COVID-19 Knowledge, Attitudes, and Practices and Perceived Risk: Cross-Sectional Mixed Methods Study.

Background: The COVID-19 pandemic was marked by rapidly evolving and inconsistent public health messaging, contributing to confusion regarding recommended preventive behaviors. Knowledge, attitudes, and practices (KAP) and perceived risk frameworks offer a structured approach to examine how education, personal beliefs, and contextual factors influence health behaviors during public health emergencies. Vulnerable populations, such as patients with multiple sclerosis (MS), experience heightened risk perception compared with the general population, which may further shape behavioral responses. Objective: This study aimed to examine COVID-19-related KAP and perceived risk among patients with MS, health care providers, and laypeople during the first 6 months of the pandemic. The aim of mixed methods was to explore quantitative factors associated with KAP and perceived risk and to qualitatively describe participants' perceptions and emotional responses to the pandemic. Methods: A descriptive, cross-sectional, partially mixed methods explanatory sequential design was used. Participants were recruited using convenience sampling and completed an online demographic questionnaire and a COVID-19 KAP instrument that included perceived risk items. Quantitative data were analyzed using descriptive statistics and inferential analyses to examine group differences and associations between perceived risk and preventive behaviors. Chi-square testing was applied to compare perceived risk across groups, and correlational analyses were used to examine the relationships between perceived risk and behavioral practices. Qualitative comments provided by participants were analyzed using thematic analysis to further contextualize quantitative findings and to explore perceived risk experiences. Results: A total of 148 participants were included, comprising 43 (29%) individuals with MS, 50 (33.8%) health care providers, and 55 (37.2%) laypeople. Overall, 90% (n=133) of participants demonstrated basic knowledge of COVID-19 transmission and prevention. Attitudes toward public health guidance and self-reported preventive behaviors varied across groups. Lay participants most frequently reported a moderate perceived risk of COVID-19 infection, whereas participants with MS and health care providers more commonly reported high perceived risk (χ²6=12.65, P=.049). Neither immunosuppressive treatment status nor vaccine hesitancy significantly predicted perceived risk. However, higher perceived risk was significantly associated with greater avoidance of crowded and public places. Qualitative analysis yielded 5 interrelated themes describing participants' perceived risk experiences: uncertainty related to evolving scientific information; anxiety regarding personal and family safety; fear of infection and long-term consequences; vulnerability, particularly among individuals with chronic illness and frontline exposure; and accountability toward protecting others through adherence to preventive measures. These themes provided contextual insight into the emotional and cognitive processes underlying reported attitudes and behaviors. Conclusions: Knowledge of COVID-19 is associated with favorable attitudes and engagement in preventive practices across populations. Differences in perceived risk highlight the importance of tailoring risk communication and educational strategies to specific populations. KAP-focused educational interventions that explicitly address uncertainty, emotional responses, and behavioral translation may strengthen preparedness and promote sustained protective behaviors during future public health emergencies.