Rapid initiation of nasal saline irrigation to reduce severity in high-risk COVID+ outpatients: a randomized clinical trial compared to a national dataset observational arm

Abstract Importance SARS-CoV-2 enters the nasopharynx to replicate; nasal irrigation soon after diagnosis could reduce viral load and inhibit furin cleavage necessary for cell entry, thereby reducing morbidity and mortality. Objective To determine whether initiating nasal irrigation after COVID-19 diagnosis reduces hospitalizations and death in high-risk outpatients, and whether irrigant composition impacts severity. Design Unblinded randomized clinical trial of two nasal irrigation protocols in older outpatients PCR positive for SARS-CoV-2, with an observational arm using laboratory-confirmed cases in the CDC COVID-19 Case Surveillance dataset. Setting Single-lab community testing facility associated with the emergency department (ED) in Augusta, GA. Participants A consecutive sample of high-risk adults were enrolled within 24 hours of a positive COVID-19 test between September 24 and December 21 of 2020. Patients aged 55 and older were remotely consented. Among 826 screened, 321 of 694 eligible patients were unable to be reached, 294 refused participation, and 79 participants were enrolled. Interventions Participants were randomly assigned adding 2.5 mL povidone-iodine 10% or 2.5 mL sodium bicarbonate to 240 mL of isotonic nasal irrigation twice daily for 14 days. Main Outcomes and Measures The primary outcome was hospitalization or death from COVID-19 within 28 days of enrollment by daily self-report confirmed with phone calls and hospital records, compared to the CDC Surveillance Dataset covering the same time. Secondary outcomes compared symptom resolution by irrigant additive. Results Seventy-nine high-risk participants were enrolled (mean [SD] age, 64 [8] years; 36 [46%] women; 71% Non-Hispanic White), with mean BMI 30.3. Analyzed by intention-to-treat, by day 28, COVID-19 symptoms resulted in one ED visit and no hospitalizations in 42 irrigating with alkalinization, one hospitalization of 37 in the povidone-iodine group, (1.27%) and no deaths. Of nearly three million CDC cases, 9.47% were known to be hospitalized, with an additional 1.5% mortality in those without hospitalization data. The total risk of hospitalization or death (11%) was 8.57 times that of enrolled patients (SE=2.74; P=.006). 62 completed daily surveys (78%), averaging 1.8 irrigations/day. Eleven had irrigation complaints, and four discontinued. There were no significant differences by additive. Conclusion SARS-CoV-2+ participants initiating nasal irrigation were over 8 times less likely to be hospitalized than the national rate. Trial Registration ClinicalTrial.gov Identifier: NCT04559035 Author Approval All authors have filled out ICMJE and approved submission. Conflict of Interest Statement Materials were provided by Neilmed Inc. and Rhinosystems Inc. The study was supported by funding from the Bernard and Anne Gray Donor Advised Fund Community Foundation for Greater Atlanta, Neilmed Inc., and Rhinosystems. No authors have conflict of interest. Key Points Question After testing positive for COVID-19, will rapidly initiating nasal irrigation reduce the risk of morbidity and mortality compared to a national dataset? Findings A consecutive sample of 79 high-risk adults (mean age 64, BMI 30.3) were randomized to initiate one of two nasal irrigation protocols within 24 hours of a positive COVID-19 test. Compared to a CDC COVID-19 National Dataset observational arm, 1.27% of participants initiating twice daily nasal irrigation were hospitalized or died, compared to 11%, a significant difference. Meaning In high-risk outpatients testing positive for SARS-CoV-2 who initiated nasal irrigation rapidly after diagnosis, risk of hospitalization or death was eight times lower than national rates reported by the CDC.