Timing dependent associations of acute phase laboratory and antibody parameters with post-acute sequelae of SARS-CoV-2 infection in unvaccinated individuals
9 affiliations
- 1Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo
- 2Medical & Biological Laboratories Co., LTD.
- 3Department of Infectious Diseases, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo
- 4Department of Infection Control and Prevention, Graduate School of Medicine, The University of Tokyo
- 5The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics – Hubei Bioinformatics and Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology
- 6Shenzhen Drawray Biotech Co., Ltd
- 7Division of Infection Control and Prevention, Education Research Center, Tokyo Health Care University
- 8Research Center for Advanced Science and Technology, The University of Tokyo
- 9Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo
Abstract
Introduction: Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) affects a substantial minority of individuals after acute COVID-19, and immune dysregulation is widely implicated in its pathogenesis. Reported associations between SARS-CoV-2-specific antibody responses and PASC have nonetheless been inconsistent. Because antibody levels change rapidly in the weeks after symptom onset, the timing of sampling may itself account for much of this heterogeneity, yet few studies have examined humoral responses along the time axis from symptom onset in combination with routinely available hematological, biochemical, and coagulation parameters.
Methods: Eight hundred seventy-two serial serum samples were retrospectively analyzed from 213 unvaccinated individuals experiencing their first SARS-CoV-2 infection, sampled between April 2020 and June 2021, before vaccine rollout and before the emergence of Omicron; 13 individuals subsequently met the World Health Organization definition of PASC. Sixty-seven parameters, comprising antiviral antibodies, autoantibodies and immune markers, complete blood count, biochemistry and coagulation tests, were compared between groups within four windows defined by days since symptom onset: ≤ 7, 8–14, 15–28, and > 28 days.
Results: The pattern of association shifted markedly across windows. Within seven days of onset, innate inflammatory and coagulation markers predominated. Between days 8 and 14, when adaptive humoral responses first become measurable, red cell indices differed between groups, with lower mean corpuscular hemoglobin concentration remaining significant when each patient contributed a single value. Anti-spike IgM levels tended to be higher in individuals who later developed PASC, although the difference was not statistically significant. Exploratory multivariable models combining humoral and hematological features discriminated better than either domain alone, although the small number of PASC cases precludes any claim of predictive validity.
Discussion: These findings identify days 8–14 after symptom onset as a potentially informative window during which acute-phase laboratory parameters, and possibly early humoral responses, differ between individuals who do and do not subsequently develop PASC, and suggest that the timing and quality of the early antibody response, rather than antibody magnitude measured at a single late time point, merit systematic investigation in PASC.
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BibTeX
@article{yamamoto2026timing,
title = {{Timing dependent associations of acute phase laboratory and antibody parameters with post-acute sequelae of SARS-CoV-2 infection in unvaccinated individuals}},
author = {Shinya Yamamoto and Takeshi Ohtsuka and Yoshiro Kishi and Koh Okamoto and Takeya Tsutsumi and Chungen Qian and Fan He and Kyoji Moriya and Tatsuhiko Kodama and Makoto Kurano},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1984598},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1984598/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Timing dependent associations of acute phase laboratory and antibody parameters with post-acute sequelae of SARS-CoV-2 infection in unvaccinated individuals
AU - Shinya Yamamoto
AU - Takeshi Ohtsuka
AU - Yoshiro Kishi
AU - Koh Okamoto
AU - Takeya Tsutsumi
AU - Chungen Qian
AU - Fan He
AU - Kyoji Moriya
AU - Tatsuhiko Kodama
AU - Makoto Kurano
PY - 2026
DA - 2026/11/04
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1984598
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1984598/full
AB - Introduction: Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) affects a substantial minority of individuals after acute COVID-19, and immune dysregulation is widely implicated in its pathogenesis. Reported associations between SARS-CoV-2-specific antibody responses and PASC have nonetheless been inconsistent. Because antibody levels change rapidly in the weeks after symptom onset, the timing of sampling may itself account for much of this heterogeneity, yet few studies have examined humoral responses along the time axis from symptom onset in combination with routinely available hematological, biochemical, and coagulation parameters. Methods: Eight hundred seventy-two serial serum samples were retrospectively analyzed from 213 unvaccinated individuals experiencing their first SARS-CoV-2 infection, sampled between April 2020 and June 2021, before vaccine rollout and before the emergence of Omicron; 13 individuals subsequently met the World Health Organization definition of PASC. Sixty-seven parameters, comprising antiviral antibodies, autoantibodies and immune markers, complete blood count, biochemistry and coagulation tests, were compared between groups within four windows defined by days since symptom onset: ≤ 7, 8–14, 15–28, and > 28 days. Results: The pattern of association shifted markedly across windows. Within seven days of onset, innate inflammatory and coagulation markers predominated. Between days 8 and 14, when adaptive humoral responses first become measurable, red cell indices differed between groups, with lower mean corpuscular hemoglobin concentration remaining significant when each patient contributed a single value. Anti-spike IgM levels tended to be higher in individuals who later developed PASC, although the difference was not statistically significant. Exploratory multivariable models combining humoral and hematological features discriminated better than either domain alone, although the small number of PASC cases precludes any claim of predictive validity. Discussion: These findings identify days 8–14 after symptom onset as a potentially informative window during which acute-phase laboratory parameters, and possibly early humoral responses, differ between individuals who do and do not subsequently develop PASC, and suggest that the timing and quality of the early antibody response, rather than antibody magnitude measured at a single late time point, merit systematic investigation in PASC.
SN - 1664-3224
ER -