Genomic Biomarker Heterogeneities between SARS-CoV-2 and COVID-19

Area of Science:

• Genomics
• Infectious Disease Research
• Biomarker Discovery

Background:

• Distinguishing genes for SARS-CoV-2 infection versus COVID-19 disease is crucial but incomplete.
• Existing research has not fully differentiated the genetic responses to viral infection and the resulting disease.

Purpose of the Study:

• To identify critical genes involved in the transcriptional response to SARS-CoV-2 infection.
• To develop accurate gene classifiers for predicting COVID-19 disease status.
• To explore the distinct genetic signatures of viral infection and disease pathology.

Main Methods:

• Utilized a novel max-competing logistic classifier.
• Analyzed differential gene expression from NP/OP swab PCR samples.
• Validated findings across fourteen cohort studies (1481 samples), including breakthrough infections and Omicron variants.

Main Results:

• Identified ATP6V1B2 and IFI27 as critical genes in the transcriptional response to SARS-CoV-2 infection.
• A classifier combining these two genes demonstrated superior accuracy in predicting disease status compared to existing methods.
• A five-gene classifier significantly outperformed larger gene sets in prediction accuracy.
• Found significant differences in gene transcriptional response and functional effects between SARS-CoV-2 infection and COVID-19 antibodies.

Conclusions:

• ATP6V1B2 and IFI27 represent a new focus for combating the COVID-19 pandemic due to their predictive accuracy.
• These findings can elucidate causal links between SARS-CoV-2 infection and COVID-19 disease.
• The identified genes offer potential for developing targeted vaccines, antiviral drugs, and therapies.