Abstract: Journal of Infection and Chemotherapy xxx (xxxx) xxx Contents lists available at ScienceDirect Journal of Infection and Chemotherapy journal homepage: www.elsevier.com/locate/jic Original Article Timing of REGEN-COV administration and progression to severe COVID-19 Tomoka Kadowaki a, *, Sato Imajou b, Naomi Matsumoto a, Soshi Takao a, Takashi Yorifuji a a b Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan COVID-19 Infection Control Group, Okayama Prefecture Department of Health and Social Welfare, Okayama, Japan A R T I C L E I N F O A B S T R A C T Keywords: REGEN-COV COVID-19 Timing of administration Severe disease Epidemiology Introduction: Several clinical trials have demonstrated that REGEN-COV (casirivimab and imdevimab) decreases the risk of hospitalization and death among COVID-19 patients. However, these trials did not evaluate the optimal timing of its administration, and evidence is limited regarding the relationship between the timing of administration and progression to severe COVID-19 among patients who receive REGEN-COV in a real-world setting. We examined the association between the timing of REGEN-COV administration and progression to severe COVID-19 among patients who received REGEN-COV in Japan. Methods: We included a total of 342 COVID-19 patients (37 hospitals) who received REGEN-COV between July 19 and September 30, 2021. We calculated the difference between the date of symptom onset and the date of administration as an indicator of the timing of REGEN-COV administration and determined progression to severe COVID-19 after REGEN-COV administration. We conducted a logistic regression analysis, adjusting for potential confounders. Results: The proportion of cases progressing to severe COVID-19 increased daily from symptom onset and sharply increased from day 5 of onset. The early administration (days 0–4) decreased the risk of progression to severity compared with late administration (after day 5), with an adjusted odds ratio of 0.29 (95% confidence interval: 0.11–0.56). Conclusions: The early administration of REGEN-COV was associated with a decreased risk of progression to severe COVID-19 when the delta variant was dominant. The present epidemiological findings indicate that this monoclonal antibody therapy should be implemented very early in the clinical course probably even for emerging variants such as omicron BA.2.