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Vancomycin and digoxin are associated with potential toxicity and serum concentrations need to be monitored in certain patients. Previous reports suggested IgM paraproteins could interfere with vancomycin assays, and no paraprotein interference has been reported with digoxin assays. Here we present a suspected case of free-kappa light chains-mediated falsely low digoxin and vancomycin concentrations with Abbott particle-enhanced turbidimetric inhibition immunoassay (PETINIA) method. A 53-year-old patient received multiple doses of vancomycin and digoxin intravenously, but trough vancomycin and random digoxin concentrations repeatedly measured as <1.1 µg/mL and <0.2 ng/mL respectively with Abbott PETINIA method. Results from alternative methods showed concentrations reaching toxic levels and administration of the drugs was immediately terminated. A significantly elevated level of free-kappa light chains, possibly in polymeric form as suggested by protein electrophoresis result, was suspected to be the cause of falsely low results. During the laboratory investigation, absorbance curves revealed increased agglutination in the patient's samples in the latter part of the reaction, suggesting interfering substances led to production of turbidity after reagents were added. Protein-free filtration partially recovered the drugs with Abbott PETINIA. When drug concentrations do not correlate with clinical judgment, clinicians and pharmacists should consult clinical laboratories for investigation of potential interfering substances.
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INTRODUCTION: Serological testing is an important tool to assist with assessing the immune response to SARS-CoV-2 infections, the causative agent of COVID-19. A quantitative assay was recently developed by Abbott Laboratories to measures antibodies against the receptor binding domain of the spike protein. In addition to assessing disease prevalence, this assay is useful towards determining the scale and duration of the humoral response to infection and vaccination. Here we evaluated the clinical and analytical performance of the quantitative Abbott AdviseDx SARS-CoV-2 IgG II assay and characterized the longitudinal dynamics of the IgG response against SARS-CoV-2 in 402 infected individuals up to 322 days post-symptom onset. METHODS: To assess test sensitivity, 1257 serum specimens derived from 402 patients positive for SARS-CoV-2 by RT-PCR were analyzed on the Abbott Alinity platform. To evaluate test specificity, 394 specimens were tested from patients who were symptomatic but PCR negative for SARS-CoV-2, as well as 305 archived pre-pandemic samples. To further characterize test performance metrics, we evaluated assay precision and linearity. RESULTS: The Abbott AdviseDx SARS-CoV-2 IgG II assay exhibited diagnostic specificity of 99.02% using 305 pre - COVID-19 serum specimens and 98.73% using 394 PCR negative specimens. Using 1257 sequential serum samples collected from PCR-confirmed individuals, clinical test sensitivity of the assay was 39.7% at 3-7 days, 75.9% at 8-14 days, 95.6% at 15-21 days, and 98.7% at 4-5 weeks post-symptom onset. The assay is linear across the analytical measurement range claimed by the manufacturer (22-25,000 AU/mL) and exhibited good analytical precision. The median concentration of IgG increased steadily from <22 AU/mL at 3-7 days post-symptom onset, to a peak of 14,421 AU/mL at 6-7 weeks. Although antibody concentration started to decline at 8-9 weeks following symptom onset, all patients remained seropositive during the observation period. When the positivity rate of this assay was compared with the Abbott anti-NP IgG and EUROIMMUN anti-S1 IgG tests, clinical sensitivity of the Abbott AdviseDx SARS-CoV-2 IgG II assay was the highest at all time points with the exception of 4-5 weeks after symptom onset. CONCLUSION: The Abbott AdviseDx SARS-CoV-2 IgG II assay offers high test specificity and sensitivity across a broad reportable range. We anticipate this assay will be a useful towards quantitatively assessing the humoral immune response to COVID-19 infection and vaccination.