Background: The third round of the global pulse survey demonstrated that the abrupt and rapid progression of the COVID-19 pandemic significantly disrupted childhood immunization in many countries. Although Cameroon has reported over 120,000 COVID-19 cases, the reported national childhood vaccination coverage during the pandemic seems to have increased compared to that during the pre-COVID-19 period. Indeed, the first dose of the diphtheria, tetanus, and pertussis-containing vaccine (DTP-1) coverage increased from 85.4% in 2019 to 87.7% in 2020, and DTP-3 coverage increased from 79.5% in 2019 to 81.2% in 2020. The paucity of literature on the impact of COVID-19 on childhood vaccination in COVID-19 hotspot regions poses a challenge in developing a context-specific immunization recovery plan, hence the need to conduct this study. Methodology: We conducted a cross-sectional study using 2019 (pre-pandemic period) and 2020 (pandemic period) district childhood immunization data from the DHIS-2 database, weighted using completeness for each data entry against regional data completeness in 2020. Based on COVID-19 incidence, two hotspot regions were selected, with all districts (56/56) included in the final analysis. The Chi-square test was used to compare DTP-1 and DTP-3 coverage during the pre-pandemic and pandemic periods. Results: In the two hotspot regions, 8247 children missed DTP-1, and 12,896 children did not receive DTP-3 vaccines in the pandemic period compared to the results from the pre-pandemic period. Indeed, there was a significant drop in DTP-1 and DTP-3 coverage of 0.8% (p = 0.0002) and 3.1% (p = 0.0003), respectively, in the Littoral Region. Moreover, the Centre Region reported a 5.7% (p < 0.0001) and 7.6% (p < 0.0001) drop in DTP-1 and DTP-3 coverage, respectively. Most districts in the hotspot regions reported a decline in childhood immunization access (62.5%) and utilization (71.4%). Indeed, in the Littoral Region, 46% (11/24) and 58% (14/24) of districts experienced decreased vaccination access and utilization, respectively. Meanwhile, 75% (24/32) and 81% (26/32) of districts in the Centre Region experienced a drop in vaccination access and utilization, respectively. Conclusion: This study reported a situation where the national immunization indicators mask the impact of COVID-19 on childhood immunization in heavily hit regions. Therefore, this study presents valuable information for ensuring continuous vaccination service delivery during public health emergencies. The findings could also contribute to developing an immunization recovery plan and informing policy on future pandemic preparedness and response.

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