Comprehensive Immune Profiling of a Kidney Transplant Recipient With Peri-Operative SARS-CoV-2 Infection: A Case Report

Abstract

To date there is limited data on the immune profile and outcomes of solid organ transplant recipients who encounter COVID-19 infection early post-transplant. Here we present a unique case where the kidney recipient's transplant surgery coincided with a positive SARS-CoV-2 test and the patient subsequently developed symptomatic COVID-19 perioperatively. We performed comprehensive immunological monitoring of cellular, proteomic, and serological changes during the first 4 critical months post-infection. We showed that continuation of basiliximab induction and maintenance of triple immunosuppression did not significantly impair the host's ability to mount a robust immune response against symptomatic COVID-19 infection diagnosed within the first week post-transplant.

Keywords: COVID-19; immune response; immunosuppressants; induction therapy; transplant.

Figure 1

Study time points and data collection points. (A) Graphical representation of pertinent clinical data, sample collection time points and immune monitoring testing. (B) CBC differentials (lymphocyte count, giga/L), average serum creatinine levels (μmol/L) and serum C-reactive protein levels (mg/ml) over the course of the patient’s transplant and infection disease course (days).

Figure 2

SARS-CoV2 and non-CoV-2 antibody profiling using Luminex based assays and immunoglobulin subclass assays. (A) Reactivity of serum IgG antibody to CoV-2 proteins (Full Spike, S1, S2, RBD and NC) and non-SARS-CoV-2 proteins from community coronaviruses (CoV-229E-S1, HCoV-HKU1-S1, HCoV-NL63-S1, HCoV-OC43-S1), and novel coronaviruses (MERS-S1 and SARS-S1). X-axis represents days relative to first positive SARS-CoV-2 test in chronological serum dates. Y-axis represents the Mean Florescence Intensity (MFI) value of the reactivity. (B) Anti-SARS-CoV-2 IgG, IgA and IgM serum concentrations measured using the immunIQ assay (mg/L).

Figure 3

T cell repertoire sequencing of patient at study time points. (A) Differential abundance analysis comparing clonotypes that have significantly increased or decreased in frequency across baseline and post-infection Day 2, Day 5, and Day 111. This is based on a beta-binomial model where normal repertoire changes in healthy adults over time are accounted for while measuring clonal expansion. (B) Locations on the SARS-CoV-2 genome where TCR binding has likely occurring; different colours specify open reading frame, and size of dots indicate number of TCRβ rearrangements associated with SARS-CoV-2 at a particular position. Screening was performed based on the ImmuneCODE database (Adaptive Biotechnologies). (C) Changes in frequencies of the 15 most frequently observed TCR clonotypes, relative to total TCR repertoire, across baseline and post-infection day 2, 5, and 111.

Figure 4

Immunophenotyping of PBMCs of patient at study time points. (A) Absolute numbers of T cells. (B) CD4 and CD8 T cell frequencies. (C) Subpopulations frequencies of CD4 T cells. (D) Subpopulation frequencies of CD8 T cells. (E) CD38⁺ HLA-DR⁺ frequencies of CD8 non-naïve T cells. (F) Absolute numbers of B cells. (G) B cell frequencies of lymphocytes. (H) Class switched -, non-class switched – and naïve B cell frequencies of naïve and memory B cells. (I) Plasmablast - and transitional B cell frequencies of total B cells. (J) Non-T- and Non-B-cell frequencies of lymphocytes. CM, central memory; EM, effector memory; SCM, stem cell memory; CS, class-switched; NCS, non class-switched; Non_T_B, non-T, and non-B cells.