Abstract
Background: The emergence of local SARS-CoV2 variants has motivated research communities to uncover immunological mechanisms of COVID-19 pathogenesis, also on regional level. Methods: 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). The study also included 28 convalescent patients and 28 healthy controls. Furthermore, six severe patients that recovered from the disease were longitudinally followed over 300 days. Results: Severe and moderate COVID-19 patients showed neutrophilia and lymphopenia. Severe patients also displayed increase in 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 displayed higher frequencies of plasmablasts, monocytes, eosinophils, Th1 cells and SARS-CoV-2-specific IgG than patients under high flow oxygen nasal cannula. Finally, patients that recovered from severe COVID-19 begin to regain normal proportions of immune cells 100 days after hospital discharge and maintained high levels of SARS-CoV-2-specific IgG throughout the study.Interpretation: Our data indicate that oxygen therapy in severe COVID-19 patients is linked to immunity. Furthermore, patients that recovered from severe disease show signs of immunological memory. Long term studies such this work can provide a useful benchmark for improvement of disease outcomes.Funding: ANID/COVID-19 grant 0752Declaration of Interest: All authors declare that no competing interest exist.Ethical Approval: This study was approved by the Institutional Review Boards at Hospital Clínico Universidad de Chile and at the Faculty of Medicine, Universidad de Chile (Protocol ID. Number 1151/20 and Protocol ID. Number N° 074-2020).
Highlights
The pandemic of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has led to millions of infections and deaths worldwide, with numbers continuing to increase (WHO dashboard information: https://covid19.who.int)
We report that severe patients who rapidly require invasive mechanical ventilation display an immunological profile typified by increased frequencies of plasmablasts, monocytes, eosinophils and Th1 equivalents, which distinguished this group from more stable severe COVID-19 patients treated with high flow nasal cannula
This protocol was applied to whole blood or to peripheral blood mononuclear cells (PBMC, for analysis of lymphocytes and monocytes) (Scheme of the study is depicted in Supplementary Figure 1 and gating strategy is depicted in Supplementary Figure 2)
Summary
The pandemic of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has led to millions of infections and deaths worldwide, with numbers continuing to increase (WHO dashboard information: https://covid19.who.int). The risk of developing severe disease has been associated with advanced age, comorbidities such as metabolic syndrome, lung and heart conditions and other factors such as poverty and social determinants in health [3,4,5,6,7]. In this context, symptomatic COVID-19 patients develop clinical manifestations within a 14-days window and can exhibit fever and dry cough, fatigue, anosmia, dyspnea, muscle and joint pain, headache, diarrhea and other symptoms [3, 8, 9]. The association between oxygen dependency, disease severity and mortality, is a parameter that the World Health Organization (WHO) considers for clinical classification of patients [13]
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