Intranasal SARS-CoV-2 infection of <i>hACE2</i>^fl/y mice confers weight loss and lethality reversed by Cre recombination.

(A) Experimental design for acute infection with SARS-CoV-2 virus. (B, C) Weight loss and survival of hACE2fl/y and hACE2del/y mice after infection with 105 viral titer per mouse. n = 8 for both genotypes, two independent experiments. (D, E) Weight loss and survival of hACE2fl/y and hACE2hypo/y mice after infection with 105 viral titer per mouse. n = 8 for both genotypes, two independent experiments. (F, G) Weight loss and survival of hACE2fl/y and hACE2Wentworth/y mice after infection with 105 PFU of SARS-CoV-2 virus. n = 8 (hACE2fl/y) and 5 (hACE2Wentworth/y), one experiment. (H, I) Weight loss and survival of littermate male and female hACE2fl/y mice after infection with 104 titer of SARS-CoV-2 virus. n = 11 (male) and 6 (female), one experiment. (J, K) Weight loss and survival of littermate male hACE2fl/y mice after infection with 105 titer of the USA-WA1 or Omicron BA.1 strains of SARS-CoV-2 virus. n = 10 (USA-WA1) and 7 (Omicron BA.1), two experiments. Note: Data for hACE2fl/y infections at 105 titer are reused throughout panels (B-E) in this figure as littermate controls were not applicable and infections done contemporaneously with the same viral stock. ns p > 0.05; *p p p p t test or log-rank Mantel Cox test. Numerical data in corresponding S1 Metadata tab. DPI, days postinfection; hACE2, human ACE2; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2.