Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID
Abstract Background The symptomatic and immune responses to COVID-19 vaccination of people with Long COVID are poorly characterized. Methods In this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-naïve individuals with Long COVID. Su...
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Nature Portfolio
2025-05-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-00829-3 |
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| author | Connor B. Grady Bornali Bhattacharjee Julio Silva Jillian Jaycox Lik Wee Lee Valter Silva Monteiro Mitsuaki Sawano Daisy Massey César Caraballo Jeff R. Gehlhausen Alexandra Tabachnikova Tianyang Mao Carolina Lucas Mario A. Peña-Hernandez Lan Xu Tiffany J. Tzeng Takehiro Takahashi Jeph Herrin Diana Berrent Güthe Athena Akrami Gina Assaf Hannah Davis Karen Harris Lisa McCorkell Wade L. Schulz Daniel Griffin Hannah Wei Aaron M. Ring Leying Guan Charles Dela Cruz Harlan M. Krumholz Akiko Iwasaki |
| author_facet | Connor B. Grady Bornali Bhattacharjee Julio Silva Jillian Jaycox Lik Wee Lee Valter Silva Monteiro Mitsuaki Sawano Daisy Massey César Caraballo Jeff R. Gehlhausen Alexandra Tabachnikova Tianyang Mao Carolina Lucas Mario A. Peña-Hernandez Lan Xu Tiffany J. Tzeng Takehiro Takahashi Jeph Herrin Diana Berrent Güthe Athena Akrami Gina Assaf Hannah Davis Karen Harris Lisa McCorkell Wade L. Schulz Daniel Griffin Hannah Wei Aaron M. Ring Leying Guan Charles Dela Cruz Harlan M. Krumholz Akiko Iwasaki |
| author_sort | Connor B. Grady |
| collection | DOAJ |
| description | Abstract Background The symptomatic and immune responses to COVID-19 vaccination of people with Long COVID are poorly characterized. Methods In this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-naïve individuals with Long COVID. Surveys were administered before vaccination and at 2, 6, and 12 weeks after receiving the first vaccine dose of the primary series. Simultaneously, SARS-CoV-2-reactive TCR enrichment, SARS-CoV-2-specific antibody responses, antibody responses to other viral and self-antigens, and circulating cytokines were quantified before vaccination and at 6 and 12 weeks after vaccination. Results At 12 weeks post-vaccination, self-reported improved health is seen in 10 out of 16 participants, 3 have no change, and 3 have worse health although 2 report transient improvement after vaccination. One participant reporting worse health was hospitalized twice with chest pain (after each dose). Symptom outcomes are most associated with plasma biosignatures. Higher baseline sIL-6R is associated with symptom improvement, and stably elevated levels of IFN-β and CNTF are associated with no improvement. Significant elevation in SARS-CoV-2-specific TCRs and spike protein-specific IgG are observed at 6 and 12 weeks after vaccination. No changes in reactivities are observed against herpes viruses and self-antigens. Conclusions In this study of 16 people with Long COVID, vaccination is associated with increased SARS-CoV-2 spike protein-specific IgG and T cell expansion in most participants. Specific immune features are associated with symptom change after vaccination and most participants experience improved health or no change following vaccination. |
| format | Article |
| id | doaj-art-ec3bb72ce7dd4e358bca137684804a5c |
| institution | Kabale University |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-ec3bb72ce7dd4e358bca137684804a5c2025-08-20T03:53:13ZengNature PortfolioCommunications Medicine2730-664X2025-05-015111210.1038/s43856-025-00829-3Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVIDConnor B. Grady0Bornali Bhattacharjee1Julio Silva2Jillian Jaycox3Lik Wee Lee4Valter Silva Monteiro5Mitsuaki Sawano6Daisy Massey7César Caraballo8Jeff R. Gehlhausen9Alexandra Tabachnikova10Tianyang Mao11Carolina Lucas12Mario A. Peña-Hernandez13Lan Xu14Tiffany J. Tzeng15Takehiro Takahashi16Jeph Herrin17Diana Berrent Güthe18Athena Akrami19Gina Assaf20Hannah Davis21Karen Harris22Lisa McCorkell23Wade L. Schulz24Daniel Griffin25Hannah Wei26Aaron M. Ring27Leying Guan28Charles Dela Cruz29Harlan M. Krumholz30Akiko Iwasaki31Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of PennsylvaniaDepartment of Immunobiology, Yale University School of MedicineDepartment of Immunobiology, Yale University School of MedicineDepartment of Immunobiology, Yale University School of MedicineAdaptive BiotechnologiesDepartment of Immunobiology, Yale University School of MedicineCenter for Outcomes Research and Evaluation, Yale New Haven HospitalCenter for Outcomes Research and Evaluation, Yale New Haven HospitalCenter for Outcomes Research and Evaluation, Yale New Haven HospitalDepartment of Immunobiology, Yale University School of MedicineDepartment of Immunobiology, Yale University School of MedicineDepartment of Immunobiology, Yale University School of MedicineDepartment of Immunobiology, Yale University School of MedicineDepartment of Immunobiology, Yale University School of MedicineDepartment of Immunobiology, Yale University School of MedicineDepartment of Immunobiology, Yale University School of MedicineDepartment of Immunobiology, Yale University School of MedicineDepartment of Internal Medicine, Yale School of MedicineSurvivor CorpsSainsbury Wellcome Centre, University College LondonPatient-Led Research CollaborativePatient-Led Research CollaborativeSurvivor CorpsPatient-Led Research CollaborativeCenter for Infection and Immunity, Yale School of MedicineDepartment of Medicine, Columbia University Vagelos College of Physicians and SurgeonsPatient-Led Research CollaborativeDepartment of Immunobiology, Yale University School of MedicineCenter for Infection and Immunity, Yale School of MedicineCenter for Infection and Immunity, Yale School of MedicineCenter for Infection and Immunity, Yale School of MedicineDepartment of Immunobiology, Yale University School of MedicineAbstract Background The symptomatic and immune responses to COVID-19 vaccination of people with Long COVID are poorly characterized. Methods In this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-naïve individuals with Long COVID. Surveys were administered before vaccination and at 2, 6, and 12 weeks after receiving the first vaccine dose of the primary series. Simultaneously, SARS-CoV-2-reactive TCR enrichment, SARS-CoV-2-specific antibody responses, antibody responses to other viral and self-antigens, and circulating cytokines were quantified before vaccination and at 6 and 12 weeks after vaccination. Results At 12 weeks post-vaccination, self-reported improved health is seen in 10 out of 16 participants, 3 have no change, and 3 have worse health although 2 report transient improvement after vaccination. One participant reporting worse health was hospitalized twice with chest pain (after each dose). Symptom outcomes are most associated with plasma biosignatures. Higher baseline sIL-6R is associated with symptom improvement, and stably elevated levels of IFN-β and CNTF are associated with no improvement. Significant elevation in SARS-CoV-2-specific TCRs and spike protein-specific IgG are observed at 6 and 12 weeks after vaccination. No changes in reactivities are observed against herpes viruses and self-antigens. Conclusions In this study of 16 people with Long COVID, vaccination is associated with increased SARS-CoV-2 spike protein-specific IgG and T cell expansion in most participants. Specific immune features are associated with symptom change after vaccination and most participants experience improved health or no change following vaccination.https://doi.org/10.1038/s43856-025-00829-3 |
| spellingShingle | Connor B. Grady Bornali Bhattacharjee Julio Silva Jillian Jaycox Lik Wee Lee Valter Silva Monteiro Mitsuaki Sawano Daisy Massey César Caraballo Jeff R. Gehlhausen Alexandra Tabachnikova Tianyang Mao Carolina Lucas Mario A. Peña-Hernandez Lan Xu Tiffany J. Tzeng Takehiro Takahashi Jeph Herrin Diana Berrent Güthe Athena Akrami Gina Assaf Hannah Davis Karen Harris Lisa McCorkell Wade L. Schulz Daniel Griffin Hannah Wei Aaron M. Ring Leying Guan Charles Dela Cruz Harlan M. Krumholz Akiko Iwasaki Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID Communications Medicine |
| title | Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID |
| title_full | Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID |
| title_fullStr | Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID |
| title_full_unstemmed | Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID |
| title_short | Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID |
| title_sort | impact of covid 19 vaccination on symptoms and immune phenotypes in vaccine naive individuals with long covid |
| url | https://doi.org/10.1038/s43856-025-00829-3 |
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