Reply to Comment on: “Reduced humoral response to two doses of COVID-19 vaccine in patients with inflammatory bowel disease”

First, we would like to thank Dr. Sookaromdee and colleagues for the interest in our study []. Currently, there is general consensus on the strong utility of the COVID-19 vaccines, particularly for “frail” subjects and this includes patients with chronic conditions such as inflammatory bowel disease (IBD) []. Our study's focus moved from the necessity to understand which factors could have a substantial impact on the efficacy and safety of COVID-19 vaccines. In this regard, the influence of the variables at baseline was investigated using binary logistic regression multivariate analyses for seropositivity rates, and using linear regression multivariate analyses for anti-SARS-CoV-2 IgG levels. Sookaromdee and colleagues emphasized the possible role of a previous unknown/asymptomatic infection with SARS-CoV-2. Indeed, it is well known that any previous immunological contact with the virus determines an enhanced immune response to COVID-19 vaccines []. We fully agree with this point, which, indeed, we had analyzed. Anti-SARS-CoV-2 IgG positivity at baseline was assessed in both IBD patients and healthy controls. The rates were comparable between the two groups (8.9% vs. 10.7%, respectively; p = 0.17). Therefore, the difference in the magnitude of the humoral response between patients and controls is not related to any difference in previous unknown infections with SARS-CoV-2. Conversely, a deregulation of the immune system in IBD patients could be hypothesized, including a defective spleen function []. Furthermore, restricting the analysis only to patients with IBD, anti-SARS-CoV-2 IgG positivity at baseline was independently associated with the median levels of IgG anti-SARS-CoV-2 after 8 weeks from the second dose of COVID-19 vaccine, together with age, treatment for IBD, and use of mRNA-1273 compared with BNT162b2 vaccine []. Finally, we agree with the fact that tracking underlying immunological disorders may help to identify those patients who could need additional/booster doses of vaccine, including the analysis of genetic polymorphisms []. Obviously, more research is needed in this setting before these tests can be applied in clinical practice.