Evaluation of Quantiferon Sars-Cov-2 Interferong (Inf G) Release Assay in Two Cohort of Bnt162b Vaccinated Fragile Patients

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is the standard of care for the prevention of COVID-19 disease, with a positive impact in countries in which vaccination has been promoted. Since the emergence of variants of concern (VOCs) European Medicines Agency (EMA) recommended an extra dose of the COVID-19 vaccines Comirnaty (BioNTech/Pfizer) and Spikevax (Moderna) for patients with severely weakened immune system and booster doses for subjects with normal immune system to ensure a lasting response. Although Vaccination triggers both humoral and cellular immune response, COVID-19 vaccination efficacy is evaluated by measuring antibodies only, whereas adaptative cellular immunity is unexplored. Our aim is to test this new kit QuantiFERON SARS-CoV-2 to evaluate the immune response after three doses of BNT162b vaccine in healthy donors compared to two cohort of fragile patients Common Variable Immunodeficiency (CVID) patients and Kidney Transplant Recipients (KTR) patients. Method(s) Blood samples were collected from eight health care workers in our department, fourteen CVID patients and eight KTR patients. All the individuals recruited were naive to SARS-COV2 and immunized by three doses of BNT162b vaccine. We examined humoral responses to vaccinations using the LIAISON DIASORIN SARSCOV-2 S1/S2 IgG. Next blood from all participants was subjected to the novel Interferon gamma (INF-gamma) Release Assay (IGRA) from Qiagen, measuring INF-gamma release induced by two proprietary SARS-CoV-2 peptide pools (Ag1 and Ag2) encompassing the spike protein and designed to stimulate CD4+ and CD8+ T cells and induce the releases of INF-gamma. Result(s) Using LIAISON SARS-COV-2 S1/S2 IgG assay from DIASORIN we confirm that in healthy subjects BNT162b third dose had successfully mounted humoral immune response with a S1/S2 IgG mean of 17100 BAU/ml. Conversely, the CVID group and KTR group shown a statistically significant reduction of IGg levels with a mean of 978 BAU/ml and 1029 respectively. Notably seven patients (five CVID and two KTR) presented IGg levels below the cut-off (33,8 BAU/ml). Next, we evaluated the INF-gamma response to SARS-CoV-2 Ag1 and Ag2 founding seven non-reactive subjects (three CVID and four KTR). Surprisingly three of non-reactive patients shown a good humoral response, whereas three patients with a negative humoral immune response shown reactiveness to IGRA assay. Conclusion(s) Assessing cellular immunity for SARSCOV-2 in addition to humoral immunity is important taking into account that cellular immunity plays a pivotal role against the virus and likely its variants. Some patients with weakened immune response have no correlation between humoral and cellular immunity, suggesting that the evaluation of T cell responses could be a more sensitive clinical marker of immunization. In this scenario the evaluation of cellular immunity might be informative for clinicians to identify patients more susceptible to a severe COVID-19 disease.