{"doi":"10.1002/alr.22703","title":"Interim analysis of an open‐label randomized controlled trial evaluating nasal irrigations in non‐hospitalized patients with coronavirus disease 2019","abstract":"Response to the coronavirus disease 2019 (COVID-19) pandemic has primarily focused on pharmacologic and medical interventions, including antivirals,1 convalescent sera,2 and vaccinations,3 with each potentially critical in the fight against COVID-19, particularly among high-risk and hospitalized populations. Non-hospitalized patients with mild to moderate disease comprise an estimated 81% of those affected with COVID-19,4 and there are currently no widely available interventions with proven ability to hasten symptom resolution or reduce viral shedding. We started an open-label randomized controlled trial (RCT) to evaluate the effect of nasal irrigation with hypertonic saline (HTS) or saline with surfactant on upper respiratory symptoms and viral load. Viral shedding is highest in the nasal cavity and nasopharynx,5 and prior RCTs of saline irrigations for the common cold, including non–severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) coronaviruses, have shown that saline rinses can reduce symptom burden and decrease viral shedding.6 We identified patients diagnosed with a positive qualitative real-time polymerase chain reaction (qRT-PCR) SARS-CoV-2 diagnostic test obtained from Vanderbilt University Medical Center and affiliated testing centers. Patients were enrolled in the study within 24 hours of testing and were given swabs, viral preservation media, and a symptom diary incorporating a modified version of the validated Wisconsin Upper Respiratory Symptom-21 Survey (WURSS-21) (Supplementary Fig. 1).7 Patients were randomized to 1 of 3 treatment arms: (1) twice-daily irrigation with 250 mL HTS; (2) twice-daily irrigation with HTS with 1% surfactant (HTSS); and (3) a nonintervention (NI) group (Supplementary Fig. 2). Participants performed scheduled mid-turbinate swabs and recorded daily temperatures and symptom scores over the 21-day study duration. A prior cross-sectional study found equivalent sensitivity and high correlation between patient-performed mid-turbinate swabs and nasopharyngeal swabs performed by healthcare workers.8 Comprehensive details of study methodology and power analysis are provided in the Methods section in the Supplementary Appendix. We performed an interim analysis on the first 45 patients with completed symptom questionnaires, which included 17 patients in the NI group, and 14 each in the HTS and HTSS groups (Supplementary Table 1). The groups were similar with respect to age, sex, comorbidities, and other demographic and/or clinical factors. The median number of symptomatic days before diagnosis ranged from 2.0 to 2.5 and did not differ between the groups. Study completion was also similar with 3 patients lost to follow-up in each treatment arm. The global symptom score for the question “How sick do you feel today,” continually declined during the study duration for all treatment groups (Fig. 1A), with a trend toward earlier time to symptom resolution in the intervention groups (median 14 days for NI, 10 days for HTS and HTSS; p = 0.16). There was a significant difference in median days to symptom resolution for nasal congestion (NI 14 days; HTS 5 days; HTSS 7 days; p = 0.04) and headache (NI, 12 days; HTS, 3 days; HTSS, 5 days; p = 0.02) (Fig. 1B, Table 1). Additionally, there was a trend toward differences between groups for cough (p = 0.19) and fatigue (p = 0.17). Comparison of viral load between groups is awaiting batch analysis and is pending completion of study enrollment. Nasal saline irrigation is a commonly accepted and inexpensive therapy with proven efficacy as a treatment for viral upper respiratory infections and has been proposed as a potentially beneficial treatment for COVID-19.9 Here, we present initial findings from the first RCT evaluating nasal irrigations in non-hospitalized patients with COVID-19. The effect of nasal irrigation on symptom resolution was substantial, with nasal congestion and headache resolving a median of 7 to 9 days earlier in the intervention grou","journal":"International Forum of Allergy & Rhinology","year":2020,"id":93446,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":40,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":350692,"name":"M.H. Freeman","orcid":"0000-0002-5232-8695","position":1,"is_corresponding":false},{"id":466282,"name":"Bronson C. Wessinger","orcid":"0000-0002-4195-6346","position":2,"is_corresponding":false},{"id":466283,"name":"Veerain Gupta","orcid":"0000-0002-6909-0361","position":3,"is_corresponding":false},{"id":86835,"name":"Quanhu Sheng","orcid":"0000-0001-8951-9295","position":4,"is_corresponding":false},{"id":395505,"name":"Li Huang","orcid":"0000-0002-8732-9129","position":5,"is_corresponding":false},{"id":466884,"name":"Kate Von Wahlde","orcid":null,"position":6,"is_corresponding":false},{"id":270036,"name":"Suman R. Das","orcid":"0000-0003-2496-9724","position":7,"is_corresponding":false},{"id":343813,"name":"Naweed I. Chowdhury","orcid":"0000-0001-9826-4917","position":8,"is_corresponding":false},{"id":343814,"name":"Justin H. Turner","orcid":"0000-0002-5501-9900","position":9,"is_corresponding":false},{"id":466281,"name":"Kyle S. Kimura","orcid":"0000-0002-9947-9626","position":0,"is_corresponding":true}],"reference_count":13,"raw_metadata":null,"created_at":"2026-07-18T22:30:54.208860Z","pmid":"32914928","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}