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

May 18, 2026Frontiers in immunology

Safety, immune response, and long COVID after inactivated COVID-19 vaccine boosters in older Chinese adults

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Abstract

A third booster of inactivated SARS-CoV-2 vaccine administered within 2-6 months significantly boosts immunity in adults aged ≥60 years.

The incidence of adverse reactions to vaccines was low, ranging from 0.0% to 8.0%, with higher local reactions observed in CoronaVac-S3 recipients.
One month after vaccination, the highest geometric mean titers (GMTs) of neutralizing antibodies were recorded in the S3 groups for both vaccines (Covilo: 57.2; CoronaVac: 59.4).
At 12 months post vaccination, GMTs were highest in the Covilo-S3 group (9.9), while CoronaVac-S2 showed higher GMTs than Covilo-S2 (8.0 vs. 5.1).
Covilo-S2 and -S3 exhibited superior inhibition against the wild-type strain and Delta variant compared to their CoronaVac counterparts at one month post vaccination.
Multivariate analysis revealed that male sex is associated with lower risks of COVID-19 symptoms, long COVID, and fatigue.

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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.