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). LumiraDx is 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, namely culture, Xpert MTB/RIF Ultra, or both.

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.