Omicron sub-lineage BA.5 infection results in attenuated pathology in hACE2 transgenic mice

Omicron recently emerged sub-lineage BA.5, together with BA.4, caused a
5th wave of coronavirus disease (COVID-19) in South Africa and
subsequently emerged as a predominant strain globally due to its high
transmissibility. The lethality of BA.5 infection has not been studied in
acute hACE2 transgenic (hACE2.Tg) mice models. Here, we investigated
tissue-tropism and immuno-pathology induced by BA.5 infection in hACE2.Tg
mice. Our data show that intranasal BA.5 infection in hACE2.Tg mice result
in attenuated pulmonary infection and pathology with diminished
COVID-19-induced clinical and pathological manifestations. BA.5, similar
to Omicron (B.1.1.529), infection led to attenuated production of
inflammatory cytokines, anti-viral response and effector T cell response
as compared to the ancestral strain. Mice recovered from B.1.1.529
infection showed robust protection against BA.5 infection with reduced
lung viral load and pathology. Our data provide insights as to why BA.5
infection escapes previous SARS-CoV-2 exposure induced-T cell immunity but
may result in milder immuno-pathology and alleviated chances of
re-infectivity in Omicron-recovered individuals.