BackgroundNasopharyngeal　carcinoma　(NPC)　is　prevalent　in　southern　China.　EBV　DNA　is　the　most　useful　biomarker　in　NPC.　However,　the　value　of　EBV　DNA　in　posttreatment　NPC　patients　infected　with　severe　acute　respiratory　syndrome　coronavirus　2　(SARS-CoV-2)　remains　unclear.MethodsSixty-four　eligible　NPC　patients　were　enrolled　between　December　2022　and　February　2023.　Patients　who　met　the　following　criteria　were　included:　had　non-metastatic　NPC,　completed　radical　treatment,　were　first　firstly　infected　with　SARS-CoV-2　and　their　EBV　DNA　changed　from　undetectable　to　detectable.ResultsAt　the　end　of　follow-up,　81.25%　(52/64)　of　patients　were　confirmed　not　to　relapse　with　undetectable　EBV　DNA　(no-relapse).　In　addition,　18.75%　(12/64)　of　patients　experienced　relapse　with　consistent　detection　of　EBV　DNA　(yes-relapse).　For　all　64　patients,　the　average　time　from　diagnosis　of　coronavirus　disease　2019　(COVID-19)　to　detection　of　detectable　EBV　DNA　was　35.41　days　(2　to　139　days).　For　52　no-relapse　patients,　the　average　time　from　EBV　DNA　changing　from　detectable　to　undetectable　was　63.12　days　(6　to　147　days).　The　levels　of　EBV　DNA　were　greater　in　yes-relapse　patients　than　that　in　no-relapse　patients,　and　the　average　of　EBV　DNA　levels　were　1216　copies/ml　and　53.18　copies/ml,　respectively.　Using　62.3　copies/mL　as　the　threshold,　the　area　under　the　curve　for　EBV　DNA　was　0.88　for　distinguishing　yes-relapse　patients　from　no-relapse　patients.　The　sensitivity　and　specificity　were　81.97%　(95%　CI　0.71-0.95)　and　86.67%　(95%　CI　0.70-0.95),　respectively.ConclusionFor　NPC　patients　infected　with　SARS-CoV-2,　EBV　DNA　alone　is　insufficient　for　monitoring　relapse　after　radical　therapy.　Long-term　follow-up　and　underlying　mechanistic　investigations　of　EBV　DNA　changes　are　urgently　needed.