The COVID-19 pandemic exposed the vulnerabilities of developing nations, particularly the Philippines, where geographic fragmentation and socio-demographic diversity posed unique challenges to disease control. As an archipelagic country composed of Luzon, Visayas, and Mindanao, the Philippines presents a distinct opportunity to examine how geographic, political, and cultural factors shape pandemic dynamics. While previous studies have focused on SARS-CoV-2 genomics, few have integrated epidemiological trends, mobility patterns, and viral evolution across the islands. This study addresses that gap by analyzing data from January 2020 to June 2022 to identify island-specific variations in COVID-19 transmission and response. Epidemiological records, mobility data, and SARS-CoV-2 genome sequences were processed using Python and R, with data completion via forward-filling and linear interpolation. Phylogenetic analyses were performed using Nextstrain. Results showed that early lockdowns reduced cases and deaths across all islands, with Luzon experiencing the most sustained improvements. Visayas and Mindanao showed higher mobility throughout, which may have contributed to delayed case reductions and greater mortality during the Delta wave. Luzon also saw earlier and sharper declines in severe cases and fatalities, possibly due to more efficient vaccine rollout. While overall viral evolution was similar across regions, minor genomic variations were noted in Visayas and Mindanao. This study offers the first comparative assessment of epidemiological, mobility, and genomic patterns across the three major Philippine islands. Findings emphasize the need to tailor public health strategies to regional contexts, supporting more responsive and resilient pandemic preparedness across geographically diverse nations.

The authors have declared no competing interest.

Our laboratory is supported by a grant-in-aid from the Philippine Council for Health Research and Development (PCHRD) of the Department of Science and Technology (DOST) of the Philippines.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

GISAID database Department of Health (DOH) of the Philippines

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data are available in the manuscript.