Elevated Extracellular HSP72 and Blunted Heat Shock Response in Severe COVID-19 Patients
Mariana Kras Borges Russo,
Lucas Stahlhöfer Kowalewski,
Gabriella Richter da Natividade,
Carlos Henrique de Lemos Muller,
Helena Trevisan Schroeder,
Patrícia Martins Bock,
Layane Ramos Ayres,
Bernardo Urbano Cardoso,
Caroline Zanotto,
Julia Tsao Schein,
Tatiana Helena Rech,
Daisy Crispim,
Luis Henrique Canani,
Rogério Friedman,
Cristiane Bauermann Leitão,
Fernando Gerchman,
Mauricio Krause
Affiliations
Mariana Kras Borges Russo
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
Lucas Stahlhöfer Kowalewski
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
Gabriella Richter da Natividade
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
Carlos Henrique de Lemos Muller
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
Helena Trevisan Schroeder
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
Patrícia Martins Bock
Faculdades Integradas de Taquara, Taquara 95612-150, RS, Brazil
Layane Ramos Ayres
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
Bernardo Urbano Cardoso
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
Caroline Zanotto
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
Julia Tsao Schein
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
Tatiana Helena Rech
Intensive Care Unit, Hospital de Clinicas de Porto Alegre, Porto Alegre 90035-903, RS, Brazil
Daisy Crispim
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
Luis Henrique Canani
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
Rogério Friedman
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
Cristiane Bauermann Leitão
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
Fernando Gerchman
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
Mauricio Krause
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
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.
