Assessing the association between antibody status and symptoms of long COVID: A multisite study
Ingrid A. Binswanger, Darryl E. Palmer-Toy, Jennifer C. Barrow, Komal J. Narwaney, Katia J. Bruxvoort, Courtney R. Kraus, Jason A. Lyons, Jessica A. Lam, Jason M. Shine
Abstract
The association between SARS-CoV-2 humoral immunity and post-acute sequelae of COVID-19 (long COVID) remains uncertain. The objective of this population-based cohort study was to assess the association between SARS-CoV-2 seropositivity and symptoms consistent with long COVID. English and Spanish-speaking members ≥ 18 years old with SARS-CoV-2 serologic testing conducted prior to August 2021 were recruited from Kaiser Permanente Southern California and Kaiser Permanente Colorado. Between November 2021 and April 2022, participants completed a survey assessing symptoms, physical health, mental health, and cognitive function consistent with long COVID. Survey results were linked to SARS-CoV-2 antibody (Ab) and viral (RNA) lab results in electronic health records. Weighted descriptive analyses were generated for five mutually exclusive patient groups: (1) +Ab/+RNA; (2) +Ab/- or missing RNA; (3) -Ab/+RNA; (4a) -Ab/-RNA reporting no prior infection; and (4b) -Ab/-RNA reporting prior infection. The proportions reporting symptoms between the +Ab/+RNA and -Ab/+RNA groups were compared, adjusted for covariates. Among 3,946 participants, the mean age was 52.1 years old (SD 15.6), 68.3% were female, 28.4% were Hispanic, and the serologic testing occurred a median of 15 months prior (IQR = 12–18). Three quarters (74.5%) reported having had COVID-19.
Introduction
With much of the population having been infected with SARS-CoV-2, complications of COVID-19 may affect millions of global survivors, resulting in lost economic productivity, quality of life reductions, functional limitations, and disability [1–7]. Chronic post-acute sequelae of COVID-19 (PASC, also called “long COVID”) involves multisystemic symptoms, signs, and health conditions that develop during or following a confirmed or suspected COVID-19 case, that may be persistent, recurrent, or new [8–11]. Common symptoms include dyspnea, fatigue, insomnia, joint and muscle pain, and anosmia [6,12–17], with prevalence estimates varying across symptoms, severity of the initial infection, and population studied [18–22].
Methods
Study design and study settings
We conducted a population-based cohort study of adults who received commercially available serologic tests for SARS-CoV-2 antibodies to assess how mutually exclusive combinations of serologic and molecular results, supplemented with survey data on prior COVID-19, were associated with symptoms and health domains consistent with long COVID (S1 Fig in S1 File). The survey was conducted in Kaiser Permanente Southern California (KPSC) and Colorado (KPCO) integrated health care delivery systems, which comprise employer-based and individual insurance, and Medicare and Medicaid plans. KPSC serves approximately 4.8 million members and KPCO serves approximately 0.5 million members. For context in these study settings, the first California and Colorado COVID-19 cases were identified in January and March of 2020, respectively. California experienced a peak of Alpha variant mid-May 2021, Delta from June to mid-December 2021, and Omicron starting in late December 2021. Alpha peaked in Colorado prior to May, Delta from May to December, and Omicron after December 2021 [28]. Vaccines (Pfizer-BioNTech BNT162b2, Moderna mRNA-1273, and Janssen JNJ-7846725) became available in December 2020. This study was conducted as part of a multisite collaboration to assess the clinical roles of serology across our health systems [29,30].
Results
Of 15,491 recruited members (KPSC: 11,023; KPCO: 4,468), 4,018 (25.9%) members completed the survey, and 3,946 (25.5%) represented the final study population (Fig 1). Participation rates differed by site, and there were differences between respondents and non-respondents by language, recruitment group, and demographics in the EHR (S2 Table in S1 File). Eligible index RNA tests were unavailable for 14.5% of participants. The mean age of participants was 52.1 years (SD = 15.6) and 4.4% (n = 173) completed the survey in Spanish and 33.4% (n = 1317) by paper. The median time between PCR and serology was approximately 2 months (median = 59 days, range 1–470; IQR 29–113) and the median time between serology and survey completion was over a year (median = 446 days, range 121–773; IQR 366–542).
Discussion
In this multi-site, population-based study, we identified no differences in symptoms and health domains consistent with long COVID based on antibody status among people with laboratory evidence of prior COVID-19. In contrast to prior studies showing an association between antibody response and long COVID [22,47,48], our findings suggest that, among people with prior infection, serologic status using commercially available antibody tests in use at the time this study was completed were not associated with long COVID symptoms, as assessed a mean of 15 months after infection. As a result, in this study, serologic status among people with known infections could not be used to predict symptoms of long COVID.
Acknowledgments
We acknowledge the following individuals who assisted with the implementation of the study Ruth Bedoy, Megan Baldwin, America Elias Martinez, Jennifer Sawyer, Laura Bechtel, William Duran, Ben Dubbeld, Duy Do, Hubert Song, Jiaxiao M. Shi, Cecilia Portugal, Boris Bayerman, and John Chang. The authors thank the patients of Kaiser Permanente and their partnership with us to improve their health.
Citation: Binswanger IA, Palmer-Toy DE, Barrow JC, Narwaney KJ, Bruxvoort KJ, Kraus CR, et al. (2024) Assessing the association between antibody status and symptoms of long COVID: A multisite study. PLoS ONE 19(6): e0304262. https://doi.org/10.1371/journal.pone.0304262
Editor: Antonio Carlos Rosario Vallinoto, Universidade Federal do Para, BRAZIL
Received: August 31, 2023; Accepted: May 9, 2024; Published: June 6, 2024
Copyright: © 2024 Binswanger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: Individual-level data reported in this study are not publicly shared due to potentially identifying or sensitive patient information. Upon request, and subject to review, deidentified aggregate level data that support the findings of this study may be made available from the investigative team under the following conditions: 1) agreement to collaborate with the study team on all publications, 2) provision of external funding for administrative and investigator time necessary for this collaboration, 3) demonstration that the external investigative team is qualified and has documented evidence of training for human subjects protections, and 4) agreement to abide by the terms outlined in data use agreements between institutions. Interested researchers should contact Kaiser Permanente Colorado Institute for Health Research at [email protected].
Funding: Grant funding for this study came from the Garfield Memorial Research Fund and Kaiser Permanente Community Health Fund, which funded the research staff who worked on the study and authors on this manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: “I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Binswanger received royalties from UpToDate (Wolters Kluwer) for unrelated educational content on the health of incarcerated persons. Dr. Bruxvoort has received funding from Moderna, Pfizer, Dynavax, Gilead, and GlaxoSmithKline for unrelated research. This commercial funding does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors have declared that no competing interests exist.”
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0304262#abstract0
