Increasing viral transmission paradoxically reduces progression rates to severe COVID-19 during endemic transition

Natural infection with SARS-CoV-2 or vaccination induces virus-specific immunity protecting hosts from infection and severe disease. While the infection-preventing immunity gradually declines, the severity-reducing immunity is relatively well preserved. Here, based on the different longevity of these distinct immunities, we develop a mathematical model to estimate courses of endemic transition of COVID-19. Our analysis demonstrates that high viral transmission unexpectedly reduces the rates of progression to severe COVID-19 during the course of endemic transition despite increased numbers of infection cases. Our study also shows that high viral transmission amongst populations with high vaccination coverages paradoxically accelerates the endemic transition of COVID-19 with reduced numbers of severe cases. These results provide critical insights for driving public health policies in the era of ‘living with COVID-19’. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement the Institute for Basic Science (IBS-R801-D2 to E.-C.S. and IBS-R029-C3 to J.K.K.), Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea HI20C0452 (J.Y.N.), National Research Foundation of Korea (NRF-2021R1A2C1095639 to S.C., NRF-2020R1F1A1A01066082 to B.C., and 2019H1A2A1075303 to H.H.) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript.