Virology: Omicron replication in explant cultures of human respiratory tract

Omicron replicates faster than other SARS-CoV-2 variants of concern in human bronchi tissue, which makes up the airways to the lungs, but less efficiently in the lung, according to a study published in Nature. These findings may help to elucidate the mechanisms underlying the severity of disease caused by Omicron.

Michael Chan and colleagues compared the replication ability of SARS-CoV-2 wild type and its variants D614G, Alpha, Beta, Delta and Omicron in cultures of human bronchus and lung tissue. The authors found that, over the first two days after infection, Omicron replicated substantially faster than all other SARS-CoV-2 variants (a 70-fold increase) in the bronchi — tubes that carry air from your windpipe to your lungs. Replication was less efficient in the lung tissue.

The authors did not see a difference in the types of cells infected with Omicron compared with other variants, but did see a difference in the dependency of Omicron infection on host proteases: infection with Omicron was more susceptible to inhibition of cathepsin proteins, which might indicate that it makes better use of the endocytic pathway of cell entry than other variants.

Whether the faster replication of Omicron in the conducting airways influences the transmission of the virus is unclear. Omicron also evades immunity from natural infection and vaccines, which probably contributes to its rapid transmission. But the lower viral replication in the lung (which was confirmed by immunohistochemistry analysis) suggests that Omicron may cause less-severe COVID-19 symptoms than the Delta variant; however, further research is needed.