{"doi":"10.1007/s40620-021-01173-0","title":"Activation of STAT3 signaling pathway in the kidney of COVID-19 patients","abstract":"BACKGROUND: Acute kidney injury is common in patients with COVID-19, however mechanisms of kidney injury remain unclear. Since cytokine storm is likely a cause of AKI and glomerular disease, we investigated the two major transcription factors, STAT3 and NF-kB, which are known to be activated by cytokines. METHODS: This is an observational study of the postmortem kidneys of 50 patients who died with COVID-19 in the Mount Sinai Hospital during the first pandemic surge. All samples were reviewed under light microscopy, electron microscopy, and immunofluorescence by trained renal pathologists. In situ hybridization evaluation for SARS-CoV-2 and immunostaining of transcription factors STAT3 and NF-kB were performed. RESULTS: Consistent with previous findings, acute tubular injury was the major pathological finding, together with global or focal glomerulosclerosis. We were not able to detect SARS-CoV-2 in kidney cells. ACE2 expression was reduced in the tubular cells of patients who died with COVID-19 and did not co-localize with TMPRSS2. SARS-CoV-2 was identified occasionally in the mononuclear cells in the peritubular capillary and interstitium. STAT3 phosphorylation at Tyr705 was increased in 2 cases in the glomeruli and in 3 cases in the tubulointerstitial compartments. Interestingly, STAT3 phosphorylation at Ser727 increased in 9 cases but only in the tubulointerstitial compartment. A significant increase in NF-kB phosphorylation at Ser276 was also found in the tubulointerstitium of the two patients with increased p-STAT3 (Tyr705). CONCLUSIONS: Our findings suggest that, instead of tyrosine phosphorylation, serine phosphorylation of STAT3 is commonly activated in the kidney of patients with COVID-19.","journal":"Journal of Nephrology","year":2021,"id":177766,"datarank":0.4566783656585135,"base_score":3.044522437723423,"endowment":3.044522437723423,"self_citation_contribution":0.4566783656585135,"citation_network_contribution":0.0,"self_endowment_contribution":0.4566783656585135,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9367,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":722736,"name":"Xue Zhu Li","orcid":null,"position":1,"is_corresponding":false},{"id":377586,"name":"Judy Hindi","orcid":null,"position":2,"is_corresponding":false},{"id":722737,"name":"Nitzy Munoz Casablanca","orcid":null,"position":3,"is_corresponding":false},{"id":289959,"name":"Fang Zhong","orcid":"0000-0002-3165-6884","position":4,"is_corresponding":false},{"id":679754,"name":"Siraj M. El Jamal","orcid":"0000-0001-6299-1071","position":5,"is_corresponding":false},{"id":649559,"name":"Mohamed Rizwan Haroon Al Rasheed","orcid":"0000-0002-0572-0387","position":6,"is_corresponding":false},{"id":2699,"name":"Li Li","orcid":"0000-0001-6746-4297","position":7,"is_corresponding":false},{"id":289963,"name":"Kyung Lee","orcid":"0000-0002-9756-1765","position":8,"is_corresponding":false},{"id":241216,"name":"Lili Chan","orcid":"0000-0003-4300-5760","position":9,"is_corresponding":false},{"id":263575,"name":"John Cijiang He","orcid":"0000-0002-1502-2849","position":10,"is_corresponding":false},{"id":439527,"name":"Fadi Salem","orcid":"0000-0002-2603-2778","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:47:32.096934Z","pmid":"34626364","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":[]}