Comparability of venous and capillary blood measurements for a host-protein test differentiating bacterial from viral infections

Background MeMed BV (MMBV) is a host-protein test for discriminating between bacterial and viral infections. It was analytically and clinically validated in serum and whole blood samples. Here we investigated the comparability of venous versus capillary blood measurements of the MeMed BV score and of the composite TRAIL, IP-10 and CRP biomarkers.

A prospective cohort study enrolled adult patients presenting with suspected acute infection between Oct-2024 till Jan-2025 at three medical centers. Eligibility criteria were according to the MeMed BV’s instructions for use. Paired venous and capillary blood specimens were collected from each patient. Each sample (50 µL) was measured on MeMed Key® (MeMed, US) with a next generation MeMed BV cartridge. Passing-Bablok regression was used to evaluate the relationship between venous and capillary measurements for each biomarker and the MeMed BV score. For the MeMed BV score, the first accuracy requirement was that the slope should fall in the range 0.9-1.1 and the intercept in the range of −5 to 5. The second accuracy requirement was that the 95% confidence intervals for the bias at all score bin cutoffs should fall within the interval [−12.5,12.5]. The clinical acceptance criterion for the score was that less than 5% of the paired sample measurements should fall into non-adjacent score bins.

The study population comprised 58 patients with median age 58.5 (interquartile range: 36.25-75.75). Venous versus capillary blood measurements for TRAIL, IP-10 and CRP demonstrated high correlation with coefficients of 0.98, 0.98 and 0.99 respectively. For the MeMed BV score, the slope in the Passing-Bablok regression analysis was 1.00 (95% confidence interval, CI: 0.99 – 1.00) and the intercept 0.00 (0.00 – 0.08), satisfying the first accuracy requirement. The estimate of bias at each cutoff satisfied the second accuracy requirement: score 10, −0.57 (95%CI: −3.00 – 0.56); score 35, −0.47 (−2.10 – 0.38); score 65, −0.34 (−1.28 – 0.22); and score 90, −0.24 (−0.76 – 0.44). None of the paired samples generated MeMed BV scores falling into non-adjacent bins, satisfying the clinical criterion.

TRAIL, IP-10, CRP and MeMed BV score measurements are comparable in venous and capillary blood when performed using the next generation MeMed BV cartridge and MeMed Key. The present findings can serve as the basis for expanding MeMed BV’s use to include capillary blood specimens, potentially widening its clinical utility. Competing Interest Statement Husein Darawsha, Ayelet Raz and Salim Halabi declare that they have no competing interests. Mary Hainrichson, Nitzan Shamir, Naftalie Sederovich, Oded Shaham, Roy Navon, Tanya Gottlieb and Barak Hershovikz are employees of MeMed. Funding Statement The study was funded by MeMed. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of Lin Clinic, Clalit Health Services, Haifa, Israel gave ethical approval for this work (IRB 0001-24-COM1). Ethics committee/IRB of Rambam Health Care Campus, Haifa, Israel gave ethical approval for this work (IRB 0285-17-RMB). Ethics committee/IRB of Carmel Medical Center, Haifa, Israel have ethical approval for this work (IRB 0031-21-CMC). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes Competing Interest Statement: HD, AR and SH declare that they have no competing interests. MH, NSh, NSe, OS, RN, TG and BH are employees of MeMed. Funding: Comparability study was funded by MeMed. Data Availability All data produced in the present study are available upon reasonable request to the authors. Abbreviations - MMBV - MeMed BV - TRAIL TNF - TNF related apoptosis-inducing ligand - IP-10 - interferon-gamma inducible protein of 10 kDa - CRP - C-reactive protein - IQR - interquartile range - UCC - urgent care center - ED - emergency department - LoQ - limit of quantitation - CI - confidence interval.