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

<p>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.</p>