Immunogenicity of COVID-19 Vaccination in Immunocompromised Patients (Auto-COVID-VACC): Protocol for Multicenter Prospective Noninterventional Study.

Background: Despite the availability of vaccines, immunocompromised patients are still at high risk for severe COVID-19. Vaccination has been proven to be an effective measure in preventing severe SARS-CoV-2 infections; however, data on B- and T-cell responses are lacking. While vaccination schedules for the general population have been defined, achieving immunogenicity in patients who are immunocompromised remains a challenge.

Objective: The primary objective is to analyze anti-spike-immunoglobulin G (IgG) titers after repeated messenger ribonucleic acid vaccinations in patients who are immunocompromised. Further objectives are to analyze data on humoral immune responses and to evaluate data on cellular immune responses.

Methods: This multicenter, prospective, noninterventional study aims to determine the immunogenicity and reactogenicity of an implemented standard-of-care COVID-19 vaccination strategy in patients who are immunocompromised. A total of 100 patients will be recruited at three study sites. Patients are eligible for study inclusion when they are 18 years or older, vaccinated according to the recent version of the COVID-19 vaccination standard, and if the patient is immunocompromised according to stage 3 of the classification "Stages of Immunosuppression." The study analyzes B- and T-cell responses generated within the standard-of-care COVID-19 vaccination strategy. Additional blood samples will be drawn at each scheduled outpatient visit. Study-related blood samples will be used to extract ethylenediaminetetraacetic acid plasma and peripheral blood mononuclear cells for evaluation of B- and T-cell responses to COVID-19 vaccinations. For this study, no additional visits or invasive procedures will be performed in addition to standard care.

Results: As of August 2024, the study has enrolled 32 patients. The recruitment phase is still ongoing.

Conclusions: Results will be used to optimize vaccination and booster schedules for patients who are immunocompromised and to increase rates of protection against severe SARS-CoV-2 infections. Further, results may identify risk and treatment factors, which lead to low immune responses in patients vaccinated against COVID-19, as well as the impact of repeated vaccination on B- and T-cell responses.

Trial Registration: ClinicalTrials.gov NCT05597761; https://clinicaltrials.gov/study/NCT05597761.

International Registered Report Identifier (irrid): DERR1-10.2196/60675.