Cytokine signatures of end organ injury in COVID-19.

TitleCytokine signatures of end organ injury in COVID-19.
Publication TypeJournal Article
Year of Publication2021
AuthorsGómez-Escobar LG, Hoffman KL, Choi JJ, Borczuk A, Salvatore S, Alvarez-Mulett SL, Galvan MD, Zhao Z, Racine-Brzostek SE, Yang HS, Stout-Delgado HW, Choi ME, Choi AMK, Cho SJung, Schenck EJ
JournalSci Rep
Volume11
Issue1
Pagination12606
Date Published2021 06 15
ISSN2045-2322
KeywordsAcute Kidney Injury, Aged, Case-Control Studies, COVID-19, Cytokine Release Syndrome, Cytokines, Female, Hospitals, Humans, Lung, Male, Middle Aged, New York City, Respiration, Artificial, Respiratory Distress Syndrome, Treatment Outcome
Abstract

Increasing evidence has shown that Coronavirus disease 19 (COVID-19) severity is driven by a dysregulated immunologic response. We aimed to assess the differences in inflammatory cytokines in COVID-19 patients compared to contemporaneously hospitalized controls and then analyze the relationship between these cytokines and the development of Acute Respiratory Distress Syndrome (ARDS), Acute Kidney Injury (AKI) and mortality. In this cohort study of hospitalized patients, done between March third, 2020 and April first, 2020 at a quaternary referral center in New York City we included adult hospitalized patients with COVID-19 and negative controls. Serum specimens were obtained on the first, second, and third hospital day and cytokines were measured by Luminex. Autopsies of nine cohort patients were examined. We identified 90 COVID-19 patients and 51 controls. Analysis of 48 inflammatory cytokines revealed upregulation of macrophage induced chemokines, T-cell related interleukines and stromal cell producing cytokines in COVID-19 patients compared to the controls. Moreover, distinctive cytokine signatures predicted the development of ARDS, AKI and mortality in COVID-19 patients. Specifically, macrophage-associated cytokines predicted ARDS, T cell immunity related cytokines predicted AKI and mortality was associated with cytokines of activated immune pathways, of which IL-13 was universally correlated with ARDS, AKI and mortality. Histopathological examination of the autopsies showed diffuse alveolar damage with significant mononuclear inflammatory cell infiltration. Additionally, the kidneys demonstrated glomerular sclerosis, tubulointerstitial lymphocyte infiltration and cortical and medullary atrophy. These patterns of cytokine expression offer insight into the pathogenesis of COVID-19 disease, its severity, and subsequent lung and kidney injury suggesting more targeted treatment strategies.

DOI10.1038/s41598-021-91859-z
Alternate JournalSci Rep
PubMed ID34131192
PubMed Central IDPMC8206105
Grant ListKL2 TR000458-10 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
R01 AG056699 / AG / NIA NIH HHS / United States
R01 HL055330 / HL / NHLBI NIH HHS / United States
R01 AG052530 / AG / NIA NIH HHS / United States
KL2-TR-00238 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
K08 HL138285 / HL / NHLBI NIH HHS / United States
R01 HL133801 / HL / NHLBI NIH HHS / United States
Related Faculty: 
He Sarina Yang, Ph.D. Sabrina Racine-Brzostek, M.D., Ph.D. Zhen Zhao, Ph.D.

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