Authors' response

Sir,

We appreciate Dr. Daungsupawong and Dr. Wiwanitkit for their interest in our article¹ and their thoughtful commentary². This study¹ was a longitudinal, observational investigation conducted in a real-world healthcare setting during an active pandemic. By design, it did not employ randomization. Participants were systematically stratified post hoc into four groups (A-D) based on pre-vaccination RT-PCR results and serological profiles to enable meaningful differentiation of immune responses in infected, exposed, and exposure-naïve individuals. This stratification, grounded in documented infection history and institutional sero-surveillance data, was integral to the study's objectives.

The final analytical cohort of 84 participants emerged from an initial pool of 225, with exclusions made for interim breakthrough infections and precautionary dose administration. Sample size estimation was rigorously performed using G*Power 3.1.9.2 to detect intergroup differences in IgG levels, ensuring adequate statistical power. The study successfully captured significant longitudinal trends in both humoral and cellular immunity, including a highly significant decline in anti-spike IgG antibodies (P<0.0001) and group-wise differences in IFN-γ levels (P=0.0299), indicating the robustness of the cohort size and design.

While P values were the primary statistical measure, as is standard in immunological literature^3,4, we recognize the added value of effect sizes and confidence intervals. These will be incorporated in future work to enhance interpretability. Nonetheless, the reported statistical significance was strong, biologically plausible, and corroborated by emerging international literature.

Demographic and clinical variables - including age, gender, and comorbidities - were systematically documented and analysed. The cohort exhibited balanced representation across age (mean: 35–47 yr) and gender, with comorbid conditions such as hypertension and diabetes present in 32 per cent of participants. Only one individual was immunocompromised. These factors were transparently reported in table III and were not found to introduce systematic bias into the immunological trends observed.

The scope of this study was immunological surveillance rather than clinical outcome prediction. Therefore, parameters such as reinfection rates and symptom severity, while important, fell outside its intended focus. Notwithstanding, the results substantiate the concept of hybrid immunity, with individuals previously exposed to SARS-CoV-2 exhibiting stronger and more durable antibody and T-cell responses. The use of validated, FDA-authorized assays (Elecsys Anti-SARS-CoV-2) for serological assessments⁵, along with ELISpot and flow cytometry for cellular markers, added to the methodological rigor and distinguished this study from comparable cohort analyses⁶. Regarding the implications for booster strategies, our findings provide evidence that individuals with hybrid immunity mount superior and longer-lasting immune responses^7,8. While the study was not designed to dictate vaccination policy, it does underscore the potential merit of stratifying booster recommendations based on infection history. The persistence of T-cell immunity in exposed groups, despite waning antibodies, reinforces this viewpoint and aligns with existing global data^9,10.

We acknowledge that long-term follow up studies with larger and more diverse cohorts, along with multivariate modelling, would yield additional insights. However, such studies must also address the practical challenges of participant attrition beyond one year, which we encountered. These include logistical constraints, work-related limitations, and reduced willingness for repeated sampling which were common barriers in longitudinal cohort research during a pandemic.

Overall, we consider the findings to be a valuable contribution to the evolving evidence base and remain committed towards strengthening the understanding of long-term vaccine-induced immunity in diverse populations. We thank the authors again for their engagement that allowed us to clarify the scope, design, and impact of our study.