550. Bamlanivimab and Casirivimab/Imdevimab Treatment Outcomes: Results from a Large Healthcare System’s Structured Implementation Experience

Abstract Background Neutralizing antibody therapies targeting SARS-CoV-2 have been released for emergency use authorization by the FDA. Little is published on their real-world experience. In this retrospective study we share the results of our early experience on patient outcomes from use of these neutralizing antibodies within a large healthcare system. Methods We retrospectively analyzed results of a healthcare system wide program to pro-actively identify and treat COVID-19 patients with neutralizing antibody therapy. Results The 449 patients identified for SARS-CoV-2 neutralizing antibody therapy during the study period were retrospectively classified as falling in one of the three groups: untreated (199), bamlanivimab (87) and casirivimab/indevimab (125) treated patients (Table 1). Reasons identified patients were not treated most commonly were patient declined (n=74), unable to be contacted (n=36), out of treatment window (n=23), asymptomatic and feeling better (n=21) or did not have transportation (n=9). Bamlanivimab infusion did not reduce emergency room (ER) visits or hospitalization compared to untreated patient within 30-days of follow up (Table 2), and among all patients treated with antibody therapy only treatment with bamlanivimab and non-white race were predictors of need for hospitalization (Table 3). Casirivimab/indevimab did reduce subsequent ER visits or hospitalization within 30 days post-infusion when compared to the untreated group. However, patients treated with either antibody therapy had lower acuity of COVID-19 disease as reflected in need for intensive care unit (ICU) stay, mechanical ventilation or death (Table 2). Table 1. Characteristics of infused vs uninfused patients Table 2. Outcomes in treated vs untreated patients Table 3. Risk factors for ED visits or hospitalization in infused patients Conclusion Either neutralizing antibody therapy appears to markedly reduce acuity of COVID-19 disease even if patients do progress to requiring hospitalization. However, casirivimab/indevimab therapy also decreased ER visits and hospitalization suggesting better efficacy in our experience. Disclosures Christopher Polk, MD, Atea (Research Grant or Support)Gilead (Advisor or Review Panel member, Research Grant or Support)Humanigen (Research Grant or Support)Regeneron (Research Grant or Support) Mindy Sampson, MD, Regeneron (Grant/Research Support)

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Models to inform neutralizing antibody therapy strategies during pandemics: the case of SARS-CoV-2

Antibody Therapeutics ◽

10.1093/abt/tbab006 ◽

2021 ◽

Vol 4 (1) ◽

pp. 60-71

Author(s):

Donovan Guttieres ◽

Anthony J Sinskey ◽

Stacy L Springs

Keyword(s):

Value Chain ◽

Neutralizing Antibodies ◽

Resource Constraints ◽

Antibody Therapy ◽

Neutralizing Antibody ◽

Epidemiological Data ◽

Production Costs ◽

Production Scale ◽

Design And Optimization ◽

Critical Components

Abstract Background Neutralizing antibodies (nAbs) against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) can play an important role in reducing impacts of the COVID-19 pandemic, complementing ongoing public health efforts such as diagnostics and vaccination. Rapidly designing, manufacturing and distributing nAbs requires significant planning across the product value chain and an understanding of the opportunities, challenges and risks throughout. Methods A systems framework comprised of four critical components is presented to aid in developing effective end-to-end nAbs strategies in the context of a pandemic: (1) product design and optimization, (2) epidemiology, (3) demand and (4) supply. Quantitative models are used to estimate product demand using available epidemiological data, simulate biomanufacturing operations from typical bioprocess parameters and calculate antibody production costs to meet clinical needs under various realistic scenarios. Results In a US-based case study during the 9-month period from March 15 to December 15, 2020, the projected number of SARS-CoV-2 infections was 15.73 million. The estimated product volume needed to meet therapeutic demand for the maximum number of clinically eligible patients ranged between 6.3 and 31.5 tons for 0.5 and 2.5 g dose sizes, respectively. The relative production scale and cost needed to meet demand are calculated for different centralized and distributed manufacturing scenarios. Conclusions Meeting demand for anti-SARS-CoV-2 nAbs requires significant manufacturing capacity and planning for appropriate administration in clinical settings. MIT Center for Biomedical Innovation’s data-driven tools presented can help inform time-critical decisions by providing insight into important operational and policy considerations for making nAbs broadly accessible, while considering time and resource constraints.

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2855. Respiratory Syncytial Virus Neutralizing Antibodies in Cord Blood and Serum from Infants up to 2 Years of Age in a Multinational Prospective Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz359.160 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S74-S75

Author(s):

Joseph B Domachowske ◽

Veronique Bianco ◽

Ana Ceballos ◽

Luis Cousin ◽

Ulises D’Andrea ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Cord Blood ◽

Neutralizing Antibodies ◽

Geometric Mean ◽

Neutralizing Antibody ◽

Neutralization Assay ◽

Entire Cohort ◽

Syncytial Virus ◽

Tract Infections

Abstract Background Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections (LRTI) during infancy worldwide. High cord blood (CB) concentrations of anti-RSV neutralizing antibody (nAb) may attenuate, delay, or prevent infant infection. We report RSV A and B nAb concentrations in CB and serum from a birth cohort at different time points through 2 years of age. Methods Between 2013 and 2017, newborns from 8 countries were studied prospectively from birth to 2 years of age (NCT01995175). CB was collected at birth for the entire cohort. A subcohort of children was randomly assigned to have one blood sample collected again at either 2, 4, 6, 12, 18, or 24 months of age. Sera were analyzed for RSV A and B nAb concentrations by serum neutralization assay. Active surveillance was used to identify LRTIs during the 2-year follow-up as previously reported. Results In total, 2,401 newborns were enrolled and followed up. >99% of infants had detectable CB RSV A and B nAb. Geometric mean antibody titers (GMTs) varied by country, but were overall higher for RSV B than for RSV A (327 vs. 251; Figure 1). The lowest GMTs were seen from CB sera collected from South African newborns (197 RSV A, 255 RSV B); Canadian newborns had the highest RSV A GMT (383), while Hondurans had the highest RSV B GMT (460). 1380 infants provided follow-up serum nAb results as part of the subcohort (Figure 2). Dramatic waning of GMTs was evident, with a ~3-fold drop in GMTs at 2 months of age, and an additional ~2-fold drop between 2 and 4 months of age. At 6 and 12 months of age, 71% and 50% of infants had RSV A nAb and GMTs were at a nadir of 14. At 6, 12, and 18 months of age, RSV B nAb was detected in 98%, 69%, and 63% of infants, respectively. The RSV B nAb nadir GMT of 20 was observed at 12 months of age, while the 6- and 18-month RSV B nAb GMTs were 30 and 31, respectively. A total of 1,017 LRTIs were identified during the 2-year study period; of which, 94 (9%) were caused by RSV A and 132 (13%) by RSV B. Associations between CB nAb levels and RSV infection will be presented. Conclusion Neutralizing Ab to RSV A and B was present at birth in infants from 8 countries, and waned over time. GMTs were at a nadir at 6 to 12 months of age. Funding. GlaxoSmithKline Biologicals SA. Disclosures All Authors: No reported Disclosures.

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Function is more reliable than quantity to follow up the humoral response to the Receptor Binding Domain of SARS- CoV-2 Spike Protein after Natural Infection or COVID-19 vaccination

10.1101/2021.06.02.21257975 ◽

2021 ◽

Author(s):

Carlos A Sariol ◽

Petraleigh Pantoja ◽

Crisanta Serrano-Collazo ◽

Tiffant Rosa-Arocho ◽

Albersy Armina ◽

...

Keyword(s):

Immune Response ◽

Neutralizing Antibodies ◽

Natural Infection ◽

Vaccine Dose ◽

Humoral Response ◽

Neutralizing Antibody ◽

Viral Neutralization ◽

Neutralizing Activity ◽

Robust Immune Response

On this work we report that despite of a decline in the total anti-Spike antibodies the neutralizing antibodies remains at a similar level for an average of 98 days in a longitudinal cohort of 59 Hispanic/Latino exposed to SARS-CoV-2. We are also reporting that the percentage of neutralization correlates with the IgG titers and that in the first collected samples, IgG1 was the predominant isotype (62.71%), followed by IgG4 (15.25%), IgG3 (13.56%), and IgG2 (8.47%) during the tested period. The IgA was detectable in 28.81% of subjects. Only 62.71% of all subjects have detectable IgM in the first sample despite of confirmed infection by a molecular method. Our data suggests that 100% that seroconvert make detectable neutralizing antibody responses measured by a surrogate viral neutralization test. We also found that the IgG titers and neutralizing activity were higher after the first dose in 10 vaccinated subjects out of the 59 with prior infection compare to a subgroup of 21 subjects naive to SARS-CoV-2. One dose was enough but two were necessary to reach the maximum percentage of neutralization in subjects with previous natural infection or naive to SARS-CoV-2 respectively. Like the pattern seen after the natural infection, after the second vaccine dose, the total anti-S antibodies and titers declined but not the neutralizing activity which remains at same levels for more than 80 days after the first vaccine dose. That decline, however, was significantly lower in pre-exposed individuals which denotes the contribution of the natural infection priming a more robust immune response to the vaccine. Also, our data indicates that the natural infection induces a more robust humoral immune response than the first vaccine dose in unexposed subjects. However, the difference was significant only when the neutralization was measured but not by assessing the total anti-S antibodies or the IgG titers. This work is an important contribution to understand the natural immune response to the novel coronavirus in a population severely hit by the virus. Also provide an invaluable data by comparing the dynamic of the immune response after the natural infection vs. the vaccination and suggesting that a functional test is a better marker than the presence or not of antibodies. On this context our results are also highly relevant to consider standardizing methods that in addition to serve as a tool to follow up the immune response to the vaccines may also provide a correlate of protection.

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LB2. Safety and Efficacy of Combination SARS-CoV-2 Monoclonal Neutralizing Antibodies (mAb) BRII-196 and BRII-198 in Non-Hospitalized COVID-19 Patients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1643 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S807-S808

Author(s):

Teresa H Evering ◽

Mark Giganti ◽

Kara W Chew ◽

Michael Hughes ◽

Carlee Moser ◽

...

Keyword(s):

High Risk ◽

Symptom Onset ◽

Interim Analysis ◽

Neutralizing Antibodies ◽

Severe Disease ◽

Panel Member ◽

The Philippines ◽

Research Support ◽

Review Panel ◽

Research Grant

Abstract Background SARS-CoV-2 continues to spread and the development of safe and effective therapeutics for the prevention of severe disease remains a priority. BRII-196 and BRII-198 are non-competing anti-SARS-CoV-2 mAbs with YTE triple amino acid substitution in Fc to extend half-life and reduce receptor binding, that are being studied for treatment of COVID-19 in the ACTIV-2 Trial, sponsored by NIAID and led by ACTG. Methods ACTIV-2 evaluates safety/efficacy of investigational agents for treatment of non-hospitalized adults with mild-moderate COVID-19 under a randomized, blinded, controlled adaptive platform. BRII-196/BRII-198 (1000 mg each) as a single dose given as sequential infusions, or placebo to those at high risk of clinical progression (i.e., age ≥ 60 years or presence of other medical conditions) within 10 days of symptom onset and positive test for SARS-CoV-2. The primary endpoint was hospitalization and/or death through day 28. We report Phase 3 BRII-196/BRII-198 trial results per DSMB recommendation following an interim analysis. Results Between January and July 2021, 837 participants (418 active, 419 placebo) from sites in the US (66%), Brazil, South Africa, Mexico, Argentina and the Philippines were randomized and received study product at time of emerging variants. Median age 49 years (Q1, Q3: 39, 58), 51% female, 17% Black/African-American and 49% Hispanic/Latino, with median 6 days from symptom onset. At interim analysis 71% and 97% had a day 28 and 7 visit, respectively. For all available data at interim review, BRII-196/BRII-198 compared to placebo had fewer hospitalizations (12 vs. 45) and deaths (1 vs. 9). At day 28 of follow-up, there was an estimated 78% reduction in hospitalization and/or death (2.4 vs. 11.1%), relative risk 0.22 (95% CI: 0.05, 0.86), P=0.00001 (nominal one-sided). Grade 3 or higher adverse events (AEs) were observed less frequently among BRII-196/BRII-198 participants than placebo (3.8% vs. 13.4%) with no severe infusion reactions or drug related serious AEs. Conclusion BRII-196/BRII-198 was safe, well-tolerated, and demonstrated significant reduction compared to placebo in the risk of hospitalization and/or death among adults with mild-moderate COVID-19 at high risk for progression to severe disease. Disclosures Kara W. Chew, MD, MS, Amgen (Individual(s) Involved: Self): Grant/Research Support; Merck Sharp & Dohme (Individual(s) Involved: Self): Grant/Research Support David Alain Wohl, MD, Gilead Sciences (Individual(s) Involved: Self): Advisor or Review Panel member, Consultant, Research Grant or Support, Scientific Research Study Investigator; Janssen (Individual(s) Involved: Self): Advisor or Review Panel member; Merck (Individual(s) Involved: Self): Advisor or Review Panel member, Research Grant or Support; ViiV (Individual(s) Involved: Self): Advisor or Review Panel member, Research Grant or Support Joseph J. Eron, MD, Gilead Sciences (Consultant, Research Grant or Support)Janssen (Consultant, Research Grant or Support)Merck (Consultant)ViiV (Consultant, Research Grant or Support) David A. Margolis, MD MPH, Brii Biosciences (Employee) Courtney Fletcher, Pharm.D., National Institute of Allergy and Infectious Diseases, NIH (Grant/Research Support) Davey Smith, M.D., Linear Therapies, Matrix Biomed, Bayer (Consultant, Shareholder) Eric Daar, Gilead (Consultant, Grant/Research Support)Merck (Consultant)ViiV (Consultant, Grant/Research Support)

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Antigen-specific tolerization in human autoimmunity: Inhibition of interferon-beta1a anti-drug antibodies in multiple sclerosis

10.1101/2021.01.24.21250414 ◽

2021 ◽

Author(s):

Monica Marta ◽

David Baker ◽

Paul Creeke ◽

Gareth Pryce ◽

Sharmilee Gnanapavan ◽

...

Keyword(s):

Multiple Sclerosis ◽

Neutralizing Antibodies ◽

Tolerance Induction ◽

Neutralizing Antibody ◽

Immune Tolerance Induction ◽

Autoimmune Condition ◽

Potential Risks ◽

Treatment Alternatives ◽

Specific Tolerance

ABSTRACTBackgroundAntigen-specific tolerance in auto-immune diseases is the goal for effective treatment with minimal side-effects. Whilst this is achievable in animal models, notably via intravenous delivery of the model-specific autoantigen following transient CD4 T cell depletion, specific multiple sclerosis autoantigens remain unproven. However, anti-drug antibodies to human therapeutic proteins represent a model human autoimmune condition, which may be used to examine immune-tolerance induction. Some people with MS (PwMS) on interferon-beta1a (IFNβ1a) develop neutralizing antibodies to IFNβ1a that do not disappear in repeated tests over years.MethodsOne PwMS was recruited, as part of a planned phase IIa trial (n=15), who had developed neutralizing antibodies to subcutaneous IFNβ1a. Mitoxantrone (12mg/m2) was administered as a lymphocyte depleting agent followed by four days of (88μg/day + three 132μg/day) intravenous IFNβ1a. Subcutaneous IFNβ1a three times a week was maintained during follow-up. IFNβ1a neutralizing antibody responses in serum were measured during treatment and three-monthly for 12 months.FindingsOne participant was recruited and, within 6 months of tolerization, the neutralizing antibodies were undetectable. The tolerization treatment was well tolerated. However, the study was terminated after the first enrolment, on ethical grounds, as treatment alternatives became available and the potential risks of mitoxantrone use increased.InterpretationThe data suggest that it may be possible to induce antigen-specific tolerance by providing tolerogenic antigen following transient immune depletion. Further studies are warranted.FundingThe study was supported by an unrestricted research grant from Merck-Serono.

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SARS-CoV-2 Neutralizing Antibody Levels Post COVID-19 Vaccination Based on ELISA Method—A Small Real-World Sample Exploration

Vaccines ◽

10.3390/vaccines9101139 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1139

Author(s):

Xiaoguang Li ◽

Chao Liang ◽

Xiumei Xiao

Keyword(s):

Neutralizing Antibodies ◽

Detection Rate ◽

Neutralizing Antibody ◽

Population Characteristics ◽

Detection Rates ◽

Positive Detection Rate ◽

Significant Difference ◽

Positive Rate ◽

Antibody Levels

This study investigated the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies following inoculation with the coronavirus disease (COVID-19) vaccine. From June to July 2021, 127 participants who had completed COVID-19 vaccination (inactivated SARS-CoV-2 vaccine, 64; CoronaVac, 61; CanSino, 2) were recruited and tested using SARS-CoV-2 neutralizing antibody kits. The positive detection rate (inhibition of neutralizing antibodies ≥ 30%) was calculated and stratified according to population characteristics and inoculation time. The positive rate of neutralizing antibody was 47.22% (17/36) in men and 53.85% (49/91) in women, and 54.55% (24/44) in BMI ≥ 24 and 50.60% (42/83) in BMI < 24. Age was stratified as 20–29, 30–39, 40–49, and ≥50; positive detection rates of SARS-CoV-2 neutralizing antibodies were observed in 60.00% (24/40), 50.00% (21/42), 48.39% (15/31), and 42.86% (6/14), respectively, but with no significant difference (x2 = 1.724, p = 0.632). Among 127 vaccinated participants, 66 (51.97%) were positive. The positive detection rate was 63.93% (39/61) with CoronaVac and 42.19% (27/64) with the inactivated SARS-CoV-2 vaccine (significance x2 = 5.927, p = 0.015). Multivariate analysis revealed a significant difference in vaccination times, with average vaccination weeks in the positive and negative groups of 11.57 ± 6.48 and 17.87 ± 9.17, respectively (t= −4.501, p < 0.001). The positive neutralizing antibody rate was 100.00%, 60.00%, 58.33%, 55.56%, 43.14%, 28.57%, and 0.00% at 2–4, 5–8, 9–12, 13–16,17–20, 21–24, and >24 weeks, respectively (x2 = 18.030, p = 0.006). Neutralizing antibodies were detected after COVID-19 inoculation, with differences relating to inoculation timing. This study provides a reference for vaccine evaluation and follow-up immunization strengthening.

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The Trend of Neutralizing Antibody Response Against SARS-CoV-2 and the Cytokine/Chemokine Release in Patients with Differing Severities of COVID-19: All Individuals Infected with SARS-CoV-2 Obtained Neutralizing Antibody

10.1101/2020.08.05.20168682 ◽

2020 ◽

Author(s):

Lidya Handayani Tjan ◽

Tatsuya Nagano ◽

Koichi Furukawa ◽

Mitsuhiro Nishimura ◽

Jun Arii ◽

...

Keyword(s):

Antibody Production ◽

Neutralizing Antibodies ◽

Clinical Course ◽

Antibody Therapy ◽

Neutralizing Antibody ◽

Older Individuals ◽

First Line ◽

Critical Patients ◽

High Level ◽

Different Levels

Background: COVID-19 patients show a wide clinical spectrum ranging from mild respiratory symptoms to severe and fatal disease, and older individuals are known to be affected more severely. Neutralizing antibody for viruses is critical for their elimination, and increased cytokine/chemokine levels are thought to be related to COVID-19 severity. However, the trend of the neutralizing antibody production and cytokine/chemokine levels during the clinical course of COVID-19 patients with differing levels of severity has not been established. Methods: We serially collected 45 blood samples from 12 patients with different levels of COVID-19 severity, and investigated the trend of neutralizing antibody production using authentic SARS-CoV-2 and cytokine/chemokine release in the patients' clinical courses. Results: All 12 individuals infected with SARS-CoV-2 had the neutralizing antibody against it, and the antibodies were induced at approx. 4-10 days after the patients' onsets. The antibodies in the critical and severe cases showed high neutralizing activity in all clinical courses. Most cytokine/chemokine levels were clearly high in the critical patients compared to those with milder symptoms. Conclusion: Neutralizing antibodies against SARS-CoV-2 were induced at a high level in the severe COVID-19 patients, indicating that abundant virus replication occurred. Cytokines/chemokines were expressed more in the critical patients, indicating that high productions of cytokines/chemokines have roles in the disease severity. These results may indicate that plasma or neutralizing antibody therapy could be a first-line treatment for older patients to eliminate the virus, and corticosteroid therapy could be effective to suppress the cytokine storm after the viral genome's disappearance.

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SARS-CoV-2 Neutralizing Antibodies for COVID-19 Prevention and Treatment

Annual Review of Medicine ◽

10.1146/annurev-med-042420-113838 ◽

2021 ◽

Vol 73 (1) ◽

Author(s):

Dapeng Li ◽

Gregory D. Sempowski ◽

Kevin O. Saunders ◽

Priyamvada Acharya ◽

Barton F. Haynes

Keyword(s):

Neutralizing Antibodies ◽

Antibody Therapy ◽

Neutralizing Antibody ◽

Annual Review ◽

Publication Date ◽

The Past ◽

Therapeutic Drugs ◽

Therapeutic Uses ◽

The Us ◽

Prevention And Treatment

Prophylactic and therapeutic drugs are urgently needed to combat coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Over the past year, SARS-CoV-2 neutralizing antibodies have been developed for preventive or therapeutic uses. While neutralizing antibodies target the spike protein, their neutralization potency and breadth vary according to recognition epitopes. Several potent SARS-CoV-2 antibodies have shown degrees of success in preclinical or clinical trials, and the US Food and Drug Administration has issued emergency use authorization for two neutralizing antibody cocktails. Nevertheless, antibody therapy for SARS-CoV-2 still faces potential challenges, including emerging viral variants of concern that have antibody-escape mutations and the potential for antibody-mediated enhancement of infection or inflammation. This review summarizes representative SARS-CoV-2 neutralizing antibodies that have been reported and discusses prospects and challenges for the development of the next generation of COVID-19 preventive or therapeutic antibodies. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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847. Trends in Stenotrophomonas maltophilia Antibiotic Resistance Rates

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1036 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S463-S464

Author(s):

Aisling Caffrey ◽

Emily T O’Neill ◽

Haley J Appaneal ◽

Vrishali Lopes ◽

Kerry LaPlante

Keyword(s):

Healthcare System ◽

Stenotrophomonas Maltophilia ◽

Panel Member ◽

Positive Culture ◽

Outpatient Setting ◽

Medical Centers ◽

Ocean Spray ◽

Community Living Centers ◽

Resistance Rates ◽

Research Grant

Abstract Background Studies from the 1990’s and 2000’s identified increasing rates of Stenotrophomonas maltophilia, particularly among respiratory isolates and in intensive care populations. Additionally, resistance in S. maltophilia was found to be worsening. We aimed to quantify recent trends in prevalence and resistance of S. maltophilia in the national Veterans Affairs (VA) Healthcare system. Methods We identified positive S. maltophilia clinical cultures among VA adult patients from 2010 to 2018, collected in either VA medical centers (VAMCs), community living centers (CLCs), or the outpatient (Outpt) setting. Multidrug resistance (MDR) was defined as resistance to sulfamethoxazole/trimethoprim (SMX/TMP) and minocycline or levofloxacin. Time trends were assessed with regression analyses to estimate annual average percent changes (AAPC) with 95% confidence intervals using Joinpoint Software. Results Over the 9-year study period, we identified 18,285 S. maltophilia cultures (57% VAMCs, 3% CLCs, 40% Outpt). S. maltophilia cultures made up 0.4% of all positive cultures in the VA. In VAMCs and CLCs, the number of S. maltophilia cultures decreased 5.1% and 8.5% per year, respectively. Alternatively, of all positive cultures in VAMCs, the proportion that were S. maltophilia increased significantly by 2.6% per year. SMX/TMP resistance decreased significantly by 8.5% (2010, 15%; 2018, 6%) per year in VAMCs, and decreased non-significantly by 8.7% (2010, 13%, 2018, 6%) per year in CLCs and 6.0% (2010, 12%; 2018, 7%) in the outpatient setting. No other significant changes in resistance were observed over the study period. MDR increased non-significantly by 1.2% per year. Conclusion While previous studies found increasing rates of S. maltophilia, the number of positive S. maltophilia cultures decreased in the national VA Healthcare System between 2010 and 2018. However, S. maltophilia is making up a greater proportion of positive culture over time. During the study period, resistance to SMX/TMP decreased and now more closely reflects previously reported resistance rates worldwide (0-10%). Disclosures Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi (Research Grant or Support) Haley J. Appaneal, Pharm.D, Shionogi, Inc. (Research Grant or Support) Kerry LaPlante, PharmD, Merck (Advisor or Review Panel member, Research Grant or Support)Ocean Spray Cranberries, Inc. (Research Grant or Support)Pfizer Pharmaceuticals (Research Grant or Support)Shionogi, Inc. (Research Grant or Support)

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178. Vaccine Effectiveness Against Influenza-associated Hospitalizations and Emergency Department (ED) Visits Among Children in the United States in the 2019–2020 Season

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.488 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S217-S218

Author(s):

Angela P Campbell ◽

Constance E Ogokeh ◽

Geoffrey A Weinberg ◽

Julie A Boom ◽

Janet A Englund ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Panel Member ◽

Influenza B ◽

Research Support ◽

Review Panel ◽

Study Investigator ◽

Influenza A H1n1 ◽

Ed Visits ◽

Research Grant

Abstract Background The 2019–20 influenza season was predominated by early onset B/Victoria viruses followed by A(H1N1)pdm09 virus circulation. Over 95% of circulating B/Victoria viruses were subclade V1A.3, different from the Northern Hemisphere vaccine strain. Annual estimates of influenza vaccine effectiveness (VE) are important because of frequent changes in circulating and vaccine viruses. Methods We assessed VE among children 6 months–17 years old with acute respiratory illness and <10 days of symptoms enrolled during the 2019–20 influenza season at 7 pediatric hospitals (ED patients < 5 years at 3 sites) in the New Vaccine Surveillance Network. Combined mid-turbinate/throat swabs were tested for influenza virus using molecular assays. We estimated age-stratified VE from a test-negative design using logistic regression to compare odds of vaccination among children testing positive versus negative for influenza, adjusting for age in years, enrollment month, and site. For these preliminary analyses, vaccination status was by parental report. Results Among 2022 inpatients, 324 (16%) were influenza positive: 38% with influenza B/Victoria alone and 44% with influenza A(H1N1)pdm09 alone (Table). Among 2066 ED children, 653 (32%) were influenza positive: 45% with influenza B/Victoria alone and 43% with influenza A(H1N1)pdm09 alone. VE was 62% (95% confidence interval [CI], 51%–70%) against any influenza-related hospitalizations, 68% (95% CI, 55%–78%) for A(H1N1)pdm09 and 55% (95% CI, 35%–69%) for B/Victoria. VE by age group for any influenza-related hospitalizations was 57% (95% CI, 40%–69%) among children 6 months to < 5 years and 66% (95% CI, 49%–77%) among children 5–17 years. VE was 53% (95% CI, 42%–62%) against any influenza-related ED visits, 46% (95% CI, 28%–60%) for A(H1N1)pdm09 and 54% (95% CI, 39%–66%) for B/Victoria. VE by age group was 52% (95% CI, 37%–63%) among children 6 months to < 5 years and 42% (95% CI, 16%–60%) among children 5–17 years. Conclusion Influenza vaccination in the 2019–20 season provided substantial protection against laboratory-confirmed influenza-associated hospitalizations and ED visits associated with the two predominantly circulating influenza viruses among children, including against the emerging B/Victoria virus V1A.3 subclade. Disclosures Janet A. Englund, MD, AstraZeneca (Scientific Research Study Investigator)GSK group of companies (Scientific Research Study Investigator)Meissa vaccines (Consultant)Merck (Scientific Research Study Investigator)Sanofi Pasteur (Consultant) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member)IDConnect (Advisor or Review Panel member)Quidel (Advisor or Review Panel member) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support) Christopher J. Harrison, MD, GSK (Grant/Research Support, Infant menigiciccal B conjugate vaccine trial)Merck (Research Grant or Support, Infant pneumococcal conjugate vaccine trial)

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