Comparing SARS-CoV-2 variants is harder than it sounds, because studies conducted years apart use different cell systems and different protocols. Researchers at the School of Public Health in the LKS Faculty of Medicine at HKU addressed this by testing Omicron variants from BA.1 through JN.1 side by side under identical laboratory conditions, using human airway, lung and intestinal tissue models. The resulting comparison reveals a change in tissue preference across the lineage.
The earlier variants behaved much as expected. BA.5, BA.5.2.1, XBB.1.5 and EG.5.1 all replicated efficiently in human respiratory tissues, with XBB.1.5 and EG.5.1 appearing better adapted for respiratory spread. EG.5.1 proved able to enter cells by two distinct pathways and showed enhanced growth in alveolar epithelial cells, consistent with its clinical prominence during the period it circulated.
The more recent variants diverged from that pattern. BA.2.86 and JN.1 replicated more effectively in intestinal tissue, and JN.1 grew in gut tissue while provoking relatively little inflammation, a combination that could allow it to persist without producing obvious symptoms. The team also concluded that airway organoids give more reliable results for studying viral entry, and that the proximal intestine is a more relevant model than the colon when investigating possible faecal transmission. Findings were published in Nature Communications.
For surveillance the implication is methodological as much as virological. If viral tropism is drifting away from the respiratory tract, then monitoring systems built entirely around respiratory sampling may become progressively less sensitive to what the virus is actually doing. The study also offers the field something it has largely lacked: a controlled baseline against which future variants can be measured.