Dysregulated immune responses in COVID-19 patients correlating with disease severity and invasive oxygen requirements.

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dc.contributor.authorGarcía-González, Paulina
dc.contributor.authorTempio, Fabian
dc.contributor.authorFuentes, Camila
dc.contributor.authorMerino, Consuelo
dc.contributor.authorVargas, Leonardo
dc.contributor.authorSimon, Valeska
dc.contributor.authorRamirez-Pereira, Mirliana
dc.contributor.authorRojas, Verónica
dc.contributor.authorTobar, Eduardo
dc.contributor.authorLandskron, Glauben
dc.contributor.authorAraya, Juan Pablo
dc.contributor.authorNavarrete, Mariela
dc.contributor.authorBastias, Carla
dc.contributor.authorTordecilla, Rocío
dc.contributor.authorVaras, Macarena A
dc.contributor.authorMaturana, Pablo
dc.contributor.authorMarcoleta, Andrés E
dc.contributor.authorAllende, Miguel L
dc.contributor.authorNaves, Rodrigo
dc.contributor.authorHermoso, Marcela A
dc.contributor.authorSalazar-Onfray, Flavio
dc.contributor.authorLopez, Mercedes
dc.contributor.authorBono, María-Rosa
dc.contributor.authorOsorio, Fabiola
dc.date.accessioned2022-11-03T13:11:17Z
dc.date.available2022-11-03T13:11:17Z
dc.date.issued2021-10-21
dc.description.abstractThe 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.es
dc.description.sponsorshipThis 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.es
dc.identifier.citationFrontiers in Immunology, Vol. 12, N° 769059 (2021) p. 1-14.en
dc.identifier.doihttps://doi.org/10.3389/fimmu.2021.769059
dc.identifier.issn1664-3224
dc.identifier.orcidhttps://orcid.org/0000-0002-7953-6769
dc.identifier.urihttp://hdl.handle.net/20.500.12254/2588
dc.language.isoenen
dc.publisherFrontiers Media S.A.en
dc.rightsAtribución-NoComercial-CompartirIgual 3.0 Chile (CC BY-NC-SA 3.0 CL)
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/cl/
dc.subject.otherCOVID-19en
dc.subject.otherOxygen therapyen
dc.subject.otherInvasive mechanical ventilationen
dc.subject.otherImmunityen
dc.subject.otherImmunological memoryen
dc.titleDysregulated immune responses in COVID-19 patients correlating with disease severity and invasive oxygen requirements.en
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