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Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.4/5] in the COVAIL trial (NCT05289037), titers against 5 strains were assessed as correlates of risk of symptomatic COVID-19 ("COVID-19") and as correlates of relative (Pfizer-BioNTech Omicron vs. Prototype) booster protection against COVID-19 over 6 months of follow-up during the BA.2-BA.5 Omicron-dominant period. Consistently across the Moderna and Pfizer-BioNTech vaccine platforms and across all variant Spike inserts assessed, both peak and exposure-proximal ("predicted-at-exposure") titers correlated with lower Omicron COVID-19 risk in individuals previously infected with SARS-CoV-2, albeit significantly less so in naïve individuals [e.g., exposure-proximal hazard ratio per 10-fold increase in BA.1 titer 0.74 (95% CI 0.59, 0.94) for naïve vs. 0.41 (95% CI 0.23, 0.64) for non-naïve; interaction p = 0.013]. Neutralizing antibody titer was a strong inverse correlate of Omicron COVID-19 in non-naïve individuals and a weaker correlate in naïve individuals, posing questions about how prior infection alters the neutralization correlate., Competing Interests: Competing interests: N.G.R. is a paid safety consultant for ICON, CyanVac, Imunon, and EMMES, and has served on selected advisory boards for Sanofi, Seqirus, Pfizer-BioNTech and Moderna. Emory receives funds for N.G.R. to conduct research from Sanofi, Lilly, Merck, Quidel, Immorna, Vaccine Company, and Pfizer-BioNTech. S.K. reports research support to his institution from Pfizer-BioNTech, Moderna, Bavarian Nordic, Meissa, Centers for Disease Control and Prevention, and National Institutes of Health. E.B.W. has served as an investigator for clinical trials or studies sponsored by Pfizer-BioNTech, Moderna, Seqirus, Najit, and Clinetic; on advisory boards for Pfizer-BioNTech and Vaxcyte; as a consultant to IliAD Biotechnologies; and as a DSMB member for Shionogi. T.M.B. has served on an Advisory Board for Sanofi. D.N.F. has served on an Advisory Board for Gilead Sciences and for AXCELLA, and as site PI for clinical trials sponsored by Gilead Sciences, Regeneron, MetroBiotech LLC, and the NIH (DMID COVAIL). The remaining authors declare no competing interests., (© 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

For COVAIL recipients of a COVID-19 Sanofi booster vaccine, neutralizing antibody titers were assessed as a correlate of risk (CoR) of COVID-19. Peak and exposure-proximal titers were inverse CoRs with covariate-adjusted hazard ratios (95% confidence intervals) 0.30 (0.11, 0.78) and 0.25 (0.07, 0.85) per 10-fold increase in weighted average titer., (© 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.)

We compared the serologic responses of 1 dose versus 2 doses of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults. A 2-dose boosting regimen with a variant vaccine did not increase the magnitude or the durability of the serological responses compared to a single variant vaccine boost., Competing Interests: Potential conflicts of interest. A. R. B. has received research support from NIH-NIAID, grants from Pfizer, Cyanvac, Moderna, Vaccine.co and Merck as well as consulting fees from Janssen and GSK. She serves as DSMB member for NIH, IDSA Public Health Committee. Honoraria as a speaker from Virology Education. L. R. B. has received grants from Wellcome Trust, Gates Foundation, NIH/Harvard Medical School through institution. Serves as member of DSMB for NIH and AMDAC for FDA. Dr Baden is involved in HIV and SARS-CoV-2 vaccine clinical trials conducted in collaboration with the NIH, HIV Vaccine Trials Network (HVTN), Covid Vaccine Prevention Network (CoVPN), International AIDS Vaccine Initiative (IAVI), Crucell/Janssen, Moderna, Military HIV Research Program (MHRP), the Gates Foundation, and Harvard Medical School. D. J. D. has received a contract from Leidos Biomedical/NIH research to conduct the clinical trial through institution. A. R. F. has received grants from Janssen, Pfizer, Merck, BioFire Diagnostics, Moderna, Vaccine company and CyanVac through institution. Consultant fees from Arrow Pharmaceutical, ADMA biologics, GSK, and honoraria as a speaker from Sanofi and GlaxoSmithKline. Serves as DSMB advisory boards for Novavax and received travel/meeting support from GlaxoSmithKline. S. E. F. has received funding from Leidos to Saint Louis University to conduct Protocol DMID 22-0004. Funding was also received to conduct the Moderna and Janssen trials phase 3 SARS-CoV-2 trials. Serves as DSMB for HVTN Safety Monitoring Board. D. N. F. has as a contract from CDC and is the site PI for DN Fusco study of COVID in Special Populations. D. N. F. served on an HBV Advisory board for Gilead related to hepatitis C & B viruses and Axcella related to Long COVID. P. A. G. has received funding from NIH. PAG has a patent for COVID-19 monoclonal not developed clinically and received consulting fees from International AIDS Society as speaker. L. C. I. has received support from NIH, Moderna, Pfizer, and Sanofi. L. C. I. has also received grants from GSK, Merck, Sharpe & Dohme Corp, CDC, Novavax, Pediatric Emergency Medicine Associates, and NIH/NLM/National Institute on Minority Health and Health Disparities as well as consulting fees from Moderna. L. C. I. has received honoraria as a speaker from American Academy of Pediatrics, Rockefeller University, Moderna, CDC and American Academy of Pediatrics- Georgia Chapter. L. C. I. Serves on Data Safety Monitoring for NIH-Phase 2 Vaccine Trial for Monkeypox, Moderna Scientific Advisory Board- North America, and CoVID-19 Task Force, Georgia. L. C. I. has a leadership role Break the Cycle of Health Disparities Inc, the Center for Spatial Analytics of the Georgia Institute of Technology, and the American Academy of Pediatrics (Executive Board for Section on Infectious Diseases). L. C. I. has received travel/meeting support from the American Academy of Pediatrics and Moderna. L. A. J. has received funding from NIH for support for this study, funding from Pfizer to support a clinical trial and contract funding for research support from the CDC and the NIH, all through institution. L. A. J. also reports unpaid participation on Data Safety Monitoring Boards for NIH funded clinical trials. S. K. has received research grants from NIH, Pfizer, U.S. Centers for Disease Control and Prevention, Meisa, Emergent BioSolutions. S. K. also received support from American Academy of Pediatrics as speaker. A. C. K. has received research support from COVID-19 Adaptive Variance Immunologic Landscape Trial # 28C15000NYUPG266894. S. J. L. has received NIH grants through institution. Consulting fees from Hookipa Pharma. A. F. L. has received grants from Merck, Gilead and, GSK through institution as well as consulting fees from Vir Biotechnology. A. F. L. has also received travel support from Merck to attend a required investigator meeting, testing kits and supplies to support research study from Hologic, Cepheid and medication donated by Mayne Pharma to support research study. M. M. has received funding from Emmes through NIH contract # HHSN272201500002C. L. J. M. has received funding from Emmes through NIH contract # HHSN272201500002C. D. C. M. has received funding from NIH/75N93019C00050-21A: CIVICS A- Option 21A-DMID Trials of COVID-19 Vaccines. J. M. has received funding from Division of Microbiology and Infectious Diseases, contract # 75N93021C00012. A. N. has received support from NIH-NIAID, CEIRR (Centers of Excellence for Influenza Research and Response) and Gates Cambridge Trust as well as grants from NIH-NIAID R01. R. M. N. has received grants from NIAID-DMID and travel/meeting support from Moderna. C. M. P. has received funding from NIAID UM1AI148684. R. M. P. has received funding from NIH DMID COVAIL as well as grants from Janssen, Moderna and NIH through institution. N. G. R. has received research grants from NIH, Pfizer, Merck, Sanofi, Quidel, Immorna, Vaccine Company and Lilly through her institution, consulting fees from Krog, honoraria as speaker for Virology education, and travel support from Sanofi and Moderna. N. G. R. serves as DSMB on safety committees for ICON, Micron and EMMES and is a member of the Moderna, Sanofi, Seqirus and Pfizer selected Advisory boards. Plays leadership advisory role for ARLG, TMRC, CDC-Pertussis challenge, Clinical Infectious Diseases. Equipment supports from Georgia Research Alliance. D. J. S. has received support from NIH-NIAID CEIRR, grants from NIH-NIAID R01, and travel support from NIH-NIAID CEIRR for NIH-related meetings. K. T. has received funding from Emmes through NIH contract # HHSN272201500002C. E. B. W. has received funding from Leidos Biomedical Research AGREEMENT NO. 22CTA-DM0009 as well as grants from Pfizer, Moderna, Sequiris, Clinetic, and Najit Technologies, with payments made to institution. E. B. W. has also received honoraria as a speaker from College of Diplomates of the American Board of Pediatric Dentistry, consulting fees from Iliad Biotechnologies, and travel/meeting support from the American Academy of Pediatrics. E. B. W. serves as member of Vaxcyte Scientific Advisory board. P. L. W. has received subcontract funding from NIH for this study as well as NIH grant funding and contract funding from Pfizer through University of Iowa. P. L. W. has also received consulting fees from Pfizer and serves on DSMB advisory board for Emmes Corporation, Blue Lake. M. B. has received research grants from Leidos Biomedical Research and Pfizer through institution. J. A. W. has received funding from NIH-DMID 75N91019D00024. R. L. A., T. M. B., S. M. M., M. K. M., J. H. B., S. C., C. L., P. C. R., R. R. authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID 50 titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID 50 titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037 ., (© 2023. The Author(s).)

The 2022 mpox outbreak in New York City posed challenges to rapidly scaling up treatment capacity. We describe a telehealth treatment model launched during this outbreak that facilitated healthcare provider treatment capacity, and was able to adhere to a Centers for Disease Control and Prevention (CDC)-sponsored expanded access investigational new drug (EA-IND) protocol for tecovirimat. Sixty-nine patients were evaluated and prescribed tecovirimat for mpox through telehealth visits at NYC Health + Hospitals/Bellevue and NYU Langone Health from June to August 2022. Thirty-two (46.4%) were previously diagnosed with HIV. Forty-four (63.8%) reported full recovery, with the remainder lost to follow-up. Most patients ( n  = 60, 87.0%) attended at least one follow-up visit (either in person or through telehealth) after starting treatment. We observed favorable treatment outcomes, with no serious adverse events, hospitalizations, or deaths related to mpox. While equitable access to telehealth remains a limitation that needs to be addressed, this telehealth model enabled a rapid scale-up of tecovirimat prescription during the mpox outbreak, and should be considered as an important tool used to respond to future infectious disease outbreaks.

In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wild-type spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines., Competing Interests: Potential conflicts of interest. E. J. A. has received grants from Pfizer, Moderna, Janssen, GSK, Sanofi, Micron, and Regeneron through institution as well as consulting fees from Pfizer, Janssen, Moderna, and Sanofi. E. J. A. serves on safety/advisory boards for Sanofi, ACI Clinical/WCG and Kentucky Bioscience, Inc. A. R. B. has received research support from NIH-NIAID, grants from Pfizer, Cyanvac, and Merck as well as consulting fees from Janssen and GSK. L. R. B. has received grants from Wellcome Trust, Gates Foundation, NIH/Harvard Medical School through institution. Serves as member of DSMB for NIH and AMDAC for Food and Drug Administration (FDA). L. R. B. is involved in HIV and SARS-CoV-2 vaccine clinical trials conducted in collaboration with the NIH, HIV Vaccine Trials Network (HVTN), COVID Vaccine Prevention Network (CoVPN), International AIDS Vaccine Initiative (IAVI), Crucell/Janssen, Moderna, Military HIV Research Program (MHRP), the Gates Foundation, and Harvard Medical School. D. J. D. has received a contract from Leidos Biomedical research to conduct the clinical trial through institution. A. R. F. has received grants from Janssen, Pfizer, Merck, BioFire Diagnostics, and CyanVac through institution, consultant fees from Arrowhead and Icosavax, and honoraria as a speaker from Moderna and GlaxoSmithKline. A. R. F. also serves on safety/advisory boards for Novavax and received travel/meeting support from GlaxoSmithKline. S. E. F. has received funding from Leidos to Saint Louis University to conduct Protocol DMID22-0004. D. N. F. has as a contract from Centers for Disease Control and Prevention (CDC) and is the site principal investigator (PI) for clinical trials from Gilead, Regeneron, and MetroBiotech, LLC. She is the PI on 1 investigator-initiated award from Gilead and the co-PI on another investigator-initiated award from Gilead. D. N. F. served on an HBV Advisory board for Gilead in 2021 and received payment for expert testimony not related to COVID in 2022. P. A. G. has received funding for COVAIL clinical trial. P. A. G. has also received consulting fees from Janssen Vaccines. L. C. I. has received support for the present manuscript from NIH-NIAID/DMID, Moderna, Pfizer, and Sanofi. L. C. I. has also received grants from GSK, Merck, Sharpe & Dohme Corp, CDC, Novavax, AHRQ, and NIH/NLM/NIMHD as well as consulting fees from Moderna, CDC, and Pediatric Emergency Medicine Associates, LLC. L. C. I. has received honoraria as a speaker from American Academy of Pediatrics, Rockefeller University, and American Academy of Pediatrics- Georgia Chapter. L. C. I. serves on Data Safety Monitoring for NIH-Phase 2 Vaccine Trial for Monkeypox, Moderna Scientific Advisory Board- North America, and COVID-19 Task Force, Georgia. L. C. I. has a leadership role in the Pediatric Infectious Disease Society, serves as board member on the Emory University- Pediatric and Reproductive Environmental Health Scholars-Southeastern, the Center for Spatial Analytics of the Georgia Institute of Technology, and the American Academy of Pediatrics (Executive Board for Section on Infectious Diseases). L. C. I. has received travel/meeting support from the American Academy of Pediatrics and Moderna. L. A. J. has received funding from NIH for support for this study, funding from Pfizer to support a clinical trial and contract funding for research support from the CDC and the NIH, all through institution. L. A. J. also reports unpaid participation on Data Safety Monitoring Boards for NIH funded clinical trials. S. J. L. has received NIH grants through institution. A. F. L. has received grants from Merck, Gilead, and ViiV through institution as well as consulting fees from Vir Biotechnology. A. F. L. has also received travel support from Merck to attend a required investigator meeting, testing kits and supplies to support research study from Hologic, and medication donated by Mayne Pharma to support research study. M. M. has received funding from Division of Microbiology and Infectious Diseases for contract number 75N93021C00012. D. C. M. has received funding from NIH/75N93019C00050-21A: CIVICS A- Option 21A-DMID Trials of COVID-19 Vaccines. J. M. has received funding from Division of Microbiology and Infectious Diseases, contract number 75N93021C00012. A. N. has received support from NIH-NIAID, CEIRR (Centers of Excellence for Influenza Research and Response) and Gates Cambridge Trust as well as grants from NIH-NIAID R01. R. M. N. has received grants from Moderna and Janssen and travel/meeting support from Moderna. C. M. P. has received funding from NIAID UM1AI148684. R. M. P. has received funding from NIH DMID COVAIL as well as grants from Janssen, Moderna, and NIH through institution. N. G. R. has received research grants from Pfizer, Merck, Sanofi, Quidel, and Lilly through institution, consulting fees from Krog, honoraria as speaker for Virology education, and travel support from Sanofi. N. G. R. serves on safety committees for ICON and EMMES and is a member of the Moderna Advisory board. D. J. S. has received support from NIH-NIAID CEIRR, grants from NIH-NIAID R01, and travel support from NIH-NIAID CEIRR for NIH-related meetings. K. T. has received funding from Division of Microbiology and Infectious Diseases contract number 75N93021C00012. E. B. W. has received funding from Leidos Biomedical Research agreement number. 22CTA-DM0009 as well as grants from Pfizer, Moderna, Sequiris, Clinetic, and Najit Technologies, with payments made to institution. E. B. W. has also received honoraria as a speaker from College of Diplomates of the American Board of Pediatric Dentistry, consulting fees from Iliad Biotechnologies, and travel/meeting support from the American Academy of Pediatrics. E. B. W. serves as member of Vaxcyte Scientific Advisory board. P. L. W. has received subcontract funding from NIH for this study as well as NIH grant funding and contract funding from Pfizer through University of Iowa. P. L. W. has also received consulting fees from Pfizer and serves on safety/advisory board for Emmes Corporation. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

As part of a multicenter study evaluating homologous and heterologous COVID-19 booster vaccines, we assessed the magnitude, breadth, and short-term durability of binding and pseudovirus-neutralizing antibody (PsVNA) responses following a single booster dose of NVX-CoV2373 in adults primed with either Ad26.COV2.S, mRNA-1273, or BNT162b2 vaccines. NVX-CoV2373 as a heterologous booster was immunogenic and associated with no safety concerns through Day 91. Fold-rises in PsVNA titers from baseline (Day 1) to Day 29 were highest for prototypic D614G variant and lowest for more recent Omicron sub-lineages BQ.1.1 and XBB.1. Peak humoral responses against all SARS-CoV-2 variants were lower in those primed with Ad26.COV2.S than with mRNA vaccines. Prior SARS CoV-2 infection was associated with substantially higher baseline PsVNA titers, which remained elevated relative to previously uninfected participants through Day 91. These data support the use of heterologous protein-based booster vaccines as an acceptable alternative to mRNA or adenoviral-based COVID-19 booster vaccines. This trial was conducted under ClinicalTrials.gov: NCT04889209., (© 2023. The Author(s).)

In this brief report, we compare the magnitude and durability of the serologic response of one versus two doses (separated by 56 days) of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults.

In a randomized clinical trial, we compare early neutralizing antibody responses after boosting with bivalent SARS-CoV-2 mRNA vaccines based on either BA.1 or BA.4/BA.5 Omicron spike protein combined with wildtype spike. Responses against SARS-CoV-2 variants exhibited the greatest reduction in titers against currently circulating Omicron subvariants for both bivalent vaccines., Competing Interests: EJA has received grants from Pfizer, Moderna, Janssen, GSK, Sanofi, Micron, and Regeneron through institution as well as consulting fees from Pfizer, Janssen, Moderna, and Sanofi. EJA serves on safety/advisory boards for Sanofi, ACI Clinical/WCG and Kentucky Bioscience, Inc.ARB has received research support from NIH-NIAID, grants from Pfizer, Cyanvac, and Merck as well as consulting fees from Janssen and GSK.LRB has received grants from Wellcome Trust, Gates Foundation, NIH/Harvard Medical School through institution. Serves as member of DSMB for NIH and AMDAC for FDA. Dr Baden is involved in HIV and SARS-CoV-2 vaccine clinical trials conducted in collaboration with the NIH, HIV Vaccine Trials Network (HVTN), Covid Vaccine Prevention Network (CoVPN), International AIDS Vaccine Initiative (IAVI), Crucell/Janssen, Moderna, Military HIV Research Program (MHRP), the Gates Foundation, and Harvard Medical School.DJD has received a contract from Leidos Biomedical research to conduct the clinical trial through institution.ARF has received grants from Janssen, Pfizer, Merck, BioFire Diagnostics, and CyanVac through institution, consultant fees from Arrowhead and Icosavax, and honoraria as a speaker from Moderna and GlaxoSmithKline. ARF also serves on safety/advisory boards for Novavax and received travel/meeting support from GlaxoSmithKline.SEF has received f unding from Leidos to Saint Louis University to conduct Protocol DMID22-0004.DNF has as a contract from CDC and is the site PI for clinical trials from Gilead, Regeneron and MetroBiotech LLC. She is the PI on one investigator-initiated award from Gilead and the co-PI on another investigator initiated award from Gilead. DNF served on an HBV Advisory board for Gilead in 2021 and received payment for expert testimony not related to COVID in 2022.PAG has received funding for COVAIL clinical trial. PAG has also received consulting fees from Janssen Vaccines.LCI has received support for the present manuscript from NIH-NIAID/DMID, Moderna, Pfizer, and Sanofi. LCI has also received grants from GSK, Merck, Sharpe & Dohme Corp, CDC, Novavax, AHRQ, and NIH/NLM/NIMHD as well as consulting fees from Moderna, CDC, and Pediatric Emergency Medicine Associates, LLC. LCI has received honoraria as a speaker from American Academy of Pediatrics, Rockefeller University, and American Academy of Pediatrics- Georgia Chapter. LCI Serves on Data Safety Monitoring for NIH-Phase 2 Vaccine Trial for Monkeypox, Moderna Scientific Advisory Board- North America, and CoVID-19 Task Force, Georgia. LCI has a leadership role in the Pediatric Infectious Disease Society and serves as board member on the Emory University- Pediatric and Reproductive Environmental Health Scholars-Southeastern, the Center for Spatial Analytics of the Georgia Institute of Technology, and the American Academy of Pediatrics (Executive Board for Section on Infectious Diseases). LCI has received travel/meeting support from the American Academy of Pediatrics and Moderna.LAJ has received funding from NIH for support for this study, funding from Pfizer to support a clinical trial and contract funding for research support from the CDC and the NIH, all through institution. LAJ also reports unpaid participation on Data Safety Monitoring Boards for NIH funded clinical trials.SJL has received NIH grants through institution.AFL has received grants from Merck, Gilead and, Viiv through institution as well as consulting fees from Vir Biotechnology. AFL has also received travel support from Merck to attend a required investigator meeting, testing kits and supplies to support research study from Hologic, and medication donated by Mayne Pharma to support research study.MM has received funding from Division of Microbiology and Infectious Diseases for contract # 75N93021C00012.DCM has received funding from NIH/75N93019C00050-21A: CIVICS A- Option 21A-DMID Trials of COVID-19 Vaccines.JM has received funding from Division of Microbiology and Infectious Diseases, contract # 75N93021C00012.AN has received support from NIH-NIAID, CEIRR (Centers of Excellence for Influenza Research and Response) and Gates Cambridge Trust as well as grants from NIH-NIAID R01.RMN has received grants from Moderna and Janssen and travel/meeting support from Moderna.CMP has received funding from NIAID UM1AI148684.RMP has received funding from NIH DMID COVAIL as well as grants from Janssen, Moderna and NIH through institution.NGR has received research grants from Pfizer, Merck, Sanofi, Quidel and Lilly through institution, consulting fees from Krog, honoraria as speaker for Virology education, and travel support from Sanofi. NGR serves on safety committees for ICON and EMMES and is a member of the Moderna Advisory board.DJS has received support from NIH-NIAID CEIRR , grants from NIH-NIAID R01, and travel support from NIH-NIAID CEIRR for NIH-related meetings.KT has received funding from Division of Microbiology and Infectious Diseases contract # 75N93021C00012.EBW has received funding from Leidos Biomedical Research AGREEMENT NO. 22CTA-DM0009 as well as grants from Pfizer, Moderna, Sequiris, Clinetic, and Najit Technologies, with payments made to institution. EBW has also received honoraria as a speaker from College of Diplomates of the American Board of Pediatric Dentistry, consulting fees from Iliad Biotechnologies, and travel/meeting support from the American Academy of Pediatrics. EBW serves as member of Vaxcyte Scientific Advisory board.PLW has received subcontract funding from NIH for this study as well as NIH grant funding and contract funding from Pfizer through University of Iowa. PLW has also received consulting fees from Pfizer and serves on safety/advisory board for Emmes Corporation.The following group has no conflicts to declare: RLA, TMB, SMM, MB, MKM, JHB , SC, ACK, CL, PCR, RR, JAW.

The coronavirus disease 2019 (COVID-19) pandemic and associated increase in family care responsibilities resulted in unsustainable personal and professional workloads for infectious diseases (ID) faculty on the front lines. This was especially true for early-stage faculty (ESF), many of whom had caregiving responsibilities. In addition, female faculty, underrepresented in medicine and science faculty and particularly ESF, experienced marked declines in research productivity, which significantly impacts career trajectories. When combined with staffing shortages due to an aging workforce and suboptimal recruitment and retention in ID, these work-life imbalances have brought the field to an inflection point. We propose actionable recommendations and call on ID leaders to act to close the gender, racial, and ethnic gaps to improve the recruitment, retention, and advancement of ESF in ID. By investing in systemic change to make the ID workforce more equitable, we can embody the shared ideals of diversity and inclusion and prepare for the next pandemic., Competing Interests: Potential conflicts of interest. The authors disclose the following relationships unrelated to the manuscript: grants or contracts: NIH, Sanofi, and GSK (A. W.); Centers for Disease Control and Prevention for vaccine safety studies (K. M. E.); NIH (1UM1AI148372-01HHSN272201600016C, HHSN272201600014C, 5UL1TR000077, and 5U101AI163099 to L. D. I.); Ansun BioPharma, Astellas, Pfizer, Takeda, and AiCuris (L. D. I.); Merck (L. D. I. and I. O.); National Cancer Institute at the NIH (R01 CA213130-S), Department of Medicine Diversity Academic Development Scholar Award at the University of Washington, and Bristol-Myers Squibb Foundation–National Medical Fellowships (H. S. K.); Pfizer and AstraZeneca (F. S. H.). Royalties or licenses: UpToDate (A. W.). Consulting fees: Bionet and IBM (K. M. E.); Takeda (L. D. I.); and Aicuris, Crozet, Auritec, Dxnow, and Gilead (A. W.). Payment or honoraria: RMEI (L. D. I.). Support for attending meetings/travel: ID SAFE: Swiss Infectious Disease Meeting (L. D. I.); Innovative Molecules (A. W.). Participation on a data and safety monitoring board or advisory board: Pfizer, Sanofi, Seqirus, Merck, Moderna, Roche, X-4 Pharma (K. M. E.); Merck (L. D. I.); Merck, X-Vax, Vir, and Curevo (A. W.). Leadership or fiduciary role: Executive Board and Past President, International Society of Heart and Lung Transplantation (L. D. I.); Chair for Disease Transmission Ad Hoc committee, Organ Procurement and Transplantation Network/United Network for Organ Sharing (L. D. I.); Research Affairs Committee, Pediatric Infectious Diseases Society (L. M. H.). Receipt of equipment, materials, drugs, medical writing, gifts, or other services: Merck vaccine for a clinical trial (A. W.). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

While detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by diagnostic reverse-transcription polymerase chain reaction (RT-PCR) is highly sensitive for viral RNA, the nucleic acid amplification of subgenomic RNAs (sgRNAs) that are the product of viral replication may more accurately identify replication. We characterized the diagnostic RNA and sgRNA detection by RT-PCR from nasal swab samples collected daily by participants in postexposure prophylaxis or treatment studies for SARS-CoV-2. Among 1932 RT-PCR-positive swab samples with sgRNA tests, 40% (767) had detectable sgRNA. Above a diagnostic RNA viral load (VL) threshold of 5.1 log10 copies/mL, 96% of samples had detectable sgRNA with VLs that followed a linear trend. The trajectories of diagnostic RNA and sgRNA VLs differed, with 80% peaking on the same day but duration of sgRNA detection being shorter (8 vs 14 days). With a large sample of daily swab samples we provide comparative sgRNA kinetics and a diagnostic RNA threshold that correlates with replicating virus independent of symptoms or duration of illness., Competing Interests: Potential conflicts of interest. M. E. D. is funded by the Infectious Diseases Clinical Research Consortium through the National Institute for Allergy and Infectious Diseases, National Institutes of Health (NIH; award UM1AI148684), outside the submitted work. M. L. W. H. and M. H. W. report funding from the BMGF, outside the submitted work. A. B. reports personal fees from Gates Ventures and grant funding from the NIH, the BMGF, and the New York City Department of Health and Mental Hygiene, outside the submitted work. H. Y. C. reports consulting with Ellume, Pfizer, the BMGF, GlaxoSmithKline, and Merck; she has also received research funding from Gates Ventures and Sanofi Pasteur and support and reagents from Ellume and Cepheid, outside the submitted work. H. C. S. K. is funded by the Research Supplement to Promote Diversity in Health-Related Research Program, the National Cancer Institute, NIH (grant R01 CA213130-S) and a Department of Medicine Diversity Academic Development Scholar Award from the University of Washington. C. M. J. reports consulting with AbbVie and Gilead, outside the submitted work. R. B. reports funding from BMGF and the NIH, outside the submitted work, and support for abstract and manuscript writing from Regeneron Pharmaceuticals, also outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Coronavirus disease 2019 symptom definitions rarely include symptom severity. We collected daily nasal swab samples and symptom diaries from contacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case patients. Requiring ≥1 moderate or severe symptom reduced sensitivity to predict SARS-CoV-2 shedding from 60.0% (95% confidence interval [CI], 52.9%-66.7%) to 31.5% (95% CI, 25.7%- 38.0%) but increased specificity from 77.5% (95% CI, 75.3%-79.5%) to 93.8% (95% CI, 92.7%-94.8%)., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.)

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron, although the boosted titers decline rapidly within 2 months from the peak response compared with boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared with homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared with BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2. This trial was conducted under ClincalTrials.gov: NCT04889209., Competing Interests: Declaration of interests R.L.A., C.D.I., C.M.P., D.S., R.P.C., M.E.D., A.E., H.M.E.S., R.E.R., M.B., A.C.K., T.M.B., D.D., R.N.C., J.I.A., S.C., J.A.Z., S.U.N., E.R.B., and D.J.P. report no competing interests. K.E.L. receives grant awards from Pfizer, Inc., COVID-19 vaccine research. L.A.J.’s institution receives grant funding from NIH and CDC for vaccine-related assessments, including those of COVID-19 vaccines. A.R.B. has grant funding from Pfizer, Janssen, Merck, and Cyanvac for non-COVID-19-related work and serves as a consultant for GSK and Janssen. C.A.R.'s institution has received funds to conduct clinical research from the National Institutes of Health, CDC, BioFire, Inc., Genentech, GSK, Janssen, MedImmune, Merck, Micron, Moderna, Novavax, PaxVax, Pfizer, Regeneron, and Sanofi-Pasteur. She is co-inventor of patented RSV vaccine technology, which has been licensed to Meissa Vaccines, Inc. J.M.M. has served as a consultant for Merck, Sharp, and Dohme for non-Covid-related work. C.J. receives funding from the Bill and Melinda Gates Foundation, NIH, and CDC, consults for Gilead and Abbvie, serves on a DSMB for MedPace, and receives royalties from UpToDate. M.J.M. has laboratory research and clinical trials contracts for vaccines or MAB versus SARS-CoV-2 with Lilly, Pfizer (exclusive of the current work), and Sanofi and personal fees for Scientific Advisory Board service from Merck, Meissa Vaccines, Inc., and Pfizer. R.C.B. receives funding for vaccine trials from Path Nipah and Pfizer. R.W.F. receives funding to perform clinical trials from Pfizer, Moderna, Astra Zeneca, and Emergent Health, and he serves on advisory boards for Johnson & Johnson, Merck, Sanofi Pasteur, and Seqirus. S.E. receives funding to her institution from Sanofi Pasteur for a non-COVID-19 vaccine study. K.M.N. holds a grant from Pfizer, without salary support, for a COVID-19 vaccine study and salary support from the National Institutes of Health (NIH) for work on multiple COVID-19 vaccine trials. D.S.S. is supported by grant awards from NIH/NIAID. P.C.R. and J.H.B. report a pending US patent application no. 63/025918 entitled “Coronavirus RNA vaccines and methods of use.” D.C.M. receives funding from NIH and Moderna for laboratory studies of COVID-19 vaccine antibody responses. M.S.S. receives funding from Moderna, Inc., and Ocugen. D.C.M. receives funding from Moderna, Inc., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Protection from SARS-CoV-2 vaccines wanes over time and is compounded by emerging variants including Omicron subvariants. This study evaluated safety and immunogenicity of SARS-CoV-2 variant vaccines., Methods: This phase 2 open-label, randomized trial enrolled healthy adults previously vaccinated with a SARS-CoV-2 primary series and a single boost. Eligible participants were randomized to one of six Moderna COVID19 mRNA vaccine arms (50µg dose): Prototype (mRNA-1273), Omicron BA.1+Beta (1 or 2 doses), Omicron BA.1+Delta, Omicron BA.1 monovalent, and Omicron BA.1+Prototype. Neutralization antibody titers (ID 50 ) were assessed for D614G, Delta, Beta and Omicron BA.1 variants and Omicron BA.2.12.1 and BA.4/BA.5 subvariants 15 days after vaccination., Results: From March 30 to May 6, 2022, 597 participants were randomized and vaccinated. Median age was 53 years, and 20% had a prior SARS-CoV-2 infection. All vaccines were safe and well-tolerated. Day 15 geometric mean titers (GMT) against D614G were similar across arms and ages, and higher with prior infection. For uninfected participants, Day 15 Omicron BA.1 GMTs were similar across Omicron-containing vaccine arms (3724-4561) and higher than Prototype (1,997 [95%CI:1,482-2,692]). The Omicron BA.1 monovalent and Omicron BA.1+Prototype vaccines induced a geometric mean ratio (GMR) to Prototype for Omicron BA.1 of 2.03 (97.5%CI:1.37-3.00) and 1.56 (97.5%CI:1.06-2.31), respectively. A subset of samples from uninfected participants in four arms were also tested in a different laboratory at Day 15 for neutralizing antibody titers to D614G and Omicron subvariants BA.1, BA.2.12.2 and BA.4/BA.5. Omicron BA.4/BA.5 GMTs were approximately one third BA.1 GMTs (Prototype 517 [95%CI:324-826] vs. 1503 [95%CI:949-2381]; Omicron BA.1+Beta 628 [95%CI:367-1,074] vs. 2125 [95%CI:1139-3965]; Omicron BA.1+Delta 765 [95%CI:443-1,322] vs. 2242 [95%CI:1218-4128] and Omicron BA.1+Prototype 635 [95%CI:447-903] vs. 1972 [95%CI:1337-2907)., Conclusions: Higher Omicron BA.1 titers were observed with Omicron-containing vaccines compared to Prototype vaccine and titers against Omicron BA.4/BA.5 were lower than against BA.1 for all candidate vaccines., Clinicaltrialsgov: NCT05289037.

Background: Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homologous boosters (same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in fully vaccinated recipients., Methods: In this phase 1-2, open-label clinical trial conducted at 10 sites in the United States, adults who had completed a Covid-19 vaccine regimen at least 12 weeks earlier and had no reported history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection received a booster injection with one of three vaccines: mRNA-1273 (Moderna) at a dose of 100 μg, Ad26.COV2.S (Johnson & Johnson-Janssen) at a dose of 5×10 10 virus particles, or BNT162b2 (Pfizer-BioNTech) at a dose of 30 μg. The primary end points were safety, reactogenicity, and humoral immunogenicity on trial days 15 and 29., Results: Of the 458 participants who were enrolled in the trial, 154 received mRNA-1273, 150 received Ad26.COV2.S, and 153 received BNT162b2 as booster vaccines; 1 participant did not receive the assigned vaccine. Reactogenicity was similar to that reported for the primary series. More than half the recipients reported having injection-site pain, malaise, headache, or myalgia. For all combinations, antibody neutralizing titers against a SARS-CoV-2 D614G pseudovirus increased by a factor of 4 to 73, and binding titers increased by a factor of 5 to 55. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20, whereas heterologous boosters increased titers by a factor of 6 to 73. Spike-specific T-cell responses increased in all but the homologous Ad26.COV2.S-boosted subgroup. CD8+ T-cell levels were more durable in the Ad26.COV2.S-primed recipients, and heterologous boosting with the Ad26.COV2.S vaccine substantially increased spike-specific CD8+ T cells in the mRNA vaccine recipients., Conclusions: Homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. (Funded by the National Institute of Allergy and Infectious Diseases; DMID 21-0012 ClinicalTrials.gov number, NCT04889209.)., (Copyright © 2022 Massachusetts Medical Society.)

Background: While Coronavirus disease 2019 (Covid-19) vaccines are highly effective, breakthrough infections are occurring. Booster vaccinations have recently received emergency use authorization (EUA) for certain populations but are restricted to homologous mRNA vaccines. We evaluated homologous and heterologous booster vaccination in persons who had received an EUA Covid-19 vaccine regimen., Methods: In this phase 1/2 open-label clinical trial conducted at ten U.S. sites, adults who received one of three EUA Covid-19 vaccines at least 12 weeks prior to enrollment and had no reported history of SARS-CoV-2 infection received a booster injection with one of three vaccines (Moderna mRNA-1273 100-μg, Janssen Ad26.COV2.S 5×10 10 virus particles, or Pfizer-BioNTech BNT162b2 30-μg; nine combinations). The primary outcomes were safety, reactogenicity, and humoral immunogenicity on study days 15 and 29., Results: 458 individuals were enrolled: 154 received mRNA-1273, 150 received Ad26.CoV2.S, and 153 received BNT162b2 booster vaccines. Reactogenicity was similar to that reported for the primary series. Injection site pain, malaise, headache, and myalgia occurred in more than half the participants. Booster vaccines increased the neutralizing activity against a D614G pseudovirus (4.2-76-fold) and binding antibody titers (4.6-56-fold) for all combinations; homologous boost increased neutralizing antibody titers 4.2-20-fold whereas heterologous boost increased titers 6.2-76-fold. Day 15 neutralizing and binding antibody titers varied by 28.7-fold and 20.9-fold, respectively, across the nine prime-boost combinations., Conclusion: Homologous and heterologous booster vaccinations were well-tolerated and immunogenic in adults who completed a primary Covid-19 vaccine regimen at least 12 weeks earlier.

Disseminated strongyloidiasis and hyperinfection syndrome can cause significant morbidity and mortality after transplantation. Screening and treatment prior to transplantation can reduce or prevent this disease. Targeted screening of transplant candidates based on assessed risk, fails to identify all who would benefit. We implemented universal serology-based screening for Strongyloides at our transplant center, located in a non-endemic area. Of 200 transplant candidates who were evaluated for cardiothoracic transplant from January 2018 to June 2019, 169 were screened serologically and 21 (12.4%) were seropositive. Among seropositive patients, 57% reported travel to an endemic region, 38% were born outside the USA, 38% had eosinophilia, and 5% had history of gram-negative bacteremia. We estimate that universal screening for strongyloidiasis could identify an average of 17 additional candidates for preventive treatment for every 200 transplant candidates., (© 2021 Wiley Periodicals LLC.)