Activation of STAT3 signaling pathway in the kidney of COVID-19 patients

Fadi Salem, Xue Zhu Li, Judy Hindi, Nitzy Munoz Casablanca, Fang Zhong, Siraj M. El Jamal, Mohamed Rizwan Haroon Al Rasheed, Li Li, Kyung Lee, Lili Chan, John Cijiang He

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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.

Original languageEnglish
Pages (from-to)735-743
Number of pages9
JournalJournal of Nephrology
Issue number3
StatePublished - Apr 2022


  • Autopsy
  • COVID-19
  • Cytokines
  • Renal pathology


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