OBJECTIVES: The COVID-19 pandemic highlighted the need for data-driven decision making in managing public health crises. This study aims to extend previous research by incorporating infection-related mortality (IRM) to evaluate the discrepancies between seroprevalence data and infection rates reported to the Centers for Disease Control and Prevention (CDC), and to assess the implications for public health policy. STUDY DESIGN: We conducted a comparative analysis of seroprevalence data collected as part of an NIH study and CDC-reported infection rates across ten U.S. regions, focusing on their correlation with IRM calculations. METHODS: The analysis includes a revision of prior estimates of IRM using updated seroprevalence rates. Correlations were calculated and their statistical relevance assessed. RESULTS: Findings indicate that COVID-19 is approximately 2.7 times more prevalent than what CDC infection data suggest. Utilizing the lower CDC-reported rates to calculate IRM leads to a significant overestimation by a factor of 2.7. When both seroprevalence and CDC infection data are combined, the overestimation of IRM increases to a factor of 3.79. CONCLUSION: The study highlights the importance of integrating multiple data dimensions to accurately understand and manage public health emergencies. The results suggest that public health agencies should enhance their capacity for collecting and analyzing seroprevalence data regularly, given its stronger correlation with IRM than other estimates. This approach will better inform policy decisions and direct effective interventions.