Educator Perspectives on Stressors and Health: A qualitative study of U.S. K-12 educators in February 2022 (preprint)

Background The teaching profession, already characterized by high stress and burnout, experienced exacerbated challenges during the height of the COVID-19 pandemic. While educators faced changing job demands over the course of the pandemic with switches in remote and in-person teaching along with COVID-19 transmission prevention strategies, the demands and resulting impact in the years that follow are still being explored. We sought to understand the stressors and health impacts of U.S. educators in the 2021–2022 school year, 2 years following the acute phase of the pandemic.Methods Thirty-four certified educators based in Connecticut, USA participated in 4 virtual focus groups in February 2022. A semi-structured focus group script, designed by the research team and guided by the job demands-resources model, was administered to understand stress impacts and stressors. Data were transcribed and analyzed using the constant comparative method to identify themes and sub-themes. Themes were summarized by frequency as well as by individuals.Results The majority of respondents reported educator well-being impacts of stress fell into three categories: physical health impacts and behaviors (76%; e.g. poor sleep, physical exhaustion, lack of exercise, unhealthy eating), psychological health impacts (62%; e.g. emotional exhaustion, anxiety, negative self-evaluation); and social well-being impacts and behaviors (68%; e.g. connections with family or friends, connections with others, relationships with coworkers). Sources of reported stressors included the school or district (94%), personal (65%), situational (35%), and to a lesser extent parents (24%), other work factors (15%), community (12%), students (12%), and state or national level (9%) factors. At the school/district level, stressors were related to protocols/expectations (91%, e.g. excessive or increased demands, insufficient or decreased resources) or administrators (38%). Personal level stressors included personal life (41%); other personal factors (20%); and income (17%); situational factors included the pandemic (26%) and safety concerns (9%).Conclusion Focus groups allowed us to assess the health and working conditions of Connecticut’s public education workforce 2 years following the acute phase of the pandemic. Lasting effects are relevant in the post-pandemic era and continue to pose challenges as teacher shortages increase. Targeted interventions are needed to reduce school and district-related demands and to address stress-related educator well-being.

Mutational Profiling of SARS-CoV-2 PLpro in human cells reveals requirements for function, structure, and drug escape (preprint)

SARS-CoV-2, the causative agent of COVID-19, is responsible for the recent global pandemic and remains a major source of mortality. Papain-like protease (PLpro) is a target for SARS-CoV-2 inhibitor development, as it is not only essential for viral replication through cleavage of the viral poly-proteins pp1a and pp1ab, but also has de-ubiquitylation and de-ISGylation activities, which can affect innate immune responses. To understand the features of PLpro that dictate activity and anticipate how emerging PLpro variants will affect function, we employed Deep Mutational Scanning to evaluate the mutational effects on enzymatic activity and protein stability in mammalian cells. We confirm features of the active site and identify all mutations in neighboring residues that support or ablate activity. We characterize residues responsible for substrate binding and demonstrate that although the blocking loop is remarkably tolerant to nearly all mutations, its flexibility is important for enzymatic function. We additionally find a connected network of mutations affecting function but not structure that extends far from the active site. Using our DMS libraries we were able to identify drug-escape variants to a common PLpro inhibitor scaffold and predict that plasticity in both the S4 pocket and blocking loop sequence should be considered during the drug design process.

Proportion of Hospitalizations Preventable with Increased Oral SARS-CoV-2 Antiviral Treatment (preprint)

We estimated the proportion of hospitalizations that could have been averted had all eligible high-risk adults with SARS-CoV-2 infection in a clinical cohort been treated with an oral SARS-CoV-2 antiviral agent early in infection. Among 3,037 patients with risk factors for progressing to severe COVID-19, 946 (31.1%) received an oral antiviral prescription (834 nirmatrelvir and 112 molnupiravir). Only 3.0% of treated patients vs 9.1% of untreated patients were hospitalized (adjusted risk ratio [RR]=0.27; 95% confidence interval [CI]: 0.18-0.41). If all patients had been treated, an estimated 63.3% (95% CI: 50.4-75.1) of hospitalizations within 30 days could have been prevented. This finding is attributed to large gaps in treatment and a strong protective association of antiviral treatment with subsequent hospitalization.

Efflux-Related Carbapenem Resistance in Acinetobacter baumannii Is Associated with Two-Component Regulatory Efflux Systems' Alteration and Insertion of ΔAbaR25-Type Island Fragment.

The efflux pumps, beside the class D carbapenem-hydrolysing enzymes (CHLDs), are being increasingly investigated as a mechanism of carbapenem resistance in Acinetobacter baumannii. This study investigates the contribution of efflux mechanism to carbapenem resistance in 61 acquired blaCHDL-genes-carrying A. baumannii clinical strains isolated in Warsaw, Poland. Studies were conducted using phenotypic (susceptibility testing to carbapenems ± efflux pump inhibitors (EPIs)) and molecular (determining expression levels of efflux operon with regulatory-gene and whole genome sequencing (WGS)) methods. EPIs reduced carbapenem resistance of 14/61 isolates. Upregulation (5-67-fold) of adeB was observed together with mutations in the sequences of AdeRS local and of BaeS global regulators in all 15 selected isolates. Long-read WGS of isolate no. AB96 revealed the presence of AbaR25 resistance island and its two disrupted elements: the first contained a duplicate ISAba1-blaOXA-23, and the second was located between adeR and adeA in the efflux operon. This insert was flanked by two copies of ISAba1, and one of them provides a strong promoter for adeABC, elevating the adeB expression levels. Our study for the first time reports the involvement of the insertion of the ΔAbaR25-type resistance island fragment with ISAba1 element upstream the efflux operon in the carbapenem resistance of A. baumannii.

Changing Severity and Epidemiology of Adults Hospitalized With Coronavirus Disease 2019 (COVID-19) in the United States After Introduction of COVID-19 Vaccines, March 2021-August 2022.

INTRODUCTION: Understanding the changing epidemiology of adults hospitalized with coronavirus disease 2019 (COVID-19) informs research priorities and public health policies. METHODS: Among adults (≥18 years) hospitalized with laboratory-confirmed, acute COVID-19 between 11 March 2021, and 31 August 2022 at 21 hospitals in 18 states, those hospitalized during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-predominant period (BA.1, BA.2, BA.4/BA.5) were compared to those from earlier Alpha- and Delta-predominant periods. Demographic characteristics, biomarkers within 24 hours of admission, and outcomes, including oxygen support and death, were assessed. RESULTS: Among 9825 patients, median (interquartile range [IQR]) age was 60 years (47-72), 47% were women, and 21% non-Hispanic Black. From the Alpha-predominant period (Mar-Jul 2021; N = 1312) to the Omicron BA.4/BA.5 sublineage-predominant period (Jun-Aug 2022; N = 1307): the percentage of patients who had ≥4 categories of underlying medical conditions increased from 11% to 21%; those vaccinated with at least a primary COVID-19 vaccine series increased from 7% to 67%; those ≥75 years old increased from 11% to 33%; those who did not receive any supplemental oxygen increased from 18% to 42%. Median (IQR) highest C-reactive protein and D-dimer concentration decreased from 42.0 mg/L (9.9-122.0) to 11.5 mg/L (2.7-42.8) and 3.1 mcg/mL (0.8-640.0) to 1.0 mcg/mL (0.5-2.2), respectively. In-hospital death peaked at 12% in the Delta-predominant period and declined to 4% during the BA.4/BA.5-predominant period. CONCLUSIONS: Compared to adults hospitalized during early COVID-19 variant periods, those hospitalized during Omicron-variant COVID-19 were older, had multiple co-morbidities, were more likely to be vaccinated, and less likely to experience severe respiratory disease, systemic inflammation, coagulopathy, and death.

Effect of P2Y12 Inhibitors on Organ Support-Free Survival in Critically Ill Patients Hospitalized for COVID-19: A Randomized Clinical Trial.

Importance: Platelet activation is a potential therapeutic target in patients with COVID-19. Objective: To evaluate the effect of P2Y12 inhibition among critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: This international, open-label, adaptive platform, 1:1 randomized clinical trial included critically ill (requiring intensive care-level support) patients hospitalized with COVID-19. Patients were enrolled between February 26, 2021, through June 22, 2022. Enrollment was discontinued on June 22, 2022, by the trial leadership in coordination with the study sponsor given a marked slowing of the enrollment rate of critically ill patients. Intervention: Participants were randomly assigned to receive a P2Y12 inhibitor or no P2Y12 inhibitor (usual care) for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures: The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death and, for participants who survived to hospital discharge, the number of days free of cardiovascular or respiratory organ support up to day 21 of the index hospitalization. The primary safety outcome was major bleeding, as defined by the International Society on Thrombosis and Hemostasis. Results: At the time of trial termination, 949 participants (median [IQR] age, 56 [46-65] years; 603 male [63.5%]) had been randomly assigned, 479 to the P2Y12 inhibitor group and 470 to usual care. In the P2Y12 inhibitor group, ticagrelor was used in 372 participants (78.8%) and clopidogrel in 100 participants (21.2%). The estimated adjusted odds ratio (AOR) for the effect of P2Y12 inhibitor on organ support-free days was 1.07 (95% credible interval, 0.85-1.33). The posterior probability of superiority (defined as an OR > 1.0) was 72.9%. Overall, 354 participants (74.5%) in the P2Y12 inhibitor group and 339 participants (72.4%) in the usual care group survived to hospital discharge (median AOR, 1.15; 95% credible interval, 0.84-1.55; posterior probability of superiority, 80.8%). Major bleeding occurred in 13 participants (2.7%) in the P2Y12 inhibitor group and 13 (2.8%) in the usual care group. The estimated mortality rate at 90 days for the P2Y12 inhibitor group was 25.5% and for the usual care group was 27.0% (adjusted hazard ratio, 0.96; 95% CI, 0.76-1.23; P = .77). Conclusions and Relevance: In this randomized clinical trial of critically ill participants hospitalized for COVID-19, treatment with a P2Y12 inhibitor did not improve the number of days alive and free of cardiovascular or respiratory organ support. The use of the P2Y12 inhibitor did not increase major bleeding compared with usual care. These data do not support routine use of a P2Y12 inhibitor in critically ill patients hospitalized for COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04505774.

Effectiveness of COVID-19 Vaccines at Preventing Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompromised Adults: An Observational Study of Real-World Data Across 10 US States from August-December 2021

Background Immunocompromised (IC) persons are at increased risk for severe COVID-19 outcomes and are less protected by 1-2 COVID-19 vaccine doses than are immunocompetent (non-IC) persons. We compared vaccine effectiveness (VE) against medically attended COVID-19 of 2-3 mRNA and 1-2 viral-vector vaccine doses between IC and non-IC adults. Methods Using a test-negative design among eight VISION Network sites, VE against laboratory-confirmed COVID-19–associated emergency department (ED) or urgent care (UC) events and hospitalizations from 26 August-25 December 2021 was estimated separately among IC and non-IC adults and among specific IC condition subgroups. Vaccination status was defined using number and timing of doses. VE for each status (versus unvaccinated) was adjusted for age, geography, time, prior positive test result, and local SARS-CoV-2 circulation. Results We analyzed 8,848 ED/UC events and 18,843 hospitalizations among IC patients and 200,071 ED/UC events and 70,882 hospitalizations among non-IC patients. Among IC patients, 3-dose mRNA VE against ED/UC (73% [95% CI: 64-80]) and hospitalization (81% [95% CI: 76-86]) was lower than that among non-IC patients (ED/UC: 94% [95% CI: 93-94];hospitalization: 96% [95% CI: 95-97]). Similar patterns were observed for viral-vector vaccines. Transplant recipients had lower VE than other IC subgroups. Conclusions During B.1.617.2 (Delta) variant predominance, IC adults received moderate protection against COVID-19–associated medical events from three mRNA doses, or one viral-vector dose plus a second dose of any product. However, protection was lower in IC versus non-IC patients, especially among transplant recipients, underscoring the need for additional protection among IC adults.

Cardiac complications in children with acute COVID-19 vs multisystem inflammatory syndrome in children (MIS-C).

BACKGROUND: Cardiac involvement can lead to significant morbidity in children with acute COVID-19 or multisystem inflammatory syndrome in children (MIS-C). However, the presentation and outcomes of cardiac involvement may differ among these 2 conditions. We aimed to compare the frequency and extent of cardiac involvement among children admitted with acute COVID-19 vs those with MIS-C. METHODS: We conducted a cross sectional study of patients admitted to our hospital from March 2020 to August 2021 with symptomatic acute COVID-19 or MIS-C. Cardiac involvement was defined by presence of 1 or more of the following: elevated troponin, elevated brain natriuretic peptide, reduced left ventricular ejection fraction on echocardiogram, coronary dilation on echocardiogram, or abnormal electrocardiogram reading. RESULTS: Among 346 acute COVID-19 patients with median age of 8.9 years and 304 MIS-C patients with median age of 9.1 years, cardiac involvement was present in 33 acute COVID-19 patients (9.5%) and 253 MIS-C patients (83.2%). The most common cardiac abnormality was abnormal electrocardiogram in acute COVID-19 patients (7.5%) and elevated troponin in MIS-C patients (67.8%). Among acute COVID-19 patients, obesity was significantly associated with cardiac involvement. Among MIS-C patients, non-Hispanic Black race/ethnicity was significantly associated with cardiac involvement. CONCLUSIONS: Cardiac involvement is much more common in children with MIS-C than in those with acute COVID-19. These results reinforce our standardized practice of performing full cardiac evaluations and follow-up in all patients with MIS-C but only in acute COVID-19 patients with signs or symptoms of cardiac involvement.

Lessons Learned From Limited Overlap of 15 In Vitro COVID-19 Drug Repurposing Screens.

Drug repurposing can quickly and cost-effectively identify medical countermeasures against pathogens with pandemic potential and could be used as a down-selection method for selecting US Food and Drug Administration-approved drugs to test in clinical trials. We compared results from 15 high-throughput in vitro screening efforts that tested approved and clinically evaluated drugs for activity against SARS-CoV-2 replication. From the 15 studies, 304 drugs were identified as displaying the highest level of confidence from the individual screens. Of those 304 drugs, 30 were identified in 2 or more screens, while only 3 drugs (apilimod, tetrandrine, and salinomycin) were identified in 4 screens. The lack of concordance in high-confidence hits and variations in protocols makes it challenging to use the collective data as down-selection criteria for identifying repurposing candidates to move into a clinical trial.

Cardiac Magnetic Resonance Findings of COVID-19 Vaccine-Associated Myopericarditis at Intermediate Follow Up: A Comparison with Classic Myocarditis.

OBJECTIVE: To report intermediate cardiac magnetic resonance (CMR) findings of COVID-19 vaccine associated myopericarditis (C-VAM) and compare with classic myocarditis. STUDY DESIGN: Retrospective cohort study including children diagnosed with C-VAM from 5/2021 through 12/2021 with early and intermediate CMR. Patients with classic myocarditis from 1/2015 through 12/2021 and intermediate CMR were included for comparison. RESULTS: There were 8 patients with C-VAM and 20 with classic myocarditis. Among those with C-VAM, CMR performed at median 3 days (IQR 3, 7) revealed 2/8 patients with left ventricular ejection fraction (LVEF)<55%, 7/7 patients receiving contrast with late gadolinium enhancement (LGE), and 5/8 patients with elevated native T1 values. Borderline T2 values suggestive of myocardial edema were present in 6/8. Follow-up CMRs performed at median 107 days (IQR 97, 177) showed normal ventricular systolic function, T1, and T2 values; 3/7 patients had LGE. At intermediate follow-up, C-VAM patients had fewer myocardial segments with LGE than classic myocarditis patients (4/119 vs 42/340, p=0.004). C-VAM patients also had a lower frequency of LGE (42.9 vs 75.0%) and lower percentage of LVEF<55% compared with classic myocarditis (0.0 vs 30.0%), although these differences were not statistically significant. Five classic myocarditis patients did not receive an early CMR, leading to some selection bias in study design. CONCLUSION: Patients with C-VAM had no evidence of active inflammation or ventricular dysfunction on intermediate CMR, although a minority had persistent LGE. Intermediate findings in C-VAM revealed less LGE burden compared with classic myocarditis.

Comparison of mRNA vaccine effectiveness against COVID-19-associated hospitalization by vaccination source: Immunization information systems, electronic medical records, and self-report-IVY Network, February 1-August 31, 2022.

BACKGROUND: Accurate determination of COVID-19 vaccination status is necessary to produce reliable COVID-19 vaccine effectiveness (VE) estimates. Data comparing differences in COVID-19 VE by vaccination sources (i.e., immunization information systems [IIS], electronic medical records [EMR], and self-report) are limited. We compared the number of mRNA COVID-19 vaccine doses identified by each of these sources to assess agreement as well as differences in VE estimates using vaccination data from each individual source and vaccination data adjudicated from all sources combined. METHODS: Adults aged ≥18 years who were hospitalized with COVID-like illness at 21 hospitals in 18 U.S. states participating in the IVY Network during February 1-August 31, 2022, were enrolled. Numbers of COVID-19 vaccine doses identified by IIS, EMR, and self-report were compared in kappa agreement analyses. Effectiveness of mRNA COVID-19 vaccines against COVID-19-associated hospitalization was estimated using multivariable logistic regression models to compare the odds of COVID-19 vaccination between SARS-CoV-2-positive case-patients and SARS-CoV-2-negative control-patients. VE was estimated using each source of vaccination data separately and all sources combined. RESULTS: A total of 4499 patients were included. Patients with ≥1 mRNA COVID-19 vaccine dose were identified most frequently by self-report (n = 3570, 79 %), followed by IIS (n = 3272, 73 %) and EMR (n = 3057, 68 %). Agreement was highest between IIS and self-report for 4 doses with a kappa of 0.77 (95 % CI = 0.73-0.81). VE point estimates of 3 doses against COVID-19 hospitalization were substantially lower when using vaccination data from EMR only (VE = 31 %, 95 % CI = 16 %-43 %) than when using all sources combined (VE = 53 %, 95 % CI = 41 %-62%). CONCLUSION: Vaccination data from EMR only may substantially underestimate COVID-19 VE.

Early Serial Echocardiographic and Ultrasonographic Findings in Critically Ill Patients With COVID-19

Background Cardiac function of critically ill patients with COVID-19 generally has been reported from clinically obtained data. Echocardiographic deformation imaging can identify ventricular dysfunction missed by traditional echocardiographic assessment. Research Question What is the prevalence of ventricular dysfunction and what are its implications for the natural history of critical COVID-19? Study Design and Methods This is a multicenter prospective cohort of critically ill patients with COVID-19. We performed serial echocardiography and lower extremity vascular ultrasound on hospitalization days 1, 3, and 8. We defined left ventricular (LV) dysfunction as the absolute value of longitudinal strain of < 17% or LV ejection fraction (LVEF) of < 50%. Primary clinical outcome was inpatient survival. Results We enrolled 110 patients. Thirty-nine (35.5%) died before hospital discharge. LV dysfunction was present at admission in 38 patients (34.5%) and in 21 patients (36.2%) on day 8 (P = .59). Median baseline LVEF was 62% (interquartile range [IQR], 52%-69%), whereas median absolute value of baseline LV strain was 16% (IQR, 14%-19%). Survivors and nonsurvivors did not differ statistically significantly with respect to day 1 LV strain (17.9% vs 14.4%;P = .12) or day 1 LVEF (60.5% vs 65%;P = .06). Nonsurvivors showed worse day 1 right ventricle (RV) strain than survivors (16.3% vs 21.2%;P = .04). Interpretation Among patients with critical COVID-19, LV and RV dysfunction is common, frequently identified only through deformation imaging, and early (day 1) RV dysfunction may be associated with clinical outcome.

Six-month cardiac outcomes in children with multisystem inflammatory syndrome in children.

BACKGROUND: Multisystem inflammatory syndrome in children is a rare, post-infectious complication of SARS-CoV-2 infection in children. We aimed to assess the long-term sequelae, particularly cardiac, in a large, diverse population. METHODS: We performed a retrospective cohort study of all children (aged 0-20 years, n = 304) admitted to a tertiary care centre with a diagnosis of multisystem inflammatory syndrome in children from March 1, 2020 to August 31, 2021 and had at least one follow-up visit through December 31, 2021. Data were collected at hospitalisation, 2 weeks, 6 weeks, 3 months, and 1 year after diagnosis, where applicable. Cardiovascular outcomes included left ventricular ejection fraction, presence or absence of pericardial effusion, coronary artery abnormalities, and abnormal electrocardiogram findings. RESULTS: Population was median age 9 years (IQR 5-12), 62.2% male, 61.8% African American (AA), and 15.8% Hispanic. Hospitalisation findings included abnormal echocardiogram 57.2%, mean worst recorded left ventricular ejection fraction 52.4% ± 12.4%, non-trivial pericardial effusion 13.4%, coronary artery abnormalities 10.6%, and abnormal ECG 19.6%. During follow-up, abnormal echocardiogram significantly decreased to 6.0% at 2 weeks and 4.7% at 6 weeks. Mean left ventricular ejection fraction significantly increased to 65.4% ± 5.6% at 2 weeks and stabilised. Pericardial effusion significantly decreased to 3.2% at 2 weeks and stabilised. Coronary artery abnormalities significantly decreased to 2.0% and abnormal electrocardiograms significantly decreased to 6.4% at 2 weeks and stabilised. CONCLUSION: Children with multisystem inflammatory syndrome in children have significant echocardiographic abnormalities during the acute presentation, but these findings typically improve within weeks. However, a small subset of patients may have persistent coronary abnormalities.

Effectiveness of Monovalent mRNA COVID-19 Vaccination in Preventing COVID-19-Associated Invasive Mechanical Ventilation and Death Among Immunocompetent Adults During the Omicron Variant Period - IVY Network, 19 U.S. States, February 1, 2022-January 31, 2023.

As of April 2023, the COVID-19 pandemic has resulted in 1.1 million deaths in the United States, with approximately 75% of deaths occurring among adults aged ≥65 years (1). Data on the durability of protection provided by monovalent mRNA COVID-19 vaccination against critical outcomes of COVID-19 are limited beyond the Omicron BA.1 lineage period (December 26, 2021-March 26, 2022). In this case-control analysis, the effectiveness of 2-4 monovalent mRNA COVID-19 vaccine doses was evaluated against COVID-19-associated invasive mechanical ventilation (IMV) and in-hospital death among immunocompetent adults aged ≥18 years during February 1, 2022-January 31, 2023. Vaccine effectiveness (VE) against IMV and in-hospital death was 62% among adults aged ≥18 years and 69% among those aged ≥65 years. When stratified by time since last dose, VE was 76% at 7-179 days, 54% at 180-364 days, and 56% at ≥365 days. Monovalent mRNA COVID-19 vaccination provided substantial, durable protection against IMV and in-hospital death among adults during the Omicron variant period. All adults should remain up to date with recommended COVID-19 vaccination to prevent critical COVID-19-associated outcomes.

Self-isolated but not alone: Community management work in the time of a pandemic

As the COVID-19 crisis forces individuals to self-isolate, work from home, and find new leisure activities, an increasing number are turning to online gaming. These online communities are often developed by community managers who work to engage communities and establish norms. Community management work, broadly, is considered the "soft-skilled" labor of communication, diplomacy, and empathy within an online community. Despite an obvious need for this work in mediating the myriad of personalities and sheer number of users, community management is often underpaid and precarious. Using early interviews with community managers, conducted during the COVID-19 crisis, I aim to highlight those who work promoting pro-social behavior in leisure spaces online. This work plays a vital role in community well-being, particularly for those who have not previously interacted extensively online. Community management is arguably an essential service during times of self-isolation, as they corral toxicity and shepherd users into positive online communities. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Antibody responses to SARS-CoV-2 vaccination outperform responses induced by natural infection in patients with IBD receiving immunosuppressive medications: A report from the ICARUS-IBD consortium

Background: The effects of immunosuppressive medications on immune responses to COVID-19 vaccination in patients with inflammatory bowel diseases (IBD) have been reported. However there is little data on immune responses in naturally infected SARS-CoV-2 patients compared with vaccination. We compared in a longitudinal study SARS-CoV-2 antibody and T cell responses in naturally-infected vs. vaccinated IBD patients Methods: 110 IBD patients enrolled at the Icahn School of Medicine at Mount Sinai were prospectively followed with serial blood collection between May 2020, and February 2022. Samples were screened by ELISA to determine seropositivity, and stratified by infection, vaccination status, and IBD medications. Subsequently, ELISA-based inhibition assay and pseudotyped SARS-CoV-2 microneutralization assays were used to determine the inhibition and neutralization capacity of the seropositive individuals for wild type (WT) delta variant (Dv) and Omicron. Cellular responses were measured by IFN-gamma ELIspot using nucleocapsid and spike peptide libraries Results: Overall, 64 patients had Crohn's Disease and 46 had Ulcerative Colitis (UC), 69 were naturally infected. Only Anti-TNF (N=52), Ustekinumab (N=16), and Vedolizumab (VDZ) (N=33) treatment groups were considered. Only US-available vaccinations were included. Double-vaccinated IBD patients showed greater neutralizing responses to SARS-CoV-2 WT and Dv than naturally-infected individuals (p=0.0003, p=0.0025). Moreover, double-vaccinated individuals had greater neutralizing reactions against WT than DV (p 0.017) and Omicron (p 0.001) variants. Following natural infection, there were no differences between treatment groups in neutralization response, however those double-vaccinated on anti-TNF had lower neutralization than VDZ (p=0.008). Neutralization responses were maintained for a period of 8 months following natural infection and double vaccination SARS-CoV-2 spike T cell responses were significantly higher in naturally infected (p=0.009) and double vaccinated individuals (p=0.005) with no significant differences between treatment groups (p<0.999) Conclusion(s): After a second vaccine dose, IBD patients showed stronger neutralizing antibody titers than naturally infected patients. Those on anti-TNF exhibited lower neutralizing responses than VDZ. T-cell responses were similar in infected and double-vaccinated subjects after vaccination or infection. These data imply COVID-19 immunization provides additional serological protection over natural infection.

Multiple MIS-C Readmissions and Giant Coronary Aneurysm After COVID-19 Illness and Vaccination: A Case Report.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) rarely involves delayed giant coronary aneurysms, multiple readmissions or occurrence after COVID-19 vaccination. METHODS: We describe a child with all 3 of these unusual features. We discuss his clinical presentation, medical management, review of the current literature and CDC guidance recommendations regarding further vaccinations. RESULTS: A 5-year-old boy had onset of MIS-C symptoms 55 days after COVID-19 illness and 15 days after receiving his first BNT162b2 COVID-19 vaccination. He was admitted 3 times for MIS-C, and twice after his steroid dose was tapered. On his initial admission, he was given intravenous immunoglobulin and steroids. During his second admission, new, moderate coronary dilation was noted, and he was treated with intravenous immunoglobulin and steroids. At his last admission, worsening coronary dilation was noted, and he was treated with infliximab and steroids. During follow-up, he had improvement in his coronary artery dilatation. However, his inflammatory markers increased after steroid wean, and his steroid taper was further extended, after which time his inflammatory markers improved. This is the only such reported case of a patient who was admitted 3 times for MIS-C complications after COVID-19 vaccination. CONCLUSION: MIS-C rarely involves delayed giant coronary aneurysms, multiple readmissions, or occurrence after COVID-19 vaccination. Whether our patient's COVID-19 vaccine 6 weeks after COVID-19 illness contributed to his MIS-C is unknown. After consultation with the CDC-funded Clinical Immunization Safety Assessment Project, the patient's care team decided against further COVID-19 vaccination until at least 3 months post normalization of inflammatory markers.