SARS-CoV-2 Antibody Responses Do Not Predict COVID-19 Disease Severity

Abstract

Objectives: Initial reports indicate adequate performance of some serology-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assays. However, additional studies are required to facilitate interpretation of results, including how antibody levels impact immunity and disease course.

Methods: A total of 967 subjects were tested for IgG antibodies reactive to SARS-CoV-2, including 172 suspected cases of SARS-CoV-2, 656 plasma samples from healthy donors, 49 sera from patients with rheumatic disease, and 90 specimens from individuals positive for polymerase chain reaction (PCR)-based respiratory viral panel. A subgroup of SARS-CoV-2 PCR-positive cases was tested for IgM antibodies by proteome array method.

Results: All specificity and cross-reactivity specimens were negative for SARS-CoV-2 IgG antibodies (0/795, 0%). Positive agreement of IgG with PCR was 83% of samples confirmed to be more than 14 days from symptom onset, with less than 100% sensitivity attributable to a case with severe immunosuppression. Virus-specific IgM was positive in a higher proportion of cases less than 3 days from symptom onset. No association was observed between mild and severe disease course with respect to IgG and IgM levels.

Conclusions: The studied SARS-CoV-2 IgG assay had 100% specificity and no adverse cross-reactivity. Measures of IgG and IgM antibodies did not predict disease severity in our patient population.

Keywords: COVID-19; Coronavirus; Global health; Immunology; Microbiology; SARS-CoV-2.

Figure 1

Study cases. Nine-hundred and sixty-seven unique individuals provided samples for SARS-CoV-2 IgG testing, including 15 with serial samples available. IgM testing was performed on a group of 37 specimens (17 IgG+, 20 IgG–). CMV, cytomegalovirus; PCR, polymerase chain reaction.

Figure 2

IgM proteome array analysis. Array images of IgM+ and IgM– samples are shown (A) as well as a heatmap (B) of IgM anti–SARS-CoV-2 nucleocapsid protein (NCP) for IgG+ and IgG– cases of confirmed COVID-19. PCR, polymerase chain reaction.

Figure 3

Antibody levels by disease severity for polymerase chain reaction–positive subjects. A, SARS-CoV-2–specific IgG antibody results that were positive or negative were divided by disease severity and plotted against number of days from symptom onset (B). C, SARS-CoV-2 nucleocapsid–specific IgM antibody results were divided by IgG positivity to demonstrate when a sample was IgM+ but IgG–. D, IgM antibody levels were plotted against number of days from symptom onset. Middle line is the mean; bars represent standard deviation. The dotted lines represent negative cutoff levels. S/C, specimen/calibrator.

Figure 4

Serial IgG measurements. For patients with multiple samples taken, the IgG level was plotted against time from symptom onset. Dots represent the IgG level at a specific time. Samples from the same patient are connected by either red (severe cases, based on intensive care unit admission) or black (mild/moderate cases) lines. The dotted line indicates the threshold for a sample being positive. S/C, specimen/calibrator.