Blood Transcriptomes of SARS-CoV-2-Infected Kidney Transplant Recipients Associated with Immune Insufficiency Proportionate to Severity

Zeguo Sun, Zhongyang Zhang, Khadija Banu, Yorg Al Azzi, Anand Reghuvaran, Samuel Fredericks, Marina Planoutene, Susan Hartzell, Yesl Kim, John Pell, Gregory Tietjen, William Asch, Sanjay Kulkarni, Richard Formica, Meenakshi Rana, Jonathan S. Maltzman, Weijia Zhang, Enver Akalin, Peter S. Heeger, Paolo CravediMadhav C. Menon

Research output: Contribution to journalArticlepeer-review

Abstract

Background Among patients with COVID-19, kidney transplant recipients (KTRs) have poor outcomes compared with non-KTRs. To provide insight into management of immunosuppression during acute illness, we studied immune signatures from the peripheral blood during and after COVID-19 infection from a multicenter KTR cohort. Methods We ascertained clinical data by chart review. A single sample of blood was collected for transcriptome analysis. Total RNA was poly-A selected and RNA was sequenced to evaluate transcriptome changes. We also measured cytokines and chemokines of serum samples collected during acute infection. Results A total of 64 patients with COVID-19 in KTRs were enrolled, including 31 with acute COVID-19 (<4 weeks from diagnosis) and 33 with post-acute COVID-19 (>4 weeks postdiagnosis). In the blood transcriptome of acute cases, we identified genes in positive or negative association with COVID-19 severity scores. Functional enrichment analyses showed upregulation of neutrophil and innate immune pathways but downregulation of T cell and adaptive immune activation pathways. This finding was independent of lymphocyte count, despite reduced immunosuppressant use in most KTRs. Compared with acute cases, post-acute cases showed “normalization” of these enriched pathways after 4 weeks, suggesting recovery of adaptive immune system activation despite reinstitution of immunosuppression. Analysis of the non-KTR cohort with COVID-19 showed significant overlap with KTRs in these functions. Serum inflammatory cytokines followed an opposite trend (i.e., increased with disease severity), indicating that blood lymphocytes are not the primary source. Conclusions The blood transcriptome of KTRs affected by COVID-19 shows decreases in T cell and adaptive immune activation pathways during acute disease that, despite reduced immunosuppressant use, associate with severity. These pathways show recovery after acute illness.

Original languageEnglish (US)
Pages (from-to)2108-2122
Number of pages15
JournalJournal of the American Society of Nephrology
Volume33
Issue number11
DOIs
StatePublished - Nov 2022

ASJC Scopus subject areas

  • Nephrology

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