. 2025 May 2;5(1):149.

doi: 10.1038/s43856-025-00828-4.

SARS-CoV-2 humoral immune responses in convalescent individuals over 12 months reveal severity-dependent antibody dynamics

Nadia Siles Alvarado^#¹, Maisey Schuler^#¹, Cole Maguire¹, Dzifa A Amengor², Annalee W Nguyen³, Rebecca E Wilen³, Jacob Rogers¹, Sam Bazzi¹, Blaine Caslin¹, Christopher DiPasquale⁴, Melissa Abigania⁴, Eric Olson⁴, Janelle Creaturo¹, Kerin Hurley^{1

5}, Todd A Triplett^{6

7}, Justin F Rousseau^{8

9

10}, Stephen M Strakowski^{11

12}, Dennis Wylie¹³, Jennifer A Maynard³, Lauren I R Ehrlich^{14

15}, Esther Melamed¹⁶

Affiliations

¹ Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
² Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
³ Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.
⁴ Babson Diagnostics, Austin, TX, USA.
⁵ Dell Seton Medical Center at The University of Texas, Austin, TX, USA.
⁶ Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
⁷ Department of Immunotherapeutics & Biotechnology, School of Pharmacy, Texas Tech University Health Sciences Center, Abilene, TX, USA.
⁸ Department of Population Health, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
⁹ Biostatistics and Clinical Informatics Section, Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁰ Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹¹ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
¹² Department of Psychiatry, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
¹³ Center for Biomedical Research Support, The University of Texas at Austin, Austin, TX, USA.
¹⁴ Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA. lehrlich@austin.utexas.edu.
¹⁵ Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA. lehrlich@austin.utexas.edu.
¹⁶ Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA. Esther.melamed@austin.utexas.edu.

^# Contributed equally.

PMID: 40316665
PMCID: PMC12048490
DOI: 10.1038/s43856-025-00828-4

SARS-CoV-2 humoral immune responses in convalescent individuals over 12 months reveal severity-dependent antibody dynamics

Nadia Siles Alvarado et al. Commun Med (Lond). 2025.

. 2025 May 2;5(1):149.

doi: 10.1038/s43856-025-00828-4.

Authors

Affiliations

¹ Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
² Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
³ Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.
⁴ Babson Diagnostics, Austin, TX, USA.
⁵ Dell Seton Medical Center at The University of Texas, Austin, TX, USA.
⁶ Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
⁷ Department of Immunotherapeutics & Biotechnology, School of Pharmacy, Texas Tech University Health Sciences Center, Abilene, TX, USA.
⁸ Department of Population Health, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
⁹ Biostatistics and Clinical Informatics Section, Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁰ Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹¹ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
¹² Department of Psychiatry, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
¹³ Center for Biomedical Research Support, The University of Texas at Austin, Austin, TX, USA.
¹⁴ Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA. lehrlich@austin.utexas.edu.
¹⁵ Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA. lehrlich@austin.utexas.edu.
¹⁶ Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA. Esther.melamed@austin.utexas.edu.

^# Contributed equally.

PMID: 40316665
PMCID: PMC12048490
DOI: 10.1038/s43856-025-00828-4

Abstract

Background: Defining the kinetics of SARS-CoV-2 antibody responses is critical for informing the management of reinfections, vaccinations, and therapeutics of Coronavirus disease 2019 (COVID-19).

Methods: Using four antibody assays, we evaluated antibody titers against SARS-CoV-2 nucleocapsid (N), spike (S), and receptor binding domain (RBD) in 98 convalescent participants with varying COVID-19 disease severities (asymptomatic, mild, moderate or severe) at 1, 3, 6, and 12-months post-SARS-CoV-2-positive PCR and in 17 non-vaccinated, non-infected controls.

Results: Increasing acute COVID-19 disease severity correlates with higher anti-N and anti-RBD titers throughout 12 months post-infection. Anti-N and anti-RBD titers decline over time in all participants, except for increased anti-RBD titers post-vaccination, with hospitalized participants exhibiting faster decay rates. Less than 50% of participants retain anti-N titers above controls at 12 months, with non-hospitalized participants falling below controls sooner. Nearly all participants maintain anti-RBD titers above controls for 12 months, suggesting long-term protection against severe reinfections. Nonetheless, by 6 months, few participants retain >50% of their initial 1-month anti-N or anti-RBD titers. Notably, vaccine-induced anti-RBD titers are higher in non-hospitalized participants. Lastly, early convalescent titers correlate with age but not with Post-Acute Sequelae of SARS-CoV-2 infection (PASC) status or steroid use.

Conclusion: Hospitalized participants initially develop higher anti-SARS-CoV-2 antibody titers that decline faster relative to non-hospitalized participants. While anti-N titers fall below control levels in some participants, anti-RBD titers remain above controls over 12 months, demonstrating long-lived antibody responses known to protect against severe disease. These findings advance our understanding of COVID-19 antibody dynamics.

Plain language summary

This study explores how the immune system responds to COVID-19 over time by measuring antibodies, small proteins that help fight infection. We studied 98 participants who recovered from COVID-19 with varying illness severities and 17 who were never infected. Blood samples were collected over a year to track changes in antibody levels. Our results show that severe illness leads to higher antibody levels, though with a more precipitous antibody decline than in milder cases. Notably, antibodies that offer long-term protection against severe COVID-19 remain high for 12 months after the infection in most individuals. Lastly, vaccination boosts antibody levels, particularly in individuals with milder illness. Our research enhances understanding of immunity post COVID-19 and informs vaccination and reinfection prevention strategies.

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Conflict of interest statement

Competing interests: The authors declare the following competing interests: Nadia Siles Alvarado: Recipient of National Consortium for Graduate Degrees for Minorities in Engineering and Science (GEM) Fellowship. Cole Maguire: Recipient of NIDA T32 Training Grant 5T32DA018926-18 for graduate student stipend and travel support for scientific conferences from the European Committee for Treatment and Research in Multiple Sclerosis. Sam Bazzi: Recipient of NIH NIAAA T32AA007471 and Fred Murphy Jones & Homer Lindsey Bruce Endowed Fellowships for graduate student stipend. Christopher DiPasquale: Vice President of Assay Development of Babson Diagnostics, Inc.; holder of stock/stock options for Babson; salary as employee of Babson. Eric Olson: Chairman of the Board of Babson Diagnostics, Inc.; holder of stock/stock options for Babson; salary as employee of Babson. Justin F. Rousseau: Recipient of NIH National Institute of Allergy and Infectious Diseases (NIAID) funding for another project. Stephen M. Strakowski: Recipient of NIH National Institute of Mental Health and Jassen funding for other projects and consulting fees for Sunovion, WebMD, and Meadows Mental Health Policy Institute; holds leadership role with American Brain Coalition and National Network Depression Centers. Jennifer Maynard: Recipient of grant funding from Welch Foundation, Texas Biologics, NIAID, and National Science Foundation; consulting fees from Sidley on behalf of Amgen and Genentech; and travel support for attending PEGS Protein & Antibody Engineering Summit 2023, Gordon conference on Protein Engineering 2023, and MD Anderson & UT Austin Collaborative Research Summit 2023; license holder for HexaPro (multiple non-exclusive licenses) and 3A3 antibody, specific for prefusion spike; and member of scientific advisory boards of Janux (2019–present) and Releviate (2020-present). Lauren I. R. Ehrlich: Recipient of grant funding from NIAID, NIA, CPRIT, APH, and Advanced Micro Devices; travel support for attending scientific conferences from the NIH and UT Austin. Esther Melamed: Recipient of grant funding from NIAAA, Austin Public Health, Babson Diagnostics; consulting fees from Horizon, Roche, Summus; honoraria from the National Center for Health Research and American Academy of Physical Medicine and Rehabilitation; and travel support for scientific conferences from the NIH, National Center for Health Research, and American Academy of Physical Medicine and Rehabilitation. All remaining authors have no competing interests: Maisey Schuler, Dzifa Amengor, Annalee Nguyen, Rebecca Wilen, Jacob Rogers, Blaine Caslin, Melissa Abigania, Todd Triplett, Janelle Creaturo, Kerin Hurley, and Dennis Wylie.

Figures

**Fig. 1. Participant Recruitment and Experimental Design.**
a Sample size of acute COVID-19 participants in the cohort by disease severity. b Participant serum was collected at 1, 3, 6, and 12 months post-positive PCR. c ELISA schematic of detection of N and RBD antibodies in participant serum. d Reported COVID-19 cases in the recruitment county (Travis County) over the time of recruitment. e Distribution of symptom onset or PCR+ for asymptomatic individuals in the cohort by acute COVID-19 severity. (Short tick marks = individual participants’ symptom onset or PCR+; Long tick marks = interquartile range within each disease severity group.)

**Fig. 2. SARS-CoV-2 antibody titers correlate with COVID-19 disease severity.**
Box and whisker plots of a Anti-N, b Anti-S, and c Anti-RBD (measured with the BioLegend anti-RBD ELISA kit) IgG titers for asymptomatic (A), mild (M), severe (S), and critical (Crt) groups at 1, 3, 6, and 12 months post-positive SARS-CoV-2 PCR. Sample sizes (n) for Anti-N are 1 month (n = 79), 3 months (n = 83), 6 months (n = 83), and 12 months (n = 66); for Anti-S are 1 month (n = 63), 3 months (n = 57), 6 months (n = 31), and 12 months (n = 11); and for Anti-RBD are 1 month (n = 75), 3 months (n = 61), 6 months (n = 37), and 12 months (n = 16). Global p-values were obtained using a cumulative link model testing the association between disease severity and antibody titers, controlling for age and sex. Pairwise comparisons were performed using the Wilcoxon test with FDR correction (* p.adj ≤ 0.05, ** p.adj ≤ 0.01, *** p.adj ≤ 0.001). Dotted lines indicate the 95% quantile of healthy controls.

**Fig. 3. SARS-CoV-2 vaccination increases anti-RBD titers to a greater extent in participants who experienced milder disease but reduces anti-RBD: anti-S titers.**
Log2 fold change compared to 1-month for a Anti-N and b anti-RBD IgG levels. Hospitalized sample sizes (n): 3 months before 1st vaccination (n = 25), after 1st vaccination (n = 11); 6 months before 1st vaccination (n = 14), after 1st vaccination (n = 25); 12 months non-hospitalized (n = 5), hospitalized (n = 25). Anti-N non-hospitalized sample sizes (n): 3 months non-hospitalized (n = 36), hospitalized (n = 11); 6 months non-hospitalized (n = 23), hospitalized (n = 21); 12 months non-hospitalized (n = 11), hospitalized (n = 25). c Anti-RBD to anti-S ratio at 1, 3, 6, and 12 months post-positive SARS-CoV2 PCR, separated by whether the samples were collected before or after the 1st vaccination. Before 1st vaccination sample sizes (n): 1 month non-hospitalized (n = 36), hospitalized (n = 39); 3 months non-hospitalized (n = 36), hospitalized (n = 25); 6 months non-hospitalized (n = 23), hospitalized (n = 14); 12 months non-hospitalized (n = 11), hospitalized (n = 5). After 1st vaccination sample sizes (n): 1 month non-hospitalized (n = 1), hospitalized (n = 3); 3 months non-hospitalized (n = 11), hospitalized (n = 11); 6 months non-hospitalized (n = 21), hospitalized (n = 25); 12 months non-hospitalized (n = 25), hospitalized (n = 25). d Anti-RBD to anti-S IgG ratio before and after 1st vaccination for all samples; paired sample size (n = 49). Pairwise comparisons were performed using the Wilcoxon test with FDR correction (* p.adj ≤ 0.05, ** p.adj ≤ 0.01, *** p.adj ≤ 0.001). Dashed lines indicate 1-month titer levels.

**Fig. 4. Anti-N titers decline below, while anti-RBD titers are sustained above control levels over 12 months, and anti-N IgG titers decay faster in hospitalized individuals.**
Longitudinal decay of a anti-N and b anti-RBD antibody titers in participants stratified by initial disease severity. Participant timepoints are connected by light gray lines. The healthy controls 95% confidence interval is represented by a dashed line. Percentage of participants whose c anti-N titers and d anti-RBD titers remained above 50% of their respective 1-month post-infection titers over 12 months. Percentage of participants whose e anti-N and f anti-RBD antibody titers remained above the 95th quantile of controls over 12 months in all participants. Sample sizes are provided in the tables accompanying each respective plot. Dashed lines in c–f represent 95% confidence intervals.

**Fig. 5. Age correlates with SARS-CoV-2 antibodies in convalescent participants.**
Correlation between age and a anti-N IgG levels and b anti-RBD IgG levels while controlling for disease severity. Sample sizes (n) are as follows: anti-N 1 month (n = 79), 3 months (n = 83), 6 months (n = 83), 12 months (n = 66); anti-RBD 1 month (n = 75), 3 months (n = 61), 6 months (n = 37), 12 months (n = 16). Correlation between sex and c anti-N IgG levels and d anti-RBD IgG levels while controlling for disease severity. Sample sizes (n) are as follows: anti-N 1 month female (n = 40), male (n = 39); 3 months female (n = 45), male (n = 38); 6 months female (n = 43), male (n = 40); 12 months female (n = 38), male (n = 28); anti-RBD 1 month female (n = 39), male (n = 36); 3 months female (n = 35), male (n = 26); 6 months female (n = 19), male (n = 18); 12 months female (n = 9), male (n = 7). F female, M male.

**Fig. 6. Steroid treatment did not correlate with SARS-CoV-2 antibody titers in hospitalized participants.**
a Anti-N IgG levels and b anti-RBD IgG levels in hospitalized participants across 1, 3, 6, and 12 months post-SARS-CoV-2 infection, stratified by treatment with (+) and without (−) steroid. Anti-N titers sample sizes (n): 1 month −steroid (n = 7), +steroid (n = 35); 3 months −steroid (n = 8), +steroid (n = 28); 6 months −steroid (n = 8), +steroid (n = 31); 12 months −steroid (n = 7), +steroid (n = 23). Anti-RBD titers sample sizes (n): 1 month −steroid (n = 7), +steroid (n = 32); 3 months −steroid (n = 7), +steroid (n = 18); 6 months −steroid (n = 4), +steroid (n = 10); 12 months −steroid (n = 0), +steroid (n = 5). Pairwise comparisons of titers in participants treated with and without steroids were performed using the Wilcoxon test (p > 0.05 for all comparisons).

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Update of

SARS-CoV-2 Humoral Immune Responses in Convalescent Individuals Over 12 Months Reveal Severity-Dependent Antibody Dynamics.
Siles N, Schuler M, Maguire C, Amengor D, Nguyen A, Wilen R, Rogers J, Bazzi S, Caslin B, DiPasquale C, Abigania M, Olson E, Creaturo J, Hurley K, Triplett TA, Rousseau JF, Strakowski SM, Wylie D, Maynard J, Ehrlich LIR, Melamed E. Siles N, et al. medRxiv [Preprint]. 2023 Dec 7:2023.12.05.23299462. doi: 10.1101/2023.12.05.23299462. medRxiv. 2023. Update in: Commun Med (Lond). 2025 May 2;5(1):149. doi: 10.1038/s43856-025-00828-4. PMID: 38106077 Free PMC article. Updated. Preprint.

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SARS-CoV-2 humoral immune responses in convalescent individuals over 12 months reveal severity-dependent antibody dynamics

Affiliations

SARS-CoV-2 humoral immune responses in convalescent individuals over 12 months reveal severity-dependent antibody dynamics

Authors

Affiliations

Abstract

Plain language summary

Conflict of interest statement

Figures

Update of

References

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous