Dysregulated Immune Responses in COVID-19 Patients Correlating With Disease Severity and Invasive Oxygen Requirements

Frontiers in Immunology

Carla Bastias¹  Rocío Tordecilla¹  Andrés E. Marcoleta²  Macarena A. Varas³  Miguel L. Allende³  Pablo Maturana⁴  Rodrigo Naves⁵  Eduardo Tobar⁶  Verónica Rojas⁶  Consuelo Merino⁸  Camila Fuentes⁸  Fabián Tempio⁸  Mercedes Lopez⁸  Fabiola Osorio⁹  Paulina García-González⁹  María Rosa Bono^1,10  Valeska Simon^1,10  Leonardo Vargas^1,10  Marcela A. Hermoso^1,11  Flavio Salazar-Onfray^1,12  Juan Pablo Araya^1,12  Mariela Navarrete^1,12  Mirliana Ramirez-Pereira^1,13  Glauben Landskron^1,14 

[1] 0HIV Immunology and Allergies Unit, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, Chile;1Integrative Microbiology Group, Biology Department, Faculty of Sciences, Universidad de Chile, Santiago, Chile;2Center for Genome Regulation (CGR), Biology Department, Faculty of Sciences, Universidad de Chile, Santiago, Chile;3Laboratory of Biochemistry and Molecular Biology, Biology Department, Faculty of Sciences, Universidad de Chile, Santiago, Chile;4Laboratory of Neuroimmunology, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile;Critical Care Unit, Department of Medicine, Hospital Clínico Universidad de Chile, Santiago, Chile;Laboratory of Antitumoral Immunology, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile;Laboratory of Cancer Immunoregulation, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile;Laboratory of Immunology and Cellular Stress, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile;Laboratory of Immunology, Biology Department, Faculty of Sciences, Universidad de Chile, Santiago, Chile;Laboratory of Innate Immunity, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile;Millennium Institute on Immunology and Immunotherapy, Faculty of Medicine, Universidad de Chile, Santiago, Chile;Nursing Department, Faculty of Medicine, Universidad de Chile, Santiago, Chile;School of Medicine, Universidad Finis Terrae, Santiago, Chile;

关键词: severe COVID-19;    oxygen therapy;    invasive mechanical ventilation;    immunity;    immunological memory;   

DOI  :  10.3389/fimmu.2021.769059

来源: DOAJ

【 摘 要 】

The prognosis of severe COVID-19 patients has motivated research communities to uncover mechanisms of SARS-CoV-2 pathogenesis also on a regional level. In this work, we aimed to understand the immunological dynamics of severe COVID-19 patients with different degrees of illness, and upon long-term recovery. We analyzed immune cellular subsets and SARS-CoV-2-specific antibody isotypes of 66 COVID-19 patients admitted to the Hospital Clínico Universidad de Chile, which were categorized according to the WHO ten-point clinical progression score. These included 29 moderate patients (score 4-5) and 37 severe patients under either high flow oxygen nasal cannula (18 patients, score 6), or invasive mechanical ventilation (19 patients, score 7-9), plus 28 convalescent patients and 28 healthy controls. Furthermore, six severe patients that recovered from the disease were longitudinally followed over 300 days. Our data indicate that severe COVID-19 patients display increased frequencies of plasmablasts, activated T cells and SARS-CoV-2-specific antibodies compared to moderate and convalescent patients. Remarkably, within the severe COVID-19 group, patients rapidly progressing into invasive mechanical ventilation show higher frequencies of plasmablasts, monocytes, eosinophils, Th1 cells and SARS-CoV-2-specific IgG than patients under high flow oxygen nasal cannula. These findings demonstrate that severe COVID-19 patients progressing into invasive mechanical ventilation show a distinctive type of immunity. In addition, patients that recover from severe COVID-19 begin to regain normal proportions of immune cells 100 days after hospital discharge and maintain high levels of SARS-CoV-2-specific IgG throughout the study, which is an indicative sign of immunological memory. Thus, this work can provide useful information to better understand the diverse outcomes of severe COVID-19 pathogenesis.

【 授权许可】

Unknown