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Association of mRNA Vaccination With Clinical and Virologic Features of COVID-19 Among US Essential and Frontline Workers

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To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Among a cohort of US frontline and essential workers infected with the original strain or the Delta or Omicron variants of SARS-CoV-2, is there a difference in COVID-19 symptoms or viral RNA load among those receiving mRNA vaccines compared with being unvaccinated?

Findings  In this prospective cohort study that included 1199 participants with SARS-CoV-2 infection, receipt of 2 or 3 mRNA vaccine doses before Delta infections and 3 mRNA vaccine doses before Omicron infections was significantly associated with milder COVID-19 (less frequently symptomatic, febrile, or medically attended or shorter duration of illness) compared with being unvaccinated. Receipt of 2 mRNA vaccine doses 14 to 149 days prior to either Delta or Omicron infection was significantly associated with lower viral RNA load.

Meaning  Among a cohort of US frontline and essential workers, recent vaccination with 2 or 3 mRNA vaccine doses, compared with being unvaccinated, was associated with attenuated COVID-19 symptoms and lower viral RNA load for Delta and Omicron variants of SARS-CoV-2 in some comparisons.


Importance  Data on the epidemiology of mild to moderately severe COVID-19 are needed to inform public health guidance.

Objective  To evaluate associations between 2 or 3 doses of mRNA COVID-19 vaccine and attenuation of symptoms and viral RNA load across SARS-CoV-2 viral lineages.

Design, Setting, and Participants  A prospective cohort study of essential and frontline workers in Arizona, Florida, Minnesota, Oregon, Texas, and Utah with COVID-19 infection confirmed by reverse transcriptase–polymerase chain reaction testing and lineage classified by whole genome sequencing of specimens self-collected weekly and at COVID-19 illness symptom onset. This analysis was conducted among 1199 participants with SARS-CoV-2 from December 14, 2020, to April 19, 2022, with follow-up until May 9, 2022, reported.

Exposures  SARS-CoV-2 lineage (origin strain, Delta variant, Omicron variant) and COVID-19 vaccination status.

Main Outcomes and Measures  Clinical outcomes included presence of symptoms, specific symptoms (including fever or chills), illness duration, and medical care seeking. Virologic outcomes included viral load by quantitative reverse transcriptase–polymerase chain reaction testing along with viral viability.

Results  Among 1199 participants with COVID-19 infection (714 [59.5%] women; median age, 41 years), 14.0% were infected with the origin strain, 24.0% with the Delta variant, and 62.0% with the Omicron variant. Participants vaccinated with the second vaccine dose 14 to 149 days before Delta infection were significantly less likely to be symptomatic compared with unvaccinated participants (21/27 [77.8%] vs 74/77 [96.1%]; OR, 0.13 [95% CI, 0-0.6]) and, when symptomatic, those vaccinated with the third dose 7 to 149 days before infection were significantly less likely to report fever or chills (5/13 [38.5%] vs 62/73 [84.9%]; OR, 0.07 [95% CI, 0.0-0.3]) and reported significantly fewer days of symptoms (10.2 vs 16.4; difference, −6.1 [95% CI, −11.8 to −0.4] days). Among those with Omicron infection, the risk of symptomatic infection did not differ significantly for the 2-dose vaccination status vs unvaccinated status and was significantly higher for the 3-dose recipients vs those who were unvaccinated (327/370 [88.4%] vs 85/107 [79.4%]; OR, 2.0 [95% CI, 1.1-3.5]). Among symptomatic Omicron infections, those vaccinated with the third dose 7 to 149 days before infection compared with those who were unvaccinated were significantly less likely to report fever or chills (160/311 [51.5%] vs 64/81 [79.0%]; OR, 0.25 [95% CI, 0.1-0.5]) or seek medical care (45/308 [14.6%] vs 20/81 [24.7%]; OR, 0.45 [95% CI, 0.2-0.9]). Participants with Delta and Omicron infections who received the second dose 14 to 149 days before infection had a significantly lower mean viral load compared with unvaccinated participants (3 vs 4.1 log10 copies/μL; difference, −1.0 [95% CI, −1.7 to −0.2] for Delta and 2.8 vs 3.5 log10 copies/μL, difference, −1.0 [95% CI, −1.7 to −0.3] for Omicron).

Conclusions and Relevance  In a cohort of US essential and frontline workers with SARS-CoV-2 infections, recent vaccination with 2 or 3 mRNA vaccine doses less than 150 days before infection with Delta or Omicron variants, compared with being unvaccinated, was associated with attenuated symptoms, duration of illness, medical care seeking, or viral load for some comparisons, although the precision and statistical significance of specific estimates varied.

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Article Information

Corresponding Author: Ashley L. Fowlkes, ScD, MPH, Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30333 (ahl4@cdc.gov).

Accepted for Publication: September 20, 2022.

HEROES-RECOVER Authors: Mark G. Thompson, PhD; Sarang K. Yoon, DO, MOH; Allison L. Naleway, PhD; Jennifer Meece, PhD; Thomas P. Fabrizio, PhD; Alberto J. Caban-Martinez, DO, PhD, MPH; Jefferey L. Burgess, MD, MS, MPH; Manjusha Gaglani, MBBS; Lauren E.W. Olsho, PhD; Allen Bateman, PhD; Jessica Lundgren, RN, BSN; Lauren Grant, MS; Andrew L. Phillips, MD, MOH; Holly C. Groom, MPH; Elisha Stefanski, BS; Natasha Schaefer Solle, PhD, RN; Katherine Ellingson, PhD; Karen Lutrick, PhD; Kayan Dunnigan, MPH; Meredith G. Wesley, MPH; Kyley Guenther, BS; Angela Hunt, MLT, ASCP; Josephine Mak, MPH; Kurt T. Hegmann, MD, MPH; Jennifer L. Kuntz, PhD; Adam Bissonnette, MS; James Hollister, MS; Spencer Rose, BS; Tyler C. Morrill, MS; Karley Respet, BS; Ashley L. Fowlkes, ScD, MPH; Matthew S. Thiese, PhD, MSPH; Patrick Rivers, MPP; Meghan K. Herring, MPH; Marilyn J. Odean, MS; Young M. Yoo, MSPH; Matthew Brunner, BS; Edward J. Bedrick, PhD; Deanna E. Fleary, MsC; John T. Jones, MSPH; Jenna Praggastis, BS; James Romine, PhD, MPH; Monica Dickerson, BS; Sana M. Khan, MPH; Julie Mayo Lamberte, MSPH; Shawn Beitel, MSc; Richard J. Webby, PhD; Harmony L. Tyner, MD.

Affiliations of HEROES-RECOVER Authors: Centers for Disease Control and Prevention COVID-19 Response Team, Atlanta, Georgia (Thompson, Grant, Mak, Fowlkes, Yoo, Jones, Dickerson, Lamberte); Rocky Mountain Center for Occupational and Environmental Health, Department of Family and Preventive Medicine, University of Utah Health, Salt Lake City, Utah (Yoon, Phillips, Hegmann, Thiese, Brunner, Praggastis); Kaiser Permanente Northwest Center for Health Research, Portland, Oregon (Naleway, Groom, Kuntz); Marshfield Clinic Research Institute, Marshfield, Wisconsin (Meece, Stefanski, Bissonnette); St Jude Children's Research Hospital, Memphis, Tennessee (Fabrizio, Webby); Leonard M. Miller School of Medicine, University of Miami, Miami, Florida (Caban-Martinez, Solle); Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona (Burgess, Ellingson, Hollister, Bedrick, Romine, Khan, Beitel); Baylor Scott and White Health, Temple, Texas (Gaglani, Dunnigan, Rose); Texas A&M University College of Medicine, Temple (Gaglani); Abt Associates Inc, Rockville, Maryland (Olsho, Wesley, Morrill, Herring, Fleary); Wisconsin State Laboratory of Hygiene, Madison (Bateman, Guenther); St Luke’s Regional Health Care System, Duluth, Minnesota (Lundgren, Hunt, Respet, Tyner); College of Medicine - Tucson, University of Arizona, Tucson (Lutrick, Rivers); Whiteside Institute for Clinical Research, St Luke’s, Duluth, Minnesota (Odean).

Author Contributions: Drs Thompson and Ms Grant had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Thompson, Yoon, Naleway, Meece, Fabrizio, Caban-Martinez, Burgess, Gaglani, Olsho, Grant, Phillips, Mak, Hegmann, Lutrick, Hunt, Fowlkes, Thiese, Herring, Respet, Bruner, Mayo Lamberte, Beitel, Webby, Tyner.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Thompson, Yoon, Caban-Martinez, Burgess, Grant, Lundgren, Fowlkes, Thiese, Jones, Dickerson, Mayo Lamberte.

Critical revision of the manuscript for important intellectual content: Thompson, Yoon, Naleway, Meece, Fabrizio, Caban-Martinez, Burgess, Gaglani, Olsho, Grant, Phillips, Groom, Bateman, Stefanski, Schaefer Solle, Ellingson, Dunnigan, Wesley, Mak, Hegmann, Kuntz, Guenther, Bissonnette, Lutrick, Rose, Morrill, Hunt, Fowlkes, Thiese, Hollister, Herring, Respet, Yoo, Bruner, Rivers, Fleary, Odean, Praggastis, Bedrick, Romine, Khan, Beitel, Webby, Tyner.

Statistical analysis: Thompson, Grant, Mak, Thiese, Yoo, Jones, Bedrick.

Obtained funding: Thompson, Yoon, Burgess, Olsho, Thiese.

Administrative, technical, or material support: Thompson, Yoon, Naleway, Meece, Fabrizio, Caban-Martinez, Burgess, Gaglani, Olsho, Phillips, Groom, Bateman, Stefanski, Schaefer Solle, Ellingson, Wesley, Lundgren, Hegmann, Kuntz, Bissonnette, Lutrick, Morrill, Hunt, Fowlkes, Thiese, Hollister, Herring, Respet, Bruner, Rivers, Fleary, Praggastis, Dickerson, Mayo Lamberte, Khan, Beitel, Webby, Tyner.

Supervision: Thompson, Yoon, Meece, Olsho, Lundgren, Hegmann, Kuntz, Bissonnette, Thiese, Bruner, Praggastis, Webby.

Conflict of Interest Disclosures: Dr Naleway reported receiving research funding from Pfizer and Vir Biotechnology outside the submitted work. Drs Webby and Fabrizio are funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (grant no. HHSN2272201400006C), and ALSAC. Dr Gaglani reported receiving grants from Janssen and Pfizer and serving as co-chair of the Infectious Diseases and Immunization Committee, Texas Pediatric Society, Texas Chapter of the American Academy of Pediatrics. Dr Hegmann reported receiving personal fees from the American College of Occupational and Environmental Medicine/Reed Group for work as an editor of peer-reviewed guidelines, including COVID-19 guidelines, outside the submitted work. Dr Kuntz reported receiving research grant funding to the institution from Vir Biotechnology, Pfizer, and Novartis outside the submitted work. No other disclosures were reported.

Funding/Support: Funding was provided in whole or in part by federal funds from the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC), under contract numbers 75D30120R68013 awarded to Marshfield Clinic Research Laboratory, 75D30120C08379 to University of Arizona, and 75D30120C08150 awarded to Abt Associates, Inc.

Role of the Funder/Sponsor: The CDC was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, and approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Data Sharing Statement: Data will be available by CDC when objectives of the research are complete.

Additional Information: HEROES-RECOVER Network includes Arizona Healthcare, Emergency Response and Other Essential Workers Surveillance Study (HEROES) and Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel (RECOVER).

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