In June 2022, the mRNA COVID-19 vaccination was recommended for young children. We examined clinical characteristics and factors associated with vaccination status among vaccine-eligible young ...children hospitalized for acute COVID-19.
We enrolled inpatients 8 months to <5 years of age with acute community-acquired COVID-19 across 28 US pediatric hospitals from September 20, 2022 to May 31, 2023. We assessed demographic and clinical factors, including the highest level of respiratory support, and vaccination status defined as unvaccinated, incomplete, or complete primary series at least 2 (Moderna) or 3 (Pfizer-BioNTech) mRNA vaccine doses ≥14 days before hospitalization.
Among 597 children, 174 (29.1%) patients were admitted to the intensive care unit and 75 (12.6%) had a life-threatening illness, including 51 (8.5%) requiring invasive mechanical ventilation. Children with underlying respiratory and neurologic/neuromuscular conditions more frequently received higher respiratory support. Only 4.5% of children hospitalized for COVID-19 (n = 27) had completed their primary COVID-19 vaccination series and 7.0% (n = 42) of children initiated but did not complete their primary series. Among 528 unvaccinated children, nearly half (n = 251) were previously healthy, 3 of them required extracorporeal membrane oxygenation for acute COVID-19 and 1 died.
Most young children hospitalized for acute COVID-19, including most children admitted to the intensive care unit and with life-threatening illness, had not initiated COVID-19 vaccination despite being eligible. Nearly half of these children had no underlying conditions. Of the small percentage of children who initiated a COVID-19 primary series, most had not completed it before hospitalization.
Abstract
Background
While Rhinovirus/Enterovirus (RV/EV) infections are common, the clinical characteristics of infections in hospitalized adults are not fully understood.
Methods
Adults ≥ 50 years ...of age hospitalized for Acute Respiratory Infections (ARI) or exacerbations of CHF or COPD in two hospitals in Atlanta, GA during the 2018-2019 and 2019-2020 respiratory seasons were offered enrollment. Following informed consent, participants were tested via BioFire® FilmArray® respiratory panels of nasopharyngeal and oropharyngeal swabs (combined), and standard-of-care molecular testing results were also recorded. Subjects were considered positive for RV/EV if any method of testing resulted positive. Baseline characteristics and clinical features were gathered via subject interviews and medical record abstractions. Variables were compared between subjects with RV/EV and two control groups: those negative for all pathogens and those negative for only RV/EV. Participants with RV/EV who had co-infections were excluded from the analysis. Descriptive statistics were performed using SAS v9.4.
Results
Of 1429 enrolled participants, 123 (8.6%) were positive for RV/EV, of whom 111 had RV/EV alone. When compared to those negative for all tested pathogens (n=1034), participants with RV/EV more commonly had underlying COPD (45.0% vs. 35.5%, P=0.047) and less commonly had CHF (36.0% vs. 48.3%, P=0.014) or experienced acute myocardial dysfunction (29.7% vs. 41.2%, P=0.019). Participants with RV/EV also more commonly experienced fever (39.6% vs. 27.7%, P=0.008), cough (90.1% vs. 69.0%, P< 0.001), sore throat (54.1% vs. 39.5%, P=0.003), chest pain (48.6% vs. 37.8%, P=0.026), and dyspnea/respiratory distress (25.2% vs. 13.1%, P< 0.001) than those negative for all pathogens. Differences between RV/EV positive and negative groups were similar to the all pathogen negative group, with the exception of no significant differences in acute myocardial dysfunction, fever, and COPD in the RV/EV negative group.
Conclusion
Among older adults hospitalized with ARIs, CHF, and/or COPD exacerbations, RV/EV was associated with symptoms of both upper and lower respiratory tract infection and was more frequent identified among those with COPD.
Disclosures
Elizabeth Begier, M.D., M.P.H., Pfizer: EB is an employee of Pfizer, the sponsor of this study|Pfizer: Stocks/Bonds Robin Hubler, MS, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Qing Liu, M.S., Pfizer Inc.: Stocks/Bonds Bradford J. Gessner, M.D., M.P.H., Pfizer: I am an employee of Pfizer|Pfizer: Stocks/Bonds Benjamin Lopman, PhD, Epidemiological Research and Methods, LLC: Advisor/Consultant|Hillevax, Inc: Advisor/Consultant Satoshi Kamidani, MD, CDC: Grant/Research Support|Emergent BioSolutions: Grant/Research Support|NIH: Grant/Research Support|Pfizer Inc: Grant/Research Support Nadine Rouphael, MD, Icon, EMMES, Sanofi, Seqirus, Moderna: Advisor/Consultant Evan J. Anderson, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kentucky Bioprocessing, Inc.: Safety Monitoring Board|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Moderna: Currently an employee|Moderna: Stocks/Bonds|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Safety Monitoring Board|WCG/ACI Clinical: Data Adjudication Board Christina A. Rostad, MD, BioFire Inc.: Grant/Research Support|GlaxoSmithKline Biologicals: Grant/Research Support|Janssen: Grant/Research Support|MedImmune LLC: Grant/Research Support|Meissa Vaccines, Inc.: RSV vaccine technology|Merck & Co., Inc.: Grant/Research Support|Micron Technology, Inc.: Grant/Research Support|Moderna, Inc.: Grant/Research Support|Novavax: Grant/Research Support|PaxVax: Grant/Research Support|Pfizer, Inc.: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Grant/Research Support
(Abstracted from
N Engl J Med
2022;387:109–119)
COVID-19 during pregnancy is associated with a greater risk of adverse pregnancy outcomes and neonatal complications. Studies have shown that mRNA ...vaccines are highly effective in preventing severe COVID-19 during pregnancy, and the Centers for Disease Control and Prevention recommends vaccination, including boosters, for people who are pregnant or plan to be pregnant.
Abstract
Background
A variant-adapted bivalent BNT162b2 mRNA vaccine (bivalent BNT162b2) comprising original SARS-CoV-2 and Omicron BA.4/BA.5 spike proteins is authorized by the US FDA from 6 months ...of age as a primary series or as booster doses. We studied whether bivalent BNT162b2 booster generates improved immune responses against Omicron BA.4/BA.5 and ancestral strains and had a comparable safety profile to original BNT162b2 in 5–11-year-olds.
Methods
This substudy is part of a phase 1/2/3 master study (NCT05543616) examining safety and immunogenicity of bivalent BNT162b2 in healthy children. The substudy group reported here is open label and evaluates a fourth dose with bivalent BNT162b2 10 μg (5 µg original; 5 µg BA.4/BA.5) in 5–11-year-olds who previously received 3 original BNT162b2 10 μg doses. Reactogenicity (7 day), and 1 month safety and immunogenicity were assessed. SARS-CoV-2 Omicron BA.4/BA.5 and ancestral strain neutralization titers post dose 4 were descriptive immunogenicity endpoints. The comparator group for immunogenicity assessments included 113 participants from the initial pediatric study (NCT04816643) who received 3 original BNT162b2 10 μg doses and who were matched by age and SARS-CoV-2 infection status.
Results
Of the 113 children who received bivalent BNT162b2, 50% were female, 58% White, and 58% SARS-CoV-2 positive at baseline. Median (range) time from dose 3 of original BNT162b2 to bivalent BNT162b2 was 5.5 (2.6−8.6) months. Bivalent BNT162b2 was well tolerated with mostly mild to moderate reactogenicity; no grade 4 events were observed (Figure). No serious adverse events were reported. The safety and tolerability profile was generally consistent with that of original BNT162b2. Bivalent BNT162b2 elicited higher neutralizing titers against Omicron BA.4/BA.5 and similar titers against the ancestral strain 1 month post dose 4 compared with original BNT162b2 at 1 month post dose 3 overall and in those who were SARS-CoV-2 positive (Table).
Conclusion
In 5–11-year-olds, a booster (dose 4) of bivalent BNT162b2 10 µg had a similar safety profile to original BNT162b2 10 µg and induced robust Omicron BA.4/BA.5 and ancestral strain neutralizing titers. These data support booster dosing with variant-adapted bivalent BNT162b2 in 5–11-year-olds.
Disclosures
Grant C. Paulsen, MD, Moderna: Grant/Research Support|Pfizer: Grant/Research Support Lawrence Sher, MD, Pfizer Inc: Clinical Investigator Charu Sabharwal, MD, MPH, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Nicholas Kitchin, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Sungeen Hill, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Emily Wasserman, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Xia Xu, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member Janet A. Englund, MD, Ark Biopharma: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Emmanuel Walter, MD, Clinetic: Clinical Investigator|Iliad Biotechnologies: Advisor/Consultant|Moderna: Clinical Investigator|Najit Technologies: Clinical Investigator|Pfizer Inc: Clinical Investigator|Sequiris: Clinical Investigator|Vaxcyte: Advisor/Consultant Flor M. Munoz, MD, MSc, CDC respiratory virus surveillance: Grant/Research Support|Gilead: Grant/Research Support|Moderna, sanofi, aztra zeneca, Merck, GSK: Advisor/Consultant|NIH: DSMB|NIH COVID-19 vaccines in pregnancy: Grant/Research Support|Pfizer Pediatric COVID-19 vaccines: Grant/Research Support|Pfizer, Dynavax, Monderna, Meissa, NIH: DSMB Eric Simoes, MD DCH, Abbott Diagnostics: Advisor/Consultant|Abbvie Inc: Advisor/Consultant|Abbvie Inc: DSMB study section|AstraZeneca: Grant/Research Support|AstraZeneca: travel|Bill and Melinda Gates Foundation: Advisor/Consultant|Bill and Melinda Gates Foundation: Grant/Research Support|Bill and Melinda Gates Foundation: travel, DSMB study section|CDC: Advisor/Consultant|CDC: travel|GSK plc: Advisor/Consultant|GSK plc: DSMB study section|Johnson & Johnson: Advisor/Consultant|Johnson & Johnson: Grant/Research Support|Merck & Co Inc: Grant/Research Support|National Institutes of Health: Grant/Research Support|National Institutes of Health: travel, DSMB study section|Novavax: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: travel|Regeneron: Grant/Research Support|Roche: Grant/Research Support|Roche: travel|USAID: Advisor/Consultant|USAID: Grant/Research Support|USAID: travel|WHO: Advisor/Consultant|WHO: travel Kawsar R. Talaat, MD, Intralytix: Advisor/Consultant|Merck: Advisor/Consultant|NIAID: DSMB|Pfizer: Grant/Research Support|Pfizer: Pfizer contract with institution|Sanofi: Grant/Research Support|Takeda: Advisor/Consultant Satoshi Kamidani, MD, CDC: Grant/Research Support|Emergent BioSolutions: Grant/Research Support|NIH: Grant/Research Support|Pfizer Inc: Grant/Research Support Lisa Moyer, BS, Pfizer: Employee|Pfizer: Stocks/Bonds Vrunda Parikh, PharmD, Pfizer: Employee|Pfizer: Stocks/Bonds Hua Ma, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Xingbin Wang, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Kenneth Koury, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Annaliesa S. Anderson, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Kena A. Swanson, Ph.D., Pfizer: Employee|Pfizer: Stocks/Bonds Alejandra C. Gurtman, M.D., Pfizer: Employee|Pfizer: Stocks/Bonds William C. Gruber, MD, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds
Abstract
Background
Although respiratory syncytial virus (RSV) is a common pathogen in older adults, little is known about the social risk factors for RSV hospitalization in this population. In this ...study, we sought to evaluate the social determinants of RSV-related hospitalizations in older adults.
Methods
From October 2018 to March 2020, we enrolled patients ≥50 years of age who were admitted with an acute respiratory infection (ARI) or CHF/COPD exacerbation at two Emory University hospitals. Enrolled patients were interviewed regarding their medical and social history and their medical charts were abstracted. Nasopharyngeal and oropharyngeal swabs and standard-of-care specimens were obtained for BioFire® Respiratory Panel analysis. Demographic, interview responses, and selected comorbidities were compared with bivariate analysis and generated a stepwise logistic regression model with inclusion in the model set at 0.05. Statistical analysis was performed using SAS v.9.4.
Results
Of the 1429 enrolled participants, 78 (5.5%) were RSV-positive (Table 1). Compared to RSV-negative participants, those with RSV were more commonly female (66.7% vs. 55.3%, P=0.05), immunocompromised (43.6% vs. 31.5%, P=0.03) and particularly with HIV/AIDS (11.5% vs. 3.5%, P=0.003), and had traveled > 100 miles in the prior 2 weeks (12.8% vs. 6.7%, P=0.04). No significant differences were found between the groups by baseline health status or other comorbidities. Participants with RSV had higher frequency of low to moderate activity at baseline than those who were RSV-negative. No significant differences were identified for those living with children or performing childcare ≥ 6 hours a week. Adjusting for sex, activity frequency, travel, and immunocompromised status, those who were male (OR 1.9, 95%CI 1.16, 3.15), exercised 2-3 times per week (OR 2.3, 95%CI 1.26, 4.38), traveled (OR 2.3, 95%CI 1.09, 4.70), or were immunocompromised (OR 1.8, 95%CI 1.10, 2.85) had greater odds of RSV positivity compared to the reference groups (Table 2).Table 1.Demographics, comorbidities, and outcomes of older adults (50+yo) admitted to hospital with ARI or CHF/COPD exacerbation by RSV status. *1 missing response, RSV Negative **Immunocompromised defined as patients having: cancer, HIV/AIDS, solid organ transplant, stem cell/bone marrow transplant, long-term steroid use, or other immune decreasing conditions
Conclusion
Among ARI hospitalizations, RSV prevalence was higher for female sex, immunocompromised status, and those that travelled within the preceding two weeks. Understanding risk factors for severe RSV hospitalization may inform prevention recommendations.
Disclosures
Elizabeth Begier, M.D., M.P.H., Pfizer: EB is an employee of Pfizer, the sponsor of this study|Pfizer: Stocks/Bonds Qing Liu, M.S., Pfizer Inc.: Stocks/Bonds Robin Hubler, MS, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Bradford J. Gessner, M.D., M.P.H., Pfizer: I am an employee of Pfizer|Pfizer: Stocks/Bonds Benjamin Lopman, PhD, Epidemiological Research and Methods, LLC: Advisor/Consultant|Hillevax, Inc: Advisor/Consultant Nadine Rouphael, MD, Icon, EMMES, Sanofi, Seqirus, Moderna: Advisor/Consultant Satoshi Kamidani, MD, CDC: Grant/Research Support|Emergent BioSolutions: Grant/Research Support|NIH: Grant/Research Support|Pfizer Inc: Grant/Research Support Evan J. Anderson, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kentucky Bioprocessing, Inc.: Safety Monitoring Board|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Moderna: Currently an employee|Moderna: Stocks/Bonds|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Safety Monitoring Board|WCG/ACI Clinical: Data Adjudication Board Christina A. Rostad, MD, BioFire Inc.: Grant/Research Support|GlaxoSmithKline Biologicals: Grant/Research Support|Janssen: Grant/Research Support|MedImmune LLC: Grant/Research Support|Meissa Vaccines, Inc.: RSV vaccine technology|Merck & Co., Inc.: Grant/Research Support|Micron Technology, Inc.: Grant/Research Support|Moderna, Inc.: Grant/Research Support|Novavax: Grant/Research Support|PaxVax: Grant/Research Support|Pfizer, Inc.: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Grant/Research Support
Abstract
Background
Individuals with immunocompromising conditions are at high risk of severe disease from COVID-19. The objectives of this study were to describe the clinical features, risk factors, ...and outcomes of COVID-19 in immunocompromised (IC) adults hospitalized with acute respiratory infection (ARI).
Methods
We enrolled patients ≥ 18 years of age hospitalized with ARI at two Emory University hospitals from May 2021 – Aug 2022. Patient interviews and medical abstractions were completed. Nasopharyngeal and oropharyngeal swabs were tested for SARS-CoV-2 using BioFire Respiratory Panel, and results of standard-of-care testing were recorded. IC was defined using comorbidities from the medical chart (cancer, HIV, organ/stem cell/bone marrow transplant, long-term steroid use, other immunosuppressive conditions). Primary vaccination consisted of 3 mRNA or 1 J&J + 1 other dose for IC patients, and 2 mRNA or 1 J&J for non-IC patients. Vaccine effectiveness (VE) was calculated using a test-negative case-control design. Multivariable logistic regression with stepwise selection yielded a final model controlling for employment, past COVID-19, and blood disorders using SAS v9.4.
Results
Of 1677 enrolled participants, 1653 had SARS-CoV-2 testing, of whom 850 (50.7%) were positive and 231 (27.2% of 850) were IC. Compared to non-IC patients with SARS-CoV-2, IC patients were significantly older (median 58, IQR 44-67)), male (57.1%), and had underlying comorbidities, including blood disorders (13.9%) and chronic kidney disease (36.8%). IC patients were more commonly infected with the Omicron variant, while non-IC patients were more commonly infected with Alpha or Delta. Compared to non-IC, IC patients had longer hospitalization duration (median 4.7, IQR 2.9-9.5), required positive-pressure ventilation (CPAP/BiPAP) (13.9%), and died (6.5%). IC patients had less commonly received a full COVID-19 vaccine series (19.9% vs. 25.8%) and adjusted VE of primary COVID-19 vaccine series against hospitalization for ARI was lower in the IC (48.7 (17.9, 68.0)) vs. non-IC patients (76.0 (68.4, 81.7)).Table 1:Vaccine Effectiveness in Immunosuppressed vs immunocompetent
Conclusion
Compared to non-IC hospitalized adults, COVID-19 VE against hospitalization for ARI was lower in IC patients, who were more likely to experience severe outcomes and death.
Disclosures
Laura A. Puzniak, PhD. MPH, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Robin Hubler, MS, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Srinivas Valluri, PhD, Pfizer Inc: Pfizer Employee and hold Pfizer stocks/options|Pfizer Inc: Ownership Interest|Pfizer Inc: Stocks/Bonds Timothy L. Wiemken, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Benjamin Lopman, PhD, Epidemiological Research and Methods, LLC: Advisor/Consultant|Hillevax, Inc: Advisor/Consultant Nadine Rouphael, MD, Icon, EMMES, Sanofi, Seqirus, Moderna: Advisor/Consultant Satoshi Kamidani, MD, CDC: Grant/Research Support|Emergent BioSolutions: Grant/Research Support|NIH: Grant/Research Support|Pfizer Inc: Grant/Research Support Evan J. Anderson, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kentucky Bioprocessing, Inc.: Safety Monitoring Board|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Moderna: Currently an employee|Moderna: Stocks/Bonds|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Safety Monitoring Board|WCG/ACI Clinical: Data Adjudication Board Christina A. Rostad, MD, BioFire Inc.: Grant/Research Support|GlaxoSmithKline Biologicals: Grant/Research Support|Janssen: Grant/Research Support|MedImmune LLC: Grant/Research Support|Meissa Vaccines, Inc.: RSV vaccine technology|Merck & Co., Inc.: Grant/Research Support|Micron Technology, Inc.: Grant/Research Support|Moderna, Inc.: Grant/Research Support|Novavax: Grant/Research Support|PaxVax: Grant/Research Support|Pfizer, Inc.: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Grant/Research Support
Abstract
Background
SARS-CoV-2 has changed and mutated over time. It is important to evaluate changes in clinical presentation and outcomes based on the emerging variants. In this study, we aimed to ...compare differences in symptoms and outcomes among adults hospitalized with COVID-19 by variant.
Methods
From May 2021 to August 2022, we enrolled adults ≥ 18 years of age hospitalized with acute respiratory infection (ARI) at two Emory University hospitals. Demographic and clinical information were obtained from participant interviews and medical chart abstractions. Enrolled patients provided nasopharyngeal and oropharyngeal swabs and standard-of-care specimens. Samples which tested positive for SARS-CoV-2 by molecular testing were subjected to SARS-CoV-2 targeted spike SNP PCR and viral genome sequencing to determine a variant. Statistical analysis was performed using SAS version 9.4. Bivariable analyses were conducted to compare characteristics and identify independent characteristics associated with each variant.
Results
Of 1677 ARI enrolled participants, 850 tested positive for SARS-CoV-2, of whom 592 had a variant identified by either SNP PCR or full genome sequencing. The distribution of variants among these cases were as follows: 39 Alpha (6.6%), 2 Beta (0.3%), 307 Delta (51.9%), 9 Gamma (1.5%), 5 Mu (0.8%), and 230 Omicron (38.9%). When analysis was limited to participants with Alpha, Delta, or Omicron, those with Omicron were significantly older, white, female, and had underlying comorbidities. Compared to participants with Alpha and Delta, those with Omicron more often had sore throat and abdominal pain, but less often had fever, diarrhea, anosmia, ageusia, or shortness of breath. Also, those with Omicron were more often partially or fully vaccinated, with the majority of Omicron infections occurring after vaccination (Table 1). Most clinical outcomes were better among those with Omicron infections, while participants with Delta had the highest proportion of radiographic pneumonia, mechanical ventilation, and death (Table 1).
Conclusion
SARS-CoV-2 variants were associated with distinct clinical characteristics and outcomes, and the Delta variant was associated with the highest frequency of pneumonia, mechanical ventilation, and death.
Disclosures
Laura A. Puzniak, PhD. MPH, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Robin Hubler, MS, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Timothy L. Wiemken, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Srinivas Valluri, PhD, Pfizer Inc: Pfizer Employee and hold Pfizer stocks/options|Pfizer Inc: Ownership Interest|Pfizer Inc: Stocks/Bonds Benjamin Lopman, PhD, Epidemiological Research and Methods, LLC: Advisor/Consultant|Hillevax, Inc: Advisor/Consultant Satoshi Kamidani, MD, CDC: Grant/Research Support|Emergent BioSolutions: Grant/Research Support|NIH: Grant/Research Support|Pfizer Inc: Grant/Research Support Evan J. Anderson, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kentucky Bioprocessing, Inc.: Safety Monitoring Board|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Moderna: Currently an employee|Moderna: Stocks/Bonds|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Safety Monitoring Board|WCG/ACI Clinical: Data Adjudication Board Christina A. Rostad, MD, BioFire Inc.: Grant/Research Support|GlaxoSmithKline Biologicals: Grant/Research Support|Janssen: Grant/Research Support|MedImmune LLC: Grant/Research Support|Meissa Vaccines, Inc.: RSV vaccine technology|Merck & Co., Inc.: Grant/Research Support|Micron Technology, Inc.: Grant/Research Support|Moderna, Inc.: Grant/Research Support|Novavax: Grant/Research Support|PaxVax: Grant/Research Support|Pfizer, Inc.: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Grant/Research Support
Abstract
Background
Respiratory syncytial virus (RSV) is a common viral pathogen identified in older adults with acute respiratory infections (ARIs). Data describing the durability of immune ...responses to RSV are limited but suggest responses may be short-lived. In this study, we assessed longitudinal antibody responses following RSV-associated hospitalization for 3 years.
Methods
Between September 2018 and March 2020, adults ≥ 50 years of age hospitalized with ARI at two Emory University hospitals who had a positive RSV test via PCR were enrolled. A nasopharyngeal swab, oropharyngeal swab, and 10mL blood were collected at enrollment (V1), 30 days after enrollment (V2), and in the 4 weeks prior to the start of the influenza season(s) for three years after enrollment (1 yr, 2 yr, 3 yr). Syndrome-positive, RSV-negative controls were also enrolled. Serum samples were analyzed for RSV A/B lysate antigen by enzyme-linked immunosorbent assay (ELISA) and end-point titers were interpolated to a standard curve. Geometric mean titers (GMTs) were calculated, and statistical comparisons of log-transformed titers were performed using a mixed effects model in GraphPad Prism v9.0.
Results
Of the 30 enrolled participants who completed follow-up, there were 20 RSV-positive cases and 10 controls (Table 1). Of these, 22 (73%) were female, 22 (73%) Black, and 30 (100%) non-Hispanic ethnicity. Baseline demographics were similar in cases and controls. However, being immunocompromised was more common in cases, and heart disease was more common in controls. Peak antibody titers were observed in cases at V2 (IgG GMT 642,685), and these declined non-significantly prior to the start of the next RSV season (IgG GMT 396,059, P=0.1306) (Figure 1). Titers then declined significantly 2 years (IgG GMT 134,836, P=0.0003) and 3 years (IgG GMT 117,729, P< 0.0001) after infection. RSV IgG GMTs were not significantly different between cases and controls at any time point. Results were similar when immunocompromised participants were excluded from the analysis.Table 1.Baseline characteristics of study cohort.Figure 1.RSV IgG antibody titers by ELISA in (A) Cases vs. Controls; (B) change in titer over time in Cases; and (C) change in titer over time in Controls.
Conclusion
RSV antibody responses peaked in early convalescence and persisted for 3 years after RSV-associated hospitalization. Antibody titers were similarly elevated in cases and controls, indicating the durability of RSV antibodies in older adults.
Disclosures
Elizabeth Begier, M.D, M.P.H., Pfizer: EB is an employee of Pfizer, the sponsor of this study|Pfizer: Stocks/Bonds Robin Hubler, MS, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Qing Liu, M.S., Pfizer Inc.: Stocks/Bonds Bradford J. Gessner, M.D, M.P.H., Pfizer: I am an employee of Pfizer|Pfizer: Stocks/Bonds Benjamin Lopman, PhD, Epidemiological Research and Methods, LLC: Advisor/Consultant|Hillevax, Inc: Advisor/Consultant Nadine Rouphael, MD, Icon, EMMES, Sanofi, Seqirus, Moderna: Advisor/Consultant Satoshi Kamidani, MD, CDC: Grant/Research Support|Emergent BioSolutions: Grant/Research Support|NIH: Grant/Research Support|Pfizer Inc: Grant/Research Support Evan J. Anderson, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kentucky Bioprocessing, Inc.: Safety Monitoring Board|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Moderna: Currently an employee|Moderna: Stocks/Bonds|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Safety Monitoring Board|WCG/ACI Clinical: Data Adjudication Board Christina A. Rostad, MD, BioFire Inc.: Grant/Research Support|GlaxoSmithKline Biologicals: Grant/Research Support|Janssen: Grant/Research Support|MedImmune LLC: Grant/Research Support|Meissa Vaccines, Inc.: RSV vaccine technology|Merck & Co., Inc.: Grant/Research Support|Micron Technology, Inc.: Grant/Research Support|Moderna, Inc.: Grant/Research Support|Novavax: Grant/Research Support|PaxVax: Grant/Research Support|Pfizer, Inc.: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Grant/Research Support
Abstract
Background
A variant-adapted bivalent BNT162b2 vaccine (bivalent BNT162b2) comprised of original SARS-CoV-2 and Omicron BA.4/BA.5 spike proteins was developed to improve protection against ...SARS-CoV-2 variants. Bivalent BNT162b2 is authorized by the US FDA from 6 months (mo) old; for children 6 mo to < 5 years (y), it is authorized as a 3-dose primary series and as a fourth dose (first booster).
Methods
This substudy is part of a phase 1/2/3 master study (NCT05543616) investigating safety and immunogenicity of bivalent BNT162b2. The group reported here is open label and evaluates a fourth dose (first booster) with bivalent BNT162b2 3 μg in children 6 mo to < 5 y who previously received 3 original BNT162b2 3 μg doses. Reactogenicity (7 day), and 1 mo safety and immunogenicity for a subset of 60 participants were assessed. Descriptive immunogenicity endpoints included SARS-CoV-2 Omicron BA.4/BA.5 and ancestral strain neutralization responses post dose 4. A comparator group for immunogenicity included 60 participants, matched by age and SARS-CoV-2 infection status, from the initial pediatric study (NCT04816643) who received 3 original BNT162b2 3 μg doses without a booster.
Results
Of children 6 mo to < 5 y old (6 mo to < 2 y, n = 24; 2 y to < 5 y, n = 36) who received bivalent BNT162b2 as a fourth dose, 50% were male, 58% White, 5% Black, 15% Asian, 22% multiracial, 25% Hispanic/Latino; 28.3% had evidence of past SARS-CoV-2 infection. Median time from dose 3 of original BNT162b2 to bivalent BNT162b2 was 6.5 mo. Bivalent BNT162b2 was generally well tolerated with mostly mild to moderate reactogenicity and minimal fever (Figure), few reported adverse events (AEs), no serious AEs, and no new safety signals identified. Bivalent BNT162b2 elicited higher neutralizing titers against Omicron BA.4/BA.5 and similar titers against ancestral strain 1 mo post dose 4 compared with original BNT162b2 1 mo post dose 3 (Table). Robust immune responses were observed regardless of previous SARS-CoV-2 infection status.
Conclusion
A booster (dose 4) of bivalent BNT162b2 had a similar safety profile to original BNT162b2 and induced robust Omicron BA.4/BA.5 and ancestral strain neutralizing titers in children 6 mo to < 5 y. These descriptive data reinforce the importance of a variant-adapted bivalent COVID-19 booster dose in this age group.
Disclosures
Lawrence Sher, MD, Pfizer Inc: Clinical Investigator Charu Sabharwal, MD, MPH, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Nicholas Kitchin, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Justice Kofi Boakya-Appiah, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Xia Xu, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Emmanuel Walter, MD, Clinetic: Clinical Investigator|Iliad Biotechnologies: Advisor/Consultant|Moderna: Clinical Investigator|Najit Technologies: Clinical Investigator|Pfizer Inc: Clinical Investigator|Sequiris: Clinical Investigator|Vaxcyte: Advisor/Consultant Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member Flor M. Munoz, MD, MSc, CDC respiratory virus surveillance: Grant/Research Support|Gilead: Grant/Research Support|Moderna, sanofi, aztra zeneca, Merck, GSK: Advisor/Consultant|NIH: DSMB|NIH COVID-19 vaccines in pregnancy: Grant/Research Support|Pfizer Pediatric COVID-19 vaccines: Grant/Research Support|Pfizer, Dynavax, Monderna, Meissa, NIH: DSMB Janet A. Englund, MD, Ark Biopharma: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Kawsar R. Talaat, MD, Intralytix: Advisor/Consultant|Merck: Advisor/Consultant|NIAID: DSMB|Pfizer: Grant/Research Support|Pfizer: Pfizer contract with institution|Sanofi: Grant/Research Support|Takeda: Advisor/Consultant Satoshi Kamidani, MD, CDC: Grant/Research Support|Emergent BioSolutions: Grant/Research Support|NIH: Grant/Research Support|Pfizer Inc: Grant/Research Support Grant C. Paulsen, MD, Moderna: Grant/Research Support|Pfizer: Grant/Research Support Lisa Moyer, BS, Pfizer: Employee|Pfizer: Stocks/Bonds Vrunda Parikh, PharmD, Pfizer: Employee|Pfizer: Stocks/Bonds Hua Ma, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Xingbin Wang, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Kenneth Koury, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Annaliesa S. Anderson, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Kena A. Swanson, Ph.D., Pfizer: Employee|Pfizer: Stocks/Bonds Alejandra C. Gurtman, M.D, Pfizer: Employee|Pfizer: Stocks/Bonds William C. Gruber, MD, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds
