Host transcriptional responses in nasal swabs identify potential SARS-CoV-2 infection in PCR negative patients.

We analyzed RNA sequencing data from nasal swabs used for SARS-CoV-2 testing. 13% of 317 PCR-negative samples contained over 100 reads aligned to multiple regions of the SARS-CoV-2 genome. Differential gene expression analysis compares the host gene expression in potential false-negative (FN: PCR negative, sequencing positive) samples to subjects with multiple SARS-CoV-2 viral loads. The host transcriptional response in FN samples was distinct from true negative samples (PCR & sequencing negative) and similar to low viral load samples. Gene Ontology analysis shows viral load-dependent changes in gene expression are functionally distinct; 23 common pathways include responses to viral infections and associated immune responses. GO analysis reveals FN samples had a high overlap with high viral load samples. Deconvolution of RNA-seq data shows similar cell content across viral loads. Hence, transcriptome analysis of nasal swabs provides an additional level of identifying SARS-CoV-2 infection.
Competing Interests: Dr. Mason is a cofounder for Aevum (acquired by Onegevity), Biotia, BridgeOmics, Onegevity (acquired by Thorne HealthTech), as well as a current advisor, shareholder, or compensated speaker for Acuamark Diagnostics, Allen and Company, ArcBio, BGI/MGI, Bumrungrad International Hospital, Carverr, Color Genomics, Cowen, DNA Genotek, EdenRoc, Enzymetrics, Element Bio, Foresite Capital, F!nd Genomics, Genialis, GenPro, Ginger Network, Google, Homo Deus, iCareDx, JP Morgan, Illumina, Infectious Economics, Meenta, Merck, MilliporeSigma, Mirimus, Morgan Stanley, Nano-Lit, Nanostring, New England Biolabs, Nooma, Pandemic Response Lab, Promega, Pendulum Health, Poppy Health, QIAGEN, Roche, Seed, Tecan, Tempus Labs, Testing for America, Thermo Fisher, Torus, Twist Biosciences, UBS, Ursa Bio, WorldQuant, and Zymo Research.
(© 2022 The Authors.)