Highlights d BALF cell transcriptome indicates robust innate immune responses in COVID-19 patients d COVID-19 patients exhibit chemokine-dominant hypercytokinemia d ISGs are highly expressed in COVID-19 patients and exhibit pathogenic potential

Zhou et al. reported the discovery of RmYN02, a strain closely related to SARS-CoV-2, which is claimed to contain a natural PAA amino acid insertion at the S1/S2 junction of the spike protein at the same position of the PRRA insertion that has created a polybasic furin cleavage site in SARS-CoV-2. The authors support with their findings the theory that the furin cleavage site insertion present in SARS-CoV-2 is natural. Because no nucleotide alignment with closely related strains of the region coding for the supposed insertion is provided by Zhou et al., we have applied several alignment algorithms to search for the most parsimonious alignments. We conclude that RmYN02 does not contain an insertion at the S1/S2 junction when compared to its closest relatives at the nucleotide level, but rather a 6-nucleotide deletion and that the claimed PAA insertion is more likely to be the result of mutations. A close examination of RmYN02 sequencing records and assembly methods is wishful. In conclusion, SARS-CoV-2, with its 12-nucleotide insertion at the S1/S2 junction remains unique among its sarbecovirus relatives. Recently, Zhou et al. [1] reported the discovery of a novel coronavirus strain RmYN02, which the authors claim to contain a natural PAA amino acid insertion at the S1/S2 junction of the spike protein at the same position of the PRRA insertion that has created a polybasic furin cleavage site in severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2).