key: cord-0917963-72lwwuhm
authors: Tian, Di; Lin, Zhen; Kriner, Ellie M.; Esneault, Dalton J.; Tran, Jonathan; DeVoto, Julia C.; Okami, Naima; Greenberg, Rachel; Yanofsky, Sarah; Ratnayaka, Swarnamala; Tran, Nicholas; Livaccari, Maeghan; Lampp, Marla; Wang, Noel; Tim, Scott; Norton, Patrick; Scott, John; Hu, Tony Y.; Garry, Robert; Hamm, Lee; Delafontaine, Patrice; Yin, Xiao-Ming
title: Authors' Reply
date: 2021-12-30
journal: J Mol Diagn
DOI: 10.1016/j.jmoldx.2021.10.003
sha: 88af06ade52277fb5d96cc9e003eefb6dc7a0955
doc_id: 917963
cord_uid: 72lwwuhm

nan

We read with great interest the letter by Townsend and Wells 1 that has provided a robust discussion on the viral dynamics and its influence on the detection of virus in clinical samples. The major conclusion from our research is that the cycle threshold (Ct) values cannot predict the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmissibility. The need for a sensitive detection method is a secondary conclusion aiming to control the virus spread at the early stage, with no differential consideration on the Ct values. We agree that a more frequent and timed detection would be a better approach for Ct values to have a diagnostic value. However, it is unlikely that Ct values obtained from any more sensitive methods and/or from any more refined testing regimes have a clinical value in differentiating the spreaders from the nonspreaders because viral transmissibility is affected by many factors other than viral load at any given time. Other major impacting factors would include viral virulence, individual susceptibility, and human behaviors, to name just a few. This notion has been well expressed in our paper.

A diagnostic test for SARS-CoV-2 with limited transmission predictability may still be useful in detecting the virus earlier to help limit potential virus spread. Frequent testing, such as daily testing, may compensate for the low sensitivity of some assays as Townsend and Wells proposed on the understanding of viral dynamics. However, this approach may not be cost-effective, compliant, or may not alleviate the need for a sensitive detection method. A more sensitive method could certainly detect the presence of virus at the earlier phase of its expansion without the need to repeat the assay in subsequent days when a less sensitive method is employed. For example, our studies show that 13.8% of the spreaders had a Ct value above 32. These samples would most likely be tested negative using a less sensitive method. Currently there are many SARS-CoV-2 assays on the market that have a limit of detection ranging from 100 copies/mL to 10,000 copies/mL. A more sensitive method is more useful. Though the use of a more sensitive method and/or a more frequent testing regime may help to control viral spread through early detection, they do not negate the fact that Ct values alone could not predict the viral transmissibility.

The prognostic value of an RT-PCR test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is contingent on timing across disease time course rather than assay sensitivity