Infusion Of Antibody Research Articles

Monoclonal antibody infusion reaction with bamlanivimab and etesevimab in a 5-year-old male with coronavirus disease 2019: a case report

BackgroundBamlanivimab and etesevimab had been granted emergency use authorization in children under 12 years who are at risk of progression from mild/moderate coronavirus disease 2019 to severe disease and hospitalization.Case reportWe report on a 5-year-old white male with preexisting conditions, predisposing him to severe disease, who developed hypoxia and flushing 3 minutes into his infusion, thus meeting the criteria for anaphylaxis.ConclusionsWe believe this patient developed either an immunoglobulin E-mediated anaphylactic or a non-immunoglobulin E-mediated anaphylactoid reaction to bamlanivimab and etesevimab, which is an important possibility to consider on administration.

Efficacy of oligodendrocyte precursor cells as delivery vehicles for single-chain variable fragment to misfolded SOD1 in ALS rat model

Superoxide dismutase1 (SOD 1) mutation is a leading cause of familial amyotrophic lateral sclerosis (ALS). Growing evidence suggests that antibody therapy against misfolded SOD1 protein can be therapeutic. However, the therapeutic effects are limited, partly because of the delivery system. Therefore, we investigated the efficacy of oligodendrocyte precursor cells (OPCs) as a drug delivery vehicle of single-chain variable fragments (scFv). Using a Borna disease virus vector that is pharmacologically removable and episomally replicable in the recipient cells, we successfully transformed wild-type OPCs to secrete scFv of a novel monoclonal antibody (D3-1), specific for misfolded SOD1. Single intrathecal injection of OPCs scFvD3-1, but not OPCs alone, significantly delayed disease onset and prolonged the lifespan of ALS rat models expressing SOD1 H46R . The effect of OPC scFvD3-1 surpassed that of a 1month intrathecal infusion of full-length D3-1 antibody alone. scFv-secreting OPCs suppressed neuronal loss and gliosis, reduced levels of misfolded SOD1 in the spinal cord, and suppressed the transcription of inflammatory genes, including Olr1, an oxidized low-density lipoprotein receptor 1. The use of OPCs as a delivery vehicle for therapeutic antibodies is a new option for ALS in which misfolded protein and oligodendrocyte dysfunction are implicated in the pathogenesis.

P239 Incidence of Long COVID and impact of medications on the risk of developing Long COVID in a nationwide cohort of Inflammatory Bowel Disease patients

Abstract Background With the ongoing SARS-CoV-2 pandemic there is concern for development of Long COVID in patients with immune-mediated diseases treated with immunosuppressive agents. We aimed to determine the incidence of Long COVID among Inflammatory Bowel Disease (IBD) patients and to identify associated risk factors. Our study also aimed at studying the differences in risk of Long COVID among different IBD medication exposures. Methods We conducted a retrospective cohort study utilizing a nationwide cohort of patients with IBD in the Veteran Affairs Healthcare System (VAHS). Patients diagnosed with SARS-COV-2 between March 10th, 2020, and January 24th, 2021, were included. All charts were reviewed to determine recent IBD hospitalization, hospitalization for SARS-CoV-2 infection, and stability of IBD control pre and post infection. COVID-19 hospitalizations were also reviewed for intensive care unit requirement (ICU). COVID-19 treatments including remdesivir, monoclonal antibody infusions, and corticosteroids were also ascertained. Primary outcome was development of Long COVID. Cox regression analysis was used to identify variables associated with Long COVID. Results A total of 677 patients with SARS-CoV-2 infection were included, of which 49 (7.3%) were diagnosed with Long COVID (Table 1). No significant differences in IBD medication class between patients with and without Long COVID diagnoses were noted. In multivariable regression analysis, COVID-19 hospitalization (HR 3.56, 95% CI 1.80-7.09, p<0.001), ICU requirement (HR 2.20, 95% CI 1.18-4.08, p=0.01), and COPD (HR 2.41, 95% CI 1.03-5.64, p=0.04) were significantly associated with Long COVID (Table 2). Adjusted survival curves showed that relative to patients who were not hospitalized, patients hospitalized in the ICU had an 8.61-fold increased hazard of Long COVID (HR 8.61, 95% CI 3.98-18.65, p<0.001) (Figure 1). Conclusion Hospitalization and ICU care for COVID-19, as well as pre-existing COPD, were associated with increased risk of developing Long COVID, suggesting that severity of infection with a vulnerable substrate are key drivers of risk. Medications used in the treatment of IBD did not impact the risk of Long COVID. These findings should help reassure and inform IBD patients about the risk of Long COVID.

Antibiotic Treatment is an Independent Poor Risk Factor in NSCLC But Not in Melanoma Patients Who had Received Anti-PD-1/L1 Monotherapy

BackgroundAntibiotic treatment may reduce the efficacy of cancer immunotherapy by disrupting gut microbiome. We aimed to study the association of antibiotics and survival outcomes in advanced cutaneous melanoma and non–small-cell lung cancer (NSCLC) patients who had received anti-PD-1/L1 monotherapy. Patients and MethodsA total of 222 melanoma and 199 NSCLC patients had received anti-PD-1/L1 monotherapy in 5 Finnish hospitals between January 2014 and December 2020. Clinical characteristics, antibiotic and corticosteroid treatment, and survival outcomes were retrospectively collected from hospital and national medical records. ResultsThere were 32% of melanoma and 31% of NSCLC patients who had received antibiotic treatment (ABT) 3 months before to 1 month after the first anti-PD-1/L1 antibody infusion. In survival analyses, early antibiotic treatment was associated with inferior overall survival (OS) (ABT 19.2 [17.6-43.7] vs. no ABT 35.6 [29.3-NA] months, P = .033) but not with inferior progression-free survival (PFS) (ABT 5.8 [3.0-12.6] vs. no ABT 10.2 [7.7-15.3] months, P = .3) in melanoma patients and with inferior OS (ABT 8.6 [6.4-12.3] vs. no ABT 18.5 [15.1-21.6] months, P < .001) and PFS (ABT 2.8 [2.1-4.5] vs. no ABT 5.6 [4.4-8.0] months, P = .0081) in NSCLC patients. In multivariable analyses, ABT was not an independent risk-factor for inferior OS and PFS in melanoma but was associated with inferior OS (hazard ratio [HR] 2.12 [1.37-3.28]) and PFS (HR 1.65 [1.10-2.47]) in NSCLC after adjusted for other risk factors. ConclusionsEarly ABT was an independent poor risk factor in NSCLC patients who had received anti-PD-1/L1 monotherapy but not in melanoma patients. The weight of ABT as a poor risk factor might depend on other prognostic factors in different cancers.

Association of Neutralizing Antispike Monoclonal Antibody Treatment With Coronavirus Disease 2019 Hospitalization and Assessment of the Monoclonal Antibody Screening Score

ObjectiveTo test the hypothesis that the Monoclonal Antibody Screening Score performs consistently better in identifying the need for monoclonal antibody infusion throughout each “wave” of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant predominance during the coronavirus disease 2019 (COVID-19) pandemic and that the infusion of contemporary monoclonal antibody treatments is associated with a lower risk of hospitalization. Patients and MethodsIn this retrospective cohort study, we evaluated the efficacy of monoclonal antibody treatment compared with that of no monoclonal antibody treatment in symptomatic adults who tested positive for SARS-CoV-2 regardless of their risk factors for disease progression or vaccination status during different periods of SARS-CoV-2 variant predominance. The primary outcome was hospitalization within 28 days after COVID-19 diagnosis. The study was conducted on patients with a diagnosis of COVID-19 from November 19, 2020, through May 12, 2022. ResultsOf the included 118,936 eligible patients, hospitalization within 28 days of COVID-19 diagnosis occurred in 2.52% (456/18,090) of patients who received monoclonal antibody treatment and 6.98% (7,037/100,846) of patients who did not. Treatment with monoclonal antibody therapies was associated with a lower risk of hospitalization when using stratified data analytics, propensity scoring, and regression and machine learning models with and without adjustments for putative confounding variables, such as advanced age and coexisting medical conditions (eg, relative risk, 0.15; 95% CI, 0.14-0.17). ConclusionAmong patients with mild to moderate COVID-19, including those who have been vaccinated, monoclonal antibody treatment was associated with a lower risk of hospital admission during each wave of the COVID-19 pandemic.

Rituximab Chimeric Anti-CD20 Monoclonal Antibody Therapy for Relapsed Indolent Lymphoma: Half of Patients Respond to a Four-Dose Treatment Program.

The CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies. This was a multiinstitutional trial of the chimeric anti-CD20 antibody, IDEC-C2B8. Patients with relapsed low grade or follicular lymphoma received an outpatient treatment course of IDEC-C2B8 375 mg/m2 intravenously weekly for four doses. From 31 centers, 166 patients were entered. Of this intent-to-treat group, 48% responded. With a median follow-up duration of 11.8 months, the projected median time to progression for responders is 13.0 months. Serum antibody levels were sustained longer after the fourth infusion than after the first, and were higher in responders and in patients with lower tumor burden. The majority of adverse events occurred during the first infusion and were grade 1 or 2; fever and chills were the most common events. Only 12% of patients had grade 3 and 3% grade 4 toxicities. A human antichimeric antibody was detected in only one patient. The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.

Association of Participation in the Maryland Primary Care Program With COVID-19 Outcomes Among Medicare Beneficiaries

Advanced primary care is a team-based approach to providing higher-quality primary care. The association of advanced primary care and COVID-19 outcomes is unknown. To evaluate the association of advanced primary care with COVID-19 outcomes, including vaccination, case, hospitalization, and death rates during the first 2 years of the COVID-19 pandemic. This retrospective cohort study used Medicare claims data from January 1, 2020, through January 31, 2022, and Maryland state vaccination data. All Part A and B Medicare claims for Maryland Medicare beneficiaries were included. The study population was divided into beneficiaries attributed to Maryland Primary Care Program (MDPCP) practices and a matched cohort of beneficiaries not attributed to MDPCP practices but who met the eligibility criteria for study participation from January 1, 2020, through December 31, 2021. Eligibility criteria for both groups included fee-for-service Medicare beneficiaries who were eligible for attribution to the MDPCP. A forced-match design was used to match both groups in the study population by age category, sex, race and ethnicity, Medicare-Medicaid dual eligibility status, COVID-19 Vulnerability Index score, Maryland county of residence, and primary care practice participation. Primary care practice participation in the MDPCP. Primary outcome variables included rate of vaccination, monoclonal antibody infusion uptake, and telehealth claims. Secondary outcomes included rates of COVID-19 diagnosis, COVID-19 inpatient claims, COVID-19 emergency department claims, COVID-19 deaths, and median COVID-19 inpatient admission length of stay. Claims measures were assessed from January 1, 2020, through October 31, 2021. Vaccination measures were assessed from January 1, 2020, through March 31, 2022. After matching, a total of 208 146 beneficiaries in the MDPCP group and 37 203 beneficiaries in the non-MDPCP group were included in this study, comprising 60.10% women and 39.90% men with a median age of 76 (IQR, 71-82) years. Most participants (78.40% and 78.38%, respectively) were White. There were no significant demographic nor risk measure baseline differences between the 2 groups. The MDPCP beneficiaries had more favorable primary COVID-related outcomes than non-MDPCP beneficiaries: 84.47% of MDPCP beneficiaries were fully vaccinated, compared with 77.93% of nonparticipating beneficiaries (P < .001). COVID-19-positive beneficiaries in MDPCP also received monoclonal antibody treatment more often (8.45% vs 6.11%; P < .001) and received more care via telehealth (62.95% vs 54.53%; P < .001) compared with nonparticipating counterparts. In terms of secondary outcomes, beneficiaries in the MDPCP had lower rates of COVID-19 cases (6.55% vs 7.09%; P < .001), lower rates of COVID-19 inpatient admissions (1.81% vs 2.06%; P = .001), and lower rates of death due to COVID-19 (0.56% vs 0.77%; P < .001) compared with nonparticipating beneficiaries. These findings suggest that participation in the MDPCP was associated with lower COVID-19 case, hospitalization, and death rates, and advanced primary care and COVID-19 response strategies within the MDPCP were associated with improved COVID-19 outcomes for attributed beneficiaries.

1108. Feasibility and Impact of a Monoclonal Antibody Infusion Program in Reaching Vulnerable Underserved Communities

Abstract Background Monoclonal antibodies (mAbs) against SARS-CoV-2 are potent therapeutics that prevent progression of disease in high-risk patients. Deploying mAb infusion programs and reaching communities in need remains challenging. We established a mAb infusion program centered in the emergency department (ED) fast-track. We seek to assess the feasibility and impact of our mAb infusion program in reaching vulnerable underserved communities. Methods The ED fast-track was repurposed for mAb infusions. Indications and protocols were created by the infectious disease (ID) physician and antimicrobial stewardship program (ASP). Test to treat was deployed in the ED and a referral program connected patients from telehealth and providers in the community to the infusion program (Figure 1). Data on mAb use from November 2020 to February 2022 was reviewed. To assess the reach of the program in vulnerable communities, the COVID-19 Community Vulnerability Index (CCVI) map by zip code was used. The CCVI identifies communities at risk by using variables such as sociodemographic variables, occupational factors, cumulative COVID-19 burden, vaccine uptake and other factors. Figure 1.Monoclonal antibody infusion test-to-treat and referral process in the ED fast track Results mAbs were successfully deployed and sustained throughout the pandemic, increasing its use in each COVID-19 surge by &amp;gt;103% (Figure 2). A total of 267 patients were treated, with an average age of 52 years, of which 55% (147) were female. Ethnicity was 46% Hispanic and Race was 54% White, 28% Black, 1.4% Asian, 1.8% Multiracial and 14% Other. Zip codes by CCVI were 64% high, 18% medium, and 3% low CCVI index. 15% were outside of city limits without CCVI index (Figure 3). Figure 2.COVID-19 Community Vulnerability Index (CCVI) of patients who received monoclonal antibodies at our program Figure 3 Monoclonal antibody infusions by COVID-19 Community Vulnerability Index (CCVI) and Zip codes Conclusion A mAb infusion program with test to treat and referrals from the community was successfully deployed in an ED fast track. The ED space and staff can be leveraged for mAbs during surges amid clinic staffing challenges. The program adopted novel mAbs as new COVID-19 variants emerged. Uptake increased with each wave, likely reflecting awareness of mAbs and the infusion program by patients and providers in the community. The majority of patients served (82%) were of high and medium CCVI. Thus, this mAb infusion program led by ID and ASP successfully reached predominantly underserved vulnerable populations. Disclosures All Authors: No reported disclosures.

1119. Covid-19 Mab Use in High-Risk Pediatric Patients

Abstract Background Effective therapeutic agents for the treatment of COVID-19 have been investigated since the onset of the pandemic. Monoclonal antibodies targeting the spike protein of SARS-CoV-2 have been developed for treatment of mild or moderate COVID disease in high-risk populations. Despite widespread use in the adult population, data are limited on the safety and efficacy of monoclonal antibody infusions in the adolescent and young adult population. Methods Patients who received bamlanivimab, bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab for treatment of mild COVID disease at Cincinnati Children’s Hospital Medical Center from 5/1/2020 through 3/1/2022 were identified retrospectively. In accordance with the FDA EUA, patients were eligible for monoclonal antibody administration if they were ≥12 years of age, weighed ≥40kg, and were at high risk of progressing to severe disease or hospitalization. Results Ninety-four patients received monoclonal antibody therapy, of which 14 (13.5%) received either bamlanivimab or bamlanivimab-etesevimab, 54 (51.9%) received casirivimab-imdevimab, and 26 (25%) received sotrovimab. Ten patients (10.6%) experienced one or more adverse events. Of those, 2 (14.3%) received either bamlanivimab or bamlanivimab-etesivimab, 7 (12.9%) received casirivimab-imdevimab, and 1 (3.8%) received sotrovimab. Most common symptoms include rash, nausea, and throat irritation (table R1), the majority (90%) of which were mild, either self-resolving with infusion cessation (60%) or persistent but requiring no medical intervention (30%) (table R2). Of the patients who experienced adverse events, only 1 (10%) received medical intervention - epinephrine. No life-threatening events or deaths occurred. Within 90 days of receiving a monoclonal antibody, 15 patients (15.9%) required additional medical care for ongoing COVID symptoms (table R3). Eight (53.3%) of these were either hospitalized or received escalation of care while already in the hospital. Table R1. Infusion-related adverse events. Of note, several patients had more than one symptom. Table R2. Classification of adverse events by grade and monoclonal antibody. Grade I events are defined as mild and generally not bothersome. Grade II events are defined as moderate: bothersome, but not dangerous. Grade III events are defined as medically significant, but not immediately life-threatening, and often require medical intervention. Table R3. Patients who required additional medical care for ongoing COVID-19 symptoms within 90 days of receiving a monoclonal antibody. Conclusion Overall, monoclonal antibodies are safe, largely well-tolerated COVID-19 therapies in high-risk adolescent and young adult populations. Disclosures Grant Schulert, MD, PhD, Novartis: Advisor/Consultant Paul Spearman, MD, CyanVac: Grant/Research Support|Meissa Vaccines: Grant/Research Support Grant C. Paulsen, MD, AstraZeneca: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Lara A. Danziger-Isakov, MD, Ansun BioPharma: Contracted clinical research|Astellas: Contracted clinical research|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Contracted clinical research|Pfizer: Contracted clinical research|Takeda: Grant/Research Support|Takeda: Contracted clinical research|Viracor: Grant/Research Support.

Upper gut heat shock proteins HSP70 and GRP78 promote insulin resistance, hyperglycemia, and non-alcoholic steatohepatitis

A high-fat diet increases the risk of insulin resistance, type-2 diabetes, and non-alcoholic steato-hepatitis. Here we identified two heat-shock proteins, Heat-Shock-Protein70 and Glucose-Regulated Protein78, which are increased in the jejunum of rats on a high-fat diet. We demonstrated a causal link between these proteins and hepatic and whole-body insulin-resistance, as well as the metabolic response to bariatric/metabolic surgery. Long-term continuous infusion of Heat-Shock-Protein70 and Glucose-Regulated Protein78 caused insulin-resistance, hyperglycemia, and non-alcoholic steato-hepatitis in rats on a chow diet, while in rats on a high-fat diet continuous infusion of monoclonal antibodies reversed these phenotypes, mimicking metabolic surgery. Infusion of these proteins or their antibodies was also associated with shifts in fecal microbiota composition. Serum levels of Heat-Shock-Protein70 and Glucose-Regulated Protein78were elevated in patients with non-alcoholic steato-hepatitis, but decreased following metabolic surgery. Understanding the intestinal regulation of metabolism may provide options to reverse metabolic diseases.

GluN1 antibody causes behavioral deficits in prepulse inhibition and memory through CaMKIIβ signaling

Accumulating evidence suggests that some patients with schizophrenia have high production of autoantibodies against the N-methyl-d-aspartate receptor (NMDAR) subunit GluN1 and that these antibodies lead to cognitive impairment. However, the molecular mechanisms of the deficits seen in these patients are largely unknown. In the present study, we found that passive infusion of GluN1 antibody into the hippocampus of mice for 7 days led to decreased expression of GluN1, phosphor-Ser897-GluN1, and EphrinB2 receptor (EphB2R); deficits in long-term potentiation (LTP) and synaptic transmission in the hippocampal CA1 area; impairment in prepulse inhibition (PPI); and deterioration of recognition memory in novel object recognition test. We also found decreased expression of CaMKIIβ, ERK1/2, CREB, and NF-κB after 7 days of GluN1 antibody exposure, as was the phosphorylation of these signaling molecules. The decrease in GluN1 and phosphor-Ser897-GluN1 expression and the deficits in LTP, PPI, and recognition memory were ameliorated by CaMKIIβ overexpression. These results suggest that downregulation of CaMKIIβ–ERK1/2–CREB–NF-κB signaling is responsiable for GluN1 antibody-associated impairment in PPI and memory and that GluN1 antibody-induced NMDAR hypofunction is the underlying mechanism of this impairment. Our findings indicate possible strategies to ameliorate NMDAR antibody-associated cognitive impairment in neuropsychiatric disease. They also provide evidence that NMDAR hypofunction is an underlying mechanism for cognitive impairment in schizophrenia.

Comparison of Short-Term Outcomes for Standard Versus Nonstandard Induction Dosing of Infliximab for Pediatric Inflammatory Bowel Disease.

Recent studies have emphasized the early use of infliximab (IFX) in pediatric patients with inflammatory bowel disease. Standard dosing of 5 mg/kg/dose may not be sufficient to achieve optimal clinical outcomes. The aim of our study was to compare short-term outcomes with standard dosing of IFX to higher, nonstandard dosing of IFX for induction therapy. Retrospective study of 162 pediatric patients receiving either standard (5-6 mg/kg, n = 90) or nonstandard (>6 mg/kg, n = 72) dosing of IFX during induction was performed. Patient demographics, clinical outcomes, and laboratory data were collected. Need for dose escalation during the first 6 months, combination therapy with immunomodulators, and steroid-free progression were investigated. Clinical remission rates between the 2 groups were significantly different, with patients receiving nonstandard dosing demonstrating higher rates (58% vs 78%; p = 0.012). Use of combination therapy with immunomodulators was significantly different between standard and nonstandard groups (80% vs 48%; p < 0.001). Numeric trend in need for IFX dose escalation in the first 6 months was seen between standard and nonstandard groups (54% vs 39%, respectively; p = 0.087). Post-induction IFX trough concentrations, rates of antibody development, drug discontinuation, and infusion reaction were similar. Nonstandard induction dosing of IFX was associated with higher rates of clinical remission, despite similar rates of serum IFX trough concentrations. There was a numeric trend towards the standard group requiring dose escalation within the first 6 months of therapy. Patients given nonstandard dosing may achieve superior clinical outcomes compared with those on standard dosing.

Predicting Risk of Infection Based on Immunoglobulin Nadirs after CD38 Monoclonal Antibody Treatment in Multiple Myeloma

Background: Anti-CD38 monoclonal antibodies are used to treat newly diagnosed and relapsed or refractory multiple myeloma. Previous studies have shown an increased risk of infection while on daratumumab due to the immunosuppressive effect on malignant and normal plasma cells. We sought to retrospectively analyze and further understand the correlation of immunoglobin levels and risk of infection during treatment with anti-CD38 monoclonal antibodies in Multiple Myeloma. Methods: Analysis was performed on data from 261 patients who had received anti-CD38 monoclonal antibody therapy as part of treatment for multiple myeloma between November 11, 2016, and May 11, 2022. 51.7% were male and 48.3% were female. 47.1% of the patients identified as Black, 46% as White, and 6.9% as other races. 14.9% of the patients had Stage I, 41.8% had Stage II and 17.2% had Stage III disease, based on the Revised International Staging System (RISS). Baseline renal disease was present in 35.6% of patients. Median number of anti-CD38 Monoclonal antibody infusions was 16. We examined rates of specific infections (determined by ICD-10 codes), including pneumonia, urinary tract infection, bacteremia, and sepsis, as well as emergency room visits, hospitalizations including ICU stays for up to a year after completing treatment. These rates were correlated with immunoglobulin levels, absolute lymphocyte count, and the presence of concomitant treatment with a proteasome inhibitor or immunomodulator. Results: The overall infection rate among patients receiving anti-CD 38 monoclonal antibody treatment was 32.6%. Bacterial infection developed in 22.2%, viral infections in 17.6%, and fungal infections in 3.4% of patients. SARS-CoV-2 infection rate was 13.4%. The median number of infusions was 15 in those without an infection and 20 in those who developed an infection (p<0.001).19.2% of patients who began anti-CD38 monoclonal antibody treatment during the study period have expired, of whom 56.0 % had an infection. Higher rates of infection were noted with lower IgA levels (p=0.007). There was no significant difference in infection rate with lower IgG and IgA levels or lower absolute lymphocyte levels (p=0.054). However, in patients with an infection there was a longer duration of sub-normal IgG days (114 vs 287 days, p=<0.001), IgA (119.5 vs 215, p=0.006), and IgM (161 vs 274.5, p=0.011). 44.4% of patients had an emergency room visit of whom 40.0% were due to infections (p=0.113). 66.9% of patents required hospital admissions of whom 43.2% had an infection) p<0.001). 18.5% of treated patients required ICU stays of whom 63.9% had an infection) p<0.001). Discussion:Conclusions: A longer duration of subnormal Immunoglobulin levels correlated with higher risk of infection in Multiple Myeloma patients treated with anti-CD 38 monoclonal antibodies. Lowest Ig A levels during treatment correlated with a higher rate of infection while lowest IgG levels did not. Patients who developed infectious complications while on treatment with anti-CD 38 monoclonal antibodies had a significantly higher risk of hospitalization, ICU stays, and death. Prophylactic intravenous immunoglobulin can be studied to evaluate mitigation of infection in the highest risk subpopulation identified in this analysis such as those with prolonged subnormal Immunoglobulin levels. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Post-vaccination SARS-CoV-2 seroprevalence in children aged 3-11 years and the positivity in unvaccinated children: A retrospective, single-center study.

To analyze the positivity and levels of SARS-CoV-2 antibodies in vaccinated children to evaluate the humoral immune response of vaccination on pediatric population. Analysis on the causes of antibody positivity in unvaccinated children. A retrospective study was conducted on children who were admitted to the Children's Hospital Affiliated to Capital Institute of Pediatrics. The clinical data of serological testing of SARS-CoV-2 immunoglobulin M (IgM) and IgG antibodies were collected from SARS-CoV-2 vaccinated or unvaccinated children with no evidence of prior novel coronavirus infection. Chemiluminescence immunoassay was utilized for the in vitro determination of SARS-CoV-2 antibodies. A total of 3,321 healthy children aged 6-11 years received two doses of inactivated SARS-CoV-2 vaccine. At 1 month after the second dose, the positive rate (96.5%) and levels [8.039 (interquartile range (IQR), 6.067-9.098)] of SARS-CoV-2 IgG antibodies reached the peak and remained at a high level for 2-3 months, after which the positive rate and level of vaccine-induced IgG antibody gradually decreased. Compared with 1 month after the second dose of vaccine, the positive rate of IgG antibody decreased to 70.4% at 7 months, and the antibody level decreased by 69.0%. A total of 945 children aged 3-5 years received one or two doses of inactivated vaccine. The positive rate and levels of SARS-CoV-2 IgG antibody in participants remained high for 3 months after vaccination. There was no gender-based difference in positive rate of IgG antibody in children aged 3-11 years old (P>0.05). Among the 5,309 unvaccinated children aged 0 day to 11 years, 105 (2.0%) were positive for SARS-CoV-2 IgG antibody, which was associated with passive infusion. The maternal humoral response to COVID-19 vaccination in noninfected pregnant women was transferred through the placenta to the fetus, and some children obtained SARS-CoV-2-positive antibodies through blood transfusion. Inactivated SARS-CoV-2 vaccines could induce robust humoral immune response that gradually declined within several months after the second dose. Therefore, it helps to determine whether children receive a booster dose and elicit a long-term memory immune response. Positive SARS-CoV-2 antibodies in unvaccinated children were associated with passive IgG antibody infusion.

Early treatment with anti-α4β7 antibody facilitates increased gut macrophage maturity in SIV-infected rhesus macaques.

Despite advances in combination antiretroviral therapy (cART), people living with HIV (PLWH) continue to experience gastrointestinal dysfunction. Infusions of anti-α4β7 monoclonal antibodies (mAbs) have been proposed to increase virologic control during simian immunodeficiency virus (SIV) infection in macaques with mixed results. Recent evidences suggested that therapeutic efficacy of vedolizumab (a humanized anti-α4β7 mAb), during inflammatory bowel diseases depends on microbiome composition, myeloid cell differentiation, and macrophage phenotype. We tested this hypothesis in SIV-infected, anti-α4β7 mAb-treated macaques and provide flow cytometric and microscopic evidence that anti-α4β7 administered to SIV-infected macaques increases the maturity of macrophage phenotypes typically lost in the small intestines during SIV disease progression. Further, this increase in mature macrophage phenotype was associated with tissue viral loads. These phenotypes were also associated with dysbiosis markers in the gut previously identified as predictors of HIV replication and immune activation in PLWH. These findings provide a novel model of anti-α4β7 efficacy offering new avenues for targeting pathogenic mucosal immune response during HIV/SIV infection.

A retrospective investigation of the relationship between neuroblastoma response to anti-GD2 monoclonal antibodies and exposure to opioids for pain management.

Recent increased awareness and research studies reflect possible associations between opioid exposure and cancer outcomes. Children with neuroblastoma (NB) often require opioid treatment for pain. However, associations between tumor response to chemotherapy and opioid exposure have not been investigated in clinical settings. This is a single-institution retrospective review of patients with NB treated between 2013 and 2016. We evaluated opioid consumption quantified in morphine equivalent doses (mg/kg) based on nurse- or patient-controlled analgesia during antibody infusions. We also analyzed their associations with change in primary tumor volume and total tumor burden. Of 42 patients given opioids for pain related to anti-disialoganglioside monoclonal antibodies (anti-GD2 mAb), data completion was achieved for 36, and details of statistical analyses were entered. Median total weight-based morphine equivalent (over 8days) was 4.71mg/kg (interquartile range 3.49-7.96). We found a statistically insignificant weak negative relationship between total weight-based morphine equivalents and tumor volume ratio (correlation coefficient -.0103, p-value .9525) and a statistically insignificant weak positive relationship between total weight-based morphine equivalent and Curie score ratio (correlation coefficient .1096, p-value .5247). Our study found no statistically significant correlation between opioid consumption and natural killer (NK) cell-mediated killing of NB cells as measured by effects on tumor volume/tumor load.

Identifying HIV sequences that escape antibody neutralization using random forests and collaborative targeted learning

Abstract Recent studies have indicated that it is possible to protect individuals from HIV infection using passive infusion of monoclonal antibodies. However, in order for monoclonal antibodies to confer robust protection, the antibodies must be capable of neutralizing many possible strains of the virus. This is particularly challenging in the context of a highly diverse pathogen like HIV. It is therefore of great interest to leverage existing observational data sources to discover antibodies that are able to neutralize HIV viruses via residues where existing antibodies show modest protection. Such information feeds directly into the clinical trial pipeline for monoclonal antibody therapies by providing information on (i) whether and to what extent combinations of antibodies can generate superior protection and (ii) strategies for analyzing past clinical trials to identify in vivo evidence of antibody resistance. These observational data include genetic features of many diverse HIV genetic sequences, as well as in vitro measures of antibody resistance. The statistical learning problem we are interested in is developing statistical methodology that can be used to analyze these data to identify important genetic features that are significantly associated with antibody resistance. This is a challenging problem owing to the high-dimensional and strongly correlated nature of the genetic sequence data. To overcome these challenges, we propose an outcome-adaptive, collaborative targeted minimum loss-based estimation approach using random forests. We demonstrate via simulation that the approach enjoys important statistical benefits over existing approaches in terms of bias, mean squared error, and type I error. We apply the approach to the Compile, Analyze, and Tally Nab Panels database to identify AA positions that are potentially causally related to resistance to neutralization by several different antibodies.

Single Site Experience of the use of Monoclonal Antibodies for the Treatment of COVID-19 in High-risk Pediatric and Young Adult Patients.

Effective therapeutic agents for the treatment of COVID-19 have been investigated since the onset of the pandemic. Monoclonal antibodies targeting the spike protein of SARS-CoV-2 have been developed for the treatment of mild or moderate COVID disease in high-risk populations. Despite widespread use in the adult population, data are limited on the safety and efficacy of monoclonal antibody infusions in the adolescent and young adult population. Patients who received bamlanivimab, bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab for treatment of mild-to-moderate COVID-19 disease at Cincinnati Children's Hospital Medical Center from 5/1/2020 to 3/1/2022 were identified retrospectively. Patient data including demographics, adverse events, and outcomes were extracted from patients' charts and summarized by standard descriptive summaries. Ninety-four patients received monoclonal antibody therapy, of which 14 (14.9%) received either bamlanivimab or bamlanivimab-etesevimab, 54 (57.4%) received casirivimab-imdevimab, and 26 (27.6%) received sotrovimab. Ten patients (10.6%) experienced one or more infusion-related adverse event. Of the patients who experienced adverse events, all resolved with cessation of infusion. No life-threatening events or deaths occurred. Within 90 days of receiving a monoclonal antibody, 12 patients (12.7%) required additional medical care for ongoing COVID symptoms. Five of these were either hospitalized or received escalation of care while already in the hospital. All subsequently fully recovered. Neither infusion-related adverse events nor progression to hospitalization for ongoing COVID-19 symptoms following monoclonal antibody administration were associated with any particular underlying condition. Overall, monoclonal antibodies are reasonably well-tolerated COVID-19 therapies in high-risk adolescent and young adult populations.

An update on the considerations for patients with rheumatic disease being treated with rituximab during the COVID-19 pandemic and the potential drug treatment strategies

ABSTRACT Introduction Over the last two decades, rituximab has become an increasingly popular drug in the treatment of a wide range of rheumatic diseases. However, with the advent of the COVID-19 pandemic, clinicians face challenges in weighing risk against benefit in its use. Areas covered A review of existing data was performed to examine the relationship between rituximab use, morbidity and mortality from COVID-19, and vaccine efficacy in patients with rheumatic diseases, aiming to guide clinicians in continued use of the medication and consider the direction of future research. A literature review was performed through a search of the PubMed database, using the terms ((SARS-CoV-2) OR (COVID-19)) AND (rituximab) AND (rheumatic), which generated an initial 55 results, with relevant articles then selected for inclusion. Expert opinion In order to safeguard patients with an ongoing need for rituximab therapy, vaccination remains the primary concern. A target of performing booster doses 6 months after last rituximab dose is a reasonable estimate, which may be made more precise by use of B cell counts, although primary immunization should not be delayed. In those patients who remain seronegative, the use of newer antivirals and broadly neutralizing antibody infusions may help provide further safeguards.

Standing-up COVID-19 monoclonal antibody infusion centers: Infection prevention and control

This paper describes the creation of outpatient monoclonal antibody (mAb) infusion centers for COVID-19 patients in a large academic medical center. It shows how the early and consistent partnership between infection prevention and the clinical and operational teams to establish and implement policies and procedures led to efficient and safe workflows.