Similar to many other viruses, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) causes various symptoms in individuals who have been exposed to the virus. Individuals exposed to the virus can be asymptomatic, mild, severe, and critical for mortality. Most hypotheses explaining the uncertainty of symptoms are based on innate immunity, which is unclear in explaining some issues. For example, 1. uncertain symptoms of SARS-CoV-2 infection, 2. failure to induce immunity for prevention by vaccines in some individuals, and 3. repeated infections in some individuals. With the ambition of explaining this clearly, this article proposed another perspective to explain the cause of uncertain symptoms in SARS-CoV-2-positive individuals. This could be influenced by host factors with a variety of cellular molecules (viral receptors/co-receptors) and major histocompatibility complex (MHC) polymorphisms, which are crucial factors in explaining this question. Hopefully, this perspective could encourage further research and pave the way for developing new public health policies to deal with COVID-19 and emergent viral epidemics in the future.