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
Affiliations
Amanda M. Saravia-Butler
KBR, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USA; NASA Ames Research Center, Moffett Field, CA 94035, USA; COVID-19 International Research Team, Medford, MA, USA
Jonathan C. Schisler
COVID-19 International Research Team, Medford, MA, USA; 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
Deanne Taylor
COVID-19 International Research Team, Medford, MA, USA; Department of Biomedical and Health Informatics, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Afshin Beheshti
KBR, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035, USA; COVID-19 International Research Team, Medford, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Dan Butler
Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, New York, NY, USA
Cem Meydan
Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, New York, NY, USA; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA
Jonathon Foox
Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, New York, NY, USA; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA
Kyle Hernandez
COVID-19 International Research Team, Medford, MA, USA; Department of Medicine, University of Chicago, Chicago, IL, USA; Center for Translational Data Science, University of Chicago, Chicago, IL, USA
Chris Mozsary
The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA
Christopher E. Mason
COVID-19 International Research Team, Medford, MA, USA; Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, New York, NY, USA; The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA; New York Genome Center, New York, NY, USA; The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA; The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA
Robert Meller
COVID-19 International Research Team, Medford, MA, USA; Neuroscience Institute, Department of Neurobiology/ Department of Pharmacology and Toxicology; Morehouse School of Medicine, Atlanta, GA 30310, USA; Corresponding author
Summary: 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.
