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Detection and Profiling of Human Coronavirus Immunoglobulins in Critically Ill Coronavirus Disease 2019 Patients
Douglas D Fraser1,2,3,4, Gediminas Cepinskas1,5, Marat Slessarev1,6
1Lawson Health Research Institute, London, ON, Canada.
Insights
Critically ill patients with coronavirus disease 2019 (COVID-19) showed elevated immunoglobulin G (IgG) against SARS-CoV-2 proteins. This specific IgG response, detectable early, aids in diagnosing COVID-19 and understanding the humoral response.
Area of Science:
- Immunology
- Virology
- Critical Care Medicine
Background:
- Coronavirus disease 2019 (COVID-19) presents significant global morbidity and mortality.
- Understanding the humoral immune response in severe COVID-19 is crucial for effective treatment strategies.
Purpose of the Study:
- To profile immunoglobulin G (IgG) responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins in critically ill COVID-19 patients.
- To compare SARS-CoV-2 IgG levels with those of other human coronaviruses and in non-COVID-19 ICU patients.
Main Methods:
- Blood samples were collected from ICU patients, categorized as COVID-19 positive or negative.
- A research multiplex assay measured IgG levels against four SARS-CoV-2 proteins and six other human coronaviruses.
- Patients were compared to age- and sex-matched healthy controls.
Main Results:
- COVID-19 positive patients exhibited significantly elevated anti-SARS-CoV-2 IgG by ICU days 1-3, with responses peaking by day 3.
- Specific IgG responses were detected against SARS-CoV-2 Spike 1, Receptor Binding Domain, Spike proteins, and Nucleocapsid protein, showing high diagnostic accuracy.
- Weak or absent IgG responses were observed against other human coronaviruses, distinguishing the COVID-19 specific humoral immunity.
Conclusions:
- Critically ill COVID-19 patients demonstrate a distinct anti-SARS-CoV-2 IgG humoral response.
- Multiplex detection of coronavirus-specific IgG can aid in pathogen identification, patient stratification, and guiding convalescent plasma therapy.
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.
