{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T13:45:21Z","timestamp":1782308721282,"version":"3.54.5"},"reference-count":52,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T00:00:00Z","timestamp":1664150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brazilian National Council for Scientific and Technological Development (CNPq)","award":["#401610\/2020-9"],"award-info":[{"award-number":["#401610\/2020-9"]}]},{"name":"Brazilian National Council for Scientific and Technological Development (CNPq)","award":["#425579\/2018-2"],"award-info":[{"award-number":["#425579\/2018-2"]}]},{"name":"Brazilian National Council for Scientific and Technological Development (CNPq)","award":["#30791.434.41354.23112017"],"award-info":[{"award-number":["#30791.434.41354.23112017"]}]},{"name":"State of Rio Grande do Sul Foundation for Research Support","award":["#401610\/2020-9"],"award-info":[{"award-number":["#401610\/2020-9"]}]},{"name":"State of Rio Grande do Sul Foundation for Research Support","award":["#425579\/2018-2"],"award-info":[{"award-number":["#425579\/2018-2"]}]},{"name":"State of Rio Grande do Sul Foundation for Research Support","award":["#30791.434.41354.23112017"],"award-info":[{"award-number":["#30791.434.41354.23112017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Aims: We hypothesized that critically ill patients with SARS-CoV-2 infection and insulin resistance would present a reduced Heat Shock Response (HSR), which is a pathway involved in proteostasis and anti-inflammation, subsequently leading to worse outcomes and higher inflammation. In this work we aimed: (i) to measure the concentration of extracellular HSP72 (eHSP72) in patients with severe COVID-19 and in comparison with noninfected patients; (ii) to compare the HSR between critically ill patients with COVID-19 (with and without diabetes); and (iii) to compare the HSR in these patients with noninfected individuals. Methods: Sixty critically ill adults with acute respiratory failure with SARS-CoV-2, with or without diabetes, were selected. Noninfected subjects were included for comparison (healthy, n = 19 and patients with diabetes, n = 22). Blood samples were collected to measure metabolism (glucose and HbA1c); oxidative stress (lypoperoxidation and carbonyls); cytokine profile (IL-10 and TNF); eHSP72; and the HSR (in vitro). Results: Patients with severe COVID-19 presented higher plasma eHSP72 compared with healthy individuals and noninfected patients with diabetes. Despite the high level of plasma cytokines, no differences were found between critically ill patients with COVID-19 with or without diabetes. Critically ill patients, when compared to noninfected, presented a blunted HSR. Oxidative stress markers followed the same pattern. No differences in the HSR (extracellular\/intracellular level) were found between critically ill patients, with or without diabetes. Conclusions: We demonstrated that patients with severe COVID-19 have elevated plasma eHSP72 and that their HSR is blunted, regardless of the presence of diabetes. These results might explain the uncontrolled inflammation and also provide insights on the increased risk in developing type 2 diabetes after SARS-CoV-2 infection.<\/jats:p>","DOI":"10.3390\/biom12101374","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T01:41:58Z","timestamp":1664156518000},"page":"1374","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Elevated Extracellular HSP72 and Blunted Heat Shock Response in Severe COVID-19 Patients"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1164-566X","authenticated-orcid":false,"given":"Mariana Kras","family":"Borges Russo","sequence":"first","affiliation":[{"name":"Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX) and Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre 91509-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Stahlh\u00f6fer","family":"Kowalewski","sequence":"additional","affiliation":[{"name":"Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX) and Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre 91509-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella Richter","family":"da Natividade","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Unit, Hospital de Clinicas de Porto Alegre, Post-Graduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre 91509-900, RS, Brazil"},{"name":"Post-Graduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre 91509-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0205-7775","authenticated-orcid":false,"given":"Carlos Henrique","family":"de Lemos Muller","sequence":"additional","affiliation":[{"name":"Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX) and Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre 91509-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4000-3671","authenticated-orcid":false,"given":"Helena Trevisan","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX) and Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre 91509-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8572-3950","authenticated-orcid":false,"given":"Patr\u00edcia Martins","family":"Bock","sequence":"additional","affiliation":[{"name":"Faculdades Integradas de Taquara, Taquara 95612-150, RS, Brazil"},{"name":"Department of Pharmacology, Universidade Federal do Rio Grande do Sul, Porto Alegre 91509-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9604-693X","authenticated-orcid":false,"given":"Layane Ramos","family":"Ayres","sequence":"additional","affiliation":[{"name":"Laboratory of Inflammation, Metabolism and Exercise Research (LAPIMEX) and Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre 91509-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardo 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Tsao","family":"Schein","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Unit, Hospital de Clinicas de Porto Alegre, Post-Graduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre 91509-900, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana Helena","family":"Rech","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Hospital de Clinicas de Porto Alegre, Porto Alegre 90035-903, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy","family":"Crispim","sequence":"additional","affiliation":[{"name":"Endocrine and Metabolic Unit, Hospital de Clinicas de Porto Alegre, Post-Graduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre 91509-900, RS, Brazil"},{"name":"Post-Graduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre 91509-900, RS, 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