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

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 Pao 2 :F io 2 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 ac...

Cross-immunity against SARS-COV-2 variants of concern in naturally infected critically ill COVID-19 patients

“…Patients admitted to the ICU during Wave-1 developed increasing neutralizing antibodies to all variants with time, as did patients during Wave-3. These data are consistent with our previous reports demonstrating increased WT SARS-CoV-2 antibodies in critically ill ICU patients [ 11 , 12 ]; specifically, we had demonstrated classification accuracy of 96–100% for IgG to the SARS-CoV-2 Spike protein on ICU day-3. Wave-3 patients, when compared to Wave-1, developed more robust antibody responses, particularly for WT, alpha, beta and delta variants.…”

“…COVID-19 induces an innate immune response [ 2 , 3 ] that includes increased interferons, tumor necrosis factor, bradykinin, serine proteases, soluble thrombomodulin and clot lysis times [ 4 – 8 ], thereby contributing to microvascular and thrombotic disease [ 9 , 10 ]. A humoral immune response follows the innate reaction in critically ill COVID-19 patients, with robust production of SARS-CoV-2-specific antibodies [ 11 , 12 ].…”

Critically Ill COVID-19 Patients Exhibit Anti-SARS-CoV-2 Serological Responses

“…COVID-19 status was confirmed as part of standard hospital testing by detection of two SARS-CoV-2 viral genes using polymerase chain reaction (Roche SARS-CoV-2 PCR kits, Roche Diagnostics, Rotkreuz, Switzerland; FDA Authorized) [ 34 ]. Patient baseline characteristics were recorded on ICU admission and interventions were documented [ 5 , 6 , 7 , 15 , 22 , 23 ]. Disease severity scores were calculated [ 35 , 36 ].…”

“…Standard operating procedures were used to ensure all samples were treated rapidly and equally [ 5 , 6 , 7 , 15 , 22 , 23 , 39 ]. Daily blood was obtained from critically ill ICU patients via indwelling catheters using vacuum serum separator tubes and placed immediately on ice.…”

“…The IgM response is detected by 6–14 days after infection, while an IgG response begins shortly thereafter [ 13 ]. Serological studies in critically ill patients are few and limited by insufficient sampling time points and/or focus on only one immunoglobulin isotype [ 14 , 15 ].…”