SARS-CoV-2-specific Cell-mediated Immunity in Kidney Transplant Recipients Recovered From COVID-19

Transplantation. 2021 Jun 1;105(6):1372-1380. doi: 10.1097/TP.0000000000003672.

Abstract

Background: The magnitude and kinetics of severe acute respiratory syndrome coronavirus 2-specific cell-mediated immunity (SARS-CoV-2-CMI) in kidney transplant (KT) recipients remain largely unknown.

Methods: We enumerated SARS-CoV-2-specific interferon-γ-producing CD69+ CD4+ and CD8+ T cells at months 4 and 6 from the diagnosis of coronavirus disease 2019 (COVID-19) in 21 KT recipients by intracellular cytokine staining. Overlapping peptides encompassing the SARS-CoV-2 spike (S) glycoprotein N-terminal 1- to 643-amino acid sequence and the membrane protein were used as stimulus. SARS-CoV-2 IgG antibodies targeting the S1 protein were assessed by ELISA at month 6.

Results: Detectable (≥0.1%) SARS-CoV-2-specific CD4+ T-cell response was found in 57.1% and 47.4% of patients at months 4 and 6. Corresponding rates for CD8+ T cells were 19.0% and 42.1%, respectively. Absolute SARS-CoV-2-specific T-cell counts increased from month 4 to month 6 in CD8+ (P = 0.086) but not CD4+ subsets (P = 0.349). Four of 10 patients with any detectable response at month 4 had lost SARS-CoV-2-CMI by month 6, whereas 5 of 9 patients mounted SARS-CoV-2-CMI within this period. All but 2 patients (89.5%) tested positive for SARS-CoV-2 IgG. Patients lacking detectable SARS-CoV-2-specific CD4+ response by month 6 were more likely to be under tacrolimus (100.0% versus 66.7%; P = 0.087) and to have received tocilizumab for the previous COVID-19 episode (40.0% versus 0.0%; P = 0.087).

Conclusions: Although still exploratory and limited by small sample size, the present study suggests that a substantial proportion of KT recipients exhibited detectable SARS-CoV-2-CMI after 6 months from COVID-19 diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • COVID-19 / blood
  • COVID-19 / diagnosis
  • COVID-19 / immunology*
  • COVID-19 Drug Treatment
  • COVID-19 Testing
  • Female
  • Follow-Up Studies
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Humans
  • Immunity, Cellular*
  • Immunocompromised Host*
  • Immunosuppressive Agents / adverse effects
  • Interferon-gamma / metabolism
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • SARS-CoV-2 / immunology*
  • Transplant Recipients

Substances

  • Antibodies, Monoclonal, Humanized
  • IFNG protein, human
  • Immunosuppressive Agents
  • Interferon-gamma
  • tocilizumab