Safety, immunogenicity, and long COVID outcomes following inactivated COVID-19 vaccine boosters in elderly Chinese: a prospective cohort study

Background Adults aged ≥60 years face elevated risks of severe COVID-19 and long COVID. Although inactivated SARS-CoV-2 vaccines are safe and effective, critical gaps remain regarding optimal booster timing, durability of immune responses, and protection against emerging variants in this vulnerable population. Methods In this prospective cohort study in Zhejiang Province, China, 450 adults aged ≥60 years were randomized to receive an inactivated SARS-Cov-2 vaccine (CoronaVac or Covilo) under three dosing schedules. Neutralizing antibody titers, SARS-CoV-2-specific IgG, and variant-specific neutralization were evaluated using serum samples collected at multiple timepoints. Safety outcomes included local and systemic adverse reactions and long COVID symptoms. Results Participants (age: 60–80 years; 50.9% male) with balanced baseline demographics were stratified into six subgroups by vaccine type and schedule (S1/S2/S3; n=75 each; all P>0.05). Adverse reaction incidence was low (0.0%–8.0%), with CoronaVac-S3 recipients experiencing significantly more local reactions than Covilo-S3 recipients (8.0% vs. 0.0%; P = 0.0124). Immunogenicity varied markedly at 1 month post vaccination, with the highest geometric mean titers (GMTs) of neutralizing antibodies in both S3 groups (Covilo: 57.2; CoronaVac: 59.4; P<0.001 vs. respective S1/S2 groups), and CoronaVac-S1 inducing higher GMTs than Covilo-S1 (21.8 vs. 15.4; P = 0.009). At 12 months post vaccination, GMTs remained highest in Covilo-S3 (9.9), while CoronaVac-S2 exceeded Covilo-S2 (8.0 vs. 5.1; P = 0.021). Covilo-S2 and -S3 were superior to their CoronaVac counterparts in inhibition against the wild-type strain and Delta variant at 1 month post vaccination (all P<0.05). Multivariate analysis identified male sex as a protective factor against COVID-19 symptoms, long COVID, and fatigue (odds ratios <0.5 and P<0.05 for all). Conclusions A third booster of inactivated SARS-CoV-2 vaccine administered within 2–6 months of the second dose is safe and significantly boosts humoral immunity in adults ≥60 years. The three-dose Covilo regimen and a 6-month dosing interval optimized immunogenicity and were associated with the lowest risks of COVID-19 symptoms and long COVID, highlighting the importance of vaccine-specific and interval-adjusted booster strategies for older populations.