Journal Article

Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID

Lucas, Carolina, Bhattacharjee, Bornali, Tzeng, Tiffany J., Wei, Hannah, Grady, Connor B., Xu, Lan, Griffin, Daniel, Gehlhausen, Jeff R., Davis, Hannah, McCorkell, Lisa, Peña-Hernandez, Mario A., Tabachnikova, Alexandra, Silva Monteiro, Valter, Mao, Tianyang, Iwasaki, Akiko, Harris, Karen, Takahashi, Takehiro, Silva, Julio, Guan, Leying, Herrin, Jeph, Akrami, Athena, Sawano, Mitsuaki, Jaycox, Jillian, Massey, Daisy, Caraballo, César, Lee, Lik Wee, Schulz, Wade L., Dela Cruz, Charles, Ring, Aaron M., Assaf, Gina, Krumholz, Harlan M., Güthe, Diana Berrent

2025

Overview

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. Plain language summary The impact of the COVID-19 vaccine on unvaccinated individuals suffering from Long COVID is uncertain. This study assessed the experience and biological markers of 16 unvaccinated participants with Long COVID. A total of 10 participants had improved health after vaccination, three reported worsening health, with one hospitalized twice with chest pain. Vaccination boosted the body’s immune responses against the virus that causes COVID-19. We identified biological markers that correlate with the changes in overall health after vaccination. Given that the study was small, more research is needed to confirm these results. Grady, Bhattacharjee and Silva et al. examine the effects of COVID-19 vaccination on 16 vaccine-naive individuals with Long COVID, finding that 10 reported improvements, 3 had no change, and 3 experienced worse overall health post-vaccination. Specific immune signatures correlate with these health changes following vaccination.

• Publisher: Nature Publishing Group UK,Springer Nature B.V,Nature Portfolio
• Subject: 631/250/255/2514 / 692/53/2423 / 692/699/255/2514 / Antibodies / Antigens / COVID-19 vaccines / Data collection / Infections / Long COVID / Lymphocytes / Medical research / Medicine / Medicine & Public Health / Observational studies / Polls & surveys / Proteins / Self report / Severe acute respiratory syndrome coronavirus 2 / Social networks