A pilot study of 0.4% povidone-iodine nasal spray to eradicate SARS-CoV-2 in the nasopharynx
Rujipas Sirijatuphat, Amorn Leelarasamee, Thanapat Puangpet, Arunee Thitithanyanont
doi:10.1101/2022.08.18.22278340
We studied the virucidal efficacy of 0.4% povidone-iodine (PVP-I) nasal spray against SARS-CoV-2 in the patients' nasopharynx at 3 minutes and 4 hours after PVP-I exposure. We used an open-label, before and after design, single arm pilot study of adult patients with RT-PCRconfirmed COVID-19 within 24 hours. All patients received three puffs of 0.4% PVP-I nasal spray in each nostril. Nasopharyngeal (NP) swabs were collected before the PVP-I spray (baseline, left NP samples), and at 3 minutes (left and right NP samples) and 4 hours post-PVP-I spray (right NP samples). All swabs were coded to blind assessors and transported to diagnostic laboratory and tested by RT-PCR and cultured to measure the viable SARS-CoV-2 within 24 hours after collection. Fourteen patients were enrolled but viable SARS-CoV-2 was cultured from 12 patients (85.7%). The median viral titer at baseline was 3.5 log TCID 50 /mL (IQR 2.8-4.0 log TCID 50 /mL). At 3 minutes post-PVP-I spray via the left nostril, viral titers were reduced in 8 patients (66.7%). At 3 minutes post-PVP-I, the median viral titer was 3.4 log TCID 50 /mL (IQR 1.8-4.4 log TCID 50 /mL) (P=0.162). At 4 hours post-PVP-I spray via the right nostril, 6 of 11 patients (54.5%) had either the same or minimal change in viral titers. The median viral titer 3 minutes post-PVP-I spray was 2.7 log TCID 50 /mL (IQR 2.0-3.9 log TCID 50 /mL). Four hours post-PVP-I spray the median titer was 2.8 log TCID 50 /mL (IQR 2.2-3.9 log TCID 50 /mL) (P=0.704). No adverse effects of 0.4% PVP-I nasal spray were detected. We concluded that 0.4% PVP-I nasal spray demonstrated minimal virucidal efficacy at 3 minutes post-exposure. At 4 hours post-exposure, the viral titer was considerably unchanged from baseline in 10 cases. The 0.4% PVP-I nasal spray showed poor virucidal activity and is unlikely to reduce transmission of SARS-CoV-2 in prophylaxis use. .
Discussion The TCID 50 /mL of the 12 patients with culturable NP samples varied from 640 to 40,960, which was not related to either disease severity or the onset of clinical symptoms when NP swabs were taken. Because all cases recovered uneventfully, the initial values of TCID 50 /ml did not predict the treatment outcome. However, the sample size was small and we did not plan to study the relationship between the initial viral titers and disease severity or clinical outcome. We found a median one-fold reduction of SARS-CoV-2 viral titer from nasopharyngeal swabs at 3 minute post-PVP-I exposure in the left side of nasopharynx. This was in marked contrast to in vitro studies that reported as much as a 100-fold reduction in viral titer [5] . At 4 hour post-exposure to 0.4% PVP-I nasal spray, the viral titer in the right side of nasopharynx was unchanged from baseline in 10 cases. Although the in vitro rapid activity of PVP-I against SARS-CoV-2 has been established in several studies [5] [6] [7] , evidence of in vivo activity in humans is limited. Two studies have reported that PVP-I administration into the upper aerodigestive tract of COVID-19 patients was associated with lower SARS-CoV-2 viral load and Ct values [12, 13] . However, other studies have not confirmed their results [14] [15] [16] . To measure potential reductions in viral shedding, we believe that RT-PCR alone is insufficient and viral culture is needed. Using viral culture, PVP-I administration probably..
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