Interestingly, Omicron patients infected with BA.1 or BA.2 had detectable neutralizing antibody titers to BA.5, but these titers were lower than neutralization titers to BA.1 and BA.2. In striking contrast, both unvaccinated and vaccinated Omicron patients exhibited a more balanced ratio of Omicron virus neutralization compared to neutralization of ancestral strains. Delta infected patients that had been previously vaccinated with the WA1 containing COVID vaccine made equivalent responses to WA1 and Delta strains, but still had very low neutralizing antibody responses to Omicron strains. Our results show that unvaccinated Delta infected patients made a highly biased neutralizing antibody response towards the infecting Delta strain with slightly lower responses against the WA1 strain, but with strikingly lower titers against BA.1, BA.2, and BA.5. This information will be useful in selection of the SARS-CoV-2 strains to include in an updated vaccine. In this study, we have analyzed live virus neutralization titers against WA1, Delta, BA.1, BA.2, and BA.5 in 187 hospitalized patients infected with Delta or Omicron strains. As increasingly distinct variants circulate, debate continues regarding the value of adding novel variants to SARS-CoV-2 vaccines. Neutralizing antibody plays a key role in protective immunity against COVID-19.