Characterising Humoral Immune Signatures: IgG and IgM Reactivity Patterns in Post-COVID-19 Pandemic Cohort in the UK
Abstract:
The persistence of SARS-CoV-2-specific antibodies, particularly Immunoglobulin G (IgG) and Immunoglobulin M (IgM), is fundamental for understanding long-term immunity, informing public health policy, and optimizing vaccination strategies. IgM generally appears early during infection and declines within weeks, whereas IgG is linked to sustained immune memory and protection. This study characterizes post-COVID-19 serological profiles in a volunteer cohort, revealing several notable immunological phenomena. First, despite documented prior exposure to SARS-CoV-2, 2% of individuals lacked detectable IgG antibodies, indicating seronegative immune responses. These profiles may reflect impaired humoral immunity, rapid antibody decline, or a predominance of cellular im mune responses, as previously described in cohorts where T-cell immunity compensates for absent humoral mark ers. Elevated IgM in IgG-negative individuals suggests recent antigenic stimulation or delayed class switching, consistent with reports of non-standard immune trajectories. Second, the cohort demonstrated near-universal IgG positivity (98%) and persistent IgM reactivity in 47% of participants. While IgG seropositivity aligns with durable immune memory, sustained IgM presence months after infection suggests ongoing immune activation, incomplete viral clearance, or dysregulated B-cell maturation, as increasingly recognized in the literature. Third, females exhibited higher overall IgM levels, whereas males showed lower baseline IgM with occasional high outliers. Both groups had broadly similar IgG averages, reflecting established sex-based differences in immune responses. These findings challenge traditional models of humoral resolution and emphasize the complexity of SARS-CoV-2 immunodynamics. Collectively, these observations highlight the necessity for integrated serological and cellular profiling in post-infection surveillance. Such approaches have implications for vaccine responsiveness, diagnostic interpretation, and identification of individuals at risk for prolonged immune perturbation or autoimmune sequelae.
