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Sensitivity in Detection of Antibodies to Nucleocapsid and Spike Proteins of Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Coronavirus Disease 2019

Our take —

Results using the LIPS (luciferase immunoprecipitation system) assay provide high levels of sensitivity and specificity to antibodies using plasma samples >14 days since symptom onset, and could be used in addition to other serological testing. Additionally, heat inactivation did not impact assay performance and can be used to improve laboratory safety.

Study design

Cross-Sectional, Retrospective Cohort

Study population and setting

Blood samples were collected from 35 confirmed COVID-19 cases by PCR and 10 with COVID-19 like symptoms and/or who were household contacts of persons with COVID-19 (not tested). Samples were collected from four sites: University of California, San Diego (n=3); University of Washington, Seattle (n=17), Evergreen Health, Kirkland Washington (n=23) and National Institutes of Health Clinical Center, Bethesda, Maryland (n=6). Blood from blood bank donor controls collected prior to 2018 were collected from NIH Clinical Center (n=23). Samples were analyzed using the luciferase immunoprecipitation system assay (LIPS) to identify antibodies against nucleocapsid (N) and spike (S) proteins

Summary of Main Findings

Using the LIPS assay, 35/35 samples collected >14 days after symptom onset and 0/23 controls were seropositive for nucleocapsid antibodies (100% specificity and sensitivity) and 32/35 samples collected >14 days after symptom onset and 0/23 controls were seropositive for spike antibodies (91% sensitivity and 100% specificity). Samples <14 days after symptom onset had reduced sensitivity 33/65 were positive for nucleocapsid antibodies (51%) and 28/65 were positive for spike antibodies (43%). In patients with suspected COVID-19 (non-PCR tested), 9/10 tested negative for both nucleocapsid and spike antibodies, but 1 household contact of a RT-PCR confirmed SARS-CoV-2 infected individual tested positive for both nucleocapsid and spike antibodies. No differences in antibody levels was observed in heated versus unheated plasma samples

Study Strengths

This study compared performance of this assay of non-heat treated samples to heat-inactivated plasma samples. Tests analyzed antibody titers and dynamics against both spike and nucleocapid proteins using serial samples from some patients.


This study included a small number of cases focused on severe COVID-19 cases instead of including mild and/or asymptomatic cases. The conclusions are likely specific to IgG and do not provide insight into the titers and dynamics of IgM in this assay.

Value added

No difference in antibody levels in US-based patients between heat-inactivated plasma samples compared to untreated samples, indicating a way to protect lab workers. The study also provided insight into the higher sensitivity of assays targeting N compared to S. They also demonstrated a slower and lower overall titer antibody response among immunocompromised patients compared to immunocompetent patients, although the sample size was small

This review was posted on: 10 August 2020