To the Editor—We previously reported serological findings of 302 healthcare workers (HCWs) who completed two doses of mRNA (BNT162b2/Comirnaty; Fosun-BioNTech Pharma) and inactivated COVID-19 vaccine (CoronaVac; Sinovac Life Sciences, Beijing, China).1 Both vaccines were found to be immunogenic in the majority of HCWs. The BNT162b2 resulted in a 11-fold higher level of anti-spike IgG (Abbott SARS-CoV-2 IgG II Quant assay, mean=11572.6 AU/mL vs 1005.2 AU/mL; P<0.001) and a higher surrogate neutralising antibody (sNAb) [GenScript cPass SARS-CoV-2 Surrogate Virus Neutralization Test Kit] positive rate (100% vs 94.4%; P<0.001).

We report week 12 serological data of our cohort. Among 197 CoronaVac and 100 BNT162b2 recipients, baseline characteristics of the two vaccine arms were comparable except sex (60.9% and 38% female in CoronaVac and BNT162b2, respectively) [online supplementary Table 1]. There was no difference in anti-spike immunoglobulin G (IgG) positive rate at week 12 (98.5% in CoronaVac vs 99% in BNT162b2; P=1) [Table 1]. Waning of IgG level was observed in both vaccine arms with a larger magnitude of decline in BNT162b2 (-72% vs -64.6%; P<0.001). Despite the more pronounced decline, the median anti-spike IgG of BNT162b2 remained 11-fold higher than that of CoronaVac at week 12 (2840.25 AU/mL vs 253.60 AU/mL; P<0.001).

Decline in sNAb was also observed in both arms but the magnitude was significantly smaller in BNT162b2 (-28.3% in CoronaVac vs -2.3% in BNT162b2; P<0.001). Using the manufacturer’s positive cut-off at 30% signal inhibition or above, significantly more CoronaVac recipients had lost their sNAb at week 12 (94.4% sNAb positive at week 2, 62.4% at week 12) whereas 99% of BNT162b2 recipients remained sNAb positive. Throughout the three time points, BNT162b2 arm had higher levels of anti-spike IgG and sNAb (P<0.001) [Fig].

Among the 286 HCWs who had positive sNAb after two doses of vaccine, 64 had lost their sNAb while 222 had sustained sNAb at week 12. Sustained sNAb at week 12 were associated with younger age, BNT162b2 and higher antibody at any time point (Table 2). Multivariate logistic regression analysis showed that only higher IgG and sNAb level at 2 weeks after the second dose were significantly associated with sustained sNAb at week 12 (online supplementary Table 2).

These results demonstrate rapid antibody decline after both mRNA and inactivated vaccine with a more durable sNAb in the BNT162b2 arm. However, further studies are needed to clarify the impact of waning antibody on vaccine efficacy and protection against severe infection.

Concept or design: All authors.
Acquisition of data: All authors.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: JST Zee.
Critical revision of the manuscript for important intellectual content: All authors.

All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

All authors have disclosed no conflicts of interest.

The authors acknowledge the excellent work and contributions by staff at the Clinical Pathology Laboratory of Hong Kong Sanatorium & Hospital.

This letter received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

This study obtained ethics approval (Ref RC-2021-07) from the Research Ethics Committee of the Hong Kong Sanatorium & Hospital Medical Group.

1. Zee JS, Lai KT, Ho MK, et al. Serological response to mRNA and inactivated COVID-19 vaccine in healthcare workers in Hong Kong: preliminary results. Hong Kong Med J 2021;27:312-3. Crossref