# Whole Blood as a Sample Matrix in Homogeneous Time-Resolved Assay—Förster Resonance Energy Transfer-Based Antibody Detection

## TL;DR

This study shows that a new test called LFRET can detect antibodies in whole blood as effectively as in serum, making it a fast and versatile tool for assessing immune responses to infections and vaccines.

## Contribution

The study demonstrates the feasibility of using whole blood in LFRET assays for antibody detection, expanding the practicality of this method.

## Key findings

- LFRET showed strong correlation between serum and whole blood samples from confirmed COVID-19 patients.
- LFRET results in whole blood correlated moderately with ELISA results for samples up to 14 months post-diagnosis.
- Strong correlation was found between WB LFRET results and neutralizing antibody titers for samples up to 14 months post-diagnosis.

## Abstract

The protein-L-utilizing Förster resonance energy transfer (LFRET) assay enables mix-and-read antibody detection, as demonstrated for sera from patients with, e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Zika virus, and orthohantavirus infections. In this study, we compared paired serum and whole blood (WB) samples of COVID-19 patients and SARS-CoV-2 vaccine recipients. We found that LFRET also detects specific antibodies in WB samples. In 44 serum–WB pairs from patients with laboratory-confirmed COVID-19, LFRET showed a strong correlation between the sample materials. By analyzing 89 additional WB samples, totaling 133 WB samples, we found that LFRET results were moderately correlated with enzyme-linked immunosorbent assay results for samples collected 2 to 14 months after receiving COVID-19 diagnosis. However, the correlation decreased for samples >14 months after receiving a diagnosis. When comparing the WB LFRET results to neutralizing antibody titers, a strong correlation emerged for samples collected 1 to 14 months after receiving a diagnosis. This study also highlights the versatility of LFRET in detecting antibodies directly from WB samples and suggests that it could be employed for rapidly assessing antibody responses to infectious agents or vaccines.