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0 0.5 1 1.5 2+ Viral load, 3m left 33% Improvement Relative Risk Viral load, 3m right 88% Viral load, 4h right 83% Povidone-Iodine  Sirijatuphat et al.  EARLY TREATMENT Does povidone-iodine reduce short-term viral load for COVID-19? Prospective study of 12 patients in Thailand (Feb - Mar 2021) Improved viral load with povidone-iodine (not stat. sig., p=0.58) Sirijatuphat et al., medRxiv, August 2022 Favors povidone-iodine Favors control

A pilot study of 0.4% povidone-iodine nasal spray to eradicate SARS-CoV-2 in the nasopharynx

Sirijatuphat et al., medRxiv, doi:10.1101/2022.08.18.22278340, TCTR20210125002
Aug 2022  
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Small single-arm trial testing short-term viral load change after a single administration of three puffs of 0.4% PVP-I, showing lower viral titer at 3 minutes and 4 hours, not reaching statistical significance. Authors note that one reason for the lower change compared to in vitro results is that the spray administration may be less effective.
Analysis of short-term changes in viral load using PCR may not detect effective treatments because PCR is unable to differentiate between intact infectious virus and non-infectious or destroyed virus particles. For example Alemany, Tarragó‐Gil perform RCTs with cetylpyridinium chloride (CPC) mouthwash that show no difference in PCR viral load, however there was significantly increased detection of SARS-CoV-2 nucleocapsid protein, indicating viral lysis. CPC inactivates SARS-CoV-2 by degrading its membrane, exposing the nucleocapsid of the virus. To better estimate changes in viral load and infectivity, methods like viral culture or antigen detection that can differentiate intact vs. degraded virus are preferred.
This study is excluded in the after exclusion results of meta analysis: study only provides short-term viral load results.
viral load, 33.3% lower, relative load 0.67, p = 0.58, after median 2560.0 IQR 17790.0 n=12, before median 3840.0 IQR 9600.0 n=12, before values 640.0 640.0 40960.0 2560.0 10240.0 10240.0 640.0 2560.0 10240.0 5120.0 40960.0 640.0, after values 10.0 40.0 2560.0 40960.0 5120.0 1280.0 160.0 2560.0 40960.0 40960.0 10240.0 40.0, relative median viral titer, 3 min, left vs. baseline, Mann-Whitney, Table 3.
viral load, 87.5% lower, relative load 0.12, p = 0.04, after median 480.0 IQR 4340.0 n=12, before median 3840.0 IQR 9600.0 n=12, before values 640.0 640.0 40960.0 2560.0 10240.0 10240.0 640.0 2560.0 10240.0 5120.0 40960.0 640.0, after values 80.0 160.0 10240.0 320.0 320.0 10240.0 40.0 640.0 640.0 40960.0 2560.0 0.0, relative median viral titer, 3 min, right vs. baseline, Mann-Whitney, Table 3.
viral load, 83.3% lower, relative load 0.17, p = 0.11, after median 640.0 IQR 6240.0 n=12, before median 3840.0 IQR 9600.0 n=12, before values 640.0 640.0 40960.0 2560.0 10240.0 10240.0 640.0 2560.0 10240.0 5120.0 40960.0 640.0, after values 160.0 10.0 10240.0 640.0 160.0 1280.0 320.0 640.0 5120.0 40960.0 20480.0 0.0, relative median viral titer, 4 hours, right vs. baseline, Mann-Whitney, Table 3.
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Sirijatuphat et al., 22 Aug 2022, prospective, Thailand, preprint, median age 34.0, 4 authors, study period 15 February, 2021 - 15 March, 2021, trial TCTR20210125002.
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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
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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