TY - JOUR
T1 - Blood Transcriptomes of SARS-CoV-2-Infected Kidney Transplant Recipients Associated with Immune Insufficiency Proportionate to Severity
AU - Sun, Zeguo
AU - Zhang, Zhongyang
AU - Banu, Khadija
AU - Al Azzi, Yorg
AU - Reghuvaran, Anand
AU - Fredericks, Samuel
AU - Planoutene, Marina
AU - Hartzell, Susan
AU - Kim, Yesl
AU - Pell, John
AU - Tietjen, Gregory
AU - Asch, William
AU - Kulkarni, Sanjay
AU - Formica, Richard
AU - Rana, Meenakshi
AU - Maltzman, Jonathan S.
AU - Zhang, Weijia
AU - Akalin, Enver
AU - Heeger, Peter S.
AU - Cravedi, Paolo
AU - Menon, Madhav C.
N1 - Publisher Copyright:
Copyright © 2022 by the American Society of Nephrology.
PY - 2022/11
Y1 - 2022/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85141005259&partnerID=8YFLogxK
U2 - 10.1681/ASN.2022010125
DO - 10.1681/ASN.2022010125
M3 - Article
C2 - 36041788
AN - SCOPUS:85141005259
SN - 1046-6673
VL - 33
SP - 2108
EP - 2122
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 11
ER -