Hypertonic saline nasal irrigationand gargling should be considered asa treatment option for COVID-19
Sandeep Ramalingam1, Catriona Graham2, Jenny Dove1, Lynn Morrice3, Aziz Sheikh3

Department of Laboratory Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK
Edinburgh Clinical Research Facility, University of Edinburgh, Western General Hospital, Edinburgh, UK
3Centre of Medical Informatics, Usher Institute, The University of Edinburgh, Edinburgh, UK12P

ost-hoc secondary analysis of data from our recent Edinburgh and Lothians Viral Intervention Study(ELVIS) pilot randomised controlled trial (RCT) indicates that hypertonic saline nasal irrigation andgargling (HSNIG) reduced the duration of coronavirus upper respiratory tract infection (URTI) by
an average of two-and-a-half days. As such, it may offer a potentially safe, effective and scalable intervention in those with Coronavirus Disease-19 (COVID-19) following infection with the betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) [1].
ELVIS was undertaken in 66 adults with URTI. Results have been reported in detail elsewhere [2]. Briefly, volunteers with URTI were within 48 hours of symptom onset randomised to intervention (n = 32) orcontrol (n = 34) arms. The intervention arm made hypertonic saline at home and performed HSNIG as
many times as needed (maximum of 12 times/day). Control arm participants dealt with their URTI as
they normally did. Nose swabs collected at recruitment and first thing in the morning on four consecutive days were sent to the laboratory for testing. Both arms kept a diary (which included the Wisconsin
Upper Respiratory Symptom Survey-21 questionnaire) for a maximum of 14 days or until they were wellfor two consecutive days. Follow-up data were available for 92% of individuals (intervention arm: n = 30;
control arm: n = 31). HSNIG reduced the duration of URTI by 1.9 days (P = 0.01), over-the-counter medication use by 36% (P = 0.004), transmission within household contacts by 35% (P = 0.006) and viral
shedding by ≥0.5 log10/d (P = 0.04) in the intervention arm when compared to controls [2].
We also recently reported that epithelial cells mount an antiviral effect by producing hypochlorous acid(HOCl) from chloride ions [3]. HOCl is the active ingredient in bleach. Epithelial cells have this innate
antiviral immune mechanism to clear viral infections. Since bleach is effective against all virus types [4],we tested to see if a range of DNA, RNA, enveloped and non-enveloped viruses were inhibited in thepresence of chloride ions supplied via salt (NaCl). All the viruses
we tested were inhibited in the presence of NaCl. The human viPost-hoc analysis of a pilot randomised
ruses we tested were: DNA/enveloped: herpes simplex virus;
controlled trial of hypertonic saline nasal irRNA/enveloped: human coronavirus 229E (HCoV-229E), respirigation and gargling in adults with upper
ratory syncytial virus, influenza A virus; and RNA/non-envelrespiratory tract infection found that in aoped: coxsackievirus B3 [3].

subgroup with alpha and beta coronavirus
infection, the intervention appeared likely
to be effective in reducing symptoms andduration of the illness.

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In COVID-19, high titres of SARS-CoV-2 are detectable in theupper respiratory tract of asymptomatic and symptomatic individuals [5]. The titres are higher in the nose than the throat suggesting measures that control the infection and viral shedding
will help reduce transmission [5]. In the context of the COVID-19

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VIEWPOINTS© 2020 The Author(s)JoGH © 2020 ISGH

VIEWPOINTSIt is unclear if hypertonic saline nasal irrigation and gargling is also effective in COVID-19 caused by SARS-CoV-2;
a trial is therefore urgently needed.

pandemic, we have undertaken a post-hoc
re-analysis of the ELVIS data with a focus on
those infected with coronaviruses. Coronaviruses were the second most common cause of
URTI (after rhinoviruses). Fifteen individuals
were infected by a coronavirus: 7 in the intervention arm, 8 in the control arm. In the intervention arm, four participants were infectedby an alphacoronavirus (HCoV 229E = 3,
HCoV NL63 = 1) and three by a betacoronavirus (HCoV HKU1 = 3). In the control arm, twowere infected by an alphacoronavirus (HCoVNL63 = 2) and six by a betacoronavirus (HCoV
OC43 = 1, HCoV HKU1 = 5). An individual in
the control arm with HCoV HKU1 had dual
infection with rhinovirus.

The duration of illness was lower in the intervention arm compared to the control arm inthe subset of patients infected with coronaviPhoto: Nasal irrigation and gargling (from the ELVIS study video, used with permission).
rus (mean days (SD): 5.6 (1.4) vs 8.1 (2.9)).
Using a two-sample t test, this was difference of -2.6 days (95% confidence interval (CI) = -5.2, 0.05;
P = 0.054). The difference in the duration of blocked nose was -3.1 days (95% CI = -6.0, -0.2; P = 0.04),
cough -3.3 days (95% CI = -5.9, -0.7; P = 0.02) and hoarseness of voice -2.9 days (95% CI = -5.6, -0.3;
P = 0.03) in favour of HSNIG (Table 1). The severity of symptoms in individuals in the two arms can beseen in Figure 1.
The individual in the control arm with a co-existing rhinovirus infection could have affected the results.
Excluding this individual, the duration of illness in the control arm was a mean of 7.3 days (SD = 1.8).
The impact on the intervention control comparison was to reduce the size of the difference to -1.7 days
(95% CI = -3.6, 0.2; P = 0.07).
In the absence of a suitable antiviral agent or a vaccine, we need a safe and effective intervention that canbe globally implemented. Our in-vitro data gives the evidence that NaCl has an antiviral effect that works
across viral types. The findings from this post-hoc analysis of ELVIS need to be interpreted with caution.
These data do however suggest that HSNIG may have a role to play in reducing symptoms and durationof illness in COVID-19.

Table 1. Number of days for self reported symptom improvement in the control and intervention arms infected bya coronavirus

Variable label

Treatment

NMeanSD

Blocked nose
Blocked nose
Chest congestion
Chest congestion
CoughCoughHead congestion
Head congestion
HoarsenessHoarsenessScratchy throat
Scratchy throat
Sneezing
Sneezing
Sore throat
Sore throat
Runny nose
Runny nose
Feeling tired
Feeling tired

Intervention
ControlIntervention
ControlIntervention
ControlIntervention
ControlIntervention
ControlIntervention
ControlIntervention
ControlInterventionControl
Intervention
ControlIntervention
Control

78787878
7878
7878
7878

4.0
7.1
1.9
2.6
2.7
6.0
3.4
5.4
2.4
5.4
2.6
4.6
3.9
4.9
3.6
4.6
4.4
6.0
3.6
5.6

2.2
2.9
1.2
2.1
1.3
3.0
1.9
3.3
1.6
2.9
1.0
3.6
1.7
3.0
1.9
3.7
1.3
2.8
1.8
3.3

Difference in mean (intervention – control) (95% CI for difference) P-value-3.1 (-6.0, -0.2)

0.0362-0.8 (-2.7, 1.2)

0.4056-3.3 (-5.9, -0.7)

0.0179-1.9 (-5.0, 1.1)

0.1931-2.9 (-5.6, -0.3)

0.0325-2.1 (-5.1, 1.0)

0.1712-1.0 (-3.8, 1.8)

0.4469-1.1 (-4.4, 2.3)

0.5139-1.6 (-4.1, 0.9)

0.1999-2.1 (-5.1, 1.0)

0.1671

SD – standard deviation, CI – confidence interval

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VIEWPOINTS
Figure 1. Response to global severity question and severity of symptoms. Response from participants over the studyperiod: Each line represents response of a participant over 14 days. Data are shown by treatment group (Top panel– Control Arm; Bottom panel – Intervention Arm). The global severity question was “How unwell do you feeltoday”. The responses were graded from 0 (Not unwell), 1 (very mildly), 3 (mildly), 5 (moderately) and 7 (severelyunwell). Likewise, each symptom was graded 0 (no symptom) to 7 (severe). WURSS-21 Score was the sum of theseverity of individual symptoms.

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Funding: The study was funded by Edinburgh and Lothians Health Foundation. The funder reviewed the grantapplication, but had no role in the study design, collection, analysis, interpretation of data, writing of the reportor and in the decision to submit the paper for publication.

VIEWPOINTS

Authorship contributions: SR conceived the ELVIS trial and was PI on this leading it together with AS. SR, ASand CG planned this post-hoc subgroup analysis. CG was the trial statistician and undertook the secondary analysis. JD managed the virological testing, LM supported with project management expertise. SR and AS jointly
drafted the manuscript, which was contributed to by LM and CG. All authors approved the final version of themanuscript.

REFERENCES

Competing interests: The authors have completed the ICMJE uniform disclosure form (available upon requestfrom the corresponding author) and declare no conflicts of interest.

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3 Ramalingam S, Cai B, Wong J, Twomey M, Chen R, Fu RM, et al. Antiviral innate immune response in non-myeloid cells
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S0950268800030211
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Correspondence to:
Dr. Sandeep Ramalingam
Consultant Virologist
Royal Infirmary of Edinburgh
51 Little France Crescent
Edinburgh EH16 4SAUK
sandeep.ramalingam@nhslothian.scot.nhs.uk

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