{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T06:10:00Z","timestamp":1781935800631,"version":"3.54.5"},"reference-count":59,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Association of Friends of the National Cancer Institute","award":["COVID-SA"],"award-info":[{"award-number":["COVID-SA"]}]},{"name":"The Children's Cancer Hospital Egypt","award":["SA-Start up"],"award-info":[{"award-number":["SA-Start up"]}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,11,24]]},"abstract":"<jats:p>\n                    Human serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here, we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 39 patients who were followed up for a median of 12.5 days (1\u201335 days), among them 23 had died. Analyzing blood samples from patients and healthy individuals (n=11), we provide evidence that neutrophils are major sources of oxidative stress in blood and that hydrogen peroxide is highly accumulated in plasmas of non-survivors. We then analyzed electron paramagnetic resonance spectra of spin-labeled fatty acids (SLFAs) bound with HSA in whole blood of control, survivor, and non-survivor subjects (n=10\u201311). Non-survivors\u2019 HSA showed dramatically reduced protein packing order parameter, faster SLFA correlational rotational time, and smaller S\/W ratio (strong-binding\/weak-binding sites within HSA), all reflecting remarkably fluid protein microenvironments. Following loading\/unloading of 16-DSA, we show that the transport function of HSA may be impaired in severe patients. Stratified at the means, Kaplan\u2013Meier survival analysis indicated that lower values of S\/W ratio and accumulated H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    in plasma significantly predicted in-hospital mortality (S\/W\u22640.15, 81.8% (18\/22) vs. S\/W&gt;0.15, 18.2% (4\/22), p=0.023; plasma [H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ]&gt;8.6 \u03bcM, 65.2% (15\/23) vs. 34.8% (8\/23), p=0.043). When we combined these two parameters as the ratio ((S\/W)\/[H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ]) to derive a risk score, the resultant risk score lower than the mean (&lt;0.019) predicted mortality with high fidelity (95.5% (21\/22) vs. 4.5% (1\/22), log-rank \u03c7\n                    <jats:sup>2<\/jats:sup>\n                    =12.1, p=4.9\u00d710\n                    <jats:sup>\u22124<\/jats:sup>\n                    ). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements and\/or oxidative stress.\n                  <\/jats:p>","DOI":"10.7554\/elife.69417","type":"journal-article","created":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T08:01:15Z","timestamp":1637827275000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.69417","source":"Crossref","is-referenced-by-count":39,"title":["Neutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1691-0167","authenticated-orcid":true,"given":"Mohamed A","family":"Badawy","sequence":"first","affiliation":[{"name":"Research Department, Children\u2019s Cancer Hospital","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basma A","family":"Yasseen","sequence":"first","affiliation":[{"name":"Research Department, Children\u2019s Cancer Hospital","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riem M","family":"El-Messiery","sequence":"first","affiliation":[{"name":"Infectious Disease Unit, Internal Medicine Department, Faculty of Medicine, Cairo University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Engy A","family":"Abdel-Rahman","sequence":"first","affiliation":[{"name":"Research Department, Children\u2019s Cancer Hospital","place":["Cairo, Egypt"]},{"name":"Pharmacology Department, Faculty of Medicine, Assuit University","place":["Assuit, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5684-0242","authenticated-orcid":true,"given":"Aya A","family":"Elkhodiry","sequence":"first","affiliation":[{"name":"Research Department, Children\u2019s Cancer Hospital","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azza G","family":"Kamel","sequence":"first","affiliation":[{"name":"Research Department, Children\u2019s Cancer Hospital","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajar","family":"El-sayed","sequence":"additional","affiliation":[{"name":"Research Department, Children\u2019s Cancer Hospital","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa M","family":"Shedra","sequence":"additional","affiliation":[{"name":"Research Department, Children\u2019s Cancer Hospital","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehab","family":"Hamdy","sequence":"additional","affiliation":[{"name":"Research Department, Children\u2019s Cancer Hospital","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Zidan","sequence":"additional","affiliation":[{"name":"Research Department, Children\u2019s Cancer Hospital","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diaa","family":"Al-Raawi","sequence":"additional","affiliation":[{"name":"Research Department, Children\u2019s Cancer Hospital","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1677-0360","authenticated-orcid":true,"given":"Mahmoud","family":"Hammad","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Department, National Cancer Institute, Cairo University and Children's Cancer Hospital","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahla","family":"Elsharkawy","sequence":"additional","affiliation":[{"name":"Clinical pathology department, National Cancer Institute, Cairo University and Children's Cancer Hospital","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El Ansary","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Faculty of Medicine, Cairo University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Al-Halfawy","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Faculty of Medicine, Cairo University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Elhadad","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Department, National Cancer Institute, Cairo University and Children's Cancer Hospital","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf","family":"Hatem","sequence":"additional","affiliation":[{"name":"Department of Chest Diseases, Faculty of Medicine, Cairo University","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif","family":"Abouelnaga","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Department, National Cancer Institute, Cairo University and Children's Cancer Hospital","place":["Cairo, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura L","family":"Dugan","sequence":"additional","affiliation":[{"name":"Division of Geriatric Medicine, Department of Medicine, Vanderbilt University Medical Center; and VATennessee Valley Geriatric Research, Education and Clinical Center (GRECC)","place":["Nashville, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0339-6106","authenticated-orcid":true,"given":"Sameh Saad","family":"Ali","sequence":"additional","affiliation":[{"name":"Research Department, Children\u2019s Cancer Hospital","place":["Cairo, 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