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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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Communications Medicine
Online Access:https://doi.org/10.1038/s43856-025-00829-3
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Summary: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.
ISSN:2730-664X