Characterization of the expressed RNA variants from young patients with critical and non-critical SARS-CoV-2 infection.

Background: Since the COVID-19 outbreak emerged, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continuously evolved into variants with underlying mutations associated with increased transmissibility, potential escape from neutralizing antibodies, and disease severity. Although intensive research is ongoing worldwide to understand the emergence of SARS-CoV-2 variants, there is a lack of information on what constitutes the expressed RNA variants in critical and non-critical comorbidity-free young patients. The study sought  to characterize the expressed RNA variants from young patients with critical and non-critical forms of SARS-CoV-2 infection.

Methodology: The bulk ribonucleic acid (RNA) sequencing data with the identifier GSE172114 were downloaded from the Gene Expression Omnibus (GEO) database. The study participants were divided into critical, n = 46, and non-critical, n = 23. FastQC version 0.11.9 and Cutadapt version 3.7 were used to assess the read quality and perform adapter trimming, respectively. Spliced Transcripts Alignment to a Reference (STAR) version 2.7.10a was used to align reads to the human (hg38) reference genome. Genome Analysis Tool Kit (GATK) best practice was followed to call variants using the rnavar pipeline, part of the nf-core pipelines.

Results: Our research demonstrates that critical and non-critical SARS-CoV-2-infected individuals are characterized by a unique set of expressed RNA variants. The expressed gene variants are enriched on the innate immune response, specifically neutrophil-mediated immune response. On the other hand, the expressed gene variants are involved in both innate and cellular immune responses.

Conclusion: Deeply phenotyped comorbidity-free young patients with critical and non-critical SARS-CoV-2 infection are characterized by a unique set of expressed RNA variants. The findings in this study can inform the patient classification process in health facilities globally when admitting young patients infected with SARS-CoV-2.