Fig. 4: Modelling diagnostic advantage of FND assay compared to AuNPs.

a Viral load infection dynamics adapted from Killingley et al.²⁵ human challenge trial tracking viral load over the first 15 days of infection. Black line indicates mean patient viral load over time with grey region showing the 95% credible interval, using combined uncertainty from the assay thresholds and distribution of patient viral loads. The horizontal dashed lines represent mean assay thresholds at 10³ copies/mL for RT-PCR (grey), 5.6 × 10⁴ copies/mL for FND (red) and 3.5 × 10⁶ copies/mL for AuNP (black). The mean day of initial detection was 2.6 days [95% credible interval: 2.6–2.7] with the FND assay (vertical blue dashed line), and ~4.6 days [95% credible interval: 4.4–4.8] with AuNPs (vertical green dashed line). Taking the difference in means days shows that the FND assay can 2 days earlier [95% credible interval: 1.8-2.1], on average (unpaired two-tailed t-test, p-value < 0.0001, T = 25). The vertical shaded regions represent the gap between the detection of the 50^th percentile viral load (mean) patients (vertical dashed lines) and 95^th percentile patients with 95% confidence (vertical solid lines). We also show the FND assay could detect patients within 0.6 days of RT-PCR²⁵ (b) The left plot shows the percentage of cases detected with FND and AuNP assays over time, shown as solid lines. The dashed line indicates 95% of cases detected. The FND assay will detect infection in 95% of patients no later than 3.5 days compared to the AuNP assay ≤6.3 days, a 2.8 day diagnostic advantage for detection with FNDs. The right plot shows the difference between the two assays in days (diagnostic advantage, solid line) by percentage of cases detected. The FND assay is more sensitive, so is increasingly advantageous as you get to higher percentages of cases detected (including more low-viral load patients). The dashed line indicates 95% of patients detected. c Line graph shows data adapted from Frediani et al.⁴⁸, representing the proportion of patient samples within ranges Ct ≤ 25, 25 < Ct ≤ 30, and Ct > 30 on each day from symptom onset (day 0). The bar graph shows the sensitivity of each assay weighted by proportion of high, moderate, and low viral load samples detected each day. Compared to the AuNP assay (green), the FND assay (blue) could detect ~117% (2.2-fold) more patients on the first day of infection (symptom onset) and ~57% (1.6-fold) more patients the second day. Source data are provided as Source Data file.