Dysregulated Immune Responses in COVID-19 Patients Correlating With Disease Severity and Invasive Oxygen Requirements.
Date
2021-10-21
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Frontiers Media
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1664-3224
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Abstract
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.
Description
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This work was supported by a grant from the COVID-19 research program of the National Agency for Research and Development (ANID), grant No 0752. FO is supported by an International Research Scholar grant from HHMI (HHMI#55008744) a FONDECYT grant No. 1200793, and ECOS-CONICYT grant (ECOS180052). MB is supported by a FONDECYT grant No 1191438. PG-G is supported by a postdoctoral fellowship from ANID, grant No 3190856. MA is supported by ANID/FONDAP/15200002. GL is supported by an ANID-postdoctoral fellowship, grant No 3190931. FS-O is supported by the Millennium Science Initiative from the Ministry for the Economy, Development and Tourism (P09/016-F). The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Citation
Front Immunol. 2021 Oct 21;12:769059. doi: 10.3389/fimmu.2021.769059.
Keywords
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Atribución-NoComercial-CompartirIgual 3.0 Chile (CC BY-NC-SA 3.0 CL)