Determination of the Effects of Prenatal Remdesivir Exposure on Placenta Morphology, Placental IgG Transfer, and Fetal Growth in a Humanized Mouse Model

Remdesivir (RDV) is an antiviral medication used most recently for the treatment of COVID-19. Although no adverse effects were observed on perinatal parameters in reproductive and development toxicology studies at doses up to four-fold clinical area under the curve (AUC) exposures, some researchers have reported that therapeutic levels of RDV may impair early embryogenesis, as observed by in vitro studies. In addition, the influence of prenatal RDV exposure on maternal IgG transfer in the placenta is still unknown. Administration of RDV in pregnant humanized mouse model (Tg32), which expresses the human Fc gamma receptor and transporter (FCGRT) gene, was used to further evaluate potential effects on IgG transfer and concurrent perinatal endpoints. Animals were dosed daily from gestational days (GDs) 10- 14 with 25 mg/kg RDV (GS-5734) via intravenous injection (n=3-5 per group). Concurrent vehicle control animals were dosed intravenously with 12% sulfobutyl ether- beta-cyclodextrin in water (pH3.5;NaOH/HCl). All animals were administered 2 mg/kg human IgG via intravenous injection on GD 14. Placentae and fetuses were collected from dams on GD 14, 15, 16, and 18 and evaluated using histopathology and qPCR for inflammation markers. No abnormal morphologies (necrosis/apoptosis) of placentae were observed between the concurrent control and RDVdosed groups. Additionally, no differences in maternal body weights were observed. There were no statistically significant differences in placenta weights. There were no statistically significant changes in pregnancy parameters (implantation sites and dead fetuses/litter) and fetal weights between the RDV-dosed group and concurrent controls at GD 14, 15, 16, and 18. No changes were observed in transcript levels of inflammation markers in the RDV-dosed group when compared to the concurrent control group. There was a slightly lower ratio of fetal IgG level to maternal IgG levels in the RDV-dosed group;however, no statistically significant differences were observed between the RDV-dosed group and concurrent controls on GD 14, 15, 16, and 18. Our results suggest that a daily dose of 25 mg/kg RDV on GDs 10-14 in humanized mice did not cause adverse effects on placenta and fetal development. (Funded by the Perinatal Health Center of Excellence: E0300201.).

A Constellation Model for Mentoring Undergraduates During COVID-19

Conceptualizing mentoring beyond a traditional one-to-one mentor-mentee model, we utilized a constellation framework with collaborative co-mentoring among faculty, staff, near -peers, and community partners. We conducted a multi-method study to examine faculty, staff, and students' perceptions of mentoring relationships, and we focus in this article on participants' perceptions of how the global pandemic changed their mentoring relationships. Analyses of the study's surveys and interviews yielded four primary themes: 1) scaffolded, developmental programming and a diverse set of mentors in an interconnected constellation positively impacts students' and mentors' experiences during unexpected challenges like a pandemic;2) skilled mentoring requires a dynamic, individualized balance of instrumental, psychosocial, and reciprocal mentoring practices, taking into account unique aspects of students' identities;3) reduction of in-person relational mentoring was associated with significant challenges, but occasionally offset by opportunities;and 4) gaps exist in the campus ecosystem, especially for students with minoritized identities and students who are not participants in cohorted programs. A case study of a multi-year, experientially rich, and academically rigorous program highlights the potential of collaborative, interconnected, globally oriented mentoring constellations to support students' personal, academic, and professional development, particularly when mentors were agile and adapted to new contexts. Challenges incurred in implementing a constellation model for undergraduate mentoring included scalability and capacity, particularly during the pandemic and when forming new relationships.

Clinical performance evaluation of an anti-SARS-CoV-2 IgG enzyme-linked immunosorbent assay

Background: The coronavirus disease 2019 (COVID-19) pandemic continues to cause widespread disruption to daily life globally. With increasing levels of vaccination and the emergence of new variants, it is important to monitor and identify individuals who have produced an immune response to SARS-CoV-2 and those who may remain at higher risk. Aims & Objectives: This study aimed to evaluate the clinical performance of a serological anti-SARS-CoV-2 Immunoglobulin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA), initially created by AstraZeneca and further developed and validated by ProAxsis Ltd. Method(s): The ProAxsis ELISA was used to assess anti-SARS-CoV-2 IgG levels in 402 positive and 701 negative plasma samples. Samples from each of the SARS-CoV-2 genetic variants (alpha, delta and omicron), along with the World Health Organisation International Reference Panel (NIBSC:20/268) and a panel of seroconversion samples were also tested. Result(s): Sensitivity and specificity of the ProAxsis Anti-SARS-CoV-2 IgG ELISA was 100.0% (CI 95% = 99.1- 100.0%) and 99.3% (CI 95% = 98.3-99.8%) respectively. The ProAxsis and comparator test (Euroimmun) were in almost perfect agreement, Cohen's Kappa (kappa) = 0.991 (CI 95% = 0.982-0.999, p<0.0001). Seroconversion was observed with the ProAxsis ELISA at an earlier stage than with the comparator assay. Of the 101 virology samples tested only one sample (Anti-malaria plasma P.falciparum) displayed some cross-reactivity. Conclusion(s): The ProAxsis Anti-SARS-CoV-2 IgG ELISA demonstrated excellent clinical performance in comparison to a comparator assay and will be highly useful in identifying individuals who have raised antibodies following exposure to SARS-CoV-2 or vaccination.

Impact of Intramuscular Injection Site on Sotrovimab Pharm Aco Kin Etics

BACKGROUND: Sotrovimab, a dual-action Fc-engineered human immunoglobulin G (IgG1) mAb, binds to a conserved epitope on the SARS-CoV- 2 receptor binding domain and was developed to treat mild to moderate COVID-19. A high concentration formulation is being evaluated to offer the potential for IM administration at lower volumes and at different injection sites. METHOD(S): COSMIC (NCT05280717) is a phase 1, open-label healthy volunteer study comprising three parts. Part A is an ongoing randomized, parallel group study investigating the relative bioavailability, safety, and tolerability of two concentrations of sotrovimab administered at different injection sites. A total of 215 subjects were randomized in a 2:2:1:1 ratio into 4 treatment arms: dorsogluteal injection (62.5 mg/mL), or 100 mg/mL administered as dorsogluteal, thigh, or deltoid injection(s). PK will be evaluated for 24 weeks post-dose. RESULT(S): Preliminary PK is available from 50 participants who received a 500 mg IM dose of sotrovimab of the higher concentration (100 mg/mL). Administration into thigh or deltoid resulted in higher geometric mean Cmax and AUCD1-15 and lower inter-subject variability compared to 100 mg/mL dorsogluteal. Following gluteal, thigh, or deltoid injections, the geometric mean (%CV) Cmax was 44.8 mug/mL (63.3), 70.9 mug/mL (35.5), and 65.1 mug/mL (27.1), respectively, and the geometric mean (%CV) AUCD1-15 was 534 day*mug/mL (67.5), 814 day*mug/mL (39.7), and 782 day*mug/mL (26.3), respectively. Median Tmax was earlier following thigh (4 days) and deltoid (5.5 days) injection than gluteal (7 days) injection. CONCLUSION(S): Administration of sotrovimab into thigh or deltoid muscles may improve exposure and reduce inter-subject variability compared to gluteal IM administration. These data may inform IM injection site selection for mAbs.

Putting nutrition education on the table: development of a curriculum to meet future doctors' needs.

COVID-19 has further exacerbated trends of widening health inequalities in the UK. Shockingly, the number of years of life lived in general good health differs by over 18 years between the most and least deprived areas of England. Poor diets and obesity are established major risk factors for chronic cardiometabolic diseases and cancer, as well as severe COVID-19. For doctors to provide the best care to their patients, there is an urgent need to improve nutrition education in undergraduate medical school training.With this imperative, the Association for Nutrition established an Interprofessional Working Group on Medical Education (AfN IPG) to develop a new, modern undergraduate nutrition curriculum for medical doctors. The AfN IPG brought together expertise from nutrition, dietetic and medical professionals, representing the National Health Service (NHS), royal colleges, medical schools and universities, government public health departments, learned societies, medical students, and nutrition educators. The curriculum was developed with the key objective of being implementable through integration with the current undergraduate training of medical doctors.Through an iterative and transparent consultative process, thirteen key nutritional competencies, to be achieved through mastery of eleven graduation fundamentals, were established. The curriculum to facilitate the achievement of these key competencies is divided into eight topic areas, each underpinned by a learning objective statement and teaching points detailing the knowledge and skills development required. The teaching points can be achieved through clinical teaching and a combination of facilitated learning activities and practical skill acquisition. Therefore, the nutrition curriculum enables mastery of these nutritional competencies in a way that will complement and strengthen medical students' achievement of the General Medical Council (GMC) Outcome for Graduates.As nutrition is an integrative science, the AfN IPG recommends that the curriculum is incorporated into initial undergraduate medical studies before specialist training. This will enable our future doctors to recognise how nutrition is related to multiple aspects of their training, from physiological systems to patient-centred care, and acquire a broad, inclusive understanding of health and disease. In addition, it will facilitate medical schools to embed nutrition learning opportunities within the core medical training, without the need to add in a large number of new components to an already crowded programme or with additional burden for teaching staff.The undergraduate nutrition curriculum for medical doctors is designed to support medical schools to create future doctors who will understand and recognise the role of nutrition in health. Moreover, it will equip frontline staff to feel empowered to raise nutrition-related issues with their patients as a fundamental part of enhanced care and to appropriately refer on for nutrition support with a registered associate nutritionist/registered nutritionist (ANutr/RNutr) or registered dietitian (RD) where this is likely to be beneficial.

Putting nutrition education on the table: development of a curriculum to meet future doctors' needs.

COVID-19 has further exacerbated trends of widening health inequalities in the UK. Shockingly, the number of years of life lived in general good health differs by over 18 years between the most and least deprived areas of England. Poor diets and obesity are established major risk factors for chronic cardiometabolic diseases and cancer, as well as severe COVID-19. For doctors to provide the best care to their patients, there is an urgent need to improve nutrition education in undergraduate medical school training. With this imperative, the Association for Nutrition established the Inter-Professional Working Group on Medical Education (AfN IPG) to develop a new, modern undergraduate nutrition curriculum for medical doctors. The AfN IPG brought together expertise from nutrition, dietetic and medical professionals, representing the National Health Service, royal colleges, medical schools and universities, government public health departments, learned societies, medical students and nutrition educators. The curriculum was developed with the key objective of being implementable through integration with the current undergraduate training of medical doctors. Through an iterative and transparent consultative process, 13 key nutritional competencies, to be achieved through mastery of 11 graduation fundamentals, were established. The curriculum to facilitate the achievement of these key competencies is divided into eight topic areas, each underpinned by a learning objective statement and teaching points detailing the knowledge and skills development required. The teaching points can be achieved through clinical teaching and a combination of facilitated learning activities and practical skills acquisition. Therefore, the nutrition curriculum enables mastery of these nutritional competencies in a way that will complement and strengthen medical students' achievement of the General Medical Council Outcomes for Graduates. As nutrition is an integrative science, the AfN IPG recommends the curriculum is incorporated into initial undergraduate medical studies before specialist training. This will enable our future doctors to recognise how nutrition is related to multiple aspects of their training, from physiological systems to patient-centred care, and acquire a broad, inclusive understanding of health and disease. In addition, it will facilitate medical schools to embed nutrition learning opportunities within the core medical training, without the need to add in a large number of new components to an already crowded programme or with additional burden to teaching staff. The undergraduate nutrition curriculum for medical doctors is designed to support medical schools to create future doctors who will understand and recognise the role of nutrition in health. Moreover, it will equip front-line staff to feel empowered to raise nutrition-related issues with their patients as a fundamental part of enhanced care and to appropriately refer on for nutrition support with a registered nutritionist (RNutr)/registered associate nutritionist (ANutr) or a registered dietitian (RD) where this is likely to be beneficial.

Safety, Tolerability, and Viral Pharmacodynamics of the IgG Monoclonal Antibody Sotrovimab Administered via Intramuscular Injection for the Treatment of Early Mild-to-Moderate COVID-19

Background. There is a continued need for therapeutics for the treatment of COVID-19, including intramuscular (IM) agents, which will enable broader use across a variety of healthcare delivery settings. Methods. COMET-PEAK (NCT04779879) is a 3-part study evaluating the safety, tolerability, pharmacokinetics (Part A), and viral pharmacodynamics (PD) of sotrovimab as treatment in adults >= 18 years with early mild/moderate COVID-19. In Parts B and C, the safety, tolerability and viral PD of sotrovimab administered as a 500 mg intravenous (IV) infusion or as a 500 mg or 250 mg IM injection, respectively, was evaluated. The primary objective for Parts B and C was to compare the virologic response of sotrovimab IM to IV, with an endpoint of mean area under the curve (AUC) of SARS-CoV-2 viral load as measured by qRT-PCR from Day 1 to Day 8 (AUCD1-8) in nasopharyngeal swabs and predefined 90% confidence interval (CI) limits of 0.5-2.0 indicating equivalence. Results. A total of 167 and 157 participants were enrolled in Part B and C, respectively, from February-July 2021. The median age of participants was 47 and 42 years in Part B and C, respectively, and ~50% had >= 1 risk factor for progression to severe disease. The viral load at baseline and through Day 29 of follow-up for each arm is shown in Table 1 and Figure 1. The primary objective was met for both study parts: the ratio of the least square geometric mean viral load AUC(D1-8) of sotrovimab IM vs IV was 1.04 (90% CI, 0.98, 1.09) and 1.02 (90% CI, 0.94, 1.11), for Part B and C, respectively. Through Day 29 of follow-up, the most common adverse event was injection site reactions (ISRs) in the IM arms. A total of 10 (12%) participants in the 500 mg IM group and 4 (5%) participants in the 250 mg IM group experienced an ISR, all Grade 1. Serious adverse events were uncommon, and related to COVID-19 progression, including one death in the 250 mg IM arm (Table 2). ISRs aside, there were few treatment-related AEs (2/84 IV, 1/82 IM) in Part B, none serious. Conclusion. IM administration of sotrovimab 500 mg and 250 mg each demonstrated equivalence to 500 mg sotrovimab IV in viral load assessments. Overall, there were no treatment-related serious AEs and sotrovimab was well tolerated. An 500 mg IM formulation will allow for expanded treatment potential with sotrovimab.

Viral resistance analysis in the COMET-PEAK study: sotrovimab treatment in participants with mild-to-moderate COVID-19

Background. Sotrovimab is a human monoclonal antibody targeting a conserved region of the SARS-CoV-2 spike (S) protein. COMET-PEAK was a 3-part, phase 2 study that evaluated intravenous (500 mg) and intramuscular (500 mg and 250 mg) administration of sotrovimab in outpatients (n=353) with mild-to-moderate COVID-19. We assessed amino acid substitutions in the SARS-CoV-2 S protein and circulating variants of concern/interest (VOC/VOI) in COMET-PEAK participants (enrolled Feb-July 2021). Methods. Mid-turbinate (Part A) or nasopharyngeal (Part B/C) samples were obtained from all participants at Baseline and Post-Baseline visits. Next generation sequencing of the SARS-CoV-2 S gene was conducted using Illumina MiSeq with a >=5% allelic frequency cut-off for samples with a viral load above 3.0 log10 copies/mL. Baseline, post-baseline and treatment-emergent (TE) substitutions were assessed, and prevalence of VOC/VOI was evaluated. Phenotypic analyses of epitope substitutions were conducted using a pseudotyped virus assay. Results. In total, 282/353 participants had sequencing results for >=1 visit (253 baseline, 248 post-baseline), and 219 had paired baseline and post-baseline sequences;among these, 149 (68%) had TE substitutions in the S protein (26 [12%] in the epitope). E340K was the predominant TE substitution in the epitope (15 [7%]). Across all arms 92/245 (38%) experienced virologic rebound, 8 of whom (Part A: 2;Part B: 2;Part C: 4) had TE substitutions in the epitope;none had evidence of clinical progression to severe disease. Prevalence of VOC/VOI or single amino acid substitutions of concern was 94% (266/282);the most frequent were Alpha (Part A: 8/16 [50%];Part B: 75/128 [59%]) and Delta (Part C: 99/122 [81%]). Of 7 participants with evidence of clinical progression, none had S protein substitutions in the epitope and all hadVOC/VOI (3Alpha, 3 Delta, 1 Gamma). Sotrovimab effectively neutralized most epitope substitutions tested in vitro;P337L and E340A/K/V conferred significantly reduced susceptibility. Conclusion. There was no evidence that sotrovimab epitope substitutions were associated with clinical progression or virologic rebound. These data are consistent with those from the COMET-ICE study.

Supermarket top-up of Healthy Start vouchers effectively increases fruit and vegetable purchases in low-income households

This was presented as the Food Systems Theme highlight. Diet related inequalities in the UK food system have been exacerbated by the Covid-19 pandemic, with low-income families experiencing more food insecurity(1) and purchasing less fruit and vegetables(2). To improve access to affordable and nutritious foods, UK supermarkets voluntarily increased weekly 4.25 Healthy Start voucher (HSV) amounts. Notably, one supermarket provided an additional 2 top- up voucher, redeemable against fruit and vegetables (FV) from 15th February - 31st August 2021. Investigating supermarket loyalty card transaction records, this study aimed to assess how increased HSV value affected FV purchases. Loyalty card transaction and redemption records from 150 opted in regular shoppers living in the Yorkshire and the Humber region and engaging in the HSV scheme were analysed. 133 of these shoppers' records were assessed from two equivalent time periods to the scheme in 2019 and 2020 and were analysed using a pre-post study design. The vouchers could be used on four different FV categories, plain fresh and prepared fruit and vegetables, and plain frozen, canned and packaged fruit and vegetables, according to internal definitions. The purchasing patterns of other FV were also analysed. Wilcoxon matched-pairs signed-rank tests were used to compare purchasing behaviour within the scheme period at a basket level, and against pre-scheme periods ata household level. A Spearman's Rho test was used to assess the association between behaviour and level of deprivation around stores. Examining 21,707 transactions from 133 households for 20 months before and during the scheme, showed that 0.8 more portions of FV per day per household were purchased during the scheme period compared to 2019 (pre-pandemic) baseline (2.6 in 2019 to 3.4 in 2021;P = 0.0017). The percentage of total FV weights within total food and drink baskets also increased by 1.6% (P = 0.0242), although the percentage of total FV spend did not change. Within the scheme period, 0.4% (P = 0.0012) and 1.6% (P = 0.0062) more FV was purchased according to price and weight respectively in top-up redeeming baskets compared to baskets with at least one FV item. This finding was associated with 5.5 more FV portions in top-up redeeming baskets during the scheme period (P < 0.0001). There was a higher proportion of top-up redeeming baskets in stores located in more deprived areas (r = -0.3288, P = 0.0373).In conclusion, this study provides novel data into how low-income households shop and how an increased HSV amount is associated with FV purchases. The data show that low-income families purchased more FV when supplied with an additional 2 to their HSV and provides evidence for a benefit to increasing support given to low-income families.

An evaluation of the clinical characteristics of an Anti-SARS-CoV-2 IgG enzyme-linked immunosorbent assay

Introduction and ObjectivesThe widespread disruption caused by the coronavirus disease 2019 (COVID-19) pandemic continues to impact on daily life. Despite extensive progress in combating the disease, the immunogenic mechanisms are not fully understood. With increasing vaccination rates and the emergence of new variants, it is important to monitor and identify individuals who have produced an immune response and those who remain at higher risk. This study aimed to evaluate the clinical performance of a serological anti-SARS-CoV-2 Immunoglobulin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA), initially created by AstraZeneca and further developed and validated by ProAxsis Ltd.MethodsThe ProAxsis ELISA was used to assess anti-spike protein SARS-CoV-2 IgG levels, in a total of 423 positive plasma samples including asymptomatic, symptomatic, mildly asymptomatic, early infection, post-seroconversion, low and high titre samples and vaccinated individuals. A total of 701 negative plasma samples were also assessed. Samples from each of the SARS-CoV-2 genetic variants (alpha, delta and omicron), along with the World Health Organisation (WHO) International Reference Panel (NIBSC:20/268) were assessed. In addition, 101 plasma samples from patients with antibodies to other coronaviruses or medical conditions were tested.ResultsSensitivity and specificity of the ProAxsis Anti-SARS-CoV-2 IgG ELISA was 100.0% (CI 95% = 99.1 – 100.0%) and 99.3% (CI 95% = 98.3 – 99.8%) respectively. The ProAxsis and comparator test (Euroimmun) demonstrated good agreement, Cohen’s Kappa (κ) = 0.991 (CI 95% = 0.982 – 0.999, p<0.0001). Seroconversion was observed with the ProAxsis ELISA at an earlier stage post-infection than with the comparator assay. The WHO Reference Panel was found to correlate perfectly with the Euroimmun assay and were as expected for each titre. Of the 101 virology samples tested only one sample (Anti-malaria plasma P.falciparum) displayed some cross-reactivity (33.3%).ConclusionsThe ProAxsis Anti-SARS-CoV-2 IgG ELISA demonstrated robust clinical performance, with almost perfect agreement against the comparator assay. The ProAxsis ELISA will be highly useful in identifying individuals who have raised antibodies following exposure to SARS-CoV-2 or vaccination and has the potential to play an important role in antibody analyses in clinical trials and large populations.Please refer to page A215 for declarations of interest related to this .

A rapid review investigating the potential impact of a pandemic on the mental health of young people aged 12-25 years.

OBJECTIVES: In March 2020, the World Health Organization (WHO) officially declared the spread of coronavirus disease 2019 (COVID-19) as a pandemic. Adolescence and early adulthood are peak times for the onset of mental health difficulties. Exposure to a pandemic during this vulnerable developmental period places young people at significant risk of negative psychological experiences. The objective of this research was to summarise existing evidence on the potential impact of a pandemic on the mental health of 12-25 year olds. METHODS: A rapid review of the published peer-reviewed literature, published between 1985 and 2020, using PsycINFO (Proquest) and Medline (Proquest) was conducted. Narrative synthesis was used across studies to identify key themes and concepts. RESULTS: This review found 3,359 papers, which was reduced to 12 papers for data extraction. Results regarding the prevalence of psychological difficulties in youth were mixed, with some studies finding this group experience heightened distress during an infectious disease outbreak, and others finding no age differences or higher distress among adults. Gender, coping, self-reported physical health and adoption of precautionary measures appear to play a role in moderating the psychological impact of an infectious disease outbreak. Most studies were conducted after the peak of an epidemic/pandemic or in the recovery period. CONCLUSIONS: More longitudinal research with young people, particularly adolescents in the general population, before and during the early stages of an infectious disease outbreak is needed to obtain a clear understanding of how best to support young people during these events.

INTERSTITIAL LUNG DISEASE IN SERONEGATIVE RHEUMATOID ARTHRITIS

SESSION TITLE: Autoimmune Diffuse Lung Disease Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Interstitial lung disease (ILD) associated with connective tissue diseases (CTD) present with varying degrees of severity and functional impairment. Patients with CTD-ILD may often initially present for pulmonary evaluation. Pulmonologists must be familiar with the spectrum of CTD syndromes, the associated serologic testing, and referral criteria to rheumatology. CASE PRESENTATION: A 62-year-old never-smoking female with prior mild COVID-19 infection, previously vaccinated, presented to clinic with a diagnosis of pulmonary fibrosis. She endorsed three years of progressive shortness of breath and dyspnea on exertion walking only eight blocks and with light household chores. The patient had worked as a professional chef in poorly ventilated kitchens. Review of systems was notable for morning stiffness and pain in bilateral hand joints with associated difficulty opening medication bottles secondary to symptoms. Previous computed tomography (CT) of the chest demonstrated peripheral, subpleural, and basal predominant reticulations accompanied by bronchiectasis and bronchioloectasis consistent with probable usual interstitial pneumonia (UIP). Envisia® genomic testing was performed and results were negative for idiopathic pulmonary fibrosis. Extensive serologic testing for CTD was performed, including rheumatoid factor and anti-cyclic citrullinated peptides which were normal. The patient was referred to rheumatology, and hand x-rays demonstrated diffuse MCP joint narrowing. The patient was diagnosed with seronegative rheumatoid arthritis (RA) with RA-ILD and started on treatment. DISCUSSION: Multiple society guidelines recommend serologic testing to rule out CTD-ILD in patients with new ILD. ILD has been reported to occur in 20-60% of patients with RA with multiple patterns. Patients with seronegative RA are more likely to develop extraarticular manifestations of RA including fibrotic lung disease. Patients who are asymptomatic from RA-ILD may be monitored clinically for worsening RA-ILD. The selection of patients for treatment with an immunosuppressive agent or glucocorticoids should be done with a multidisciplinary team. Patients with RA-ILD and a UIP pattern may not respond to immunosuppressive medications but are typically trialed on treatment for worsening lung disease. Randomized controlled trials that included patients with RA-ILD with fibrosis have suggested a role for nintedanib, an anti-fibrotic agent, in slowing the progression of forced vital capacity decline. CONCLUSIONS: CTD-ILD is a common diagnosis in pulmonary clinics, and ILD symptoms may be the chief complaint at presentation. Providers must be familiar with diagnostic criteria for CTD and obtain a detailed review of systems that might suggest the diagnosis of CTD. Early diagnosis of CTD-ILD and monitoring of disease activity is important to prevent progression of CTD-ILD. Reference #1: Yoo H, Hino T, Han J, et al. Connective tissue disease-related interstitial lung disease (CTD-ILD) and interstitial lung abnormality (ILA): Evolving concept of CT findings, pathology and management. Eur J Radiol Open. 2020;8:100311. Published 2020 Dec 16. doi:10.1016/j.ejro.2020.100311 Reference #2: Sahatciu-Meka V, Rexhepi S, Manxhuka-Kerliu S, Rexhepi M. Extra-articular manifestations of seronegative and seropositive rheumatoid arthritis. Bosn J Basic Med Sci. 2010;10(1):26-31. doi:10.17305/bjbms.2010.2729 Reference #3: Cottin V. Pragmatic prognostic approach of rheumatoid arthritis-associated interstitial lung disease. Eur Respir J. 2010 Jun;35(6):1206-8. doi: 10.1183/09031936.00008610. PMID: 20513909. DISCLOSURES: No relevant relationships by Brenda Garcia No relevant relationships by Zein Kattih No relevant relationships by Priyanka Makkar No relevant relationships by Jonathan Moore

MALIGNANT HYPERTHERMIA AND COVID-19: IS THERE A CORRELATION?

SESSION TITLE: COVID-19 Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Malignant hyperthermia (MH) is a hypermetabolic crisis where an increase in carbon dioxide is seen despite an increased minute ventilation with a proposed mechanism as a disturbance in calcium homeostasis. Commonly seen in volatile anesthetic agents and depolarizing neuromuscular blockers, rarely with nondepolarizing agents. There has been one reported case of cisatracurium-induced MH in the setting of ARDS. There have been two cases reported of nondepolarizing neuromuscular agents causing MH in the setting of COVID-19. CASE PRESENTATION: A 34-year-old man with severe COVID-19 complicated by ARDS on ventilator day 16, due to refractory fevers, ventilatory dyssynchrony, high minute ventilation and auto-PEEP phenomena, the decision was made to attempt neuromuscular paralysis. After one dose of cisatracurium, the patient became hyperthermic and end-tidal carbon-dioxide increased from 58-98 with inability to oxygenate. The patient developed high peak pressures, bedside ultrasound revealed no evidence of pneumothorax also confirmed with chest x-ray. The patient then received a dose of dantrolene with end-tidal improving to 60 and tachycardia also resolved. A creatinine kinase level drawn was elevated at 571. DISCUSSION: A proposed mechanism of MH is calcium release from sarcoplasmic reticulum, a mutation in skeletal muscle ryanodine receptor calcium release channels that can release IL-6 when activated leading to excessive muscular contraction. Proinflammatory cytokine IL-6, dantrolene may block IL-6 release which results in its therapeutic effect in the treatment of MH. IL-6 has been used to predict deterioration from COVID-19. Dantrolene in this sense has been proposed as a potential therapeutic agent against COVID-19, inhibiting intracellular calcium influx thus preventing the pathological feedback of viral entry into cells via endocytosis, as this is a calcium dependent process. Given the possible link between IL-6 release, calcium and MH, SARS-CoV-2 viral entry into cells may place patients at higher risk of MH. Patients with COVID-19 may be at higher risk of MH, even in rare agents such as non-depolarizing agents as seen in this case. Awareness of this potentially increased complication from these agents in those patients with COVID-19 is key as we continue in the ongoing global pandemic. CONCLUSIONS: Given the possible link between IL-6 release, calcium and MH, SARS-CoV-2 viral entry into cells may place patients at higher risk of MH. Patients with COVID-19 may be at higher risk of malignant hyperthermia, even in rare agents such as non-depolarizing agents as seen in this case. Awareness of this potentially increased complication from these agents in those patients with COVID-19 is key as we continue in the ongoing global pandemic. Reference #1: Sathyanarayanan SP, Hamza M, Hamid K, Groskreutz D. Cisatracurium-Associated Malignant Hyperthermia During Severe Sars-CoV-2 Infection. Am J Ther. 2021 Aug 10;28(5):e590-e591. doi: 10.1097/MJT.0000000000001437. PMID: 34387563;PMCID: PMC8415506. Reference #2: Chiba N, Matsuzaki M, Mawatari T, Mizuochi M, Sakurai A, Kinoshita K. Beneficial effects of dantrolene in the treatment of rhabdomyolysis as a potential late complication associated with COVID-19: a case report. Eur J Med Res. 2021 Feb 8;26(1):18. doi: 10.1186/s40001-021-00489-8. PMID: 33557936;PMCID: PMC7868892. Reference #3: Han H, Ma Q, Li C, Liu R, Zhao L, Wang W, Zhang P, Liu X, Gao G, Liu F, Jiang Y, Cheng X, Zhu C, Xia Y. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect. 2020 Dec;9(1):1123-1130. doi: 10.1080/22221751.2020.1770129. PMID: 32475230;PMCID: PMC7473317. DISCLOSURES: No relevant relationships by Hira Bakhtiar No relevant relationships by Timothy DAmico no disclosure on file for Sarah Margolskee;No relevant relationships by Carlos Merino No relevant relationships by Joanna Moore

CRYPTIC CRYPTO: PULMONARY CRYPTOCOCCOSIS IN AN IMMUNOCOMPETENT HOST

SESSION TITLE: Uncommon Presentations and Complications of Chest Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Cryptococcus is a ubiquitous fungus in the environment. Infections can occur in humans when Cryptococcus is aerosolized and inhaled. Severity of clinical presentation varies from asymptomatic pulmonary colonization to disseminated life-threatening infection such as meningitis. These infections usually occur with deficiencies in T-cell-mediated immunity, including those with HIV/AIDS and immunosuppression due to transplantation. Herein we present a case of isolated pulmonary cryptococcosis in an immunocompetent host. CASE PRESENTATION: The patient is a 36-year-old never-smoker male with history of recurrent left spontaneous pneumothorax status post VATS blebectomy, negative for alpha-1 antitrypsin deficiency and cystic fibrosis. A year later, he presented with fatigue, shortness of breath, and dry cough after a recent trip to Ohio. Viral panel including COVID-19 was negative. A chest x-ray showed a new 4 cm rounded opacity in the right middle lobe (RML). A CT scan of the chest showed 2 mass-like and nodular areas of consolidation with surrounding GGOs within the RML (Figure 1). He underwent navigational bronchoscopy with transbronchial biopsy (TBBx) of RML, BAL, and EBUS with transbronchial needle aspiration (TBNA). Cytology was negative for malignant cells. BAL showed rare yeast. Pathology of the TBBx showed the airway wall with chronic inflammation including granulomatous inflammation, positive for yeast, most consistent with Cryptococcus with positive Grocott methenamine silver (GMS) stain (Figure 2). Culture of the TBNA grew C. neoformans var. grubii. Other cultures were negative. Serum Cryptococcal antigen was positive. HIV test was negative. He started treatment with oral fluconazole with improvement of symptoms. DISCUSSION: Clinical presentation of pulmonary cryptococcosis can include a variety of symptoms in which immune status is critical for determining the course of infection. Infection can vary from asymptomatic infection to severe pneumonia and respiratory failure, and meningitis. Similarly, imaging findings can also vary and be characterized as pulmonary nodules, consolidations, cavitary lesions, and/or a diffuse interstitial pattern. The diagnosis of Cryptococcus is made using histology, fungal cultures, serum cryptococcal antigen, and radiography in the appropriate clinical and radiological context. Treatment recommendations are determinant on immune status of the patient as well as symptoms. Asymptomatic and localized disease in immunocompetent patients can be monitored and mild/moderate disease can be treated with fluconazole. Those with severe or disseminated infection warrant induction therapy with an amphotericin B and flucytosine CONCLUSIONS: Clinical and radiological presentation of cyptococcosis varies depending on immune status. Disease can occur in both immunocompromised and competent hosts. Immune status determines disease course and treatment. Reference #1: Huffnagle GB, Traynor TR, McDonald RA, Olszewski MA, Lindell DM, Herring AC, et al. Leukocyte recruitment during pulmonary Cryptococcus neoformans infection. Immunopharmacology. 2000 Jul 25;48(3):231–6. Reference #2: Kd B, Jw B, Pg P. Pulmonary cryptococcosis. Semin Respir Crit Care Med [Internet]. 2011 Dec [cited 2022 Apr 2];32(6). Available from: https://pubmed.ncbi.nlm.nih.gov/22167400/ Reference #3: Ms S, Rj G, Ra L, Pg P, Jr P, Wg P, et al. Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America. Clin Infect Dis Off Publ Infect Dis Soc Am [Internet]. 2000 Apr [cited 2022 Apr 1];30(4). Available from: https://pubmed.ncbi.nlm.nih.gov/10770733/ DISCLOSURES: No relevant relationships by Mina Elmiry No relevant relationships by Brenda Garcia No relevant relationships by Zein Kattih no disclosure on file for Priyanka Makkar;No relevant relationships by Jonathan Moore

IMPORTANCE OF HIGH CLINICAL SUSPICION FOR COVID-19-ASSOCIATED PULMONARY ASPERGILLOSIS IN PATIENTS WITH EQUIVOCAL BIOMARKERS

SESSION TITLE: Pathologies of the Post-COVID-19 World SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Pulmonary aspergillosis is a recognized complication of COVID-19. Options for diagnostic evaluation in patients with suspected pulmonary aspergillosis include serum galactomannan, beta-D-glucan, Aspergillus PCR, fungal cultures and tissue biopsy. Diagnosis is challenging due to the risks and logistical barriers associated with procedural/surgical tissue biopsy and the variable reliability of serum biomarkers. We present a case of a 76-year-old male who developed invasive pulmonary aspergillosis after a COVID-19 respiratory infection. CASE PRESENTATION: 76-year-old male with a past medical history that includes emphysematous COPD, history of chronic lymphocytic leukemia in remission, on ibrutinib, who contracted SARS-CoV-2 resulting in hypoxemic respiratory failure and requiring hospital admission and was treated with dexamethasone and remdesivir. He was discharged home and due to his worsening respiratory condition, he was readmitted to the hospital next month. Ct chest performed revealed pulmonary embolism and diffuse multifocal opacification with interspersed scattered dense opacities and nodules with cavitary lesions in the right upper lobe. A bronchoscopy was performed and the Aspergillus antibody test, beta D glucan and galactomannan antigens resulted as negative. Due to this, voriconzaole was discontinued. Subsequently CT-guided lung biopsy demonstrated Aspergillus. Eventually, fungal cultures from BAL began growing fungus. DISCUSSION: Our patient initially presented with a Covid infection in January 2022 he was initially treated with remdesivir, 14 days of baricitinib and 10 days of Decadron followed by a steroid taper (due to his underlying COPD). He did not receive tocilizumab. He was found to have progression of the cavitary lesions during a third admission. We suspect that the main contributing factors for the development of invasive pulmonary aspergillosis are related to interleukin production, distorted architecture from COVID-19 infection and multiple courses of steroids. This case report demonstrates the importance of having a high clinical suspicion for invasive pulmonary aspergillosis in all patients with COVID-19 infection. It also demonstrates that serum biomarkers are not reliable indicators of infection and cannot be used to definitively rule out infection or to exclude treatment with antifungal therapy. It should be noted that positive serum biomarkers in patients with true invasive aspergillosis have a higher mortality rate as compared to those without positive serum biomarkers. This case also underscores the importance of obtaining tissue diagnosis in patients where there is a high suspicion for fungal infection when all other studies are equivocal. CONCLUSIONS: We believe that this case underscores the importance of maintaining a high clinical suspicion for opportunistic and fungal infections in patients with COVID-19, regardless of the serum biomarkers. Reference #1: Arastehfar A, Carvalho A, van de Veerdonk FL, et al. Covid-19 associated Pulmonary Aspergillosis (capa)—from immunology to treatment. Journal of Fungi. 2020;6(2):91. doi:10.3390/jof6020091 Reference #2: Machado M, Valerio M, Álvarez-Uría A, et al. Invasive Pulmonary Aspergillosis in the COVID-19 ERA: An expected new entity. Mycoses. 2020;64(2):132-143. doi:10.1111/myc.13213 Reference #3: Maschmeyer G, Haas A, Cornely OA. Invasive aspergillosis. Drugs. 2007;67(11):1567-1601. doi:10.2165/00003495-200767110-00004 DISCLOSURES: No relevant relationships by Hira Bakhtiar No relevant relationships by Amanda Lindo No relevant relationships by Carlos Merino No relevant relationships by Joanna Moore

Evaluation of the Performance of a Lateral Flow Device for Quantitative Detection of Anti-SARS-CoV-2 IgG

Introduction: The AbC-19™ lateral flow immunoassay (LFIA) performance was evaluated on plasma samples from a SARS-CoV-2 vaccination cohort, WHO international standards for anti-SARS-CoV-2 IgG (human), individuals ≥2 weeks from infection of RT-PCR confirmed SARS-CoV-2 genetic variants, as well as microorganism serology. Methods: Pre-vaccination to three weeks post-booster samples were collected from a cohort of 111 patients (including clinically extremely vulnerable patients) from Northern Ireland. All patients received Oxford-AstraZeneca COVID-19 vaccination for the first and second dose, and Pfizer-BioNTech for the third (first booster). WHO international standards, 15 samples from 2 variants of concern (Delta and Omicron) and cross-reactivity with plasma samples from other microorganism infections were also assessed on AbC-19™. Results: All 80 (100%) participants sampled post-booster had high positive IgG responses, compared to 38/95 (40%) participants at 6 months post-first vaccination. WHO standard results correlated with information from corresponding biological data sheets, and antibodies to all genetic variants were detected by LFIA. No cross-reactivity was found with exception of one (of five) Dengue virus samples. Conclusion: These findings suggest BNT162b2 booster vaccination enhanced humoral immunity to SARS-CoV-2 from pre-booster levels, and that this antibody response was detectable by the LFIA. In combination with cross-reactivity, standards and genetic variant results would suggest LFIA may be a cost-effective measure to assess SARS-CoV-2 antibody status.

Profound racial disparities in COVID-19 associated hospitalizations in rural Southwest Georgia

Background: The coronavirus disease 2019 (COVID-19) is responsible for one of the largest public health crises the United States has seen to date. This study explores the outcomes of African American and non-African American COVID-19-positive patients hospitalized in rural Southwest Georgia to identify differences in morbidity and mortality between the groups. Methods: We performed a retrospective cohort analysis among adults aged >= 18 years admitted with COVID-19 between March 2, 2020 and June 17, 2020 at Phoebe Putney Health System. Data on demographics, comorbidities, presenting symptoms, and hospital course were obtained. Patients were divided into two groups: African Americans and non-African Americans. We examined differences in patient characteristics between groups using chi-square tests for categorical variables, t test for parametric continuous variables, and Wilcoxon rank-sum tests for non-parametric continuous variables. Statistical Analysis Software (SAS) version 9.4 was used for statistical analysis. Results: Among 710 patients, median age was 63 years, 43.8% were males, and 83.3% were African Americans. African Americans had higher prevalence of obesity and hypertension, were more likely to present with fever, and present with longer duration of symptoms prior to presentation. In-hospital mortality was similar between the groups, as was need for mechanical ventilation, ICU care, and new dialysis. African Americans were more likely to be discharged home compared to non-African Americans. Conclusions: There was no difference in in-hospital mortality;however, African Americans had disproportionately higher hospitalizations, likely to significantly increase the morbidity burden in this population. Urgent measures are needed to address this profound racial disparity.