Context: As a contagious acute respiratory disease, COVID-19 was announced by the World Health Organization (WHO) as a pandemic on 11 March 2020. The clinical manifestation of COVID-19 includes fever, cough, taste/smell loss, and acute respiratory distress syndrome (ARDS) due to viral pneumonia. The severity of symptoms varies among patients ranging from asymptomatic to acute pneumonia. Predicting patients at risk and disease severity in the different patients is controversial. The prevention of rapid progression of the disease, better prognosis, and decline of mortality are possible by knowing the risk factors of the disease. There is an essential question about different patients experiencing the infection from asymptomatic to acute disease. Methods: For this study, we searched the databases including ISI Web of Science, Scopus, and PubMed with a combination of keywords COVID-19, COVID-19 risk factors, COVID-19 causes, and personalized medicine in COVID-19. All studies related to our study were searched for data collection. Results: The clinical variability of COVID-19 infection is associated with various risk factors like age, sex, comorbidity, lifestyle, virus mutation, host immune response, and genetic background. Conclusions: The studies reported the significant heterogeneity in risk and outcome of COVID-19 infection among patients. Individualized therapy can occur by unraveling various phenotypes and underlying pathobiology of COVID-19 infection.