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

Amanda M Saravia-Butler; Jonathan C Schisler; Deanne Taylor; Afshin Beheshti; Dan Butler; Cem Meydan; Jonathon Foox; Kyle Hernandez; Chris Mozsary; Christopher E Mason; Robert Meller

doi:10.1016/j.isci.2022.105310

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

iScience. 2022 Nov 18;25(11):105310. doi: 10.1016/j.isci.2022.105310. Epub 2022 Oct 7.

Authors

Amanda M Saravia-Butler^{1

2

3}, Jonathan C Schisler^{3

4}, Deanne Taylor^{3

5

6}, Afshin Beheshti^{1

3

7}, Dan Butler⁸, Cem Meydan^{8

9}, Jonathon Foox^{8

9}, Kyle Hernandez^{3

10

11}, Chris Mozsary¹², Christopher E Mason^{3

8

9

13

12

14}, Robert Meller^{3

15}

Affiliations

¹ KBR, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USA.
² NASA Ames Research Center, Moffett Field, CA 94035, USA.
³ COVID-19 International Research Team, Medford, MA, USA.
⁴ McAllister Heart Institute, Department of Pharmacology, and Department of Pathology and Lab Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁵ Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
⁶ Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁷ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁸ Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, New York, NY, USA.
⁹ The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.
¹⁰ Department of Medicine, University of Chicago, Chicago, IL, USA.
¹¹ Center for Translational Data Science, University of Chicago, Chicago, IL, USA.
¹² The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
¹³ New York Genome Center, New York, NY, USA.
¹⁴ The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA.
¹⁵ Neuroscience Institute, Department of Neurobiology/ Department of Pharmacology and Toxicology; Morehouse School of Medicine, Atlanta, GA 30310, USA.

Abstract

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.

Keywords: Biological sciences; Immunology; Transcriptomics; Virology.

Abstract

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