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

Douglas D Fraser; Gediminas Cepinskas; Marat Slessarev; Claudio M Martin; Mark Daley; Maitray A Patel; Michael R Miller; Eric K Patterson; David B O'Gorman; Sean E Gill; Susanne Oehler; Markus Miholits; Brian Webb

doi:10.1097/CCE.0000000000000369

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

Crit Care Explor. 2021 Mar 12;3(3):e0369. doi: 10.1097/CCE.0000000000000369. eCollection 2021 Mar.

Authors

Douglas D Fraser^{1

2

3

4}, Gediminas Cepinskas^{1

5}, Marat Slessarev^{1

6}, Claudio M Martin^{1

6}, Mark Daley^{1

7

8}, Maitray A Patel⁷, Michael R Miller^{1

2}, Eric K Patterson¹, David B O'Gorman^{1

9

10}, Sean E Gill^{1

4

6}, Susanne Oehler¹¹, Markus Miholits¹¹, Brian Webb¹²

Affiliations

¹ Lawson Health Research Institute, London, ON, Canada.
² Pediatrics, Western University, London, ON, Canada.
³ Clinical Neurological Sciences, Western University, London, ON, Canada.
⁴ Physiology & Pharmacology, Western University, London, ON, Canada.
⁵ Medical Biophysics, Western University, London, ON, Canada.
⁶ Medicine, Western University, London, ON, Canada.
⁷ Computer Science, Western University, London, ON, Canada.
⁸ The Vector Institute for Artificial Intelligence, Toronto, ON, Canada.
⁹ Surgery, Western University, London, ON, Canada.
¹⁰ Biochemistry, Western University, London, ON, Canada.
¹¹ Thermo Fisher Scientific, Vienna, Austria.
¹² Thermo Fisher Scientific, Rockford, IL.

Abstract

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.

Keywords: coronavirus disease 2019; humoral response; immunoglobulins; intensive care unit; multiplex.