Association of mRNA Vaccination With Clinical and Virologic Features of COVID-19 Among US Essential and Frontline Workers
Authors:   The HEROES-RECOVER Network, Joseph Gregory , Barnes John , Azziz-Baumgartner Eduardo , Arvay Melissa , Fry Alicia , Hall Aron , Kutty Preeta , MacNeil Adam , Donald L. Clifford , Reynolds Sue , Schrag Stephan , Shang Nong , Slaughter Robert , Thornburg Natalie , Verani Jennife , Wang Rose , Hunt Danielle R. , Sokol Brian , Bloodworth Robin , Douglas Claire , Gerber Isaiah , Hadden Louise , Harder Jenna , McGarry Nancy , Pickett Steve , Poe Brandon P. , Shea Meghan , Thacker John , Zheng Pearl , Mistry Peenaz , Patlan Kelly , Flores Jessica , Duque Jazmin , Edwards Laura J. , Etolue Jini , LeClair Lindsay , Prather Khaila , Smith Michael E. , Murthy Kempapura , Calhoun Nicole , Hoffman Eric , Zayed Martha , Blais Joel , Ettlinger Jason , Settele Natalie , Patel Rupande , Priest Elisa , Thomas Jennifer , Jatla Muralidhar , Beeram Madhava , Arroliga Alejandro , Prado Yolanda , Sapp Daniel S. , Lee Mi , Hornbrook Matt , Bialobok Kristin , Alaspa Jennifer , Stafki Daniel , Robinson Mary , Dolezilek Jill , Hoffman Leia , Connor Tyna , Luzio Catherine , Kendrick Samantha , Cowling Hannah , Healy Olivia , Tovar Gavin , Jarrah Meccah , Nsengiyunva Assumpta , Slocum Alison , Steffen Lili , Smidt Saskia , Coleman Alissa , Deal Carly , Hanson Hanna , Trejo Italia , Makar Jeremy , Grijalva Sofia , Jovel Krystal , Sharma Priyanka , Sun Xiaoxiao , Nikolich-Žugich Janko  , Gerald Joe K. , Fisher Juli , Krupp Karl , Gerald Lynn , Littau Sally , Ramadan Ferris , Woods Erin , Miiro Flavia , Arani Gayatri , Tang Nicholas , Baccam Nora , Lowe Ashley , Lobos Amelia , Yingst April , Stea Danielle , Mayhew Natalya , Nava Raul , Porter Cynthia , Carmona Andrea , strong Ariyah , Flangos Ashlyn , Klinck  Caroline , Pikowski Celia , Hendrix Chloe , Perez Cielo , Morris Cierra , Goebert Erika , Taylor Gianna , Sowell Jayla , Scott Jen , Mirabito Joe , Baker Jordan , Naff Kaitlyn , Carson Karysa , Obrien Kennedy , Earley Kiara , Mevises Kristisha , Martinez Mayra , Pena Mya , Hilyard Raven , Islam Rezwana , Perlman Riley , Murray Sarah , Capell Shelby , Bigler Sienna , Thomas Ta’Nya , Butcher Tatum , Graham Taylor , Rojas Christian , Jones John , Astor Brandon , Lee Ian A. , Desai Meghal S. , Gomez Victoria , Reyes Rachael , Gallimore-Wilson Damena , Noriega Roger , Reyes Annabel , Madan Brigitte , Cruz Alexandra , Carrera Olga , Suarez Nathaly , Feliciano Paola , Garibaldi Johanna , Green Aimee , Testoff Addison , Brown Rachel T. , Schaefer Camie , Arteaga Arlyne , Bruner Matthew , Dawson Daniel , Eden Emilee , Praggastis Jenna , Stanford Joseph , Mayer Jeanma , Stucki Marcus , Campbell Riley , Tran Kathy , Smith Madele , Black Braydon , Pick Christina , Tallman Madison , Cox Chapman , Wong Derrick , Langston Michael , Fugal Adriel , Tsang Fiona , Wheeler Maya , Maughan Gretchen , Wilson Megan , Stinson Pasha , Williams Jesse , Smith Taryn , Reed Seon , Mao Jinyi , allacher Nikki , Chatard Kendal , Vo Jenna , Luong Katie , Jordin Ryder , Stewart Grace , Bourdelle Brock , Powaukee Timina , Minoughan Max , Whiting Hannah , Souza Anika , Arlington Ian , Anderson Lauren , Stubbs Trevor , Park Katherine , Jones Talesha , Thompson Mark G. , Yoon Sarang K. , Naleway Allison L. , Meece Jennifer , Fabrizio Thomas P. , Caban-Martinez Alberto J. , Burgess Jefferey L. , Gaglani Manjusha , Olsho Lauren E.W. , Bateman Allen , Lundgren Jessica , Grant Lauren , Phillips Andrew L. , Groom Holly C. , Stefanski Elisha , Solle Natasha Schaefer , Ellingson Katherine , Lutrick Karen , Dunnigan Kayan , Wesley Meredith G. , Guenther Kyley , Hunt Angela , Mak Josephine , Hegmann Kurt T. , Kuntz Jennifer L. , Bissonnette Adam , Hollister James , Rose Spencer , Morrill Tyler C. , Respet Karley , Fowlkes Ashley L. , Thiese Matthew S. , Rivers Patrick , Herring Meghan K. , Odean Marilyn J. , Yoo Young M. , Brunner Matthew , Bedrick Edward J. , Fleary Deanna E. , Jones John T. , Praggastis Jenna , Romine James , Dickerson Monica , Khan Sana M. , Lamberte Julie Mayo , Beitel Shawn , Webby Richard J. , Tyner Harmony L. 
Published: October 2022

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.