Intradermal skin test with mRNA vaccines as a surrogate marker of T cell immunity in immunocompromised patients

J Infect. 2023 Aug;87(2):111-119. doi: 10.1016/j.jinf.2023.06.005. Epub 2023 Jun 14.


Objectives: Intradermal skin test (IDT) with mRNA vaccines may represent a simple, reliable, and affordable tool to measure T cell response in immunocompromised patients who failed to mount serological responses following vaccination with mRNA covid-19 vaccines.

Methods: We compared anti-SARS-CoV-2 antibodies and cellular responses in vaccinated immunocompromised patients (n = 58), healthy seronegative naive controls (NC, n = 8), and healthy seropositive vaccinated controls (VC, n = 32) by Luminex, spike-induced IFN-γ Elispot and an IDT. A skin biopsy 24 h after IDT and single-cell RNAseq was performed in three vaccinated volunteers.

Results: Twenty-five percent of seronegative NC had a positive Elispot (2/8) and IDT (1/4), compared to 95% (20/21) and 93% (28/30) in seropositive VC, respectively. Single-cell RNAseq data in the skin of VC showed a predominant mixed population of effector helper and cytotoxic T cells. The TCR repertoire revealed 18/1064 clonotypes with known specificities against SARS-CoV-2, among which six were spike-specific. Seronegative immunocompromised patients with positive Elispot and IDT were in 83% (5/6) treated with B cell-depleting reagents, while those with negative IDT were all transplant recipients.

Conclusions: Our results indicate that delayed local reaction to IDT reflects vaccine-induced T-cell immunity opening new perspectives to monitor seronegative patients and elderly populations with waning immunity.

Keywords: COVID; Immunosuppression; SARS-CoV-2; Skin; T cells; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Viral
  • Biomarkers
  • COVID-19 Vaccines
  • COVID-19* / diagnosis
  • COVID-19* / prevention & control
  • Humans
  • Immunocompromised Host
  • SARS-CoV-2
  • Skin Tests
  • T-Lymphocytes*
  • Vaccination
  • mRNA Vaccines


  • COVID-19 Vaccines
  • Biomarkers
  • mRNA Vaccines
  • Antibodies, Viral