question: Background: The number of COVID-19 infections worldwide has reached 10 million COVID-19 caused by SARS-CoV-2 is more contagious than SARS-CoV-1 There is a dispute about the origin of COVID-19 Study results showed that all SARS-CoV-2 sequences around the world share a common ancestor towards the end of 2019 Methods: Virus sequences from COVID-19 samples at the early time should be less diversifiable than those from samples at the later time because there might be more mutations when the virus evolutes over time The diversity of virus nucleotide sequences can be measured by the nucleotide substitution distance To explore the diversity of SARS-CoV-2, we use different nucleotide substitution models to calculate the distances of SARS-CoV-2 samples from 3 different areas, China, Europe, and the USA Then, we use these distances to infer the origin of COVID-19 Results: It is known that COVID-19 originated in Wuhan China and then spread to Europe and the USA By using different substitution models, the distances of SARS-CoV-2 samples from these areas are significantly different By ANOVA testing, the p-value is less than 2 2e-16 The analyzed results in most substitution models show that China has the lowest diversity, followed by Europe and lastly by the USA This outcome coincides with the virus transmission time order that SARS-CoV-2 starts in China, then outbreaks in Europe and finally in the USA Conclusion: The magnitude of nucleotide substitution distance of SARS-CoV-2 is closely related to the transmission time order of SARS-CoV-2 This outcome reveals that the nucleotide substitution distance of SARS-CoV-2 may be used to infer the origin of COVID-19