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

• Published in: Frontiers in immunology Vol. 12; p. 769059
• Main Authors: García-González, Paulina, Tempio, Fabián, Fuentes, Camila, Merino, Consuelo, Vargas, Leonardo, Simon, Valeska, Ramirez-Pereira, Mirliana, Rojas, Verónica, Tobar, Eduardo, Landskron, Glauben, Araya, Juan Pablo, Navarrete, Mariela, Bastias, Carla, Tordecilla, Rocío, Varas, Macarena A., Maturana, Pablo, Marcoleta, Andrés E., Allende, Miguel L., Naves, Rodrigo, Hermoso, Marcela A., Salazar-Onfray, Flavio, Lopez, Mercedes, Bono, María Rosa, Osorio, Fabiola
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 21-10-2021
• Subjects: immunity; immunological memory; Immunology; invasive mechanical ventilation; oxygen therapy; severe COVID-19
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.769059

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.