SARS-CoV-2-specific humoral and cellular immunity in two renal transplants and two hemodialysis patients treated with convalescent plasma

Abstract

When patients with chronic kidney disease are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) they can face two specific problems: virus-specific immune responses may be impaired and remdesivir, an antiviral drug described to shorten recovery, is contraindicated. Antiviral treatment with convalescent plasma (CP) could be an alternative treatment option. In this case report, we present two kidney transplant recipients and two hemodialysis patients who were infected with SARS-CoV-2 and received CP. Antibodies against the receptor-binding domain in the S1 subunit of the SARS-CoV-2 spike protein were determined sequentially by immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and neutralization assay and specific cellular responses by interferon-gamma ELISpot. Before treatment, in both kidney transplant recipients and one hemodialysis patient antibodies were undetectable by ELISA (ratio < 1.1), corresponding to low neutralizing antibody titers (≤1:40). ELISpot responses in the four patients were either weak or absent. After CP treatment, we observed an increase of SARS-CoV-2-specific antibodies (IgG ratio and neutralization titer) and of specific cellular responses. After intermittent clinical improvement, one kidney transplant recipient again developed typical symptoms on Day 12 after treatment and received a second cycle of CP treatment. Altogether, three patients clinically improved and could be discharged from the hospital. However, one 83-year-old multimorbid patient deceased. Our data suggest that the success of CP therapy may only be temporary in patients with chronic kidney disease; which requires close monitoring of viral load and antiviral immunity and possibly an adaptation of the treatment regimen.

Keywords: COVID-19; ELISpot; cellular immunity; convalescent plasma; hemodialysis; kidney transplantation.

Figure 1

Course of specific humoral and cellular immunity in four patients with chronic kidney disease infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and receiving convalescent plasma treatment. Antibodies were determined by an S1 specific immunoglobulin G (IgG) enzyme‐linked immunosorbent assay (Euroimmun) and by cell‐culture based neutralization assay (NT titer). Cellular responses were analyzed by an interferon‐gamma (IFN‐γ) ELISpot assay, using peptide pools of the S1/S2, S1, and M protein and an S1 protein antigen as specific stimuli (depicted as S1/S2, S1, M, and S ELI). We here present data on two kidney transplant recipients (RTX01, RTX02) and two patients on hemodialysis (HD01, HD02) and compared their immune responses with those of the corresponding donors of convalescent plasma (CP; shaded area). SARS‐CoV‐2‐specific antibody data (IgG ratio and NT titer) are given on the left Y‐axis and ELISpot data on the right one. Horizontal dashed lines represent the cut‐off values for positive reactions (IgG ratio of 1.1 and NT titer of 1:20). Vertical dotted lines indicate the time points of convalescent plasma applications (CP1, CP2, and CP3). Related data points are connected. PBMC, peripheral blood mononuclear cells

Figure 2

Course of oxygen demand, C‐reactive protein, and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) viral load in four patients with chronic kidney disease infected with SARS‐CoV‐2 and receiving convalescent plasma treatment. We here present data on two kidney transplant recipients (RTX01, RTX02) and two patients on hemodialysis (HD01, HD02) which were tested up to Day 39 after receiving convalescent plasma (CP). Vertical dotted lines indicate the time points of convalescent plasma applications (CP1, CP2, and CP3). Of note, only RTX01 received two cycles of CP while the remaining three patients received one cycle. A ct value of SARS‐CoV‐2 RNA > 40 was considered negative