Immunological memory in post SARS-CoV-2 vaccination

Sir,

We read with interest the publication titled ‘Immunological memory in infected and exposure naive individuals one year post SARS-CoV-2 vaccination’¹ published in the March 2025 issue of Indian Journal of Medical Research. The purpose of this study was to assess the efficacy and duration of immunity from the COVISHIELD™ vaccine in healthcare workers by stratifying the sample groups based on their infection history and immune status prior to vaccination. This is an intriguing method for studying hybrid immunity, which combines spontaneous infection and vaccination. However, the study has several limitations that may affect the accuracy and generalizability of the results in terms of populations, including a sample size of only 84 people, which is insufficient for statistical comparisons between groups, and a lack of clear randomization, which may result in bias in the sample group.

In terms of methodology, while measuring both humoral (IgG) and cell-mediated immunity is comprehensive and appropriate for the study's objectives, relying solely on statistical differences (e.g., P value) without reporting effect size estimates or confidence intervals makes determining the vaccine's true impact impossible. Furthermore, no control data were discovered for other factors, such as age, gender, underlying disorders, or vaccination status.

One critical topic that could have been addressed in the academic discussion of this study is whether a population with hybrid immunity should have a different booster dose strategy than a population that only received the vaccine. An additional inquiry could have been whether this sustained T-cell immunity is sufficient to prevent severe illness or death, even with reduced IgG. These are the challenges that can pave the way for national vaccination policy evaluations beyond antibody titres.

To improve the utility of this study in the future, greater sample numbers, a broader range of demographics and areas, and follow up for more than a year should be explored for assessing long-term immunity. Furthermore, multivariate studies can aid in controlling for the influence of confounders, while the inclusion of clinical markers, such as reinfection rate or symptom severity, can help towards more objectively linking immunological outcomes to health outcomes.