While NL63 has been hypothesized to be circulating within humans for longer than SARS-CoV or SARS-Cov-2 [33], the lack of adaptation further suggests that either NL63-like CVs have not been circulating within primates on an evolutionary timescale, or that it has always been a comparatively mild infection and does not warrant the possible fitness cost of ACE2 adaptations. The gene discussed is ACE2; the disease is infection.