Bioequivalence of C-reactive protein in fingerprick blood and serum measured using the point-of-care LumiraDx test for tuberculosis diagnosis in exposed contacts

Background: C-reactive protein (CRP) is recommended to screen people living with HIV (PLWH) for tuberculosis (TB). LumiraDxis a portable platform that uses fingerprick blood. How CRP compares in fingerprick blood and serum is unknown. Methods: CRP was measured in 1034 consecutively recruited contacts of people with TB using fresh fingerprick blood (LumiraDx at point-of-care) and stored (-80°C) serum [LumiraDx and cobas C‑Reactive Protein (Latex) High Sensitive (CRPHS) in laboratories]. Agreement was assessed using Lin's concordance correlation coefficient (CCC), Passing-Bablok (PB) regression, and Bland-Altman (BA) plots. Sensitivity and specificity for TB were evaluated in 156 contacts with microbiological reference standard information. Results: Strong agreement [CCC=0.85, PB slope -0.27 (95% confidence interval -0.82, 0.2), BA mean difference 1 (-1, 3)] was observed between LumiraDx on fingerprick blood and serum. Similar agreement occurred for serum CRPHS vs. LumiraDx on serum [0.79; 1.1 (-1.1, 2.3); 11 (9, 14)] or fingerprick blood [0.75; 1.3 (-0.6, 2.5); 10 (8, 13)]. Areas under the receiver operating characteristic curves (AUROCs)were 0.747 (0.595, 0.899) for fingerprick LumiraDx, 0.761 (0.628, 0.893) for serum LumiraDx and 0.775 (0.636, 0.914) for serum CRPHS. At >5 mg/L, all tests showed identical sensitivity [77%(70, 83)]. Specificities were 60% (53, 68), 64% (57, 72) and 50% (43, 58), respectively. Serum storage duration did not affect performance. Conclusions: LumiraDx CRP readouts on fingerprick blood and serum correlate closely. Stored serum can be used for LumiraDx CRP measurement. High sensitivity methods increase the proportion of people who screen false-positive. Funding: This project is part of the EDCTP2 programme supported by the European Union and received funding under grant agreement number RIA2018D-2509.