COVID-19 has impacted millions of patients across the world. Molecular testing occurring now identifies the presence of the virus at the sampling site: nasopharynx, nares, or oral cavity.
RNA sequencing has the potential to establish both the presence of the virus and define the host's response in
COVID-19. Single center, prospective study of patients with
COVID-19 admitted to the intensive care unit where deep
RNA sequencing (> 100 million reads) of peripheral blood with computational biology analysis was done. All patients had positive SARS-CoV-2 PCR. Clinical data was prospectively collected. We enrolled fifteen patients at a single hospital. Patients were
critically ill with a mortality of 47% and 67% were on a
ventilator. All the patients had the SARS-CoV-2
RNA identified in the blood in addition to
RNA from other viruses, bacteria, and archaea. The expression of many immune modulating genes, including PD-L1 and PD-L2, were significantly different in patients who died from
COVID-19. Some
proteins were influenced by alternative transcription and splicing events, as seen in
HLA-C, HLA-E, NRP1 and NRP2. Entropy calculated from alternative RNA splicing and transcription start/end predicted mortality in these patients. Current upper respiratory tract testing for
COVID-19 only determines if the virus is present. Deep
RNA sequencing with appropriate computational biology may provide important prognostic information and point to therapeutic foci to be precisely targeted in future studies.