PMC8387963_01
PMC8387963_02
Protracted COVID-19 in a patient after CD19 CART resolved after CP therapy that coincided with increase in anti-SARS-CoV2 T cell-mediated response. (A) SARS-CoV-2 Ct values measured with RT-PCR. (B) Lung CT scan at day 51 post infection showing typical pattern of COVID-19 disease. (C) Complete B cell-deficiency in peripheral blood and bone marrow analyzed 10 months after CAR-T cell treatment shown by flow cytometry. (D) Neutralizing anti-SARS-CoV-2 antibody levels measured as inhibition of anti-SARS-CoV2 S-RBD with hACE2 at 1:20 plasma dilution by sVNT. (E) Blood NK cell show a CD16+CD56- phenotype following CP therapy. (F) Total percentage of interferon gamma (IFN-gamma) and/or tumor-necrosis factor alpha (TNF-alpha) producing CD8+ and CD4+ T cells following ex vivo stimulation with pooled spike (S)- or membrane, nucleocapsid, and envelope (MNE) peptide pools, gated as shown in Supplementary Figure 1. (G) Relative distribution of CD8+ and CD4+ T cells producing IFN-gamma and/or TNF-alpha at time-points indicated. (H) Concentration of 5 selected of 27 measured inflammatory mediators in plasma. Depicted mediators have either markedly changed their concentrations post CP treatment. The concentrations of all tested cytokines are listed in Supplementary Table 1. (A, D, F, H) Shaded area indicates hospitalization; vertical dashed line indicates treatment with CP.
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Mild symptoms persisted over the next five weeks when she was (Figure 1A and Table 1). SARS-CoV-2 infection was confirmed in house and viral genome sequencing (for details see Supplementary Materials) indicated that SARS-CoV-2 was of the B.1.36 lineage (Supplementary Figure 1). A chest CT scan showed COVID-19 pneumonia (Figure 1B). A complete B cell deficiency was demonstrated by flow cytometry on peripheral blood and bone marrow at the time of SARS-CoV-2 infection (Figure 1C). Resequencing of a PCR-positive respiratory sample taken 68 days PSO showed that the virus had acquired a V127I substitution in the N-terminal domain of the S protein (Supplementary Figure 1). At 3 months PSO, pancytopenia resolved and viral load in nasopharyngeal swabs decreased and 4 months PSO, the patient tested negative for SARS-CoV-2 (Figure 1A) and was free of any COVID-19 symptoms.