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This study was conducted to evaluate the effect of HYSSOP (composed of Hyssopus officinalis L., Echium amoenum Fisch & C. A. Mey and Glycyrrhiza glabra L.) and POLIUM (contained Teucrium polium L., Cuscuta epithymum Murr and Cichorium intybus L.) combined distilled herbal medicines compared to placebo in the prevention of COVID-19. This is a double-blind parallel placebo-controlled field trial conducted on 751 asymptomatic individuals whose one of the family members recently had a positive RT-PCR test for COVID-19. They were divided into three groups including POLIUM, HYSSOP and placebo using random blocks with a 1:1:1 allocation ratio. Participants received daily 5 cc (under 12 years) or 10 cc (over 12 years) of allocated oral medications for 20 days. The primary outcome was the frequency of positive RT-PCR test among participants who became symptomatic. The mean age of participants was 36.6. Nineteen participants get infected by COVID-19 during the intervention; fifteen of them belonged to the placebo and four to the POLIUM group. Fisher's exact test indicated significant differences between HYSSOP and placebo (p<0.001) as well as POLIUM and placebo (p=0.009) groups in terms of COVID-19 confirmed by PCR tests. Cox regression model adjusted for confounders illustrated that the hazard of getting infection by COVID-19 in POLIUM and HYSSOP groups decreased by 66% (OR (95% CI): 0.34 (0.12 to 0.94); p=0.038) and 93% (OR (95% CI): 0.07 (0.01to 0.56); p=0.012) respectively, compared to placebo. Oral administration of HYSSOP and POLIUM with the other supportive health care could decrease the risk of getting COVID-19. [ABSTRACT FROM AUTHOR]