributor to the FRAIL category of the IMWG frailty score. Concordance between IMWG frailty score and MRP was highest in FRAIL/High-risk patients. The first interim analysis of the primary objectives is planned when 50% of required participants for R1 have reached 60 days post R1, which is anticipated in Q2 of 2022. [Formula presented] Disclosures: Cook: Amgen: Consultancy, Honoraria, Research Funding;BMS: Consultancy, Honoraria, Research Funding;Sanofi: Consultancy, Honoraria;Karyopharm: Consultancy, Honoraria;Roche: Consultancy, Honoraria;Pfizer: Consultancy, Honoraria;Oncopeptides: Consultancy, Honoraria;Takeda: Consultancy, Honoraria, Research Funding;Janssen: Consultancy, Honoraria, Research Funding. Pawlyn: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees;Celgene / BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Honoraria. Royle: BMS: Research Funding;Merck Sharpe and Dohme: Research Funding;Amgen: Research Funding;Takeda: Research Funding. Coulson: BMS / Celgene: Honoraria;Merck Sharpe and Dohme: Research Funding;Amgen: Research Funding;Takeda: Research Funding. Jenner: BMS/Celgene: Consultancy, Honoraria, Speakers Bureau;Janssen: Consultancy, Honoraria, Speakers Bureau;Pfizer: Consultancy;Takeda: Consultancy. Kishore: Sanofi: Other: Attending fees;Celgene: Other: Attending fees;Takeda: Other: Attending fees;Jannsen: Other: Attending fees. Rabin: BMS / Celgene: Consultancy, Honoraria, Other: Travel support for meetings;Takeda: Consultancy, Honoraria, Other: Travel support for meetings;Janssen: Consultancy, Honoraria, Other: Travel support for meetings. Best: BMS/Celgene: Research Funding;Merck Sharpe and Dohme: Research Funding;Amgen: Research Funding;Takeda: Research Funding. Gillson: BMS / Celgene: Research Funding;Meck Sharpe and Dohme: Research Funding;Amgen: Research Funding;Takeda: Research Funding. Henderson: Takeda: Research Funding;Amgen: Research Funding;Merck Sharpe and Dohme: Research Funding;BMS / Celgene: Research Funding. Olivier: Merck Sharpe and Dohme: Research Funding;Takeda: Research Funding;Amgen: Research Funding;Celgene / BMS: Research Funding. Kaiser: AbbVie: Consultancy;GSK: Consultancy;Karyopharm: Consultancy, Research Funding;Pfizer: Consultancy;Amgen: Honoraria;Seattle Genetics: Consultancy;Takeda: Consultancy, Other: Educational support;Janssen: Consultancy, Other: Educational support, Research Funding;BMS/Celgene: Consultancy, Other: Travel support, Research Funding. Drayson: Abingdon Health: Current holder of individual stocks in a privately-held company. Jones: Janssen: Honoraria;BMS/Celgene: Other: Conference fees. Cairns: Merck Sharpe and Dohme: Research Funding;Amgen: Research Funding;Takeda: Research Funding;Celgene / BMS: Other: travel support, Research Funding. Jackson: celgene BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau;amgen: Consultancy, Honoraria, Speakers Bureau;takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau;GSK: Consultancy, Honoraria, Speakers Bureau;J and J: Consultancy, Honoraria, Speakers Bureau;oncopeptides: Consultancy;Sanofi: Honoraria, Speakers Bureau. OffLabel Disclosure: Frailty-score adapted dosing strategies