ABSTRACT
Background: The role of T cell immunity in protection against COVID-19 in immunosuppressed patients who failed to mount serological responses remains ill defined. Hypothesis: Vaccine-based intradermal skin test (IDT) serves as a surrogate marker of T cell responses in seronegative immunosuppressed patients. Methods: We compared anti-SARS-CoV-2 antibodies and cellular responses in vaccinated immunosuppressed (IS) patients (n = 58), healthy unvaccinated naive controls (NC, n = 8) and healthy vaccinated controls (VC, n = 32) by Luminex, IFN-γ ELIPSOT and IDT 3 to 6 months after vaccination. In 3 VC we performed a skin biopsy 24h after IDT and performed single-cell RNAseq of the skin-infiltrating CD45+ cells Results: Seronegative NC had no detectable T cell responses and negative IDR, whereas VC had anti-SARS-CoV-2 antibodies (100%), positive ELIPSOT (90%) and IDR (90%). Overall IS patients had significantly less antibodies up to 39 weeks after vaccination compared to VC but similar ELIPSOT responses. ELISPOT was positive in 33.3 % and 66.6 % and IDR in 62.5% and 90.5% of seronegative vs seropositive IS patients respectively. Conversely, patients with negative IDR had significantly lower T cell responses and IgG titers than those with positive IDR. Importantly, the TCR repertoire of infiltrating skin lymphocytes revealed 18/1064 clonotypes with known specificities against SARS-CoV-2. Conclusion: Our results indicate that local reaction to IDR is partially composed of SARS-CoV-2-specific T cells. IDR represents a promising tool to cost-effectively monitor SARS-CoV-2 specific T cell immunity in IS patients.