Blood transcriptomes of SARS-CoV-2 infected kidney transplant recipients demonstrate immune insufficiency

Kidney transplant recipients (KTRs) are reported to have worse outcomes with COVID-19, and empiric reduction of T-cell directed immunosuppression has been pursued. Here we evaluated the peripheral blood transcriptome of 64 KTRs either during and after acute COVID-19. We identified transcriptomic signatures of suppression of adaptive T-cell responses which significantly associated with disease severity and showed evidence of recovery after acute disease. These findings were consistent with public data from non-KTR cohorts. A total of 64 cases of COVID-19 in KTRs were enrolled, including 31 acute cases (< 4 weeks from diagnosis PCR) and 33 post-acute cases (>4 weeks from PCR). Eight COVID-19 KTRs died, and three graft losses occurred during follow-up. In the blood transcriptome of acute cases, we identified differentially expressed genes (DEGs) in positive or negative association with increasing COVID-19 severity. Functional enrichment analyses showed upregulation of neutrophil and innate immune pathways, but downregulation of adaptive immune activation pathways with increasing severity score, independent of lymphocyte count despite reduction in immunosuppression (IS) in most KTRs. Interestingly, comparison with post-acute cases showed “normalization” of these enriched pathways after >4 weeks, suggesting recovery of adaptive immune system activation despite reinstitution of IS. The latter analysis was adjusted for COVID-19 severity. Similar pathways enriched in DEGs associated with worsening disease severity was identifiable from a public dataset of non-KTRs with COVID-19 (GSE152418).