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As of August 2022, clusters of acute severe hepatitis of unknown aetiology in children have been reported from 35 countries, including the USA1,2. Previous studies have found human adenoviruses (HAdVs) in the blood from patients in Europe and the USA3-7, although it is unclear whether this virus is causative. Here we used PCR testing, viral enrichment-based sequencing and agnostic metagenomic sequencing to analyse samples from 16 HAdV-positive cases from 1 October 2021 to 22 May 2022, in parallel with 113 controls. In blood from 14 cases, adeno-associated virus type 2 (AAV2) sequences were detected in 93% (13 of 14), compared to 4 (3.5%) of 113 controls (P

It is important to understand real-world BNT162b2 COVID-19 vaccine effectiveness (VE), especially among racial and ethnic minority groups. We performed a test-negative case-control study to measure BNT162b2 COVID-19 VE in the prevention of COVID-19-associated acute respiratory illness (ARI) hospitalizations at two Atlanta hospitals from May 2021–January 2023 and adjusted for potential confounders by multivariate analysis. Among 5139 eligible adults with ARI, 2763 (53.8%) were enrolled, and 1571 (64.5%) were included in the BNT162b2 analysis. The median age was 58 years (IQR, 44–68), 889 (56.6%) were female, 1034 (65.8%) were African American, 359 (22.9%) were White, 56 (3.6%) were Hispanic ethnicity, 645 (41.1%) were SARS-CoV-2-positive, 412 (26.2%) were vaccinated with a primary series, and 273 (17.4%) had received ≥1 booster of BNT162b2. The overall adjusted VE of the BNT162b2 primary series was 58.5% (95% CI 46.0, 68.1), while the adjusted VE of ≥1 booster was 78.9% (95% CI 70.0, 85.1). The adjusted overall VE of primary series for African American/Black individuals was 64.0% (95% CI 49.9, 74.1) and 82.7% (95% CI 71.9, 89.4) in those who received ≥1 booster. When analysis was limited to the period of Omicron predominance, overall VE of the primary series decreased with widened confidence intervals (24.5%, 95% CI −4.5, 45.4%), while VE of ≥1 booster was maintained at 60.9% (95% CI 42.0, 73.6). BNT162b2 primary series and booster vaccination provided protection against COVID-19-associated ARI hospitalization among a predominantly African American population. [ABSTRACT FROM AUTHOR]

Background Data are limited on influenza vaccine effectiveness (VE) in the prevention of influenza-related hospitalizations in older adults and those with underlying high-risk comorbidities. Methods We conducted a prospective, test-negative, case-control study at 2 US hospitals from October 2018–March 2020 among adults aged ≥50 years hospitalized with acute respiratory illnesses (ARIs) and adults ≥18 years admitted with congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) exacerbations. Adults were eligible if they resided in 1 of 8 counties in metropolitan Atlanta, Georgia. Nasopharyngeal and oropharyngeal swabs were tested using BioFire FilmArray (bioMérieux, Inc.) respiratory panel, and standard-of-care molecular results were included when available. Influenza vaccination history was determined from the Georgia vaccine registry and medical records. We used multivariable logistic regression to control for potential confounders and to determine 95% confidence intervals (CIs). Results Among 3090 eligible adults, 1562 (50.6%) were enrolled. Of the 1515 with influenza vaccination history available, 701 (46.2%) had received vaccination during that season. Influenza was identified in 37 (5.3%) vaccinated versus 78 (9.6%) unvaccinated participants. After adjustment for age, race/ethnicity, immunosuppression, month, and season, pooled VE for any influenza-related hospitalization in the eligible study population was 63.1% (95% CI, 43.8–75.8%). Adjusted VE against influenza-related hospitalization for ARI in adults ≥50 years was 55.9% (29.9–72.3%) and adjusted VE against influenza-related CHF/COPD exacerbation in adults ≥18 years was 80.3% (36.3–93.9%). Conclusions Influenza vaccination was effective in preventing influenza-related hospitalizations in adults aged ≥50 years and those with CHF/COPD exacerbations during the 2018–2020 seasons. [ABSTRACT FROM AUTHOR]

Background: Severe coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G (IgG) Fc afucosylation, which induces proinflammatory cytokine secretion from innate immune cells. This study aimed to define spike IgG Fc glycosylation following SARS-CoV-2 infection in adults and children and following SARS-CoV-2 vaccination in adults and the relationships between glycan modifications and cytokines/chemokines., Methods: We analyzed longitudinal (n = 146) and cross-sectional (n = 49) serum/plasma samples from adult and pediatric COVID-19 patients, MIS-C patients, adult vaccinees, and adult and pediatric controls. We developed methods for characterizing bulk and spike IgG Fc glycosylation by capillary electrophoresis and measured levels of 10 inflammatory cytokines/chemokines by multiplexed enzyme-linked immunosorbent assay., Results: Spike IgG was more afucosylated than bulk IgG during acute adult COVID-19 and MIS-C. We observed an opposite trend following vaccination, but it was not significant. Spike IgG was more galactosylated and sialylated and less bisected than bulk IgG during adult COVID-19, with similar trends observed during pediatric COVID-19/MIS-C and following SARS-CoV-2 vaccination. Spike IgG glycosylation changed with time following adult COVID-19 or vaccination. Afucosylated spike IgG exhibited inverse and positive correlations with inflammatory markers in MIS-C and following vaccination, respectively; galactosylated and sialylated spike IgG inversely correlated with proinflammatory cytokines in adult COVID-19 and MIS-C; and bisected spike IgG positively correlated with inflammatory cytokines/chemokines in multiple groups., Conclusions: We identified previously undescribed relationships between spike IgG glycan modifications and inflammatory cytokines/chemokines that expand our understanding of IgG glycosylation changes that may impact COVID-19 and MIS-C immunopathology., Competing Interests: Potential conflicts of interest. E. J. A. is currently employed by Moderna and owns stock or stock options in Moderna. C. A. R. has received grants or contracts to Emory from BioFire Inc, GSK, MedImmune, Micron, Merck, Novavax, PaxVax, Regeneron, Pfizer, Sanofi-Pasteur, Janssen, Moderna, NIH, and CDC; is a co-inventor of patented respiratory syncytial virus (RSV) vaccine technology that has been licensed to Meissa Vaccines Inc and has received royalties from Meissa Vaccines Inc; and has patents pending or issued: “Chimeric RSV, Immunogenic Compositions, and Methods of Use,” International PCT Application No. PCT/US2016/058976, filed 28 December 2016 by Emory University and “RSV Live-Attenuated Vaccine Candidates with Deleted G-Protein Mucin Domains,” US Patent Application No. 63/411,251, filed 29 September 2022 by Emory University. N. R. has received grants or contracts to Emory from NIH, Merck, Sanofi, Pfizer, Vaccine Company, Immorna, Quidel, and Lilly; has received consulting fees from Krog; has received payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Virology Education; has received support for attending meetings and/or travel from Sanofi and Moderna; has participated in data safety monitoring boards for Emmes, ICON, Biomedical Advanced Research and Development Authority, CyanVac, and Micron and advisory boards for Moderna, Sanofi, Seqirus, and Pfizer; has held advisory roles for the Antibacterial Resistance Leadership Group, TMRC, and CDC-Pertussis challenge; is Associate Editor of Clinical Infectious Diseases; and has received equipment, materials, drugs, medical writing, gifts, or other services to Emory from Georgia Research Alliance. E. M. S. has received grants from NIH, JC Kennedy Foundation, and Georgia Clinical & Translational Science Alliance; has received materials from Merck; has received honoraria for lectures/presentations from Merck; and has patents pending or issued: “Anti-ALPP/ALPP2 Antibodies,” US Patent Provisional Application Nos. 63/162,635, 63/301,574, and 18/282,232 filed 18 March 2021, 21 January 2022, and 15 September 2023 by Seagen, “Anti-ALPP/ALPP2 Antibodies,” International PCT Application No. PCT/US2022/020697 filed 17 March 2022 by Seagen, “Antibodies that Bind CD228,” US Patent Provisional Application No. 63/408,605, filed 21 September 2022 by Seagen, “Novel Fusion Protein Specific for CD137 and CD228,” US Patent Provisional Application Nos. 63/408,634, 63/413,174, and 63/496,463 filed 21 September 2022, 4 October 2022, and 17 April 2023 by Seagen. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Severe COVID and multisystem inflammatory syndrome (MIS-C) are characterized by excessive inflammatory cytokines/chemokines. In adults, disease severity is associated with SARS-CoV-2-specific IgG Fc afucosylation, which induces pro-inflammatory cytokine secretion from innate immune cells. This study aimed to define spike IgG Fc glycosylation following SARS-CoV-2 infection in adults and children and following SARS-CoV-2 vaccination in adults and the relationships between glycan modifications and cytokine/chemokine levels., Methods: We analyzed longitudinal (n=146) and cross-sectional (n=49) serum/plasma samples from adult and pediatric COVID patients, MIS-C patients, adult vaccinees, and adult and pediatric healthy controls. We developed methods for characterizing bulk and spike IgG Fc glycosylation by capillary electrophoresis (CE) and measured levels of ten inflammatory cytokines/chemokines by multiplexed ELISA., Results: Spike IgG were more afucosylated than bulk IgG during acute adult COVID and MIS-C. We observed an opposite trend following vaccination, but it was not significant. Spike IgG were more galactosylated and sialylated and less bisected than bulk IgG during adult COVID, with similar trends observed during pediatric COVID/MIS-C and following SARS-CoV-2 vaccination. Spike IgG glycosylation changed with time following adult COVID or vaccination. Afucosylated spike IgG exhibited inverse and positive correlations with inflammatory markers in MIS-C and following vaccination, respectively; galactosylated and sialylated spike IgG inversely correlated with pro-inflammatory cytokines in adult COVID and MIS-C; and bisected spike IgG positively correlated with inflammatory cytokines/chemokines in multiple groups., Conclusions: We identified previously undescribed relationships between spike IgG glycan modifications and inflammatory cytokines/chemokines that expand our understanding of IgG glycosylation changes that may impact COVID and MIS-C immunopathology.

Background: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illness (ARI) in older adults. Optimizing diagnosis could improve understanding of RSV burden., Methods: We enrolled adults ≥50 years of age hospitalized with ARI and adults of any age hospitalized with congestive heart failure or chronic obstructive pulmonary disease exacerbations at two hospitals during two respiratory seasons (2018-2020). We collected nasopharyngeal (NP) and oropharyngeal (OP) swabs (n=1558), acute and convalescent sera (n=568), and expectorated sputum (n=153) from participants, and recorded standard-of-care (SOC) NP results (n=805). We measured RSV antibodies by two immunoassays and performed BioFire testing on respiratory specimens., Results: Of 1,558 eligible participants, 92 (5.9%) tested positive for RSV by any diagnostic method. Combined NP/OP PCR yielded 58 positives, while separate NP and OP testing identified 11 additional positives (18.9% increase). Compared to Study NP/OP PCR alone, the addition of paired serology increased RSV detection by 42.9% (28 vs 40) among those with both specimen types, while the addition of SOC swab RT-PCR results increased RSV detection by 25.9% (47 vs 59)., Conclusions: The addition of paired serology testing, SOC swab results, and separate testing of NP and OP swabs improved RSV diagnostic yield in hospitalized adults., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

In this longitudinal prospective cohort of healthy adults in the United States, we found that coronavirus disease 2019 messenger RNA primary series and booster vaccinations elicited high titers of broadly cross-reactive neutralizing and antibody-dependent cell-mediated cytotoxicity antibodies, which gradually waned over 6 months, particularly against severe acute respiratory syndrome coronavirus 2 variants. These data support the indication for a subsequent booster vaccination., Competing Interests: Potential conflicts of interest. E. J. A. has consulted for Pfizer, Sanofi Pasteur, GSK, Janssen, Moderna, and Medscape; serves on a safety monitoring board for Kentucky BioProcessing and Sanofi Pasteur; and serves on a data adjudication board for WCG and ACI Clinical. His institution has received funds to conduct clinical research unrelated to this manuscript from MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Sanofi Pasteur, Janssen, and Micron, as well as funding from the National Institutes of Health (NIH) to conduct clinical trials of COVID-19 vaccines. C. A. R. is coinventor of patented respiratory syncytial virus vaccine technology that has been licensed to Meissa Vaccines with royalties received. Her institution has received funds from BioFire, GSK, MedImmune, Micron, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, and Sanofi Pasteur to conduct clinical research unrelated to this manuscript, as well as funding from the NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)