pmc04136754830J Infect DisJ Infect DisThe Journal of infectious diseases0022-18991537-6613395317351191356410.1093/infdis/jiae556HHSPA2057633ArticleAssociation of Messenger RNA Coronavirus Disease 2019 (COVID-19) Vaccination and Reductions in Post COVID Conditions Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection in a US Prospective Cohort of Essential Workershttp://orcid.org/0000-0001-9557-2690MakJosephine1http://orcid.org/0000-0003-0699-2103KhanSana2http://orcid.org/0000-0003-2684-8846BrittonAmadea1RoseSpencer3http://orcid.org/0000-0003-2857-376XGwynnLisa4EllingsonKatherine D.2MeeceJennifer5http://orcid.org/0000-0002-4430-6760FeldsteinLeora R.1http://orcid.org/0000-0002-4130-0793TynerHarmony6EdwardsLaura J.7http://orcid.org/0000-0003-4505-2907ThieseMatthew S.8http://orcid.org/0000-0001-5747-4643NalewayAllison9http://orcid.org/0000-0002-3952-9230GaglaniManjusha310SolleNatasha11http://orcid.org/0000-0003-2362-9509BurgessJefferey L.12http://orcid.org/0000-0002-8134-9081LamberteJulie Mayo1SheaMeghan7http://orcid.org/0000-0002-9421-2105Hunt-SmithTaryn8http://orcid.org/0000-0002-5960-1308Caban-MartinezAlberto13http://orcid.org/0000-0001-9232-0279PorterCynthia2WiegandRyan1http://orcid.org/0000-0003-3225-6919RaiRamona7HegmannKurt T.8http://orcid.org/0000-0002-4328-1071HollisterJames12http://orcid.org/0000-0002-0620-6451FowlkesAshley1WesleyMeredith7http://orcid.org/0000-0003-2320-3567PhilipsAndrew L.8http://orcid.org/0000-0001-5195-518XRiversPatrick14http://orcid.org/0009-0003-0394-2861BloodworthRobin7http://orcid.org/0000-0002-4411-0370Newes-AdeyiGabriella7http://orcid.org/0000-0003-4503-9745OlshoLauren E. W.7http://orcid.org/0000-0002-8500-2886YoonSarang K.8http://orcid.org/0000-0002-6350-5300SaydahSharon1http://orcid.org/0000-0003-3480-849XLutrickKaren14National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, GeorgiaDepartment of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, ArizonaDepartment of Pediatrics, Baylor Scott and White Health, Temple, TexasDepartment of Pediatrics, Leonard M. Miller School of Medicine, University of Miami, Miami, FloridaMarshfield Clinic Research Institute, Marshfield, WisconsinDepartment of Medicine, Division of Infectious Disease, St Luke’s Regional Health Care System, Duluth, MinnesotaAbt Associates Inc, Rockville, MarylandRocky Mountain Center for Occupational and Environmental Health, Division of Occupational and Environmental Health, University of Utah Health, Salt Lake City, UtahKaiser Permanente Center for Health Research, Portland, OregonDepartment of Pediatrics, Baylor College of Medicine, Temple, TXDepartment of Medicine, Leonard M. Miller School of Medicine, University of Miami, Miami, FloridaDepartment of Community, Environment and Policy, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, ArizonaDepartment of Public Health Sciences, Leonard M. Miller School of Medicine, University of Miami, Miami, FloridaDepartment of Family and Community Medicine, College of Medicine-Tucson, University of Arizona, Tucson, ArizonaCorrespondence: Josephine Mak, MPH, Coronarvirus and Other Respiratory Viruses Division, Centers for Disease Control and Prevention, 1600 Clifton Road NE, MS H24-9, Atlanta, GA 30329 (njx4@cdc.gov).2622025173202518320252313665676Background.

Data are limited on whether vaccination reduces post COVID conditions (PCCs) risk after less severe nonhospitalized coronavirus disease 2019 (COVID-19). This study assessed whether COVID-19 vaccination protected against PCCs in persons with mild initial infections during Delta and Omicron variant predominance.

Methods.

This study utilized a case-control design, nested within the HEROES-RECOVER cohort. Participants aged ≥18 years with test–confirmed severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) between 28 June 2021 and 14 September 2022 were surveyed for PCCs, defined by symptoms lasting >4 weeks after initial infection. Cases self-reported PCCs and controls self-reported no PCCs. The exposure was messenger RNA (mRNA) COVID-19 vaccination (2 or 3 monovalent doses). Odds of PCCs among vaccinated and unvaccinated persons were compared with logistic regression.

Results.

Of 936 participants, 23.6% reported PCCs and 83.2% were vaccinated. Participants who received 3 vaccine doses had lower odds of PCC-related gastrointestinal, neurological, and other symptoms compared to unvaccinated participants (adjusted odds ratio [95% confidence interval]: 0.37 [.16–.85], 0.56 [.32–.97], and 0.48 [.25–.91], respectively).

Conclusions.

COVID-19 vaccination protected against development of PCCs among persons with mild infection during both Delta and Omicron variant predominance, supporting vaccination as an important PCCs prevention tool.

post-COVID conditionsCOVID-19 vaccinesmRNA vaccinesLong COVIDCOVID-19

Post COVID conditions (PCCs), also referred to as long COVID, are estimated to impact millions of Americans [1, 2]. A study analyzing prevalence of long COVID, using the Household Pulse Survey data, among United States (US) adults reporting previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection found that 11.0% of adults who self-reported SARS-CoV-2 infection describe having symptoms lasting 3 months or longer [3]. The Centers for Disease Control and Prevention defines PCCs as physical and mental health symptoms and conditions that persist ≥4 weeks after SARS-CoV-2 infection. PCCs may occur regardless of initial disease severity and may present as persistent symptoms that do not resolve after initial infection, symptoms that recur after a period of improvement, or symptoms that newly occur after the acute infection resolves [4]. The most common symptoms associated with PCCs are fatigue, memory problems, dyspnea, sleep problems, and joint pain [5]. Some symptoms may reflect development of new medical conditions including diseases affecting the cardiovascular system (eg, myocarditis, heart failure, cardiac dysrhythmias, stroke), chronic kidney disease, neurologic conditions, and diabetes [5–8]. When assessing symptom clusters in both vaccinated and unvaccinated persons who tested positive for SARS-CoV-2, cardiorespiratory, central neurological, and multiorgan systemic inflammatory symptom clusters were most commonly detected among self-reported symptoms lasting >28 days after acute infection [9].

Among persons who have had acute SARS-CoV-2 infection that did not require hospitalization, several risk factors for subsequent development of PCCs have been identified, including female sex, smoking, obesity, and presence of comorbidities [7]. Less is understood about factors that may reduce risk of developing PCCs. While there is growing evidence that coronavirus disease 2019 (COVID-19) vaccines reduce the frequency and symptoms of PCCs following infection, most studies have focused on persons with severe initial infection caused by ancestral and early SARS-CoV-2 variants [7, 8, 10–16]. While there is some evidence that earlier variants were associated with higher likelihood of PCCs, even when controlling for time since vaccination, this finding has not been consistent and factors that reduce risk of PCCs during predominance of the SARS-CoV-2 Omicron variant and sublineages after nonsevere COVID-19 illness, which represent the majority of ongoing infections in the US, remain less well understood [10, 17, 18].

Using a multisite prospective cohort of frontline and essential workers, a substudy was performed to assess the odds of developing PCCs after an acute SARS-CoV-2 infection during SARS-CoV-2 Delta and Omicron variant predominance among persons who had received 2 or 3 doses of a monovalent messenger RNA (mRNA) COVID-19 vaccine compared to persons who were unvaccinated at the time of infection. By focusing on persons with predominantly nonsevere initial infection during Delta and Omicron variant predominance, this study addresses an important gap in the understanding of the role of COVID-19 vaccines in preventing or mitigating PCCs and postinfection medical care.

METHODSStudy Design and Population

A retrospective nested case-control analysis was performed among participants enrolled in the preexisting HEROES-RECOVER longitudinal cohort study who tested positive for SARS-CoV-2 and completed an online survey asking about self-report of PCCs. The HEROES-RECOVER network consists of 2 jointly run prospective cohorts: the 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) [19, 20]. This network is comprised of healthcare workers, first responders, and other essential workers (such as persons working in hospitality, food service, education, and other essential infrastructure operations) across 6 US states: Arizona (Phoenix, Tucson, and other areas), Florida (Miami), Minnesota (Duluth), Oregon (Portland), Texas (Temple), and Utah (Salt Lake City). The network began data collection in July 2020 and followed participants weekly through April 2023 for HEROES and May 2023 for RECOVER to collect exposure and infection information. Participants self-collected mid-turbinate nasal swabs weekly, regardless of symptoms, and an additional nasal and saliva swab at the onset of any illness symptoms. Sociodemographic information, prescribed daily medication use, COVID-19 vaccination status, worker knowledge and perceptions of COVID-19 infections and vaccines, and COVID-19 exposure and personal protective equipment use were collected through electronic surveys. History of prior SARS-CoV-2 infection was determined based on self-report of infection at enrollment and/or presence of antibodies at enrollment blood draw. Serum was collected at enrollment, approximately every 3 months during the study, and after vaccination.

The present analysis was conducted among cohort participants following an in-study SARS-CoV-2 infection occurring between 28 June 2021 and 14 September 2022. Participants with documented infection in this timeframe were sent an online survey (“Long COVID” survey) asking them to report symptoms of PCCs, defined as any symptoms persisting 1 month or longer after the initial illness; surveys were distributed between May and December 2022. To ensure at least 1 month had elapsed since initial infection, surveys were distributed at least 60 days after the illness start date, defined as the earliest of either the initial infection symptom onset date or date of positive qualitative reverse-transcription polymerase chain reaction (RT-PCR) SARS-CoV-2 specimen collection.

Actively enrolled participants in Arizona, Florida, Minnesota, Texas, and Utah were eligible to receive the survey. The analysis excluded participants with a history of SARS-CoV-2 infection prior to study enrollment (determined through self-report at enrollment or evidence of infection-induced SARS-CoV-2 antibodies on enrollment blood draw). Participants were also excluded who (1) had an in-study infection with a SARS-CoV-2 variant other than the Delta or Omicron variant, (2) had an incomplete survey or completed the survey <60 days after infection, (3) completed the survey for an infection other than their first, (4) received a non-mRNA COVID-19 vaccine, (5) had indeterminate or partial vaccination status, (6) had an infection that occurred after ≥4 doses of COVID-19 vaccination, (7) received an mRNA COVID-19 vaccination after infection but before survey completion, or (8) had a first in-study infection that occurred between a first and second dose of mRNA COVID-19 vaccine (Figure 1).

All participants provided written informed consent, and their common protocols and procedures were approved by the institutional review boards at participating sites.

Respiratory Specimen Testing

Nasal swab specimens were tested by RT-PCR assay at the Marshfield Clinic Research Institute (Marshfield, Wisconsin). Whole genome sequencing was conducted on eligible samples to determine virus lineage. For ineligible specimens (cycle threshold value ≥30), virus sequence was presumptively assigned as the Delta variant when Delta accounted for ≥50% of viruses sequenced from other specimens at each site; specimens were presumed to be the Omicron variant when ≥50% of viruses sequenced were Omicron for each site. The detailed specimen collection and testing procedure is outlined in Supplementary Table 3.

Exposures

COVID-19 vaccination status was the primary exposure of interest. Participants self-reported vaccination dates and manufacturers through electronic or phone surveys; self-report was verified via uploaded images of vaccination cards in all sites. This was further verified by electronic medical records and state immunization registries from sites in Arizona, Minnesota, Texas, and Utah. Vaccination status was defined in relation to initial infection date: vaccinated with 2 doses if 2 doses were received ≥14 days prior to initial infection, vaccinated with 3 doses if 3 doses were received ≥7 days prior to initial infection, or unvaccinated (no doses received prior to infection). Only monovalent COVID-19 mRNA vaccines were considered in the analysis.

Outcomes

The outcome of interest was PCCs, defined as self-reported symptoms persisting ≥4 weeks after acute infection on self-report during survey. Cases were defined as participants who reported at least 1 symptom persisting for longer than a month when asked, “Since your COVID-19 illness … have you had any of the below symptoms lasting over 4 consecutive weeks?” Controls were defined as those who completed the PCC survey and did not report at least 1 symptom persisting for at least a month or longer. The full list of symptoms defining PCCs is provided in Supplementary Table 1. Symptoms could have been continuous since initial infection or relapsing/remitting since initial infection. PCCs were further subcategorized by number of symptoms (≥1 or ≥2) and by symptom category: cardiovascular/respiratory (shortness of breath, palpitations, chest pain/tightness, and runny nose/congestion), gastrointestinal (loss of appetite, nausea, vomiting, abdominal/stomach pain, constipation, and diarrhea), general (worsening of symptoms following minor mental or physical activity, fatigue, joint pain, joint swelling, and muscle pain), neurological (dizziness/lightheadedness/fainting, numbness/tingling, fogginess in thinking, change in sleeping, headache, difficulty speaking/communicating, difficulty swallowing/chewing, problems with balance/movement), and other (weight loss, hair loss, change in color of toes/fingers, rash, bruising/bleeding easily, change in menstrual cycle, change in sexual drive, and erectile dysfunction).

Statistical Analysis

Pearson χ2 tests were used to examine differences in sociodemographic characteristics and previous/current health conditions by report of PCCs and vaccination status; Fisher’s exact test was used to assess differences when frequencies were <5. Normality was assessed and t test was used to assess difference in means. The association of vaccination with PCCs was estimated using logistic regression comparing the odds of vaccination among persons with and without PCCs. Separate multivariable logistic models were conducted for PCCs with ≥1 symptom, ≥2 symptoms, and each PCC symptom category. All models were adjusted for gender, presence of chronic conditions (categorized by none or ≥1 chronic condition), age (<40 years or ≥40 years), number of symptoms experienced during acute infection (≤3 or >3), interval between initial infection and survey completion (60–119 days, 120–179 days, or ≥180 days), and the variant of infection (Delta or Omicron). Covariates of interest were selected a priori for inclusion based on literature review. Standardized mean differences were calculated to evaluate those who completed and did not complete or did not respond to the PCC survey. Analyses were conducted using SAS software (version 9.4, SAS Institute, Cary, North Carolina) and R software (version 4.3, R Foundation for Statistical Computing). The 5% level of significance was used in all statistical tests and confidence intervals (CIs).

RESULTS

A total of 2584 HEROES-RECOVER participants had a documented SARS-CoV-2 infection during the study period and were initially eligible for study inclusion and received the PCC survey. Among those who received the survey, 733 (28.4%) were excluded due to infection with a non-Delta or non-Omicron variant, 275 (10.6%) for infection prior to study enrollment, 305 (11.8%) for early survey response (defined as survey received <60 days from date of acute infection), incomplete survey response, or survey nonresponse, and 110 (4.3%) for receipt of a vaccine dose after acute infection but before the survey was received (Figure 1). The remaining 936 (36.2%) participants comprised the final analytic sample. Mean age of included participants was 44.2 years (standard deviation, 10.5 years); 571 (61.0%) were female, 826 (88.2%) were White, and 742 (79.3%) were non-Hispanic; 406 (43.4%) were healthcare personnel, 224 (23.9%) essential frontline workers, and 306 (32.7%) other frontline workers. Most participants did not report comorbidities (73.6%), were nonsmokers (76.9%), and self-reported their health as “very good” or “excellent” (70.0%) upon enrollment; 102 (10.9%) were infected during Delta variant predominance and 834 (89.1%) during Omicron predominance (Table 1). Comparing those who did and did not respond to the survey/incompletely responded to the survey, responders were more likely to be frontline workers compared to other occupations and symptomatic versus asymptomatic during acute infection (Supplementary Table 2).

In total, 779 (83.2%) participants received at least 2 doses of the mRNA COVID-19 vaccine ≥14 days prior to infection, including 478 (51.1%) who also received a third monovalent mRNA vaccine dose ≥7 days prior to their infection (Table 2). Among all vaccinated persons, 460 (59.1%) received the Pfizer-BioNTech (BNT162b2) vaccine for all doses and 285 (36.6%) received the Moderna (mRNA-1273) vaccine for all doses; 34 (4.4%) participants received a combination of these 2 products. The median time since most recent dose to infection among those who received 2 monovalent dose was 324 days (interquartile range [IQR], 249.0–419.0 days); among those who received 3 monovalent doses, the median time between the most recent dose and infection was 112 days (IQR, 76.0–214.0 days) (Table 2).

Overall, 221 (23.6%) participants reported experiencing ≥1 PCC symptom, with 158 (16.5%) reporting ≥2 symptoms. Of these, 158 (71.5%) were female, 139 (62.9%) self-rated their enrollment health as “excellent” or “very good,” and 126 (57.0%) self-reported using 1 or more physician-prescribed daily medications at enrollment (Table 1). The most reported category of symptoms was general symptoms including pain/fatigue (16.2%), followed by neurological (13.7%), cardiovascular/respiratory (11.4%), and other (8.5%); gastrointestinal symptoms were least common (4.9%) (Table 3). Persons reporting PCC symptoms compared with those who did not report PCCs were more frequently symptomatic during acute infection (97.7% vs 89.4%, P < 0.0001). Those who reported PCC symptoms also more frequently reported >3 symptoms during acute infection compared to individuals who did not report PCC symptoms (82.8% vs 69.4%, P < 0.0001, respectively) (Table 1).

After adjustment for gender, age, presence of chronic conditions, number of symptoms during acute infection, interval between infection and survey completion, and variant type, and stratified by symptom category, receipt of 3 vaccine doses ≥14 days prior to acute infection compared to being unvaccinated was associated with lower odds of PCC gastrointestinal symptoms (adjusted odds ratio [aOR], 0.37 [95% CI, .16–.85]), neurological symptoms (aOR, 0.56 [95% CI, .32–.97]), and other symptoms (aOR, 0.48 [95% CI, .25–.91]) compared to being unvaccinated (Table 3). No significant associations were found between 3 doses of vaccine and the odds of number of symptoms, cardiovascular/respiratory symptoms, and general symptoms (Table 3). Comparing receipt of 2 doses ≥14 days prior to acute infection to unvaccinated, the odds of PCCs with at least 1 symptom was 0.84 (95% CI, .53–1.32). The odds were lower compared to unvaccinated but not statistically significant. Assessing specific PCC symptom categories among those receiving 2 doses compared to unvaccinated, odds ratios were as follows: cardiovascular/respiratory symptoms (aOR, 1.12 [95% CI, .62–2.05]), gastrointestinal symptoms (aOR, 0.69 [95% CI, .31–1.53]), general symptoms (aOR, 1.08 [95% CI, .64–1.84]), neurological symptoms (aOR, 0.80 [95% CI, .46–1.40]), and other symptoms (aOR, 0.77 [95% CI, .41–1.46]) (Table 3).

DISCUSSION

In this analysis of the HEROES-RECOVER cohort of US frontline and essential workers, the odds of developing PCC-specific symptom categories (gastrointestinal, neurological, and other symptoms) after acute SARS-CoV-2 infection during circulation of both SARS-CoV-2 Omicron and Delta variants were lower among persons who received 3 doses of monovalent mRNA COVID-19 vaccine prior to acute infection compared to those who were unvaccinated at the time of acute infection. This report demonstrates the effect of COVID-19 vaccination in reducing progression to PCCs during circulation of the SARS-CoV-2 Omicron variant in the US and highlights that COVID-19 vaccination can serve as an important additional tool to prevent PCCs. Furthermore, the HEROES-RECOVER cohort is unique in that it consists of predominantly younger, healthy adult participants and almost all infections captured represented nonsevere disease. In total, approximately 28% of participants included in the analysis had 3 or fewer symptoms during their initial infection, 8.7% were asymptomatic, and only 6 of 936 (0.6%) had a hospitalization related to their infection. The findings of this report demonstrate that even among young healthy adults in whom the vaccine may not prevent infection, there is still a protective benefit offered by vaccines, which is an important potential consideration for ongoing vaccine policy.

This analysis found that receipt of 3 doses of an mRNA COVID-19 vaccine was associated with lower odds of experiencing specific categories of PCC symptoms following infection, including reducing the odds of other symptoms (weight loss, hair loss, and skin, menstrual, and sexual symptoms) by 52%, gastrointestinal symptoms by 63%, and neurological symptoms by 44%. The differential effect on the development of PCC symptoms has been identified elsewhere in the literature. For example, in a recent meta-analysis, Gao et al. identified vaccination to only be protective against some, but not all, PCC symptoms [14].

There was no association observed between development of PCCs and receipt of 2 doses of mRNA COVID-19 vaccine. This is in contrast to other studies that have demonstrated a protective effect from 2 doses, including in similar cohorts of nonsevere COVID-19 infections in the United Kingdom and in Italy [21, 22]. However, the median time between receipt of a second vaccine dose and acute infection was 324 days in the HEROES-RECOVER cohort. It is therefore possible that the lack of an association observed here is the result of waning vaccine protection against development of PCCs after infection, similar to what is observed against infection itself; smaller sample size in the 2-dose group may also have played a role, limiting power to detect an association. Although further research is needed, the potential that protection against development of PCCs after infection may wane, just as it does for other outcomes, highlights the importance of staying up to date with COVID-19 vaccination recommendations, including updated doses.

Lastly, this analysis focused on the reduction in odds of developing PCCs only among persons who had SARS-CoV-2 infection. Because these estimates do not account for PCCs averted by protection against infection, the findings here likely underestimate the overall reduction in PCCs that vaccinated persons experience compared to unvaccinated persons.

This analysis is subject to at least 6 limitations. First, only participants with a documented SARS-CoV-2 infection received the PCC survey and baseline rates of PCC-like symptoms among persons without SARS-CoV-2 infection were unknown, which meant that incidence of PCCs could not be calculated in this cohort. Second, participants were asked to report symptoms occurring after an illness that may have happened up to 2 years prior, leading to potential recall bias and under- or overreporting of PCC symptoms. To try to ensure that reported PCC symptoms were associated with the first in-study infection, individuals with any subsequent SARS-CoV-2 infections after the first in-study infection were excluded. Third, analyses rely solely on multiple regression to account for any confounding, and unmeasured confounding may have remained. Fourth, those who experienced asymptomatic acute infections were less likely to complete the survey; if acute infection symptom severity is related to likelihood of developing PCCs, excluded individuals may have had a lower likelihood of PCCs regardless of vaccination status. Fifth, this survey was voluntary and while survey nonrespondents were generally similar to respondents in observable characteristics, if nonresponse was associated both with likelihood of developing PCCs and likelihood of vaccination, estimates could be biased. Sixth, this cohort had high vaccine uptake and consisted predominantly of younger, healthier adults and frontline healthcare and essential workers. This group has a higher level of exposure to SARS-CoV-2 infection, which may limit generalizability of these results.

CONCLUSIONS

In this analysis of the HEROES-RECOVER frontline worker cohort, individuals who received 3 doses of monovalent mRNA COVID-19 vaccine prior to SARS-CoV-2 infection had a reduction in the odds of developing PCCs, specifically neurological, gastrointestinal, and general symptoms (including weight loss, hair/skin issues, and menstrual/sexual symptoms). These results confirm that COVID-19 vaccination can play an important role in protecting individuals against PCCs, including among patients who have mild initial infection during Delta and Omicron variant predominance. Further research is needed to evaluate whether this effect is even greater with additional vaccine doses and the improved variant–vaccine match of updated COVID-19 vaccines.

Supplementary MaterialAcknowledgments.

The authors wish to thank the HEROES-RECOVER participants and the following:

Centers for Disease Control and Prevention: Melissa L. Arvay, Eduardo Azziz-Baumgartner, John Barnes, Stephanie Bialek, Melissa Briggs-Hagen, Allison Ciesla, Leora Feldstein, Ashley Fowlkes, Aron Hall, Lauren Grant, Gregory Joseph, Preeta Kutty, Adam MacNeil, Julie Mayo Lamberte, L. Clifford McDonald, Morgan Najdowski, Sue Reynolds, Stephanie Schrag, Nong Shang, Matthew J. Stuckey, Natalie Thornburg, Jennifer Verani, Ryan Wiegand, Young M. Yoo.

Abt Associates: Eli Bierman, Chitralekha (Chitra) Dev, Jazmin Duque, Kate C. Durocher, Jini Etolue, Deanna E. Fleary, Sammantha Fuller, Kimberly D. Groover, Louise S. Hadden, Jenna A. Harder, Edward Hock, David Izrael, Keya Bidani Jacoby, Utsav Kattel, Brendan Kidwell, Nicole Klassen, Don Laliberty, Kelly E. Lawrence Patlan, Joanna Ivette Lopez, Nancy McGarry, Peenaz Mistry, Tyler C. Morrill, Adam Nunez, Steven L Pickett, Jessica Flores Pleasants, Brandon P. Poe, Khaila A. Prather, Brian E. Sokol, Shelly Spoeth, Arianna Summers, John F. Thacker, Eric James Tolbert, Molly Vaughan, Pearl Q. Zheng.

Baylor Scott and White Health: RECOVER: Kayan Dunnigan, Nicole Calhoun, Leah Odame-Bamfo, Clare Mathenge, Michael E. Smith, Kempapura Murthy, Martha Zayed, Ashley Graves, Joel Blais, Jason Ettlinger, Sharla Russell, Natalie Settele, Elisa Priest, Jennifer Thomas, Muralidhar Jatla, Madhava Beeram, Javed Butler, Alejandro Arroliga.

Kaiser Permanente Northwest: Holly Groom, Jennifer Kuntz, Yolanda Prado, Daniel Sapp, Mi Lee, Chris Eddy, Matt Hornbrook, Donna Eubanks, Danielle Millay, Dorothy Kurdyla, Kristin Bialobok, Ambrosia Bass, Kristi Bays, Kimberly Berame, Cathleen Bourdoin, Rashyra Brent, Carlea Buslach, Lantoria Davis, Stephen Fortmann, Jennifer Gluth, Kenni Graham, Tarika Holness, Kelley Jewell, Enedina Luis, Abreeanah Magdaleno, DeShaun Martin, Joyce Smith-McGee, Martha Perley, Sam Peterson, Aaron Peipert, Krystil Phillips, Joanna Price, Ana Reyes, Sperry Robinson, Katrina Schell, Emily Schield, Natosha Shirley, Anna Shivinsky, Valencia Smith, Britta Torgrimson-Ojerio, Brooke Wainwright, Shawn Westaway.

Marshfield Clinic: Saydee Benz, Adam Bissonnette, Krystal Boese, Riley Bonifer, Emily Botten, Jarod Boyer, Michaela Braun, Julianne Carlson, Caleb Cravillion, Amber Donnerbauer, Linda Donnerbauer, Tim Dziedzic, Joe Eddy, Heather Edgren, Alex Ermeling, Kelsey Ewert, Connie Fehrenbach, Rachel Fernandez, Wayne Frome, Emily Gruenling, Sherri Guzinski, Mitch Hertel, Garrett Heuer, Erin Higdon, Jon Hill, Cressa Huotari, Lynn Ivacic, Lee Jepsen, Steve Kaiser, Bailey Keffer, Tammy Koepel, Sarah Kohn, Alaura Lemieux, Carrie Marcis, Megan Maronde, Isaac McCready, Nidhi Mehta, Dan Miesbauer, Collin Nikolai, Brooke Olson, Jeremy Olstadt, Lisa Ott, Michael Owens, Cory Pike, Nicole Price, Chris Reardon, Logan Schafer, Alex Slenczka, Jacob Solis, Elisha Stefanski, Lydia Sterzinger, Kendra Stoltz, Melissa Strupp, Lyndsay Watkins, Roxann Weigel, Ben Zimmerman.

University of Miami: Principal investigator (PI): Alberto J. Caban-Martinez (RECOVER/PROTECT); Co-PI: Natasha Schaefer Solle (RECOVER); Co-PI: Lisa Gwynn (PROTECT); Damena Gallimore-Wilson, Roger Noriega, Cynthia Beaver, Alexandra Cruz, Annabel Reyes, Amber Balda, Sancia Noriega, Brandon Rose, Ximeng Zhao, Nakib Hasan, Rachel Reyes, E. Victoria Gomez, Meghal Desai, Ian Lee, Tavienne Steinberg, Max Ladsay, Tomilola Awojobi, Swarnam Pandey, Emilie Brown, Alex Stewart, Paola Louzado-Felicianio, Johanna Garibaldi, Aimee Green, Nathaly Suarez del Rosario, Olga Carrera, Felix Rivera-Mariani, Giana Ilarraza, Peggy Gonzalez, Thomas Stone, Nadine Philogene-Vincent, Aida Van Mossel, Sandrah Chalmers, Marta Salazar Grande, Wilmar Mondestin, Maria Ferraris, Ashley Apro, Keana Johnson, Oriana Zakharov, Monica Almirall Palenzuela, Valery Mardini Cespedes, Gabriela Guevara. The Florida RECOVER cohort study team thanks the firefighters, healthcare workers, and frontline and essential workers for participating in this occupational cohort study.

St. Luke’s: Marilyn Odean, Karley Respet, Angela Hunt, Jennifer Viergutz, Tyna O’Connor, Jessica Lundgren, Daniel Stafki, Mary Robinson, Elizabeth Kaplan, Samantha Kendrick, Abbigail Hagen, Catherine Diluzio, Kelley Phillips, Leiah Hoffman, Jill Dolezilek, Bethany Brunner, Paul Schlies, Marlene Berntson, Donna De Toffol.

University of Arizona: Gayatri Arani, Ariyah Armstrong, Nora Baccam, Jordan Baker, Shawn Beitel, Sienna Bigler, Andrea Carmona, Samantha Castro, Alissa Coleman, Samantha Favela, Julia Fisher, Ashlyn Flangos, Joe K. Gerald, Lynn Gerald, Erika Goebert, Sofia Grijalva, Hanna Hanson, Olivia Healy, Chloe Hendrix, Raven Hilyard, James Hollister, Mia Huerta, Meccah Jarrah, Hannah Jagoda, Krystal S. Jovel, Dilsharan Kaur, Sana Khan, Caroline Klinck, Karl Krupp, Sally Littau, Amelia Lobos, Ashley Lowe, Jeremy Makar, Mayra Martinez, Natalya Mayhew, Flavia Nakayima Miiro, Joe Mirabito, Aidalee Montijo, Cierra Morris, Raul Nava, Janko Nikolich-Žugich, Assumpta Nsengiyunva, Mya Pena, Cielo Perez, Cynthia Porter, Ferris A. Ramadan, Patrick Rivers, Megan Roe, James K. Romine, Priyanka Sharma, Alison Slocum, Saskia Smidt, Lili Steffen, Danielle Stea, Xiaoxiao Sun, Nicholas Tang, Gavin Tovar, Italia Trejo, Erin Woods, April Yingst.

University of Utah: Arlyne Arteaga, Braydon Black, Brock Bourdelle, Rachel T. Brown, Matthew Bruner, Riley Campbell, Aniysah Colston, Brianna Cottam, Chapman Cox, Kendal Chatard, Ben Cragun, Daniel Dawson, Anika Dsouza, Emilee Eden, Amanda Flanagan, Colton Fox, Adriele Fugal, Nikki Gallacher, Michelle Gillette, Joshua Griffin, Christian Guzman, Isaac Hansen, Addie Hunsaker, Iman Ibrahim, Nada Jabbouri, Junny Jeong, Ryder Jordin, Tori Joy, Michael Langston, Alexis Lowe, Katie Luong, Aurianna Martin, Gretchen Maughan, Jinyi Mao, Jeanmarie Mayer, Katy McCone, Renee McEntire, Jacob McKell, Tiana Miller, Max Minoughan, Naveen Naveed, Jessica Olsen, Christina Pick, Timina Powaukee, Jenna Praggastis, Lily Prentice, Seon Reed, Amber Rhodes, Griffin Rost, Camie Schaefer, Ashmita Shanthakumar, Madeleine Smith, Joseph Stanford, Grace Stewart, Pasha Stinson, Trevor Stubbs, Marcus Stucki, Madison Tallman, Sydney Taylor, Kathy Tran, Fiona Tsang, Irene Tucker, Maya Wheeler, Megan Wilson, Jesse Williams, Derrick Wong, Jenna Vo, Hannah Whiting, Iris Yang, Karly Anderson, Ian Arlington, Arlyne Arteaga, Braydon Black, Brock Bourdelle.

Disclaimer.

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

Financial 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 (contract numbers 75D30120R68013 awarded to Marshfield Clinic Research Foundation, 75D30120C08379 to University of Arizona, and 75D30120C08150 awarded to Abt Associates, Inc).

Potential conflicts of interest. M. S. T. and S. K. Y. have received funding from Novavax through their institution.

All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Supplementary Data

Supplementary materials are available at The Journal of Infectious Diseases online (http://jid.oxfordjournals.org/). Supplementary materials consist of data provided by the author that are published to benefit the reader. The posted materials are not copyedited. The contents of all supplementary data are the sole responsibility of the authors. Questions or messages regarding errors should be addressed to the author.

Presented in part: Advisory Committee on Immunization Practices meeting, Atlanta, Georgia, 12 September 2023.

ReferencesGlobal Burden of Disease Long COVID Collaborators; Wulf HansonS, AbbafatiC, AertsJG, Estimated global proportions of individuals with persistent fatigue, cognitive, and respiratory symptom clusters following symptomatic COVID-19 in 2020 and 2021. JAMA 2022; 328:1604–15.36215063 TenfordeMW, DevineOJ, ReeseHE, Point prevalence estimates of activity-limiting long-term symptoms among U.S. adults ≥1 month after reported SARS-CoV-2 infection, November 1, 2021. J Infect Dis 2022; 227:855–63.FordND, SlaughterD, EdwardsD, Long COVID and significant activity limitation among adults, by age—United States, June 1–13, 2022, to June 7–19, 2023. MMWR Morb Mortal Wkly Rep 2023; 72:866–70.37561665 Centers for Disease Control and Prevention. 2024. https://www.cdc.gov/covid/long-term-effects/index.html.ChenC, HaupertSR, ZimmermannL, ShiX, FritscheLG, MukherjeeB. Global prevalence of post-coronavirus disease 2019 (COVID-19) condition or long COVID: a meta-analysis and systematic review. J Infect Dis 2022; 226:1593–607.35429399 Bull-OttersonL, BacaS, SaydahS, Post–COVID conditions among adult COVID-19 survivors aged 18–64 and ≥ 65 years—United States, March 2020–November 2021. MMWR Morb Mortal Wkly Rep 2022; 71:713–7.SubramanianA, NirantharakumarK, HughesS, Symptoms and risk factors for long COVID in non-hospitalized adults. Nat Med 2022; 28:1706–14.35879616 PerlisRH, SantillanaM, OgnyanovaK, Prevalence and correlates of long COVID symptoms among US adults. JAMA Netw Open 2022; 5:e2238804.36301542 CanasLS, MolteniE, DengJ, Profiling post-COVID-19 condition across different variants of SARS-CoV-2: a prospective longitudinal study in unvaccinated wild-type, unvaccinated Alpha-variant, and vaccinated Delta-variant populations. Lancet Digital Health 2023; 5:e421–34.37202336 AntonelliM, PenfoldRS, MerinoJ, Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study. Lancet Infect Dis 2022; 22:43–55.34480857 Al-AlyZ, BoweB, XieY. Long COVID after breakthrough SARS-CoV-2 infection. Nat Med 2022; 28:1461–7.35614233 WatanabeA, IwagamiM, YasuharaJ, TakagiH, KunoT. Protective effect of COVID-19 vaccination against long COVID syndrome: a systematic review and meta-analysis. Vaccine 2023; 41:1783–90.36774332 RichardSA, PollettSD, FriesAC, Persistent COVID-19 symptoms at 6 months after onset and the role of vaccination before or after SARS-CoV-2 infection. JAMA Netw Open 2023; 6:e2251360.36652247 GaoP, LiuJ, LiuM. Effect of COVID-19 vaccines on reducing the risk of long COVID in the real world: a systematic review and meta-analysis. Int J Environ Res Public Health 2022; 19:12422.36231717 ByambasurenO, StehlikP, ClarkJ, AlcornK, GlasziouP. Effect of covid-19 vaccination on long covid: systematic review. BMJ Med 2023; 2:e000385.NotarteKI, CatahayJA, VelascoJV, Impact of COVID-19 vaccination on the risk of developing long-COVID and on existing long-COVID symptoms: a systematic review. EClinicalMedicine 2022; 53:101624.36051247 GottliebM, WangR, YuH, Severe fatigue and persistent symptoms at 3 months following severe acute respiratory syndrome coronavirus 2 infections during the pre-Delta, Delta, and Omicron time periods: a multicenter prospective cohort study. Clin Infect Dis 2023; 79:1930–41.BallouzT, MengesD, KaufmannM, Post COVID-19 condition after wildtype, Delta, and Omicron SARS-CoV-2 infection and prior vaccination: pooled analysis of two population-based cohorts. PLoS One 2023; 18:e0281429.36812215 Lutrick KEK, BaccamZ, RiversP, COVID-19 infection, reinfection, and vaccine effectiveness in a prospective cohort of Arizona frontline/essential workers: the AZ HEROES research protocol. JMIR Res Protoc 2021; 10:e28925.34057904 EdwardsLJ, FowlkesAL, WesleyMG, Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel (RECOVER) study: protocol for a multi-site longitudinal cohort. JMIR Res Protoc 2021; 10:e31574.34662287 AzzoliniE, LeviR, SartiR, Association between BNT162b2 vaccination and long COVID after infections not requiring hospitalization in health care workers. JAMA 2022; 328:676–8.35796131 AyoubkhaniD, BosworthML, KingS, Risk of long COVID in people infected with severe acute respiratory syndrome coronavirus 2 after 2 doses of a coronavirus disease 2019 vaccine: community-based, matched cohort study. Open Forum Infect Dis 2022; 9:ofac464.36168555

Consolidated Standards of Reporting Trials (CONSORT) diagram of HEROES-RECOVER cohort participants included in an analysis of association of messenger RNA (mRNA) coronavirus disease 2019 vaccination and occurrence of post-COVID conditions after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Characteristics of HEROES-RECOVER Cohort Participants With Severe Acute Respiratory Syndrome Coronavirus 2 Infection Included in Analysis of Post-COVID Conditions (PCCs), by Whether They Did or Did Not Report PCCs on Postinfection Survey Between 5 May 2022 and 26 November 2022

CharacteristicTotal
Did Not Report PCCsa
Reported PCCsa
P Valueb
No.(Col %)No.(Col %)No.(Col %)
No. of participants936…715(76.4)221(23.6)
Sociodemographic characteristics
 Age, y, mean (SD)44.2(10.5)44.1(10.4)44.8(10.7).413
 Gender.000
  Female571(61.0)413(57.8)158(71.5)
  Male363(38.8)300(42.0)63(28.5)
  Did not disclosec2…2…0…
 Race.297
  American Indian/Alaska Native8(0.9)7(1.0)1(0.5)
  Asiand26(2.8)22(3.1)4(1.8)
  Black or African American16(1.7)11(1.5)5(2.3)
  White826(88.2)628(87.8)198(89.6)
  Multiracial8(0.9)4(0.6)4(1.8)
  Did not disclose52…43…9…
 Ethnicity.640
  Hispanic174(18.6)131(18.3)43(19.5)
  Non-Hispanic742(79.3)571(79.9)171(77.4)
  Did not disclose20…13…7…
 Cohort location.308
  Phoenix, Arizona152(16.2)105(14.7)47(21.3)
  Tucson, Arizona391(41.8)298(41.7)93(42.1)
  Other, Arizona107(11.4)83(11.6)24(10.9)
  Miami, Florida63(6.7)52(7.3)11(5.0)
  Duluth, Minnesota81(8.7)65(9.1)16(7.2)
  Temple, Texas31(3.3)25(3.5)6(2.7)
  Salt Lake City, Utah111(11.9)87(12.2)24(10.9)
 Occupatione.001
  Primary HCP148(15.8)124(17.3)24(10.9)
  Secondary HCP258(27.6)186(26.0)72(32.6)
  First responder224(23.9)187(26.2)37(16.7)
  Frontline worker306(32.7)218(30.5)88(39.8)
SARS-CoV-2 infection characteristics
 Infection type<.0001
  Symptomatic855(91.3)639(89.4)216(97.7)
  Asymptomatic81(8.7)76(10.6)5(2.3)
 No. of symptoms reported during infection<.0001
  0–3257(27.5)219(30.6)38(17.2)
  ≥4679(72.5)496(69.4)183(82.8)
 Infection severity.150
  Nonhospitalized897(95.8)685(95.8)212(95.2)
  Hospitalized6(0.6)3(0.4)3(1.4)
  Did not respond33…27…6…
 SARS-CoV-2 lineagef.144
  Delta variant102(10.9)72(10.1)30(13.6)
  Omicron variant834(89.1)643(89.9)191(86.4)
 Medical history prior to SARS-CoV-2 infection
 No. of chronic conditions.077
  None689(73.6)538(73.6)151(68.3)
  ≥1232(24.8)168(24.8)64(29.0)
  Did not disclose15…9…6…
 Daily medication use.004
  None458(48.9)369(48.9)89(40.3)
  ≥1459(49.0)333(49.0)126(57.0)
  Did not disclose19…13…6…
 Smoking history.137
  Not current smoker 720(76.9)560(76.9)160(72.4)
  Smoke tobacco products 198(21.2)144(21.2)54(24.4)
  Did not disclose18…11…7…
 Self-rated health.009
  Excellent/very good655(70.0)516(70.0)139(62.9)
  Good/fair/poor281(30.0)199(30.0)82(37.1)

Abbreviations: Col, column; HCP, healthcare personnel; PCC, post-COVID condition; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SD, standard deviation.

PCC was defined as self-reported symptoms persisting >4 weeks after acute SARS-CoV-2 infection. Symptoms could have been continuous since initial infection or relapsing/remitting since initial infection.

P values calculated using Pearson χ2 test (cells with ≥5 observations), Fisher's exact test (cells with <5 observations), or t test to assess difference in means.

Includes 2 individuals who reported “none of these.”

Includes individuals who responded as native Hawaiian or other Pacific Islander.

Occupation categories: primary HCP (physicians, physician assistants, nurse practitioners, dentists), other allied HCP (nurses, therapists, technicians, medical assistants, orderlies, and all others providing clinical support in inpatient or outpatient settings), first responders (firefighters, law enforcement, corrections, emergency medical technicians), and essential and frontline workers (workers in hospitality, delivery, and retail; teachers; all other occupations that require contact within 3 feet of the public, customers, or coworkers as a routine part of their job).

SARS-CoV-2 lineage was determined through whole genome sequencing on eligible samples. For ineligible specimens (cycle threshold value ≥30), virus sequence was presumptively assigned as the Delta variant when Delta accounted for ≥50% of viruses sequenced from other specimens at each site location; specimens were presumed to be the Omicron variant when ≥50% of viruses sequenced were Omicron for each site.

Characteristics of HEROES-RECOVER Cohort Participants With Severe Acute Respiratory Syndrome Coronavirus 2 Infection Included in Analysis of Post-COVID Conditions, by Vaccination Status

CharacteristicTotal
Unvaccinated
Vaccinated 2 Monovalent Doses (≥14 d Prior to Initial Infection)
Vaccinated 3 Monovalent Doses (≥7 d Prior to Initial Infection)
No.(Col %)No.(Col %)No.(Col %)P ValueaNo.(Row %)P Valuea
No. of participants936…157(16.8)301(32.2)478(51.1)
Sociodemographic characteristics
 Age, y, mean (SD)44.2(10.5)45.1(11.0)44.6(10.9).68443.7(10.0).150
 Gender.647.001
  Female571(61.0)82(52.2)165(54.8)324(67.8)
  Male363(38.8)74(47.1)136(45.2)153(32.0)
  Did not discloseb2…1…0…1…
 Race.085.141
  American Indian/Alaska Native8(0.9)0(0.0)3(1.0)5(1.0)
  Asianc26(2.8)5(3.2)4(1.3)17(3.6)
  Black or African American16(1.7)0(0.0)8(2.7)8(1.7)
  White826(88.2)142(90.4)261(86.7)423(88.5)
  Multiracial8(0.9)2(1.3)5(1.7)1(0.2)
  Did not disclose52…8…20…24…
 Ethnicity.589.311
  Hispanic174(18.6)30(19.1)66(21.9)78(16.3)
  Non-Hispanic742(79.3)119(75.8)229(76.1)394(82.4)
  Did not disclose20…8…6…6…
 Cohort location.364.014
  Phoenix, Arizona152(16.2)22(14.0)49(16.3)81(16.9)
  Tucson, Arizona391(41.8)70(44.6)121(40.2)200(41.8)
  Other, Arizona107(11.4)19(12.1)28(9.3)60(12.6)
  Miami, Florida63(6.7)13(8.3)30(10.0)20(4.2)
  Duluth, Minnesota81(8.7)7(4.5)16(5.3)58(12.1)
  Temple, Texas31(3.3)2(1.3)16(5.3)13(2.7)
  Salt Lake City, Utah111(11.9)24(15.3)41(13.6)46(9.6)
 Occupationd.061<.001
  Primary HCP148(15.8)5(3.2)31(10.3)112(23.4)
  Secondary HCP258(27.6)40(25.5)75(24.9)143(29.9)
  First responder224(23.9)56(35.7)100(33.2)68(14.2)
  Frontline worker306(32.7)56(35.7)95(31.6)155(32.4)
SARS-CoV-2 infection characteristics
 Infection type.001.000
  Symptomatic855(91.3)131(83.4)280(93.0)444(92.9)
  Asymptomatic81(8.7)26(16.6)21(7.0)34(7.1)
 No. of symptoms reported during infection.097.845
  0–3257(27.5)46(29.3)67(22.3)144(30.1)
  ≥4679(72.5)111(70.7)234(77.7)334(69.9)
 Infection severity.607.2586
  Nonhospitalized897(95.8)149(94.9)293(97.3)455(95.2)
  Hospitalized6(0.6)2(1.3)2(0.7)2(0.4)
  Did not disclose33…6…6…21…
 SARS-CoV-2 lineagee.071<.0001
  Delta variant102(10.9)41(26.1)56(18.6)5(1.0)
  Omicron variant834(89.1)116(73.9)245(81.4)473(99.0)
 Days since most recent vaccine dose, median (IQR)198.0(96.0–301.0)……324.0(249.0–419.0)112.0(76.0–214.0)
 Medical history prior to SARS-CoV-2 infection
  No. of chronic conditions.877.883
   None689(73.6)113(72.0)221(73.4)355(74.3)
   ≥1232(24.8)37(23.6)75(24.9)120(25.1)
   Did not disclose15753
  Daily medication use.528.050
   None458(48.9)83(52.9)155(51.5)220(46.0)
   ≥1459(49.0)66(42.0)140(46.5)253(52.9)
   Did not disclose19…8…6…5…
  Smoking history.229.551
   Not current smoker720(76.9)121(77.1)224(74.4)375(78.5)
   Smoke tobacco products198(21.2)28(17.8)70(23.3)100(20.9)
   Did not disclose18…8…7…3…
  Self-rated health.728.363
   Excellent/very good655(70.0)106(67.5)208(69.1)341(71.3)
   Good/fair/poor281(30.0)51(32.5)93(30.9)137(28.7)
  Vaccine product
   BNT162b2 (Pfizer-BioNTech)460(49.1)……166(55.1)294(61.5)
   mRNA-1273 (Moderna)285(30.4)……133(44.2)152(31.8)
   Mixed dosingf34(3.6)……2(0.7)32(6.7)

Abbreviations: Col, column; HCP, healthcare personnel; IQR, interquartile range; mRNA, messenger RNA; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SD, standard deviation.

P values calculated using Pearson χ2 test (cells with ≥5 observations), Fisher's exact test (cells with <5 observations), or t test to assess difference in means.

Includes 2 individuals who reported “none of these.”

Includes individuals who responded as native Hawaiian or other Pacific Islander.

Occupation categories: primary HCP (physicians, physician assistants, nurse practitioners, dentists), other allied HCP (nurses, therapists, technicians, medical assistants, orderlies, and all others providing clinical support in inpatient or outpatient settings), first responders (firefighters, law enforcement, corrections, emergency medical technicians), and essential and frontline workers (workers in hospitality, delivery, and retail; teachers; all other occupations that require contact within 3 feet of the public, customers, or coworkers as a routine part of their job).

SARS-CoV-2 lineage was determined through whole genome sequencing on eligible samples. For ineligible specimens (cycle threshold value ≥30), virus sequence was presumptively assigned as the Delta variant when Delta accounted for ≥50% of viruses sequenced from other specimens at each site location; specimens were presumed to be the Omicron variant when ≥50% of viruses sequenced were Omicron for each site.

Mixed dosing defined as receiving at least 1 dose of each mRNA vaccine.

Odds of Reporting Post-COVID Conditions After Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Vaccinated Versus Unvaccinated Study Participants

Total
UnvaccinatedVaccinated 2 Monovalent Doses (≥14 d Prior to Initial Infection)
Vaccinated 3 Monovalent Doses (≥7 d Prior to Initial Infection )
OutcomeNo.(Col %)No.(Row %)No.(Row %)aOR (95% CI)aNo.(Row %)aOR (95% CI)a
All participants936…157(16.8)301(32.2)…478(51.1)…
No PCC (no symptoms)715(76.3)115(16.3)227(32.2)Ref373(52.8)Ref
PCC by No. of symptoms
 ≥1 symptomb221(23.6)42(19.0)74(33.5)0.84 (.53–1.32)105(47.5)0.71 (.45–1.12)
 ≥2 symptomsb158(16.5)27(17.1)62(39.2)1.07 (.63–1.80)69(43.7)0.65 (.39–1.11)
PCC by symptom category
 Cardiovascular/respiratoryc107(11.4)19(17.8)44(41.1)1.12 (.62–2.05)44(41.1)0.65 (.35–1.20)
 Gastrointestinald46(4.9)12(26.1)17(37.0)0.69 (.31–1.53)17(37.0)0.37 (.16-.85)
 Generale152(16.2)26(17.1)58(38.2)1.08 (.64–1.84)68(44.7)0.73 (.43–1.24)
 Neurologicalf128(13.7)26(20.3)44(34.4)0.80 (.46–1.40)58(45.3)0.56 (.32-.97)
 Otherg80(8.5)19(23.8)29(36.3)0.77 (.41–1.46)32(40.0)0.48 (.25-.91)

Abbreviations: aOR, adjusted odds ratio; CI, confidence interval; Col, column; PCC, post-COVID condition.

Odds ratio estimated using logistic regression with no PCC (no symptoms) as referent group. All models were adjusted for gender, presence of chronic conditions (categorized by none or ≥1 chronic condition), age (categorized as <40 or ≥40 years), number of symptoms experienced during acute infection (categorized as ≤3 or >3), interval between initial infection and survey completion (categorized as 60–119 days, 120–179 days, and ≥180 days), and variant of infection (Delta or Omicron).

Symptoms include shortness of breath, palpitations, chest pain/tightness, runny nose/congestion, loss of appetite, nausea, vomiting, abdominal/stomach pain, constipation, diarrhea, worsening of symptoms following minor mental or physical activity, fatigue, joint pain, joint swelling, muscle pain, dizziness/lightheadedness/fainting, numbness/tingling, fogginess in thinking, change in sleeping, headache, difficulty speaking/communicating, difficulty swallowing/chewing, problems with balance/movement.

Cardiovascular/respiratory symptoms include shortness of breath, palpitations, chest pain/tightness, and runny nose/congestion.

Gastrointestinal symptoms include loss of appetite, nausea, vomiting, abdominal/stomach pain, constipation, and diarrhea.

General symptoms include worsening of symptoms following minor mental or physical activity, fatigue, joint pain, joint swelling, and muscle pain.

Neurological symptoms include dizziness/lightheadedness/fainting, numbness/tingling, fogginess in thinking, change in sleeping, headache, difficulty speaking/communicating, difficulty swallowing/chewing, and problems with balance/movement.

Other symptoms include weight loss, hair loss, change in color of toes/fingers, rash, bruising/bleeding easily, change in menstrual cycle, change in sexual drive, and erectile dysfunction.