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Long-Term Durability and Variant-Specific Modulation of SARS-CoV-2 Humoral and Cellular Immunity over Two Years.

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|August 28, 2025
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This study shows that SARS-CoV-2 cellular immune memory is durable, while antibody responses against Omicron variants are less robust. This research informs long-term protection strategies against evolving COVID-19 variants.

Keywords:
SARS-CoV-2T-cell immunityanti-SARS-CoV-2-specific antibodiescytokine profilelong-term immunitylongitudinal analysisneutralization capacityviral variants

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Area of Science:

  • Immunology
  • Virology
  • Public Health

Background:

  • Understanding long-term SARS-CoV-2 immune memory is crucial due to emerging variants.
  • Humoral and cellular immunity dynamics require longitudinal evaluation post-infection and vaccination.

Purpose of the Study:

  • To evaluate the durability of immune memory against SARS-CoV-2 over two years.
  • To assess variant-specific modulation of immune responses, particularly against Omicron.
  • To analyze the persistence and quality of both antibody and T cell memory.

Main Methods:

  • Longitudinal analysis of anti-spike IgG and IgA levels.
  • Assessment of neutralizing activity against ancestral and Omicron variants.
  • Evaluation of T cell persistence using intracellular cytokine staining (ICS) and activation-induced marker (AIM) assays.

Main Results:

  • Anti-spike IgG levels remained stable and increased post-stimulation, indicating cumulative memory.
  • Neutralizing capacity was stable for pre-Omicron variants but moderately declined for Omicron.
  • CD4+ and CD8+ T cell responses persisted and were largely unaffected by Omicron mutations, though cytokine profiles showed subtle variant-dependent changes.

Conclusions:

  • Cellular immunity demonstrates significant durability against SARS-CoV-2, including Omicron variants.
  • Humoral responses show reduced robustness against Omicron compared to earlier variants.
  • Findings are vital for understanding long-term COVID-19 protection and informing public health strategies against evolving viral strains.