COVID-19 vaccination timing, relative to acute COVID-19, and subsequent risk of long COVID
Objectives: Long COVID is a debilitating condition that impacts millions of Americans, but patients and clinicians have little information on how to prevent this disorder. Vaccination is a vital tool in preventing acute COVID-19 and may confer additional protection against Long COVID. There is limited evidence regarding the optimal timing of COVID-19 vaccination (i.e., vaccination schedule) to minimize the risk of Long COVID. Methods: We applied Longitudinal Targeted Maximum Likelihood Estimation to electronic health record (EHR) data from a retrospective cohort of patients vaccinated against COVID-19 between December 2021 and September 2022. We evaluated the association between binary COVID-19 vaccination status (two or more doses vs. zero doses) and 12-month Long COVID risk among patients diagnosed with acute COVID-19 between December 2021 and September 2022. In addition, we compared the 12-month cumulative risk of Long COVID (ICD-10 code U09.9) among patients diagnosed with acute COVID-19 one to three months after vaccination, three to five months after vaccination, or five to seven months after vaccination while adjusting for relevant high-dimensional baseline and time-dependent covariates. Results: = 1,085,291), we did not find a significant difference in Long COVID risk comparing patients who were diagnosed with acute COVID-19 one to three months after vaccination versus patients who were diagnosed with COVID-19 three to five months (adjusted marginal risk ratio 0.93 (95% CI 0.62, 1.41) or 5 to 7 months (adjusted marginal risk ratio 1.06 (95% CI 0.72, 1.56)) after vaccination. Conclusions: We found that COVID-19 vaccination before SARS-CoV-2 infection was protective against Long COVID, and we did not find that this protection significantly waned within 7 months after vaccination. These findings suggest that COVID-19 vaccination protects against Long COVID.
Authors
- Dan Housman
- Greg Martin (ORCID: https://orcid.org/0000-0002-3095-111X)
- Rena C. Patel (ORCID: https://orcid.org/0000-0001-9893-5856)
- Amin Manna (ORCID: https://orcid.org/0000-0002-4711-2128)
- Andrew N. Mertens (ORCID: https://orcid.org/0000-0002-1050-6721)
- Alan Hubbard (ORCID: https://orcid.org/0000-0002-3769-0127)
- Jing Sun (ORCID: https://orcid.org/0000-0003-3741-0962)
- Yunwen Ji (ORCID: https://orcid.org/0000-0002-6077-5102)
- Rachael V. Phillips (ORCID: https://orcid.org/0000-0002-8474-591X)
- Jeremy Harper (ORCID: https://orcid.org/0000-0003-1244-8948)
- Farrukh M. Koraishy (ORCID: https://orcid.org/0000-0001-6974-5674)
- Emily Carlson Marti
- Spratt Heidi
- Sarang Deshpande (ORCID: https://orcid.org/0000-0001-9288-6854)
- Hythem Sidky (ORCID: https://orcid.org/0000-0003-3532-4809)
- Clare Schmitt
- John M. Colford (ORCID: https://orcid.org/0000-0002-3288-6956)
- Kenrick Cato (ORCID: https://orcid.org/0000-0002-0704-3826)
- Kellie M Walters (ORCID: https://orcid.org/0000-0002-7473-1709)
- D Eichmann
- Jeremy Coyle (ORCID: https://orcid.org/0000-0002-9874-6649)
- Alfred Anzalone (ORCID: https://orcid.org/0000-0002-3212-7845)
- Lee Allan Pyles
- McMurry Jf
- Matvey B. Palchuk (ORCID: https://orcid.org/0000-0002-7737-8752)
- Andrew T. Girvin (ORCID: https://orcid.org/0000-0002-2031-9209)
- Benjamin Amor (ORCID: https://orcid.org/0000-0002-7841-8672)
- Zachary Butzin-Dozier (ORCID: https://orcid.org/0000-0001-6419-0008)
- Mary Saltz (ORCID: https://orcid.org/0000-0002-1554-5738)
- Letianchu Wang
- Mariam Deacy
- Jaylyn Clark
- Eric Hurwitz (ORCID: https://orcid.org/0000-0002-6581-7754)
- Gagnier Jm
- Joni L. Rutter (ORCID: https://orcid.org/0000-0002-6502-2361)
- Elizabeth Zampino (ORCID: https://orcid.org/0000-0002-8233-5132)
- Alexis Graves (ORCID: https://orcid.org/0000-0002-2193-9987)
- Leonie Misquitta
- Junming Shi
- Amy Olex
- Mark J. van der Laan
- Caleb Alexander
- Andrew Southerland
- Adam B. Wilcox
- Meredith Adams
- Alfred (Jerrod) Anzalone
- Mary Emmett
- Carolyn Bramante
- Christopher Chute
- Andrea Zhou
- John Buse
- Lesley Cottrell
- Hemalkumar Mehta
- Emily R. Pfaff (ORCID: https://orcid.org/0000-0002-6840-9756)
- Fred Prior
- Eilis Boudreau
- George Sokos
- Johanna Loomba
- D R Mazzotti
- Justin Guinney
- Benjamin Bates
- Anita Walden
- Kristin Kostka
- Jami Pincavitch
- Katie Rebecca Bradwell
- Harold Lehmann
- Chunlei Wu
- Jessica Islam
- Andrew E. Williams
- Brijesh Patel
- Marshall Clark
- Elaine Hill
- Mark M. Bissell
- J.W. Awori Hayanga
- Jomol Mathew
- Lavance Northington
- Ken Wilkins
- Christine Suver
- Federico Mariona
- Kimberly Murray
- Charisse Madlock-Brown
- Evan French
- Anjali A. Sharathkumar
- Hongfang Liu
- Jin Ge
- Kenneth R. Gersing
- Melissa A. Haendel
- Justin Starren
- Joel H. Saltz
- Lili Portilla
- Cavin Ward-Caviness
- Cliff Takemoto
- Christopher Dillon
- Adam M. Lee
- Brian Hendricks
- Amit Saha
- Davera Gabriel
- Karen Crowley
- Don Brown
Institutions
- University of North Carolina at Chapel Hill (US)
- Johns Hopkins University (US)
- University of Alabama at Birmingham (US)
- Berkeley Public Health Division (US)
- University of Nebraska Medical Center (US)
- University of California, Berkeley (US)
- Stanford University (US)
Publication Details
- Journal
- EBioMedicine
- Published
- 2026-07-24
- DOI
- https://doi.org/10.1016/j.ebiom.2026.106382
- Citations
- 3
- Primary Topic
- Long-Term Effects of COVID-19
- Type
- article
- Field-Weighted Citation Impact
- 16.71
Funders
- Bill and Melinda Gates Foundation
- National Institute of Mental Health
- National Institute of General Medical Sciences
- National Institute of Allergy and Infectious Diseases