Comparison of longitudinal SARS-CoV-2 nasopharyngeal specimens reveals the transcriptomic COVIDome

Abstract

Introduction/ObjectiveSARS-Cov-2 is well established to introduce a cytokine-like storm among select individuals that results in multisystem failure and death. Comorbidities, age, oxygen status, and real-time appraisal of inflammatory markers in the blood have been used to risk stratify patients, however, these clinical markers do not comprehensively characterize the at-risk population or disease course. To understand the molecular underpinnings of the primary site of SARS-CoV-2 infection, here, we interrogated the transcriptomic profile of the nasopharyngeal tissue among paired SARS-CoV-2 specimens.Methods/Case ReportWe performed ribosomal depletion RNAseq on 24 primary samples, including 16 paired samples from 8 unique patients who converted between SARS-CoV-2 negative and positive status via clinical diagnostic qRT-PCR. Additional targeted qRT-PCR was performed for ACE2 and TMPRSS2 in an extension sample of 54 paired specimens from 27 unique patients who converted in their SARS-CoV-2 status on the basis of the qRT- PCR test. Differential gene expression, differential correlative expression with ACE2, and correlative expression with viral load was used to identify genes, which were integral to SARS-CoV-2 pathogenesis, so termed the COVIDome. Gene ontologies, pathways, and reactive infiltrate was assessed between specimens and compared with measures of clinical outcome using regression with appropriate correction for multiple hypotheses.Results (if a Case Study enter NA)We observed significant enrichment for ontologies of lymphocyte activation, specifically interferon gamma signaling; (P<1E-20) and platelet activation (P<1E-5). Genes specifically enriched across all three modules included: ADAMDEC1, EPSTI1, GRIP2, IRF7, KLHDC7B, OAS3, OASL, PIK3R4, RSAD2, and XAF1. Using CIBERSORT to approximate immune cell populations from bulk RNA, we observed and enrichment for CD4 immune cells, which was associated with viral status (P<0.01) while high-risk gene signatures were associated with measures of clinical outcome (P<0.05).ConclusionWe characterized the pathogenesis of SARS-CoV-2 in longitudinal nasopharyngeal samples of COVID- 19 patients and related these molecular manifestations with measures of clinical outcome. As proof of principal, our findings suggest additional study in a large, longitudinal extension sample is warranted to validate and assess molecular features of clinical outcome associated with SARS-CoV-2 infection.