Safety, Immunogenicity, and Long COVID Outcomes After Inactivated COVID-19 Boosters in Older Adults

Overview

In a prospective cohort of 450 adults aged ≥60 years in China, a third booster dose of inactivated SARS-CoV-2 vaccines (CoronaVac or Covilo) administered 2–6 months after the second dose was safe and significantly enhanced neutralizing antibody responses. The Covilo three-dose regimen with a 6-month interval yielded the highest durable immunity and was associated with the lowest risks of COVID-19 symptoms and long COVID.

Background

Older adults face increased risks of severe COVID-19 and long COVID due to immunosenescence and comorbidities. Inactivated vaccines like CoronaVac and Covilo are widely used and generally safe but show waning immunity within 3–6 months post-primary vaccination. Emerging variants further challenge vaccine effectiveness, emphasizing the need to optimize booster timing and vaccine choice to sustain protection in this vulnerable population.

Data Highlights

Key Findings

• Adverse reactions were low overall (0.0%–8.0%), with CoronaVac-S3 showing significantly more local reactions than Covilo-S3 (8.0% vs. 0.0%; P = 0.0124).
• At 1 month post-booster, S3 schedules induced the highest neutralizing antibody GMTs (CoronaVac: 59.4; Covilo: 57.2), significantly greater than S1 and S2 groups (P < 0.001).
• CoronaVac-S1 induced higher GMTs than Covilo-S1 at 1 month (21.8 vs. 15.4; P = 0.009), but Covilo-S3 maintained the highest GMT at 12 months (9.9).
• Covilo-S2 and S3 groups showed superior neutralization against wild-type and Delta variants compared to CoronaVac counterparts at 1 month (all P < 0.05).
• Male sex was identified as a protective factor against COVID-19 symptoms, long COVID, and fatigue, with odds ratios <0.5 (P < 0.05).
• Booster doses administered within 2–6 months of the second dose optimized immunogenicity and reduced risks of COVID-19 symptoms and long COVID in older adults.

Clinical Implications

Administering a third booster dose of inactivated SARS-CoV-2 vaccines within 2 to 6 months after the second dose is both safe and effective in enhancing humoral immunity in adults aged 60 years and older. The Covilo vaccine with a 6-month dosing interval may offer superior and more durable protection, including against variants, and reduce the incidence of long COVID symptoms. These findings support tailored booster strategies considering vaccine type and timing to optimize protection in elderly populations.

Conclusion

A three-dose regimen of inactivated SARS-CoV-2 vaccines, particularly Covilo with a 6-month interval, is safe and significantly improves immune responses and clinical outcomes in older adults. Optimizing booster timing and vaccine selection is critical to mitigating COVID-19 severity and long-term sequelae in this high-risk group.

References

1. Evaluation of Safety, Immune Response, and Long COVID Effects After Inactivated COVID-19 Vaccine Boosters in Older Adults in China: A Prospective Cohort Analysis