Critical Care Explorations (Mar 2021)

Detection and Profiling of Human Coronavirus Immunoglobulins in Critically Ill Coronavirus Disease 2019 Patients

  • Douglas D. Fraser, MD, PhD,
  • Gediminas Cepinskas, DVM, PhD,
  • Marat Slessarev, MD, MSc,
  • Claudio M. Martin, MD, MSc,
  • Mark Daley, PhD,
  • Maitray A. Patel, BSc,
  • Michael R. Miller, PhD,
  • Eric K. Patterson, PhD,
  • David B. O’Gorman, PhD,
  • Sean E. Gill, PhD,
  • Susanne Oehler, PhD,
  • Markus Miholits, MSc,
  • Brian Webb, PhD,
  • on behalf of the Lawson COVID-19 Study Team,
  • Robert Arntfield,
  • Ian Ball,
  • Gordon Barkwell,
  • Tracey Bentall,
  • Karen Bosma,
  • Saoirse Cameron,
  • Eileen Campbell,
  • David Carter,
  • Carolina Gillio-Meina,
  • Robert Hegele,
  • Natalya Odoardi,
  • Ram Singh,
  • Kelly Summers,
  • Sue Tereschyn

DOI
https://doi.org/10.1097/CCE.0000000000000369
Journal volume & issue
Vol. 3, no. 3
p. e0369

Abstract

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Objectives:. Coronavirus disease 2019 continues to spread worldwide with high levels of morbidity and mortality. We performed anticoronavirus immunoglobulin G profiling of critically ill coronavirus disease 2019 patients to better define their underlying humoral response. Design:. Blood was collected at predetermined ICU days to measure immunoglobulin G with a research multiplex assay against four severe acute respiratory syndrome coronavirus 2 proteins/subunits and against all six additionally known human coronaviruses. Setting:. Tertiary care ICU and academic laboratory. Subjects:. ICU patients suspected of being infected with severe acute respiratory syndrome coronavirus 2 had blood collected until either polymerase chain reaction testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative) or until death or discharge if the patient tested polymerase chain reaction positive (coronavirus disease 2019 positive). Interventions:. None MEASUREMENTS AND MAIN RESULTS:. Age- and sex-matched healthy controls and ICU patients who were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well-balanced with the exception that coronavirus disease 2019 positive patients had greater body mass indexes, presented with bilateral pneumonias more frequently, and suffered lower Pao2:Fio2 ratios, when compared with coronavirus disease 2019 negative patients (p < 0.05). Mortality rate for coronavirus disease 2019 positive patients was 50%. On ICU days 1–3, anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G was significantly elevated in coronavirus disease 2019 positive patients, as compared to both healthy control subjects and coronavirus disease 2019 negative patients (p < 0.001). Weak severe acute respiratory syndrome coronavirus immunoglobulin G serologic responses were also detected, but not other coronavirus subtypes. The four anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G were maximal by ICU day 3, with all four anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G providing excellent diagnostic potential (severe acute respiratory syndrome coronavirus 2 Spike 1 protein immunoglobulin G, area under the curve 1.0, p < 0.0005; severe acute respiratory syndrome coronavirus receptor binding domain immunoglobulin G, area under the curve, 0.93–1.0; p ≤ 0.0001; severe acute respiratory syndrome coronavirus 2 Spike proteins immunoglobulin G, area under the curve, 1.0; p < 0.0001; severe acute respiratory syndrome coronavirus 2 Nucleocapsid protein immunoglobulin G area under the curve, 0.90–0.95; p ≤ 0.0003). Anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G increased and/or plateaued over 10 ICU days. Conclusions:. Critically ill coronavirus disease 2019 patients exhibited anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G, whereas serologic responses to non–severe acute respiratory syndrome coronavirus 2 antigens were weak or absent. Detection of human coronavirus immunoglobulin G against the different immunogenic structural proteins/subunits with multiplex assays may be useful for pathogen identification, patient cohorting, and guiding convalescent plasma therapy.