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      Safety and Impact of Nasal Lavages During Viral Infections Such as SARS-CoV-2

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      , MD, PhD, MS 1 , 2 , , MD, PhD, MS 1 , 3 , 4 , , MD, PhD, MS 3 , , MD, PhD 5 , , MD, PhD, MS 1 , 2
      Ear, Nose, & Throat Journal
      SAGE Publications
      nasal lavages, SARS-CoV-2, viruses, viral load, coronavirus infections, pandemics

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          Abstract

          Much has been stated about the potential risks of nasal lavages (NL) during the coronavirus disease 2019 (COVID-19) pandemic for COVID-19 patients and surrounding people. Several otolaryngological societies recommended to limit NL, supposing it may be associated with viral spread to lower airway. 1 On the contrary, recent studies suggested that NL may be beneficial in upper viral respiratory infectious diseases. In order to take stock of this issue, we conducted a short literature review to address 4 main questions: What Are the Potential Benefits of NL to COVID-19 Patients? Beneficial effects on nasal mucosal Ions, pH and tonicity may influence epithelial cell function in vitro. Isotonic solutions with slightly alkaline pH optimize trophic and functional recovery of the respiratory epithelium. 2 In chronic rhinosinusitis, saline solutions improve mucociliary clearance 3 without altering commensal bacteria. 4 These actions may aid recovery of the nasal epithelium after viral injury and reduce associated symptoms of rhinitis. Direct antiviral effects Recently, Ramalingam et al reported that antiviral activity against viral infections can be augmented by increasing availability of NaCl. 5 Nasal lavages containing carrageenans, which are natural emulsifiers derived from red seaweed, seemed to reduce the Influenza A viral load in nasal secretions and positive effects on mucosal barrier function. 6,7 Hendley and Gwaltney reported lower virus concentrations after saline NL in rhinovirus infections. 8 Regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Carrouel et al found the use of a mouth rinses with local nasal applications that contain β-cyclodextrins combined with flavonoids agents reduce the viral load of saliva and nasopharyngeal microbiota, including potential SARS-CoV-2 carriage. 9 The use of copper-enhanced NL seems to be efficient to decrease viral spread and contamination, especially regarding SARS-CoV-2. 10,11 Human coronavirus 229E was rapidly inactivated on a range of copper alloys at low copper concentration, suggesting a specific antiviral effect. 12,13 In fact, exposure to copper destroyed the viral genomes and irreversibly affected virus morphology, including disintegration of envelope and dispersal of surface spikes. 14 Copper also inactivates SARS coronavirus, bacteria, and yeast in the air after 20 minutes of exposure. 15 A recent study has proposed that the combination of copper, N-acetylcysteine, colchicine, and nitric oxide with antiviral agents may be a treatment option for SARS-CoV-2-positive patients. 16 Washing and reduction of viral load in enhancing recovery Computational fluid dynamics studies demonstrate that all nasal regions are reached when using a head tilt position of 45 °C forward for NL, 17 especially with large-volume irrigations, 18 suggesting good mechanical efficiency of NL in washing the nose. Nasal mucosa have high viral loads and include cells expressing proteases responsible for virus entry (such as angiotensin-converting enzyme 2 and TMPRSS2 for SARS-CoV-2), 19,20 The upper airway has shown to be a reservoir for descending bacterial or viral infection to the lung. 21 The nose can be considered as a site of virus replication, accumulation, and human body entry. 22 Interestingly, NL tends to decrease nasal viral loads and, therefore, could reduce systemic or bronchopulmonary dissemination. 8 Nasal lavages are commonly used treatments in the upper respiratory tract infections and can decrease duration of illness in common cold. 3,23,24 Given the potential benefits summarized above, nasal saline irrigation may enhance recovery in patients known to be infected with COVID-19. Patients are currently being recruited to a randomized controlled trial to evaluate the benefits to COVID-19 patients, although no results are yet available. 25 What Are the Potential Benefits of NL to Personal Contacts/Healthcare Workers Caring for COVID-19 Patients? When properly performed, NL have shown to decrease household transmission in other viral disease. 26 The potential direct antiviral actions and reduction in viral load have led to proposals that use in patients with COVID-19 may reduce risk of nosocomial transmission. It has been proposed that regular use of NL in COVID-19 patients may reduce risk of transmission to household contacts or Healthcare Workers (HCWs), particularly if used before aerosol-generating procedures (AGPs). 27 It has also been suggested that HCWs involved in the care of COVID-19 patients could use NL with povidone–iodine before and after patient contact, particularly for high-risk procedures. 27 In asking a patient or currently healthy HCW to perform an intervention aimed at protecting others, it is important to discuss potential side effects of the intervention. What Are the Potential Harms of NL to Patients With COVID-19? Risk of toxicity Although nasal saline irrigation has been shown to have no detrimental effects on olfaction, additives to NL solutions may cause anosmia, which would be difficult to detect in trials of COVID-19 patients, where olfactory dysfunction is highly prevalent. A number of agents have been shown to cause anosmia if delivered intranasally, such as zinc gluconate and sinus surfactant solutions. 28 Although the safety of povidone–iodine has been evaluated in vitro, at concentrations above 5% it is known to be ciliotoxic. 29 Its use in mouthwash and nasal spray in COVID-19-infected patients prior to dental and other AGPs has been widely promoted in the absence of rigorous in vivo evaluation. 7,30 Risk of bronchopulmonary dissemination To date, no study suggested that NL is associated with lower respiratory disorders. What Are the Potential Harms of NL to Personal Contacts/HCWs Caring For COVID-19 Patients? Risk of droplet spread and surface contamination Irrigation is likely to generate droplets potentially carrying viruses. Sinus irrigation devices, mostly composed by plastic, can harbor viruses for hours: van Doremalen et al showed that SARS-CoV-2 is very stable on plastic and remains viable up to 72 hours. 12 As the COVID-19 status of most of patients using NL is unknown, specific measures should be undertaken to protect personal contacts or HCWs. 31 Protective measures – Clean the inside and outside of the NL device thoroughly with soap and water. For a deeper clean of components of the device that come into contact with the nose, clean with 70% isopropyl alcohol or concentrated white vinegar, rinse, and then leave to it dry before next use. Some commercial products may be suitable for sterilization in the microwave but must be replaced if there is any sign of degradation of plastic components. – Self-irrigation is important, avoiding viral exposure to others. – Ventilate the room: being able to remain suspended in the air, small droplets were shown to permit SARS-CoV-2 detection in ambient air for 3 hours. 12 Guidelines on air exchanges per hour required for airborne contaminant removal have been edited by CDC. 32 – Perform household cleaning, disinfection of high-touch surfaces, and hand hygiene. The United States Environmental Protection Agency and the CDC (Center for Disease Control and Prevention) published a list of recommended household disinfectants. 33 Consistent with current guidance, these measures will help to limit viral spreading. Conclusion Taken together, these data suggest that NL can be continued during viral infection when respecting strict conditions of use and hygienic measures. Moreover, properly performed, large-volume NL with specific composition such as copper or povidone–iodine could limit viral contamination and spreading. In vitro, in vivo, and in silico studies must confirm these data.

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          SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

          Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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            Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1

            To the Editor: A novel human coronavirus that is now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (formerly called HCoV-19) emerged in Wuhan, China, in late 2019 and is now causing a pandemic. 1 We analyzed the aerosol and surface stability of SARS-CoV-2 and compared it with SARS-CoV-1, the most closely related human coronavirus. 2 We evaluated the stability of SARS-CoV-2 and SARS-CoV-1 in aerosols and on various surfaces and estimated their decay rates using a Bayesian regression model (see the Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org). SARS-CoV-2 nCoV-WA1-2020 (MN985325.1) and SARS-CoV-1 Tor2 (AY274119.3) were the strains used. Aerosols (<5 μm) containing SARS-CoV-2 (105.25 50% tissue-culture infectious dose [TCID50] per milliliter) or SARS-CoV-1 (106.75-7.00 TCID50 per milliliter) were generated with the use of a three-jet Collison nebulizer and fed into a Goldberg drum to create an aerosolized environment. The inoculum resulted in cycle-threshold values between 20 and 22, similar to those observed in samples obtained from the upper and lower respiratory tract in humans. Our data consisted of 10 experimental conditions involving two viruses (SARS-CoV-2 and SARS-CoV-1) in five environmental conditions (aerosols, plastic, stainless steel, copper, and cardboard). All experimental measurements are reported as means across three replicates. SARS-CoV-2 remained viable in aerosols throughout the duration of our experiment (3 hours), with a reduction in infectious titer from 103.5 to 102.7 TCID50 per liter of air. This reduction was similar to that observed with SARS-CoV-1, from 104.3 to 103.5 TCID50 per milliliter (Figure 1A). SARS-CoV-2 was more stable on plastic and stainless steel than on copper and cardboard, and viable virus was detected up to 72 hours after application to these surfaces (Figure 1A), although the virus titer was greatly reduced (from 103.7 to 100.6 TCID50 per milliliter of medium after 72 hours on plastic and from 103.7 to 100.6 TCID50 per milliliter after 48 hours on stainless steel). The stability kinetics of SARS-CoV-1 were similar (from 103.4 to 100.7 TCID50 per milliliter after 72 hours on plastic and from 103.6 to 100.6 TCID50 per milliliter after 48 hours on stainless steel). On copper, no viable SARS-CoV-2 was measured after 4 hours and no viable SARS-CoV-1 was measured after 8 hours. On cardboard, no viable SARS-CoV-2 was measured after 24 hours and no viable SARS-CoV-1 was measured after 8 hours (Figure 1A). Both viruses had an exponential decay in virus titer across all experimental conditions, as indicated by a linear decrease in the log10TCID50 per liter of air or milliliter of medium over time (Figure 1B). The half-lives of SARS-CoV-2 and SARS-CoV-1 were similar in aerosols, with median estimates of approximately 1.1 to 1.2 hours and 95% credible intervals of 0.64 to 2.64 for SARS-CoV-2 and 0.78 to 2.43 for SARS-CoV-1 (Figure 1C, and Table S1 in the Supplementary Appendix). The half-lives of the two viruses were also similar on copper. On cardboard, the half-life of SARS-CoV-2 was longer than that of SARS-CoV-1. The longest viability of both viruses was on stainless steel and plastic; the estimated median half-life of SARS-CoV-2 was approximately 5.6 hours on stainless steel and 6.8 hours on plastic (Figure 1C). Estimated differences in the half-lives of the two viruses were small except for those on cardboard (Figure 1C). Individual replicate data were noticeably “noisier” (i.e., there was more variation in the experiment, resulting in a larger standard error) for cardboard than for other surfaces (Fig. S1 through S5), so we advise caution in interpreting this result. We found that the stability of SARS-CoV-2 was similar to that of SARS-CoV-1 under the experimental circumstances tested. This indicates that differences in the epidemiologic characteristics of these viruses probably arise from other factors, including high viral loads in the upper respiratory tract and the potential for persons infected with SARS-CoV-2 to shed and transmit the virus while asymptomatic. 3,4 Our results indicate that aerosol and fomite transmission of SARS-CoV-2 is plausible, since the virus can remain viable and infectious in aerosols for hours and on surfaces up to days (depending on the inoculum shed). These findings echo those with SARS-CoV-1, in which these forms of transmission were associated with nosocomial spread and super-spreading events, 5 and they provide information for pandemic mitigation efforts.
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              SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients

              To the Editor: The 2019 novel coronavirus (SARS-CoV-2) epidemic, which was first reported in December 2019 in Wuhan, China, and has been declared a public health emergency of international concern by the World Health Organization, may progress to a pandemic associated with substantial morbidity and mortality. SARS-CoV-2 is genetically related to SARS-CoV, which caused a global epidemic with 8096 confirmed cases in more than 25 countries in 2002–2003. 1 The epidemic of SARS-CoV was successfully contained through public health interventions, including case detection and isolation. Transmission of SARS-CoV occurred mainly after days of illness 2 and was associated with modest viral loads in the respiratory tract early in the illness, with viral loads peaking approximately 10 days after symptom onset. 3 We monitored SARS-CoV-2 viral loads in upper respiratory specimens obtained from 18 patients (9 men and 9 women; median age, 59 years; range, 26 to 76) in Zhuhai, Guangdong, China, including 4 patients with secondary infections (1 of whom never had symptoms) within two family clusters (Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). The patient who never had symptoms was a close contact of a patient with a known case and was therefore monitored. A total of 72 nasal swabs (sampled from the mid-turbinate and nasopharynx) (Figure 1A) and 72 throat swabs (Figure 1B) were analyzed, with 1 to 9 sequential samples obtained from each patient. Polyester flock swabs were used for all the patients. From January 7 through January 26, 2020, a total of 14 patients who had recently returned from Wuhan and had fever (≥37.3°C) received a diagnosis of Covid-19 (the illness caused by SARS-CoV-2) by means of reverse-transcriptase–polymerase-chain-reaction assay with primers and probes targeting the N and Orf1b genes of SARS-CoV-2; the assay was developed by the Chinese Center for Disease Control and Prevention. Samples were tested at the Guangdong Provincial Center for Disease Control and Prevention. Thirteen of 14 patients with imported cases had evidence of pneumonia on computed tomography (CT). None of them had visited the Huanan Seafood Wholesale Market in Wuhan within 14 days before symptom onset. Patients E, I, and P required admission to intensive care units, whereas the others had mild-to-moderate illness. Secondary infections were detected in close contacts of Patients E, I, and P. Patient E worked in Wuhan and visited his wife (Patient L), mother (Patient D), and a friend (Patient Z) in Zhuhai on January 17. Symptoms developed in Patients L and D on January 20 and January 22, respectively, with viral RNA detected in their nasal and throat swabs soon after symptom onset. Patient Z reported no clinical symptoms, but his nasal swabs (cycle threshold [Ct] values, 22 to 28) and throat swabs (Ct values, 30 to 32) tested positive on days 7, 10, and 11 after contact. A CT scan of Patient Z that was obtained on February 6 was unremarkable. Patients I and P lived in Wuhan and visited their daughter (Patient H) in Zhuhai on January 11 when their symptoms first developed. Fever developed in Patient H on January 17, with viral RNA detected in nasal and throat swabs on day 1 after symptom onset. We analyzed the viral load in nasal and throat swabs obtained from the 17 symptomatic patients in relation to day of onset of any symptoms (Figure 1C). Higher viral loads (inversely related to Ct value) were detected soon after symptom onset, with higher viral loads detected in the nose than in the throat. Our analysis suggests that the viral nucleic acid shedding pattern of patients infected with SARS-CoV-2 resembles that of patients with influenza 4 and appears different from that seen in patients infected with SARS-CoV. 3 The viral load that was detected in the asymptomatic patient was similar to that in the symptomatic patients, which suggests the transmission potential of asymptomatic or minimally symptomatic patients. These findings are in concordance with reports that transmission may occur early in the course of infection 5 and suggest that case detection and isolation may require strategies different from those required for the control of SARS-CoV. How SARS-CoV-2 viral load correlates with culturable virus needs to be determined. Identification of patients with few or no symptoms and with modest levels of detectable viral RNA in the oropharynx for at least 5 days suggests that we need better data to determine transmission dynamics and inform our screening practices.
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                Author and article information

                Journal
                Ear Nose Throat J
                Ear Nose Throat J
                EAR
                spear
                Ear, Nose, & Throat Journal
                SAGE Publications (Sage CA: Los Angeles, CA )
                0145-5613
                1942-7522
                27 August 2020
                : 0145561320950491
                Affiliations
                [1 ]COVID-19 Task Force of the Young-Otolaryngologists of the International Federations of Otorhinolaryngological Societies (YO-IFOS), Marseille, France
                [2 ]Department of Otorhinolaryngology–Head and Neck Surgery, Aix Marseille University, Ringgold 36900, universityAPHM, IUSTI, La Conception University Hospital; , Marseille, France
                [3 ]Department of Human Anatomy and Experimental Oncology, Faculty of Medicine, UMONS Research Institute for Health Sciences and Technology, Ringgold 54521, universityUniversity of Mons (UMons); , Mons, Belgium
                [4 ]Department of Otolaryngology–Head & Neck Surgery, Foch Hospital, School of Medicine, UFR Simone Veil, Université Versailles Saint-Quentin-en-Yvelines (Paris Saclay University), Paris, France
                [5 ]Ringgold 4820, universityKing’s College; , London
                Author notes
                [*]Thomas Radulesco, MD, PhD, MS, Department of Otorhinolaryngology–Head and Neck Surgery, La Conception University Hospital, 147 Bd Baille, 13005 Marseille, France. Email: thomas.radulesco@ 123456ap-hm.fr
                Author information
                https://orcid.org/0000-0002-5939-5372
                https://orcid.org/0000-0002-0845-0845
                https://orcid.org/0000-0002-3655-1854
                Article
                10.1177_0145561320950491
                10.1177/0145561320950491
                7453155
                32853040
                e5025490-f044-4125-b93e-44b69c271899
                © The Author(s) 2020

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 20 July 2020
                : 23 July 2020
                : 27 July 2020
                Categories
                Letter to the Editor
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                nasal lavages,sars-cov-2,viruses,viral load,coronavirus infections,pandemics

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