key: cord-1010762-p0yaecsh authors: Beth Yacyshyn, Mary; Collins, James; Chua, Michelle; Siegwald, Angela; Yacyshyn, Sara; Briones-Pryor, Valerie; Yacyshyn, Bruce title: Feasibility study of Bismuth Subsalicylate (BSS) as an addition to standard of care for COVID-19 therapy date: 2022-03-30 journal: Curr Ther Res Clin Exp DOI: 10.1016/j.curtheres.2022.100667 sha: 63f4c8ffee589c32e77cc08b4ee8a85c2509b362 doc_id: 1010762 cord_uid: p0yaecsh nan CoV2 at one clinical site. BSS has been shown to have anti-bacterial and anti-viral activity (6, 7) . It has been incorporated into medications used for gastrointestinal indications and has been shown to impact SARS-CoV2 replication, specifically its helicase (6) (7) (8) (9) . This communication provides preliminary data on the clinical feasibility, acceptability of dosing, outcome measures, and staff/patient participation Nineteen patients received medication. Ten completed the three-day open label study, with no reports of an AE. Of the 9 who did not complete the study, 3 reported an AE, bloating and abdominal discomfort, 5 did not continue BSS after discharge due to transportation/distance issues from hospital affecting saliva/stool collection and 1 was inconclusive for salivary SARS-CoV2 throughout the 3 days. Seventeen of 19 patients receiving drug had personal contact with coordinator. Going forward plans to complete sample acquisition within a 3-hour distance radius need to be in place and mandatory in person coordinator contact needs to be emphasized. One/44 patient became medically unstable between consent and coordinator phone contact and was transferred to ICU. Completion of 48 BSS tablets was still challenging for the patients who completed the trial. Of the first 5 who completed the study only one finished 48 BSS tablets. In Jan 2021, a protocol amendment was filed to decrease the number of total tablets from 48 to 24. The last 5 patients followed this dosing regimen. Even with this adjustment the same things impacted full dose completion. Inpatient floor nurses would forget to give BSS tablets and the combination of baseline/day1 visit led to fewer tablets taken the first day. Mandatory daily personal supervision by coordinators with patients and floor nurses needs to be implemented for the randomized placebo-controlled study. Each day patients recorded their stool frequency, provided stool and saliva samples and scored 5 common COVID-19 symptoms: cough, headache, fatigue, shortness of breath (SOB). Patients were asked by the coordinator (phone or in person) to self-score (from 0-3) the 5 symptoms at baseline/day1 (before BSS), after 24 hours/day 2 and 48 hours/ day3. The final salivary testing and symptom scores were taken prior to last dose of BSS. The primary objective was to measure diarrhea. However, it became apparent after one month that diarrhea was not a typical COVID -19 symptom at our site. Two of 44 consented patients presented with diarrhea and after analysis, stool frequency did not change during the study period. Therefore, after study completion salivary viral clearance (negative RT-LAMP test) along with a patient's daily COVID-19 symptom scores became key assessments. Due to patients' forgetfulness and staff shortage, not all fecal samples were collected. Most limiting was lack of a 4 th day of sample collection or scoring. Going forward it will be clearly outlined with staff that final samples and scoring should be carried out 24 hours after completion of final BSS dosing. Two outpatients and 8 inpatients completed the study; those with incomplete dosing were all inpatients ( Table 1 ). The baseline 5-and 3-symptom patient scores are in Table 1 . Hypertension was the most reported pre-existing comorbidity. Pneumonia and/or pleural effusions were the most reported COVID-19-related morbidity. Inpatients took an average of 4 pre-existing medicines and were given an average of 6 new medicines (for COVID-19) in hospital. The two mildly afflicted outpatients were younger, had fewer pre-existing comorbidities but a higher BL COVID-19 symptom score, 7.5 ± 1.5 /15. At the end of the 3-day open-label BSS study the mean overall mean 5-symptom score decreased after 48 hours of drug, Table 1 . Cough, headache, and fatigue changed the most during BSS treatment ( Table 1) COVID antiviral pills: what scientists still want to know A SARS-CoV-2 protein interaction map reveals targets for drug repurposing COVID-19: Drug Targets and Potential Treatments One year update on the COVID-19 pandemic: Where are we now? Acta Trop Systematic Review and Meta-Analyses Assessment of the Clinical Efficacy of Bismuth Subsalicylate for Prevention and Treatment of Infectious Diarrhea Antimicrobial activity of bismuth subsalicylate on Clostridium difficile, Escherichia coli O157:H7, norovirus, and other common enteric pathogens Metallodrug ranitidine bismuth citrate suppresses SARS-CoV-2 replication and relieves virus-associated pneumonia in Syrian hamsters SARS-Coronavirus-2 Nsp13 Possesses NTPase and RNA Helicase Activities That Can Be Inhibited by Bismuth Salts The Gastrointestinal Tract Is an Alternative Route for SARS-CoV-2 Infection in a Nonhuman Primate Model We would like to thank University of Louisville and Jewish Hospital COVID floor nurses for their unwavering support of all the COVID patients and our study patients during a very busy and trying time. We would like to thank David Rubin MD and Jose Brum MD for their thoughtful insights and guidance and Nyles Claire Suer (suercn@wfu.edu), a library specialist, for writing support. She is a freelance writer and copyeditor with over 8 years of experience. This work was made possible by grant G3282 from Procter and Gamble.