Efficacy of nasal irrigation and oral rinse with sodium bicarbonate solution on virus clearance for COVID-19 patients.

Background: Recent studies have shown that the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is reduced under alkaline conditions. The purpose of this study is to assess the effect of nasal irrigation and oral rinse with sodium bicarbonate solution on virus clearance among COVID-19 patients. Materials and methods: COVID-19 patients were recruited and randomly divided into two group, i.e., the experimental group and the control group. The experimental group received regular care plus nasal irrigation and oral rinse with 5% sodium bicarbonate solution, while the control group only received regular care. Nasopharyngeal and oropharyngeal swab samples were collected daily for reverse transcription-polymerase chain reaction (RT-PCR) assays. The negative conversion time and hospitalization time of the patients were recorded, and the results were statistically analyzed. Results: A total of 55 COVID-19 patients with mild or moderate symptoms were included in our study. There was no significant difference in gender, age and health status between the two groups. The average negative conversion time was 1.63 days after treatment with sodium bicarbonate, and the average hospitalization time of the control group and the experimental group were 12.53 and 7.7 days, respectively. Conclusions: Nasal irrigation and oral rinse with 5% sodium bicarbonate solution is effective in virus clearance for COVID-19 patients.

Effect of the povidone iodine, hypertonic alkaline solution and saline nasal lavage on nasopharyngeal viral load in COVID-19.

OBJECTIVE: The present study aimed to investigate the in vivo activity of nasal irrigation (NI) with saline, NI with povidone-iodine (PVP-I) 1%, NI with a mix of hypertonic alkaline and PVP-I 1% against Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). DESIGN: This study was a prospective randomised clinical trial. SETTING: A multicenter study involving tertiary care centres. PARTICIPANTS: The study included adult outpatients whose qualitative SARS-CoV-2 RT-PCR tests in nasopharyngeal swabs were positive. One hundred twenty patients were divided into four equal groups. Standard COVID-19 treatment was given to Group 1, NI containing saline was added to patients' treatment in Group 2, NI containing 1% PVP-I solution was added to patients' treatment in Group 3, and NI containing 1% PVP-I solution and the hypertonic alkaline solution was added to patients' treatment in Group 4. MAIN OUTCOME MEASURES: On the first day of diagnosis (Day 0), nasopharyngeal swab samples were taken, on the third and fifth days the nasopharyngeal viral load (NVL) reduction in quantitative RT-PCR test was calculated. RESULTS: Between the zeroth to third days and zeroth to fifth days, the NVL reduction was significant in all groups (p < .05). In paired comparisons of groups, the NVL decrease in Group 4 in the first 3 days was significantly lower than all groups (p < .05). The NVL decrease in Groups 3 and 4 in the first 5 days were significantly lower than Group 1 (p < .05). CONCLUSION: This study revealed that the use of NI of 1% PVP-I and the hypertonic alkaline solution mixture was more effective in reducing NVL.

Effect of nasal irrigation in adults infected with Omicron variant of COVID-19: A quasi-experimental study.

Objective: To investigate the effect of nasal irrigation on the duration of symptoms and nucleic acid conversion in adults infected with the Omicron variant of COVID-19. Methods: This quasi-experimental study enrolled patients diagnosed with asymptomatic, mild, or moderate Omicron infection at the Shandong Public Health Clinical Center between April 1, 2022 and May 1, 2022. Patients were divided into two groups to receive Lianhua Qingwen granules and traditional Chinese medicine (TCM) prescriptions (conventional group) and 3% hypertonic saline nasal irrigation based on conventional treatment (nasal irrigation groups), respectively. Primary outcomes were symptom disappearance time and nucleic acid negative conversion time. Secondary outcomes were peripheral blood white blood cell (WBC), lymphocyte (LYM) count, neutrophil (NEU) count, C-reactive protein (CRP) level, and chest CT examination findings. Results: Eighty patients were included (40 patients/group). Multiple linear regression analysis showed that, after adjustment for comorbidities, smoking history, LYM count, and Ct values of N gene, the patients in the nasal irrigation group were more likely to get lower nucleic acid negative conversion time (ß = -11.052, 95% CI: -8.277-13.827, P < 0.001) compared with the conventional group. The symptom disappearance time showed no significant improvement (P > 0.05). Subgroup analysis for treatment-naïve patients in the nasal irrigation group showed similar nucleic acid negative conversion time improvement (P = 0.038). Conclusion: Early nasal irrigation shortens the nucleic acid negative conversion time in adults infected with the Omicron variant but without improvements in symptom disappearance time.

Efficacy and safety of a hypertonic seawater nasal irrigation solution containing algal and herbal natural ingredients in patients with COVID-19.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of using a hypertonic seawater nasal irrigation solution comprising natural ingredients (HSS-Plus) with the aim of reducing viral load and ameliorating nasal symptoms in cases of COVID-19. PATIENTS AND METHODS: This single-center, prospective, single-arm, low-intervention study evaluated daily use of HSS-Plus in patients admitted to the Sotiria Hospital, Athens, Greece for a period of up to 10 days or until hospital discharge. Viral load measurements in nasopharyngeal swabs were performed on days 0 (baseline), 3 and 6, and on the final day of participation (day 10 ± 2; hospital discharge). In addition, study participants were asked to rate the severity of nasal and other symptoms using Visual Analog Scales (VAS) at the same time points. At the final day, the patients also assessed the perceived use benefit of HSS-Plus. RESULTS: 47 patients were enrolled in the study; 93.6% had a decrease in viral load of at least > 0.5 log10 on day 10 (p<0.001). Compared to values before nasal irrigation, viral load in nasopharyngeal swabs increased immediately after nasal lavage on days 3 (p=0.037) and 6 (p=0.010), indicating efficient removal of viral particles from the nasal cavity. Mean VAS symptoms' total score was reduced from 27.57 ± 15.63 at baseline to 6.73 ± 6.59 after 10 days (p<0.001). Similar reductions were also evident for individual symptoms at all time points (p<0.005). No adverse events were reported in the study. CONCLUSIONS: HSS-Plus nasal irrigation is an effective and safe method for reducing viral load and providing symptom relief in patients with COVID-19.

Can nasal irrigation with chlorine dioxide be considered as a potential alternative therapy for respiratory infectious diseases? The example of COVID-19.

Chlorine dioxide (ClO2) is a high-level disinfectant that is safe and widely used for sterilization. Due to the limitations on preparing a stable solution, direct use of ClO2 in the human body is limited. Nasal irrigation is an alternative therapy used to treat respiratory infectious diseases. This study briefly summarizes the available evidence regarding the safety/efficacy of directly using ClO2 on the human body as well as the approach of nasal irrigation to treat COVID-19. Based on the available information, as well as a preliminary experiment that comprehensively evaluated the efficacy and safety of ClO2, 25-50 ppm was deemed to be an appropriate concentration of ClO2 for nasal irrigation to treat COVID-19. This finding requires further verification. Nasal irrigation with ClO2 can be considered as a potential alternative therapy to treat respiratory infectious diseases, and COVID-19 in particular.

Efficacy and Safety of Saline Nasal Irrigation Plus Theophylline for Treatment of COVID-19-Related Olfactory Dysfunction: The SCENT2 Phase 2 Randomized Clinical Trial.

Importance: Recent studies suggest that theophylline added to saline nasal irrigation (SNI) can be an effective treatment for postviral olfactory dysfunction (OD), a growing public health concern during the COVID-19 pandemic. Objective: To evaluate the efficacy and safety of theophylline added to SNI compared with placebo for COVID-19-related OD. Design, Setting, and Participants: This triple-blinded, placebo-controlled, phase 2 randomized clinical trial was conducted virtually between March 15 and August 31, 2021. Adults residing in Missouri or Illinois were recruited during this time period if they had OD persisting for 3 to 12 months following suspected COVID-19 infection. Data analysis was conducted from October to December 2021. Interventions: Saline sinus rinse kits and bottles of identical-appearing capsules with either 400 mg of theophylline (treatment) or 500 mg of lactose powder (control) were mailed to consenting study participants. Participants were instructed to dissolve the capsule contents into the saline rinse and use the solution to irrigate their nasal cavities in the morning and at night for 6 weeks. Main Outcomes and Measures: The primary outcome was the difference in the rate of responders between the treatment and the control arms, defined as a response of at least slightly better improvement in the Clinical Global Impression-Improvement scale posttreatment. Secondary outcome measures included changes in the University of Pennsylvania Smell Identification Test (UPSIT), the Questionnaire for Olfactory Disorders, the 36-Item Short Form Health Survey on general health, and COVID-19-related questions. Results: A total of 51 participants were enrolled in the study; the mean (SD) age was 46.0 (13.1) years, and 36 (71%) participants were women. Participants were randomized to SNI with theophylline (n = 26) or to SNI with placebo (n = 25). Forty-five participants completed the study. At the end of treatment, 13 (59%) participants in the theophylline arm reported at least slight improvement in the Clinical Global Impression-Improvement scale (responders) compared with 10 (43%) in the placebo arm (absolute difference, 15.6%; 95% CI, -13.2% to 44.5%). The median difference for the UPSIT change between baseline and 6 weeks was 3.0 (95% CI, -1.0 to 7.0) for participants in the theophylline arm and 0.0 (95% CI, -2.0 to 6.0) for participants in the placebo arm. Mixed-model analysis revealed that the change in UPSIT scores through study assessments was not statistically significantly different between the 2 study arms. Eleven (50%) participants in the theophylline arm and 6 (26%) in the placebo arm had a change of 4 or more points in UPSIT scores from baseline to 6 weeks. The difference in the rate of responders as measured by the UPSIT was 24% (95% CI, -4% to 52%) in favor of theophylline. Conclusions and Relevance: This randomized clinical trial suggests that the clinical benefit of theophylline nasal irrigations on olfaction in participants with COVID-19-related OD is inconclusive, though suggested by subjective assessments. Larger studies are warranted to investigate the efficacy of this treatment more fully. Trial Registration: ClinicalTrials.gov Identifier: NCT04789499.

Human nasal wash RNA-Seq reveals distinct cell-specific innate immune responses in influenza versus SARS-CoV-2.

BACKGROUNDInfluenza A virus (IAV) and SARS-CoV-2 are pandemic viruses causing millions of deaths, yet their clinical manifestations are distinctly different.METHODSWith the hypothesis that upper airway immune and epithelial cell responses are also distinct, we performed single-cell RNA sequencing (scRNA-Seq) on nasal wash cells freshly collected from adults with either acute COVID-19 or influenza or from healthy controls. We focused on major cell types and subtypes in a subset of donor samples.ResultsNasal wash cells were enriched for macrophages and neutrophils for both individuals with influenza and those with COVID-19 compared with healthy controls. Hillock-like epithelial cells, M2-like macrophages, and age-dependent B cells were enriched in COVID-19 samples. A global decrease in IFN-associated transcripts in neutrophils, macrophages, and epithelial cells was apparent in COVID-19 samples compared with influenza samples. The innate immune response to SARS-CoV-2 appears to be maintained in macrophages, despite evidence for limited epithelial cell immune sensing. Cell-to-cell interaction analyses revealed a decrease in epithelial cell interactions in COVID-19 and highlighted differences in macrophage-macrophage interactions for COVID-19 and influenza.ConclusionsOur study demonstrates that scRNA-Seq can define host and viral transcriptional activity at the site of infection and reveal distinct local epithelial and immune cell responses for COVID-19 and influenza that may contribute to their divergent disease courses.FundingMassachusetts Consortium on Pathogen Readiness, the Mathers Foundation, and the Department of Defense (W81XWH2110029) "COVID-19 Expansion for AIRe Program."

Exercise duration modulates upper and lower respiratory fluid cellularity, antiviral activity, and lung gene expression.

Exercise has substantial health benefits, but the effects of exercise on immune status and susceptibility to respiratory infections are less clear. Furthermore, there is limited research examining the effects of prolonged exercise on local respiratory immunity and antiviral activity. To assess the upper respiratory tract in response to exercise, we collected nasal lavage fluid (NALF) from human subjects (1) at rest, (2) after 45 min of moderate-intensity exercise, and (3) after 180 min of moderate-intensity exercise. To assess immune responses of the lower respiratory tract, we utilized a murine model to examine the effect of exercise duration on bronchoalveolar lavage (BAL) fluid immune cell content and lung gene expression. NALF cell counts did not change after 45 min of exercise, whereas 180 min significantly increased total cells and leukocytes in NALF. Importantly, fold change in NALF leukocytes correlated with the post-exercise fatigue rating in the 180-min exercise condition. The acellular portion of NALF contained strong antiviral activity against Influenza A in both resting and exercise paradigms. In mice undergoing moderate-intensity exercise, BAL total cells and neutrophils decreased in response to 45 or 90 min of exercise. In lung lobes, increased expression of heat shock proteins suggested that cellular stress occurred in response to exercise. However, a broad upregulation of inflammatory genes was not observed, even at 180 min of exercise. This work demonstrates that exercise duration differentially alters the cellularity of respiratory tract fluids, antiviral activity, and gene expression. These changes in local mucosal immunity may influence resistance to respiratory viruses, including influenza or possibly other pathogens in which nasal mucosa plays a protective role, such as rhinovirus or SARS-CoV-2.

Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction.

BACKGROUND: Olfactory dysfunction is an early and sensitive marker of COVID-19 infection. Although self-limiting in the majority of cases, when hyposmia or anosmia persists it can have a profound effect on quality of life. Little guidance exists on the treatment of post-COVID-19 olfactory dysfunction, however several strategies have been proposed from the evidence relating to the treatment of post-viral anosmia (such as medication or olfactory training). OBJECTIVES: To assess the effects (benefits and harms) of interventions that have been used, or proposed, to treat persisting olfactory dysfunction due to COVID-19 infection. A secondary objective is to keep the evidence up-to-date, using a living systematic review approach.  SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane COVID-19 Study Register; Cochrane ENT Register; CENTRAL; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies. The date of the search was 16 December 2020. SELECTION CRITERIA: Randomised controlled trials including participants who had symptoms of olfactory disturbance following COVID-19 infection. Only individuals who had symptoms for at least four weeks were included in this review. Studies compared any intervention with no treatment or placebo. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Primary outcomes were the recovery of sense of smell, disease-related quality of life and serious adverse effects. Secondary outcomes were the change in sense of smell, general quality of life, prevalence of parosmia and other adverse effects (including nosebleeds/bloody discharge). We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included one study with 18 participants, which compared the use of a 15-day course of oral steroids combined with nasal irrigation (consisting of an intranasal steroid/mucolytic/decongestant solution) with no intervention. Psychophysical testing was used to assess olfactory function at baseline, 20 and 40 days. Systemic corticosteroids plus intranasal steroid/mucolytic/decongestant compared to no intervention Recovery of sense of smell was assessed after 40 days (25 days after cessation of treatment) using the Connecticut Chemosensory Clinical Research Center (CCCRC) score. This tool has a range of 0 to 100, and a score of ≥ 90 represents normal olfactory function. The evidence is very uncertain about the effect of this intervention on recovery of the sense of smell at one to three months (5/9 participants in the intervention group scored ≥ 90 compared to 0/9 in the control group; risk ratio (RR) 11.00, 95% confidence interval (CI) 0.70 to 173.66; 1 study; 18 participants; very low-certainty evidence). Change in sense of smell was assessed using the CCCRC score at 40 days. This study reported an improvement in sense of smell in the intervention group from baseline (median improvement in CCCRC score 60, interquartile range (IQR) 40) compared to the control group (median improvement in CCCRC score 30, IQR 25) (1 study; 18 participants; very low-certainty evidence). Serious adverse events andother adverse events were not identified in any participants of this study; however, it is unclear how these outcomes were assessed and recorded (1 study; 18 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: There is very limited evidence available on the efficacy and harms of treatments for persistent olfactory dysfunction following COVID-19 infection. However, we have identified other ongoing trials in this area. As this is a living systematic review we will update the data regularly, as new results become available. For this (first) version of the living review we identified only one study with a small sample size, which assessed systemic steroids and nasal irrigation (intranasal steroid/mucolytic/decongestant). However, the evidence regarding the benefits and harms from this intervention to treat persistent post-COVID-19 olfactory dysfunction is very uncertain.

A Concept for the Reduction of Mucosal SARS-CoV-2 Load using Hypochloric Acid Solutions.

During the next few months or years, vaccination against SARS-CoV-2 infection will significantly reduce the morbidity and mortality of COVID-19. However, additional measures are needed to protect those who are still not immunized. This is even more important in view of new viral mutations that result in increased transmission rates. We propose that the use of long-standing medicinal solutions based on hypochloric acid (HOCl) and intended for application on wounds may be effective as a gargling solution or nasal irrigation in blocking transmission of the virus. Here, we propose the use of HOCl-containing solutions for blocking the transmission of SARS-CoV-2 in combination with other prevention measures. This may constitute another important cornerstone in the fight against the COVID-19 pandemic.

Essentials in saline pharmacology for nasal or respiratory hygiene in times of COVID-19.

PURPOSE: Nasal irrigation or nebulizing aerosol of isotonic or hypertonic saline is a traditional method for respiratory or nasal care. A recent small study in outpatients with COVID-19 without acute respiratory distress syndrome suggests substantial symptom resolution. We therefore analyzed pharmacological/pharmacodynamic effects of isotonic or hypertonic saline, relevant to SARS-CoV-2 infection and respiratory care. METHODS: Mixed search method. RESULTS: Due to its wetting properties, saline achieves an improved spreading of alveolar lining fluid and has been shown to reduce bio-aerosols and viral load. Saline provides moisture to respiratory epithelia and gels mucus, promotes ciliary beating, and improves mucociliary clearance. Coronaviruses and SARS-CoV-2 damage ciliated epithelium in the nose and airways. Saline inhibits SARS-CoV-2 replication in Vero cells; possible interactions involve the viral ACE2-entry mechanism (chloride-dependent ACE2 configuration), furin and 3CLpro (inhibition by NaCl), and the sodium channel ENaC. Saline shifts myeloperoxidase activity in epithelial or phagocytic cells to produce hypochlorous acid. Clinically, nasal or respiratory airway care with saline reduces symptoms of seasonal coronaviruses and other common cold viruses. Its use as aerosol reduces hospitalization rates for bronchiolitis in children. Preliminary data suggest symptom reduction in symptomatic COVID-19 patients if saline is initiated within 48 h of symptom onset. CONCLUSIONS: Saline interacts at various levels relevant to nasal or respiratory hygiene (nasal irrigation, gargling or aerosol). If used from the onset of common cold symptoms, it may represent a useful add-on to first-line interventions for COVID-19. Formal evaluation in mild COVID-19 is desirable as to establish efficacy and optimal treatment regimens.

Virucidal effect of povidone iodine on COVID-19 in the nasopharynx: A structured summary of a study protocol for an open-label randomized clinical trial.

OBJECTIVE: General: To assess the virucidal efficacy of povidone iodine (PVP-I) on COVID-19 virus located in the nasopharynx Specific: i. To evaluate the efficacy of povidone iodine (PVP-I) to removeCOVID-19 virus located in the nasopharynx ii. To assess the adverse events of PVP-I TRIAL DESIGN: This is a single-center, open-label randomized clinical trial with a 7-arm parallel-group design. PARTICIPANTS: The study will be conducted at Dhaka Medical College Hospital, Dhaka, Bangladesh. INCLUSION CRITERIA: All RT-PCR-confirmed COVID-19 cases aged between 15-90 years with symptoms for the past 4 days will be screened. Those who give informed consent, are willing to participate, and accept being randomized to any assigned group will also be considered for final inclusion. EXCLUSION CRITERIA: Patients with known sensitivity to PVP-I aqueous antiseptic solution or any of its listed excipients or previously diagnosed thyroid disease or who had a history of chronic renal failure: stage ≥3 by estimated glomerular filtration rate (eGFR) Modification of Diet in Renal Disease (MDRD) or had acute renal failure (KDIGO ≥stage 2: creatinine ≥2 times from the baseline) or patients who required invasive or noninvasive ventilation or planned within the next 6 hours were considered for exclusion. Moreover, lactating or pregnant women will also be restricted to include here. INTERVENTION AND COMPARATOR: This RCT consist of seven arms: Arm-1 (intervention group): will receive povidone iodine (PVP-I) nasal irrigation (NI) at a concentration of 0.4% Arm-2 (intervention group): will receive PVP-I nasal irrigation at a concentration of 0.5% Arm-3 (intervention group): will receive PVP-I nasal irrigation at a concentration of 0.6%. Arm-4 (intervention group): will receive PVP-I nasal spray (NS) at a concentration of 0.5%. Arm-5 (intervention group): will receive PVP-I nasal spray at a concentration of 0.6%. Arm-6 (placebo comparator group): will receive distilled water through NI Arm-7 (Placebo comparator group): will receive distilled water through NS The intervention arms will be compared to the placebo comparator arms. Other supportive and routine care will be the same in both groups. MAIN OUTCOMES: The primary outcome is the proportion of cases that remain COVID-19 positive following the intervention. It will be assessed from 1 minutes to 15 minutes after the intervention. Any occurrence of adverse effects following the intervention will be documented as a secondary outcome. RANDOMIZATION: The assignment to the study (intervention) or control (comparator) group will be allocated in equal numbers through randomization using random number generation in Microsoft Excel by a statistician who is not involved in the trial. The allocation scheme will be made by an independent statistician using a sealed envelope. The participants will be allocated immediately after the eligibility assessment and consenting procedures. BLINDING (MASKING): This is an open-label clinical trial, and no blinding or masking will be performed. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 189 confirmed cases of COVID-19 will be randomized into seven groups. In each arm, a total of 27 participants will be recruited. TRIAL STATUS: The current trial protocol is Version 1.5 from September 10, 2020. Recruitment began September 30, 2020 and is anticipated to be completed, including data analysis by February 28, 2021. TRIAL REGISTRATION: The trial protocol has been registered in the ClinicalTrials.gov on September 16, 2020. NCT Identifier number: NCT04549376 . FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

Could Simultaneous Nasal and Oral Irrigation Be a Nontherapeutic Tool against SARS-CoV-2?

For the last 8 months, COronaVIrus Disease 2019 (COVID-19) has been hovering over the planet as a pandemic, and there is no sign of this virus going away anytime soon. In the meantime, life must go on, businesses must remain open, manufacturing must flow smoothly to fulfill consumers' daily demands, and education cannot be halted. Simultaneously, the frontline workers like doctors, nurses, support staff, and other essential workers are working tirelessly in their respective fields in the absence of a widely available effective vaccine. The question is: What should every citizen who needs to venture out to fulfill their daily business do in addition to wearing a mask, handwashing, and physical distancing? Could we add simultaneous nasal and oral irrigation as a nontherapeutic practice to our personal care list as an additional preventative layer?

Do saline water gargling and nasal irrigation confer protection against COVID-19?

This report provides a perspective on the relevance of saline water gargling and nasal irrigation to the COVID-19 crisis. While there is limited evidence concerning their curative or preventive role against SARS-CoV-2 infection, previous work on their utility against influenza and recent post-hoc analysis of the Edinburgh and Lothians Viral Intervention Study (ELVIS) provide compelling support to their applicability in the current crisis. Saline water gargling and nasal irrigation represent simple, economical, practically feasible, and globally implementable strategies with therapeutic and prophylactic value. These methods, rooted in the traditional Indian healthcare system, are suitable and reliable in terms of infection control and are relevant examples of harmless interventions. We attempt to derive novel insights into their usefulness, both from theoretical and practical standpoints.