At this point in the COVID-19 pandemic, there are vaccines available that can protect us against the virus. These vaccines work by creating antibodies that attach to spike proteins on the virus’ surface, inhibiting them from binding the angiotensin-converting enzyme-2 (ACE2) receptor on our cells. To date, all COVID-19 lineages infect our cells by attaching to these ACE-2 receptors. This research project presents probability estimates of a new COVID-19 lineage emerging that binds a receptor other than ACE-2. This research also discusses available research on COVID-19 in Indigenous communities and why Indigenous research is so important. The methods used in this study involve a literature review, MATLAB coding, and self-reflection. It was found that a 95% chance of a new COVID-19 lineage emerging that binds a receptor other than ACE-2 over the next decade is consistent with the observed data to date. This observation would render our current COVID-19 vaccines ineffective and could revert us to a pre-vaccine stage in the pandemic. This would have major consequences for Indigenous communities, as they have suffered from COVID-19 more than the general population. Despite this, Indigenous Peoples have remained strong by implementing coping strategies based on their own culture and traditions. Further Indigenous COVID-19 research is needed to support the inequities present in Indigenous communities but also recognize their strengths.