摘要:Background The COVID-19 pandemic has affected the health, economic, and social fabric of many nations worldwide. Identification of individual-level susceptibility factors may help people in identifying and managing their emotional, psychological, and social well-being. Objective This study is focused on learning a ranked list of factors that could indicate a predisposition to a mental disorder during the COVID-19 pandemic. Methods In this study, we have used a survey of 17,764 adults in the United States from different age groups, genders, and socioeconomic statuses. Through initial statistical analysis and Bayesian network inference, we have identified key factors affecting mental health during the COVID-19 pandemic. Integrating Bayesian networks with classical machine learning approaches led to effective modeling of the level of mental health prevalence. Results Overall, females were more stressed than males, and people in the age group 18-29 years were more vulnerable to anxiety than other age groups. Using the Bayesian network model, we found that people with a chronic mental illness were more prone to mental disorders during the COVID-19 pandemic. The new realities of working from home; homeschooling; and lack of communication with family, friends, and neighbors induces mental pressure. Financial assistance from social security helps in reducing mental stress during the COVID-19–generated economic crises. Finally, using supervised machine learning models, we predicted the most mentally vulnerable people with ~80% accuracy. Conclusions Multiple factors such as social isolation, digital communication, and working and schooling from home were identified as factors of mental illness during the COVID-19 pandemic. Regular in-person communication with friends and family, a healthy social life, and social security were key factors, and taking care of people with a history of mental disease appears to be even more important during this time.