{"doi":"10.1681/asn.2022010125","title":"Blood Transcriptomes of SARS-CoV-2–Infected Kidney Transplant Recipients Associated with Immune Insufficiency Proportionate to Severity","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.","journal":"Journal of the American Society of Nephrology","year":2022,"id":275643,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7766,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":459271,"name":"Zhongyang Zhang","orcid":"0000-0002-2521-3884","position":1,"is_corresponding":false},{"id":469752,"name":"Khadija Banu","orcid":"0000-0001-6680-2688","position":2,"is_corresponding":false},{"id":945696,"name":"Yorg Al Azzi","orcid":null,"position":3,"is_corresponding":false},{"id":714385,"name":"Anand Reghuvaran","orcid":"0000-0002-5656-0205","position":4,"is_corresponding":false},{"id":649561,"name":"Samuel Fredericks","orcid":"0000-0002-6146-5536","position":5,"is_corresponding":false},{"id":655982,"name":"Marina Planoutene","orcid":null,"position":6,"is_corresponding":false},{"id":263570,"name":"Susan Hartzell","orcid":"0000-0003-4175-4602","position":7,"is_corresponding":false},{"id":494257,"name":"Yesl Kim","orcid":"0000-0001-7749-641X","position":8,"is_corresponding":false},{"id":945184,"name":"John Pell","orcid":"0009-0000-9641-2445","position":9,"is_corresponding":false},{"id":305507,"name":"Gregory T. Tietjen","orcid":"0000-0002-7227-2887","position":10,"is_corresponding":false},{"id":718420,"name":"William S. Asch","orcid":"0000-0001-6471-1037","position":11,"is_corresponding":false},{"id":718425,"name":"Sanjay Kulkarni","orcid":"0000-0002-0835-7907","position":12,"is_corresponding":false},{"id":250556,"name":"Richard N. Formica","orcid":"0000-0001-6452-3976","position":13,"is_corresponding":false},{"id":645022,"name":"Meenakshi Rana","orcid":"0000-0001-9366-5359","position":14,"is_corresponding":false},{"id":74104,"name":"Jonathan S. Maltzman","orcid":"0000-0001-5722-269X","position":15,"is_corresponding":false},{"id":301627,"name":"Weijia Zhang","orcid":"0000-0001-6928-0416","position":16,"is_corresponding":false},{"id":247113,"name":"Enver Akalin","orcid":"0000-0003-1341-5144","position":17,"is_corresponding":false},{"id":105288,"name":"Peter S. Heeger","orcid":"0000-0003-4673-6913","position":18,"is_corresponding":false},{"id":247122,"name":"Paolo Cravedi","orcid":"0000-0001-7837-0923","position":19,"is_corresponding":false},{"id":385517,"name":"Madhav C. Menon","orcid":"0000-0002-9567-4299","position":20,"is_corresponding":false},{"id":469753,"name":"Zeguo Sun","orcid":"0000-0001-5542-2284","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T00:28:21.971703Z","pmid":"36041788","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}