Ocular tropism of SARS-CoV-2 with retinal inflammation through neuronal invasion in animal models

Although ocular manifestations are commonly reported in patients with coronavirus disease 2019 (COVID-19), there is currently no consensus on ocular tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To investigate this, we infected K18-hACE2 mice with SARS-CoV-2 using various routes. We observed ocular manifestation and retinal inflammation with cytokine production in the eyes of intranasally (IN) infected mice. An intratracheal (IT) injection resulted in virus spread from the lungs to the brain and eyes via trigeminal and optic nerves. Ocular and neuronal invasion were confirmed by an intracerebral (IC) infection. Notably, eye-dropped (ED) virus did not infect the lungs and was undetectable with time. Using infectious SARS-CoV-2-mCherry clones, we demonstrated the ocular and neurotropic distribution of the virus in vivo by a fluorescence-imaging system. Evidence for the ocular tropic and neuroinvasive characteristics of SARS-CoV-2 was confirmed in wild-type Syrian hamsters. Our data provides further understanding of the viral transmission; SARS-CoV-2 clinical characteristics; and COVID-19 control procedures. SummarySARS-CoV-2 can spread from the respiratory tract to the brain and eyes via trigeminal and optic nerves in animal models. This ocular tropism of SARS-CoV-2 through neuronal invasion likely causes ocular manifestation and retinal inflammation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=148 SRC="FIGDIR/small/488607v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@151c2d5org.highwire.dtl.DTLVardef@ce3aeforg.highwire.dtl.DTLVardef@17f453aorg.highwire.dtl.DTLVardef@99e9c2_HPS_FORMAT_FIGEXP M_FIG C_FIG