The SARS-CoV-2 pandemic demonstrated the importance of proper understanding of the epidemiology of viral infections in the modern cosmopolitan world. In this retrospective study, we analyzed different factors associated with the spread of SARS-CoV-2 in the Sandanski municipality, a small and isolated region of Bulgaria, with a classical continental Mediterranean climate. We collected 418 serum samples from people without symptoms of SARS-CoV-2 infection or other respiratory diseases. The samples were tested for COVID-19 markers with qualitative and quantitative ELISA for anti-N and anti-S antibodies, and a rapid test for (IgM/G) antibodies. The methods were applied to complement each other with the different characteristics each of them has, thus allowing us to perform more accurate and more comprehensive detection of serum antibodies and to analyze the virus spread. We compared the results with the official government data for the SARS-CoV-2 distribution in Bulgaria. Based on the obtained results and available literature data, we discuss the importance of popular diagnostic methods, the role of the climate, the travel of people and pets, psychological stress and the individual reaction of subjects related to the spread of the virus.