From the Oligonucleotide purUUpurU to Cytokine Storm, Elevated Blood Viscosity, and Complications of Coronavirus Disease 2019

Background Coronavirus disease 2019 (COVID-19) can be associated with pathologic inflammation. The authors hypothesize that a high copy number of a purine-uridine-rich nucleotide motif is present in the genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and hyperactivates innate immunity. Methods The number of purine-uridine-uridine-purine-uridine (purUUpurU) motifs was counted in the genomes of SARS-CoV-2 and other single-strand RNA viruses. The nucleotides of SARS-CoV-2 in random order were used as a control. Results PurUUpurU occurred 2.8 times more often in the actual SARS-CoV-2 genome than the randomized genome. The number of purUUpurU motifs correlates with the potential severity of acute illness caused by these viruses, except for influenza A. Conclusion The large number of purUUpurU in SARS-CoV-2 may hyperactivate innate immunity, potentially causing the markedly increased concentrations of cytokines, acute phase reactants, and blood viscosity that can be seen in COVID-19.