{
  "abstract": "Severe COVID-19 infection in patients with cancer is characterized by a unique pattern of immunologic dysfunction including muted adaptive immune responses. The molecular drivers of immune dysfunction in cancer patients with severe COVID-19 remain unclear, and therapeutic strategies to overcome immune dysfunction in this setting have not been identified.\n\nWe performed integrated proteomic and metabolomic profiling of matched cohorts of cancer and non-cancer patients with or without COVID-19 and identified dysfunctional cysteine metabolism as uniquely associated with severe COVID-19 in cancer patients. Treatment of patients with cancer and steroid-refractory COVID-19 with N-acetylcysteine in a prospective clinical trial (NCT04374461) improved clinical outcomes compared with disease severity-matched hospitalized patients during the period immediately preceding clinical trial initiation. N-AC treatment reduced circulating markers of innate inflammation, decreased severe disease-associated MHC-II low monocytes, and increased circulating CD8+ T cell abundance, activation, and effector differentiation. Mechanistically, N-AC reduced prostaglandin E2-driven interactions between suppressive monocytes and T cells, which we confirmed was sufficient to limit T cell expansion and effector differentiation in a dose- and avidity-dependent fashion. Moreover, N-AC reduced the activity of inhibitory, redox sensitive transcription factors such as KLF6, enabling clonal expansion and effector T cell differentiation. We confirmed these observations in two murine models of severe respiratory viral infection, in which N-AC treatment significantly enhanced lung-infiltrating CD8+ T cell abundance. These findings establish cysteine supplementation as a viable therapeutic strategy to reverse redox-driven immune dysregulation in severe respiratory viral infection, particularly in the high-risk cancer population.\n\nOne Sentence SummaryMerlinsky et al show that cysteine supplementation can therapeutically reverse immune dysregulation in cancer patients with severe COVID-19 infection.",
  "abstract_shown": true,
  "affiliations": [
    "Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center; New York, NY, USA"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "name": "T. Merlinsky"
    },
    {
      "name": "J. Rahman"
    },
    {
      "name": "W. T. Johnson"
    },
    {
      "name": "L. McGary"
    },
    {
      "name": "S. Grassmann"
    },
    {
      "name": "J. Zhang"
    },
    {
      "name": "A. Abdulraouf"
    },
    {
      "name": "H. L. Kalvin"
    },
    {
      "name": "K. Panageas"
    },
    {
      "name": "J. Nicodemus"
    },
    {
      "name": "E. Cathcart"
    },
    {
      "name": "Y.-H. Lin"
    },
    {
      "name": "K. K. Hosszu"
    },
    {
      "name": "M. Berisa"
    },
    {
      "name": "O. Lyudovyk"
    },
    {
      "name": "G. Salles"
    },
    {
      "name": "J. J. Boelens"
    },
    {
      "name": "N. E. Babady"
    },
    {
      "name": "J. Cao"
    },
    {
      "name": "J. D. Wolchok"
    },
    {
      "name": "J. C. Sun"
    },
    {
      "name": "J. Heath"
    },
    {
      "name": "B. Greenbaum"
    },
    {
      "affs": [
        0
      ],
      "name": "S. Vardhana"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6xzxdrsmc10y3.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.21.26363550",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.21.26363550v1.full",
  "id": "6xzxdrsmc10y3",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.21.26363550v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "infectious diseases"
    ],
    [
      "openalex",
      "2725|COVID-19 Clinical Research Studies"
    ]
  ],
  "openalex": "W7214001216",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.21.26363550v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6xzxdrsmc10y3.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:11Z",
      "native_id": "10.64898/2026.09.21.26363550",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.21.26363550v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:infectious diseases",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Cysteine supplementation reverses immune dysfunction in cancer patients with severe COVID-19",
  "title_text": "Cysteine supplementation reverses immune dysfunction in cancer patients with severe COVID-19",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:11Z",
  "url": "https://research.draconitic.com/paper/6xzxdrsmc10y3",
  "venue": "medRxiv",
  "versions": []
}