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The Use of Povidone Iodine Nasal Spray and Mouthwash During the Current COVID-19 Pandemic May Protect Healthcare Workers and Reduce Cross Infection.

Authors:
May 04, 2020 Draft version, awaiting journal acceptance and full peer review
The use of Povidone Iodine nasal spray and mouthwash during the current COVID-19
pandemic may reduce cross infection and protect healthcare workers.
J Kirk-Bayley MRCP FRCA EDIC FFICM
Consultant Intensivist & Anaesthetist, Royal Surrey County Hospital
J Combes FDS FRCS (OMFS), Lt Col RAMC
Consultant Advisor (ARMY) in OMFS, Defence Medical Services
VS Sunkaraneni LLM FRCS (2009)
Consultant Rhinologist, Royal Surrey County Hospital
SJ Challacombe, PhD, FRCPath, FDSRCS, FMedSci, DSc(h.c), FKC
Martin Rushton Professor of Oral Medicine, King’s College London
Abstract
In late 2019 a novel coronavirus, SARS-CoV-2 causing Coronavirus disease 2019 (COVID-19)
appeared in Wuhan China, and on 11th March 2020 the World Health Organisation declared it to have
developed pandemic status. In early SARS-CoV-2 infection, viral titres of greater than 107/mL in
saliva and nasal mucous can be found; minimisation of these titres should help to reduce cross
infection. Povidone-iodine (PVP-I) disinfectant has better anti-viral activity than other antiseptics
and has already been proven to be an extremely effective virucide in vitro against severe acute
respiratory syndrome and Middle East respiratory syndrome coronaviruses (SARS-CoV and MERS-
CoV). Its in vivo virucidal activity is unknown, but it retains its antimicrobial activity against bacteria
in vivo intraorally and one application can reduce oral microbial flora for greater than 3 hours.
PVP-I disinfectant has been shown to be safe when administered to the nasal cavity and as a
mouthwash. We propose a protocolised intra-nasal and oral application of PVP-I for both patients
and their attendant healthcare workers (HCWs) during the current COVID-19 pandemic to help limit
the spread of SARS-CoV-2 from patients to healthcare workers and vice versa. The aim is to reduce
the viral ‘load’ in two of the key areas from where droplets and aerosols containing the virus are
expectorated (the lower respiratory tract being the other). The aim of use in HCWs is to destroy virus
that has entered the upper aerodigestive tract before it has the opportunity to infect the host.
We suggest the protocol is considered for routine use during the care of COVID-19 patients,
particularly before any procedure that involves the upper aerodigestive tract, including intubation,
nasal and oral procedures, endoscopy and bronchoscopy. We suggest it should be considered when
such procedures are carried out in all patients during the pandemic regardless of COVID-19 status,
due to the reported significant rates of asymptomatic infection
The total iodine exposure proposed is well within previously recorded safe limits in those without
contraindications to its use. The intervention is inexpensive, low risk and potentially easy to deploy
at scale globally.
Draft version, awaiting journal acceptance and full peer review
May 04, 2020 Draft version, awaiting journal acceptance and full peer review
Background
The current COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, represents a
significant risk to healthcare workers with infection in this group representing nearly 4% of cases
early in the Chinese epidemic[1]. This may place an extra burden on healthcare environments at a
crucial time due to staff absence and spread to family members. Additionally, there is a significant
risk to non-infected patients already hospitalised and Wang et al reported in one centre that 41% of
their patients had suspected nosocomial transmission[2]. Critical care, for example, represents a
high-risk environment for nosocomial transmission of SARS-CoV-2 with procedures such as non-
invasive ventilation, intubation and suction causing a bioaerosol that may represent more of a
potential inoculum than by community transmission[3].
Saliva contains a high viral load in COVID-19 with up to 1·2×108 infective copies/mL when the
saliva of patients was analysed at the time of admission to hospital[4]. It has recently been found,
through PCR assay techniques, that the nasopharynx appears to have a higher viral load than that
found in the oropharynx[5]. As such, we feel that reduction of nasal viral titres is of at least as much
importance as in the oral cavity/oropharynx. Minimising, or at least reducing, viral titres in saliva
and nasal mucous expectorated by COVID-19 patients should be a key tenet in the battle to reduce
transmission of the disease. Doing so may well lessen the overall impact on the healthcare system by
reducing cross-infection from patients to healthcare workers and vice versa.
It is appreciated that virus in sputum from the lower respiratory tract is also of importance, but it is
not yet clear how viral titres vary between the upper and lower respiratory tracts. One small Korean
study[6] found that viral shedding was high during the early phase of illness, as did Zou[7], and was
higher in the upper compared with the lower respiratory tract, decreasing after day 7 of illness.
Povidone-iodine
Povidone-iodine (iodine with the water-soluble polymer polyvinylpyrrolidone, PVP-I) was
discovered in 1955 at the Industrial Toxicology Laboratories in Philadelphia by H. A. Shelanski and
M. V. Shelanski. It was developed in order to find an antimicrobial iodine complex that was less
toxic than tincture of iodine, which caused burns. The antimicrobial action of PVP-I occurs after free
iodine (I2) dissociates from the polymer complex. Once in the free form, iodine rapidly penetrates
microbes and disrupts proteins and oxidises nucleic acid structures. This interaction ultimately results
in microbial death. PVP-I antibacterial activity is enhanced by dilution of the usually available 10%
w/w cutaneous solution, from 1:2 dilution up to a 1:100 dilution (0·1%), with a reduction in activity
occurring beyond 1:100.[8]
Virucidal activity
PVP-I has higher virucidal activity than other commonly used antiseptic agents including
chlorhexidine and benzalkonium chloride[9]. It has been shown to be active in vitro against the
coronaviruses that have caused epidemics in the last two decades, namely SARS-CoV causing the
severe acute respiratory syndrome (SARS) epidemic of 2002–3 and MERS-CoV the agent
responsible for causing the Middle East respiratory syndrome (MERS) epidemic of 2012–13.[10,11]
SARS-CoV-2 is highly homologous with SARS-CoV, and as such it is considered a close relative of
SARS-CoV[12]. Initial in vitro work looking at the virucidal activity of PVP-I against MERS-CoV
by Eggers’ group[13] showed that the lowest concentration of PVP-I to be effective was 1% when
used for 30 seconds under “dirty” conditions, leading to a reduction of viral activity of ≥99.99%;
however this was not effective at 0·1%[12]. In subsequent in vitro work by Eggers[14], the lowest
concentration tested and yet still effective against coronaviruses, was 0·23%. Kariwa showed that
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May 04, 2020 Draft version, awaiting journal acceptance and full peer review
treatment in vitro of SARS-CoV with various preparations of PVP-I for 2 minutes was enough to
reduce viral activity to undetectable levels[10]. The lowest concentration used was 0·23%, found in
an over the counter throat spray (Isodine Nodo Fresh®) available in Japan.
Safety and tolerance
Gargled PVP-I is very well tolerated when compared with other gargled antiseptic agents in common
use[15]. It has already been shown in clinically successfully trials using nasal administration and
mouthwash to reduce the incidence of nosocomial pneumonia by reducing pharyngeal bacterial
colonisation[16]. In Japan, iodine intake, largely from seaweeds, averages 1–3 mg per day without
significant associated negative health effects, other than the very low possibility of causing or
worsening symptoms for people with previously known thyroid autoimmunity or other underlying
thyroid issues[17]. A study looking at once daily use of 5% PVP-I mouthwash over a six-month
period showed no change in thyroid hormone levels (serum T3/T4 and free T4) with a small increase
in TSH levels, although all TSH levels remained in the normal range[18].
In a study looking at the excretion of iodine in healthy subjects, average ingestion of 88 mg per day
for a period of 38 days was undertaken without deleterious effects. They found that the majority of
iodine is cleared by the kidneys in urine, but an appreciable amount is excreted in sweat (35% of the
plasma concentration) and that faecal excretion is negligible[19]. The renal iodine clearance rate is
not influenced by the iodine intake; the process is neither adaptive nor saturable[20]. The World
Health Organisation recommended daily allowance of iodine for an adult is 0·15 mg[21]. PVP-I 10%
contains an equivalent of 11 mg/mL of iodine[22]. Our protocol would deliver less than 6 mg per day
for the duration of treatment of patients and less than 4 mg per day for staff, dependent on the
method of application as described in ‘Method of application’ below.
With decades of clinical use, the safety profile of PVP-I has been well established. Allergy to PVP-I
is extremely rare[23]; and in a clinical trial only 2 out of 500 patients showed positive contact
sensitivity to PVP-I (prevalence: 0·4%)[24] and although there have been occasional reports of type 1
allergy, these are considered exceptional[25]. There have been documented cases of significant
iodine toxicity with topical PVP-I use, one after prolonged sinus irrigation[26], the other with
prolonged wound application for 3–5 weeks[27], both using a 10% solution of PVP-I.
Clinical Usage
PVP-I is in ubiquitous use worldwide, both as a handwashing agent (usually a 7·5% solution
containing foaming agents) and for pre-procedural skin antisepsis (usually simply as a 10% solution).
The 10% is commonly used, and is licensed for, use on skin (multiple applications) and mucous
membranes (single application always review summary of product charateristics)It is used in
ophthalmic surgery (often diluted to 5%) and occasionally used in oral surgery at 10%.
PVP-I is commercially available in the Far East as a 1% w/v mouthwash for use every 2–4
hours[28] and as a 0·45% w/v ‘sore throat spray’ for use every 3–4 hours[29]. Chlorhexidine
mouthwash is used as the main antibacterial mouthwash in the UK, but chlorhexidine is not effective
against coronaviruses[9]. We do not know the exact effective concentration of PVP-I in the presence
of mucins and saliva, but we assume that using a concentration twice as strong as that found to be
virucidal in vitro (0·5% versus 0·23%[10,14]) will be effective, allowing for dilution due to saliva.
The topical application of iodine intranasally for the treatment of recalcitrant chronic rhinosinusitis
has been described by the St. Paul’s Sinus Centre team in Vancouver[30,31]. They used a 0·08%
solution, which they found to be beneficial for the management of this condition, but also did not
lead to any significant effect on thyroid function, mucociliary clearance or olfaction. PVP-I use in the
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May 04, 2020 Draft version, awaiting journal acceptance and full peer review
nasal cavity to reduce infection or spread is rational for COVID-19 after two recent trials have
demonstrated higher viral load there when compared with the oral cavity.[7,32]
Higher concentrations of 2·2% and 4·4% PVP-I in liposomal dispersions were trialled by Gluck et al
in a partially blinded, monocentric, prospective, controlled, randomised, single, 3-fold crossover
phase I study. Again, no change in mucosal appearance, olfactory function, ciliary activity or
subjective perception of nasal airflow were found[33]. Additionally, they were able to show that the
treatment was tolerable by subjects, and through comet assay that there was no genotoxicity. It is
difficult to be certain whether similar observations would be seen in a pure liquid preparation.
The clearance rate of mucin layers in the oral cavity in normal subjects is between 1 and 8 mm per
minute which equates to between 200 and 20 minutes in the oral cavity depending on the site and
flow rate[34]. Halides, including fluoride, bind to mucins and would have a similar clearance rate,
though the majority would be gone in under 10 minutes[35]. The flow rate of saliva in hospital
unconscious patients is very low, and clearance of PVP-I slower than normal.
Suggested Protocol
In the hospital setting, we propose that a 0·5% PVP-I solution (0·55 mg/mL available iodine) be
applied to the oral, oropharyngeal and nasopharyngeal mucosa of patients with presumed/confirmed
COVID-19 and the healthcare personnel in close contact with this cohort. At these concentrations
antiviral activity is still optimal and staining of teeth is minimal and reversible.
Additionally, we propose the same application of PVP-I for a second cohort, that includes all patients
having procedures (including examination) in or around the mouth and nose or procedures that
transit those areas and the healthcare professional carrying out those procedures. During the current
phase (April 2020 onwards) of the COVID-19 outbreak, the second cohort should include all
patients, not just those with suspected/confirmed COVID-19 infection. Procedures in the second
cohort would include, but not be limited to, dentistry and oral surgery, ENT examination and
treatment, endo-tracheal intubation, endoscopy and bronchoscopy.
Exclusion criteria: A history of allergy to PVP-I or its relevant excipients (alkyl phenol ether
sulphate (ammonium salt), disodium hydrogen phosphate dodecahydrate), all forms of thyroid
disease or current radioactive iodine treatment, lithium therapy, known pregnancy, renal failure and
dermatitis herpetiformis. The protocol should not be used in a sustained manner in children, but can
be used as a single episode, e.g. for dental treatment.
Medicament:
There is currently no commercially available iodine based ‘mouthwash’ in the UK. Instead, a 10%
solution of PVP-I licensed for oral mucosal use is diluted to 1:20 using sterile water to yield a 0·5%
w/v solution, which has 0·55 mg/mL available iodine. This is an ‘off-label’ use of a licensed product,
although a single application of diluted (or un-diluted) PVP-I to mucosa for antisepsis may be on
licence – check summary of product characteristics.
Pre-administration:
1. Patients must have exclusion criteria checked and to be informed of the benefits and risks of
the proposed treatment, with verbal consent taken and documented.
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2. Healthcare professions to be offered the administration as a form of PPE, with risks and
potential benefits explained and consent gained akin to prior to immunisation (e.g. the ‘flu
jab’), again after checking exclusion criteria
Method of application:
Step 1for all patients/ healthcare professionals in described groups: The 0·5% PVP-I solution
is administered in a dose of 0·28–0·3 ml into each nostril, preferably using an atomising device (2
sprays for an average device) or if not from a syringe. The contralateral nostril is occluded and the
recipient, if conscious, sniffs (with mouth closed) during the atomisation/instillation in order to
maximise coverage of the nasal cavity and nasopharynx. This will give a total dose of 0·33 mg of
iodine.
Step 2 – conscious patients and healthcare professionals: 9 mL of the 0·5% PVP-I solution is then
introduced into the oral cavity and used as a mouthwash. Care is taken to ensure the solution is
distributed throughout the oral cavity for 30 seconds and then gently gargled or held at the back of
the throat for another 30 seconds before spitting out. It is assumed that at most 1 mL of the solution
will be retained (based on self-testing using high-accuracy scales, subtracting salivary production)
and absorbed, giving an anticipated maximum total dose of 0·55 mg of iodine. If a nasal pump
atomising device is used, 7 sprays are used aimed in different directions and then ‘licked’ around the
inside of the oral cavity, yielding 0·54 mg of iodine (0·14 mL per actuation for most commercially
available nasal atomisers at 0·077 mg iodine per actuation).
Step 2 – unconscious patients. At the time of routine mouthcare, an oral care sponge swab or similar
is soaked in 2 mL of 0·5% PVP-I solution and carefully wiped around all oral mucosal surfaces.
Most of this solution will be retained in the mouth/ oropharynx (a small amount remaining in the
sponge), giving a maximum total dose of 1·1 mg iodine.
Timing of delivery:
Patients hospitalised for confirmed/ suspected COVID 19 and healthcare workers engaged in
their care: Steps 1 & 2 should be undertaken every 6 hours for patients and up to four times per day
for healthcare workers (maximal frequency two hourly). For healthcare workers, it is advised that
steps 1 & 2 are performed prior to contact with the patient/patients and if repeated contact is
occurring, repeated every 2–3 hours, up to 4 times per day. This will give a maximum iodine intake
of 3·52 mg for HCW and conscious patients and 5·72 mg for unconscious patients.
Patients attending for dentistry/oral surgery, ENT examination and treatment, endoscopy and
bronchoscopy and any other action to be carried out close to or in the mouth or nose: The
patient should undergo steps 1 & 2 prior to examination or treatment. Healthcare workers conducting
the procedure or in close proximity should perform steps 1 & 2 prior to contact with the patient and if
multiple patients are being seen, repeat every 2–3 hours, up to 4 times a day. Dosages are the same as
above, but are single exposures for patients.
Discussion
The evidence presented suggests that application of povidone iodine to the nasal and oral mucosae,
including the oro/nasopharynx, of patients with COVID-19 may significantly reduce the viral load in
those key anatomical areas. This may reduce the risk of transmission to HCW providing routine care
as well as allowing a period of time to perform procedures at reduced risk. Further reduction of risk
of transmission may be achieved by similar application of PVP-I to the HCW providing the care as a
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May 04, 2020 Draft version, awaiting journal acceptance and full peer review
form of prophylaxis. We therefore propose that for the duration of the current COVID-19 pandemic
urgent consideration should be given to the application of PVP-I to patients and HCWs as described
above. This includes patients with no symptoms of COVID-19 having procedures in or around the
mouth and nose or procedures that transit those areas and the healthcare professionals carrying out
those procedures due to the high incidence of asymptomatic infection.
We accept, however, that direct testing and demonstration of the virucidal activity of PVP against
SARS-CoV-2 has not been documented. However, the evidence in the literature shows that PVP-I is
rapidly virucidal in vitro and its use in the manner we propose was recommended by Eggers et al, for
reduction of coronavirus load in the oral cavity to help prevent MERS-CoV transmission, and this
has not been contested[13]. The proposed protocol is for disinfection of the oral and nasal cavities,
akin to the recommended practice of hand sanitisation for transmission reduction, but at the major
route of spread (potentially preventing infected patients from passing on the virus) and at a portal of
virus entry for HCW (potentially protecting them from being infected via the nose/mouth). It is
accepted that aerosolised secretions from the lower respiratory tract almost certainly have a part to
play in disease transmission and therefore that this proposal forms only part of the strategy to reduce
transmission, as an adjunct to other elements of personal protective equipment.
This intervention is not provided with curative intent for the disease, but may provide a major step to
dramatically reduce viral spread within the healthcare workplace. In low and middle-income
countries that are soon likely to suffer expansion of the pandemic, the number of healthcare workers
per capita is considerably lower, and conventional physical personal protective equipment will
probably be in very short supply. Every possible step should be taken to keep HCWs from being
infected and able to offer care to reduce mortality from COVID-19. The proposed intervention is
applicable to every HCW exposed to both proven or suspected cases to reduce their risk.
Additionally, use in clinical scenarios where there is prolonged close proximity of the upper
aerodigestive tracts of patients and HCWs combined with aerosol generating procedures, such as
general dental practice and ENT clinics, may reduce transmission, especially when treating patients
with asymptomatic COVID-19.
It has been assumed that PVP-I shows the same virucidal activity to SARS-CoV-2 in vitro as has
been shown with other coronaviruses, but the exact duration of virucidal action of PVP-I once
applied to the mucosae is currently unknown, as is the length of time for the viral load to recover to
pre-treatment levels, or if it does at all. However, in ventilated patients PVP-I solution has been
shown to significantly reduce bacterial flora for at least three hours[36]. The high levels of SARS-
CoV-2 in both the nose and oral cavity strongly suggest that productive replication is occurring in the
mucosae in both sites. Both nasal and oral tissues have been shown to express the ACE-2
receptor[38] and epithelial cells lining salivary duct cells may be early targets of infection by
coronaviruses[39] as well as nasal goblet and ciliated cells in the nose[40]. On the basis of these
studies and the clearance rate of mucins from both nose and mouth, we suggest that an expectation of
a 20-minute window of lowered viral loads is reasonable, although once present on the mucosa the
time taken for viral particles to infect host cells and replicate is also unknown. Research is currently
being undertaken to determine if PVP-I kills SAR-CoV-2 in the human oral and nasal cavities and, if
so, the duration of virucidal action on mucosae.
We consider that it is important to avoid aerosols from either nose or mouth since droplets of even a
few microlitres may contain many thousands of infectious virus particles. Thus, the application of the
nasal spray requires insertion into the anterior nares and a sniff with concurrent occlusion of the
contralateral nose and a closed mouth to avoid bioaerosols from the mouth or nose. The American
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May 04, 2020 Draft version, awaiting journal acceptance and full peer review
Dental Association have recently published interim guidelines for minimising the risk of COVID-19
transmission which includes the use of a pre-operative 0·2% PVP-I mouthwash[41].
For the ventilated patient there is possible added value of the suggested PVP-I protocols. Adverse
effects of ventilation include rhinosinusitis and aspiration pneumonia. Nasal and oral bacterial
loads[37] are significantly reduced by PVP-I and PVP-I use is a recommended therapeutic
intervention for recalcitrant rhinosinusitis[30] and for prevention of aspiration pneumonia[36].
The total dose of iodine absorbed by the suggested regimen is not known exactly. If 100% of the
nasal spray used were to be absorbed and a similar amount absorbed from the mouthwash, then this
would amount to 5·72 mg of iodine per day. For staff, who would be potentially exposed to
prolonged use, this figure is 3·52 mg per day. This is far below experimental studies showing lack of
any toxicity after ingesting 88 mg daily for 28 days[19] and close to normal dietary intake in
Japan[17]. In Aders study[18], 6 months of use of daily 5% PVP-I mouthwashes, equivalent to
5·5mg per day if 1 mL is retained and absorbed as estimated in this paper, caused no change in serum
T3, T4 or free T4. While there was a small increase in TSH, in all subjects this remained within
normal range[18]. In addition, upon cessation, the extrapolation of excretion data from Nelson et
al[19], suggests complete urinary clearance by 5 days using their slowest clearance data, and our use
is far below their maxima, which yielded no ill effects. For perspective, taking 200 mg of
amiodarone once per day would be expected to release 7·5 mg of free iodide[42]. Hence we believe
that as long as the exclusion criteria are followed, there should be no deleterious effect to HCW or
patients due to increased iodine intake from this protocol.
Hence in deciding the dosing regimen for patients and healthcare workers we balance the risk of
iodine toxicity versus the protective effect of PVP-I. There are very few contraindications to using
PVP-I as a mouthwash or nasal spray. Its administration is cheap, simple and rapid using our
methods. PVP-I is readily available in healthcare worldwide. Sensitisation is extremely rare.
Conclusion
There is considerable evidence of benefit for the use of PVP-I antiseptic for the maintenance of oral
health prevention and treatment of oropharyngeal infections, but there is a noted discordance
between the evidence base and translation into clinical practice[37]. As an adjunct to currently
recommended PPE used during management of COVID-19 patients, we recommend the
consideration of immediate use of PVP-I in healthcare workers and their patients as described to
minimise the risk of spread of the disease. We acknowledge that the proposal we present extrapolates
in vitro finding into the in vivo setting and that assumptions are made that under normal
circumstances we would confirm with in vivo data prior to recommendations for use. However,
given the strength of in vitro evidence and the low risk, minimal cost and global applicability of the
proposed intervention, which amounts to disinfection of the oro/nasal cavities, we feel that there is
little to lose and potentially much to gain.
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... 27,31 Its mechanism of action occurs through the release of free iodine, which interrupts microbial metabolic pathways, destabilizes the structural components of cell membranes and leads to irreversible damage to pathogens, as it oxidizes nucleic acid molecules. 3,18 It has proven efficacy against species of influenza, such as H1N1, since it acts to block viral activity by inhibiting hemagglutinin and neuraminidases proteins, thus preventing the binding of the virus to cell receptors as well as the release of the viral particle and consequent infection of new cells. 3 The results showed that five review articles indicated the potential efficacy of PVP-I against coronavirus species (Table 1), given that it is characterized by having a larger viral spectrum than CHX, acting against enveloped or non-enveloped viruses. ...
... 2,3,5,17,23 Furthermore, three in vitro studies demonstrated the inactivation of SARS-CoV and MERS-CoV by the antiseptic. 2,17,18 Although allergic reactions have been pointed out by some studies, other studies did not find them in the literature evidence of mucosal toxicity or irritation, even with prolonged use (Table 1). 2,3,5,17,31 Regarding SARS-CoV-2, the two in vitro studies already carried out applied different concentrations of PVP-I to virus samples grown in cell media (Table 2). ...
Article
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Background and Objectives: In the context of the COVID-19 pandemic, in which the main route of transmission is through contact with contaminated saliva, routine dental procedures represent a potential risk of contagion for professionals and patients. To reduce the occurrence of cross-infection, ways of controlling oral microbial load are necessary, such as the use of preoperative mouthwashes. Thus, the aim of this literature review was to assess the potential efficacy of different intra-oral antiseptics in SARS-CoV-2 infection control in dental clinics. Content: This is a literature review, carried out in the LILACS, Cochrane Library, CAPES and MEDLINE databases, using the search terms “mouth rinse”, “dental care”, “COVID-19”, “cetylpiridinium chloride”, “povidone-iodine”, “chlorhexidine”, and “hydrogen peroxide”. Among the 46 potentially relevant articles, fourteen articles were selected, with full texts published in the last 5 years. These were analyzed and categorized according to the type of study (literature review, in vitro and in vivo studies). The antiseptics highlighted as most relevant in terms of antiviral efficacy were povidone-iodine, cetylpyridinium chloride, hydrogen peroxide and chlorhexidine. Conclusion: Little evidence has been found regarding the effectiveness of oral antiseptics against SARS-CoV-2. It is worth mentioning that some studies conducted with povidone-iodine and chlorhexidine show promising results in combating SARS-CoV-2 infection. However, conducting randomized clinical studies is extremely important to determine the effectiveness of these compounds in controlling COVID-19 in dental practice.
... El uso de peróxido de hidrógeno pre procedimental como agente oxidante, en su presentación de colutorio al 1%, sugiere una disminución en la carga viral salival debido a que el SARS-CoV-2 es vulnerable a la oxidación35,38 .Povidona yodada (PVP-I)La povidona yodada es un complemento de yodo soluble en agua, el cual ha sido utilizado ampliamente como antiséptico cutáneo prequirúrgico y como colutorio bucal33 . La acción antimicrobiana de este agente sucede luego de que el yodo libre se disocia de la polivinilpirrolidona y penetra en los microbios para alterar la conformación de las proteínas, oxidando estructuras del ácido nucleico y ocasionando la muerte del microbio39,40 . La efectivad de la povidona yodada ha sido demostrada numerosas veces en varios estudios in vitro, con diferentes tipos de virus, incluyendo el SARS-CoV y el MERS-CoV41,42 . ...
Article
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Actualmente, el odontólogo es uno de los profesionales de la salud con mayor riesgo de contagio de la COVID-19 debido a su contacto directo con la cavidad bucal. La alta exposición a los aerosoles, generados por los instrumentos rotatorios, en pacientes con la COVID-19, eleva el contacto con la carga viral del SARS-CoV-2 en los procedimientos de rutina. Se ha descrito que los colutorios bucales, previos a la atención odontológica, podrían ser soluciones efectivas para la reducción del contagio pese a su poca evidencia clínica. Los colutorios con cloruro de cetilpiridinio (CPC), peróxido de hidrógeno (H2O2), povidona yodada (PVP-I) y gluconato de clorhexidina (CHX) muestran un gran potencial para reducir la carga viral del SARS-CoV-2 en los aerosoles generados a partir de la saliva durante la consulta odontológica. Por lo expuesto, el presente artículo tuvo por objetivo hacer una revisión de la información científica actual sobre la relación del uso de los colutorios bucales con la disminución de la carga viral del SARS-CoV-2.
... Se utiliza habitualmente en una concentración del 1% para la mucositis, profilaxis de infecciones orofaríngeas y prevención de la neumonía asociada al ventilador (39) . Su acción antimicrobiana ocurre después de que el yodo libre se disocia de la polivinilpirrolidona y penetra rápidamente en los microbios para romper las proteínas y oxidar las estructuras del ácido nucleico, causando la muerte microbiana (40,41) . Estudios previos han demostrado que la PY tiene una mayor actividad viricida que otros agentes antisépticos comúnmente usados, incluyendo CHX y cloruro de benzalconio (42) . ...
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RESUMEN Introducción: La Organización Mundial de la Salud anunció a la pandemia del SARS-CoV-2 como una emergencia de salud pública de importancia internacional. Se cree que el uso de algunos enjuagues bucales podría disminuir la carga viral salival y así prevenir el riesgo de infección en profesionales de la salud. El objetivo de esta revisión fue conocer la efectividad de los distintos colutorios orales, en la disminución de la carga viral salival en pacientes COVID-19 positivos. Metodología: Se realizó una revisión sistemática en las bases de datos MEDLINE, EBSCOhost y SciELO para analizar artículos en inglés publicados entre los años 2020 y 2021. Se utilizó la pauta QUADAS para evaluar el riesgo de sesgo de los estudios. Desarrollo: De 75 artículos encontrados, cinco fueron seleccionados para un análisis cualitativo. Los enjuagues bucales analizados fueron Peróxido de Hidrógeno, Povidona Yodada, Cloruro de Cetilpiridinio y Gluconato de Clorhexidina. Cada estudio estandarizó la cantidad de colutorio utilizado, el tiempo de enjuague, el muestreo y el análisis de datos. Las soluciones de Povidona Yodada y Gluconato de Clorhexidina demostraron disminuir la carga viral salival de los pacientes COVID-19 positivos de forma significativa. Conclusión: Pese a que sí hubo colutorios que disminuyeron la carga viral salival de forma efectiva, se requiere mayor cantidad de estudios clínicos con una metodología universal y estandarizada.
... [13] Group B: Gargling with 20 mL of hypertonic saline for 15 s. [14] Group C: Gargling with 36 ml of 0.5% w/v povidone-iodine for 30 s. [15] Group D: Antipyretic, antibiotics, zinc supplements, and Vitamin C as per the standard treatment guidelines. [12] To reduce the experimenter bias, the four participants group were followed up by four different investigators. ...
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Context: In the absence of any specific treatment available for COVID-19, people started practicing traditional nonpharmacological preventive home remedies such as salt water gargling and steam inhalation. The available research evidence on some of these measures opines that steam inhalation, saline gargling, and povidone-iodine gargling does have virucidal properties and do provide symptomatic relief. Aims: The aim is to test this hypothesis, and the present trial was undertaken with an objective to assess the effect of steam inhalation, saline gargling, and povidone-iodine gargling among the COVID-19-positive patients with respect to early test negativity and clinical recovery. Methodology: Open-labeled, parallel, randomized controlled trial was conducted among asymptomatic or mild COVID-19-positive patients in Bangalore from September 2020 to February 2021. In each group of steam inhalation, saline gargling, povidone-iodine gargling, and control, twenty participants were allocated. Daily follow-up was done for 21 days to assess early test negativity and clinical recovery. Trial Registry Number: Clinical Trial Registry India/2020/09/027687. Results: Among 80 participants recruited, 65 (81.3%) were symptomatic. Early test negativity was seen in povidone-iodine gargling group of 6 days (KaplanMeier survival curve, BreslowGeneralized Wilcoxon test P = 0.7 as per the intention-to-treat and as per-protocol P = 0.8). Significant clinical recovery was seen in saline gargling group (4 days, P = 0.01). Conclusion: Povidone-iodine gargling was effective in providing early test negativity, whereas saline gargling was effective in early clinical recovery.
... Anderson et al. [10]showed that PVP-I 1% gargle and mouth wash and 0.45% throat spray were able to achieve 99.99% virucidal activity against SARS-CoV-2 in vitro. A concentration as low as 0.23% were found effective against SARS-CoV2 in vitro [21]. On the other hand, Khan, Parab and Paranjape [22] showed that 0.5% povidone iodine solution can be safely used as gargle and nasal drops. ...
Article
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To assess the virucidal effect of povidone iodine (PVP-I) on severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) located in the nasopharynx and suitable dose-formulation for nasal application were the purpose of this clinical trial. This single-center, open-label randomized clinical trial with a 7-arm parallel-group design was conducted in Dhaka Medical College (DMC) Hospital. A total of 189 reverse transcription-polymerase chain reaction (RT-PCR)-confirmed SARS CoV-2 positive cases aged 12-90 years with symptoms was sequentially enrolled following randomization. Nasopharyngeal clearance of SARS-CoV-2 was tested against PVP-I nasal irrigation (NI) at diluted concentrations of 0.4%, 0.5% and 0.6%, and PVP-I nasal spray (NS) at diluted concentrations of 0.5% and 0.6%. All groups were compared to the corresponding controls (distilled water). Written informed consent was ensured before participation. All procedures were conducted in after ethical clearance from the Ethical Review Board and in accordance with the Declaration of Helsinki. Viral clearance in a repeat RT-PCR (qualitative) was the primary outcome, and occurrence of any adverse event following administration of testing drug was considered as the secondary outcome. Analysis was performed using SPSS (Version 26). All cases were randomized into seven groups and each group consists of 27-patient. Mean age of the cases 43.98 ± 12.67 years (SD). All strength of NI were effective in nasopharyngeal clearance compared to the control (0.4%, p = 0.006; 0.5%, p < 0.001; and 0.6%, p = 0.018). Similarly, all strength of the NS is also effective than control (0.5%, p = < 0.001; and 0.6%, p ≤ 0.001). Highest nasopharyngeal clearance was observed in patients using 0.5% NI (n = 25, 92.6%, p = 0.018). Nasal irritation was the single most adverse event recorded in this trial and found in two patients using 0.4%, and 0.6% PVP-I NI, respectively. Both PVP-I NS and NI are effective for nasopharyngeal clearance in-vivo. However, further community trials are needed to repurpose these solutions as preventive agents against SARS-CoV2. Ethical clearance memo no ERC-DMC/ECC/2020/93. Trial registration NCT Identifier number NCT04549376. Supplementary information: The online version contains supplementary material available at 10.1007/s12070-022-03106-0.
... Considering the emerging evidence demonstrating in vitro and in vivo virucidal efficacy of PVP-I, it seems justified to recommend the use of PVP-I for interrupting direct SARS-CoV-2 transmission. The recommendations of Kirk-Bailey et al, [58] regarding the use of 9 ml of 0.5% PVP-I as a mouthwash both for the patient and for the clinical staff repeated every 2-3 hours up to 4 times a day, can be followed. The authors also recommend the intranasal application of 0.28-0.3 ...
Article
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This integrative review aims to provide a consolidated evidence-based appraisal of the most up-to-date guidelines and recommendations of international public and professional health regulatory bodies in relation to preparedness framework for restructuring safe delivery of dental services amid and beyond the coronavirus disease-2019 (COVID-19) pandemic. Most recent updated guidelines for dental professionals from major international health regulatory bodies were reviewed. PubMed, Google Scholar, Cochrane Central Register of Controlled Trials, WHO COVID-19 and LILACS databases, along with relevant preprints were searched, and citations were checked up to January 23, 2021. The search was performed by one author. Shortlisted articles were read and brought to consensus to be included in the study by at least two co-authors. In case of any disagreement between the judgements, an independent co-author’s decision was taken as final. Of 849 records searched, 61 articles were included in the study. Following content analysis of the global guidelines and the collected prevailing evidence, the common themes and recommendations of different guidance documents were collated and summarized into seven domains. Most guidelines have a consensus regarding implementation of rigorous administrative, engineering and environmental infection control strategies. However, variations do exist with regard to the use of respirators in non-aerosol-generating procedure (non-AGP) settings, employment of airborne precautions during non-AGPs, use of supplemental air-handling systems, and preoperative use of mouthwashes. This evidence-based analysis can serve as a useful reopening resource tool and facilitate effective restructuring for delivery of optimal, equitable and safe dental practices globally, during and while emerging from the pandemic.
Article
Coronavirus Disease 2019 (COVID 19) merupakan penyakit infeksi menular yang muncul pertama kali di Wuhan pada Desember 2019 yang disebabkan oleh Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) dan dapat bertransmisi melalui droplet saat batuk, bersin dan membran mukosa pada hidung dan mulut. Dokter gigi merupakan profesi yang rentan terinfeksi karena sering terpapar dengan saliva dan darah. Povidone iodine menunjukkan aktivitas in vitro terhadap virus, termasuk SARS-CoV. Tujuan dari scoping review ini untuk mengetahui penggunaan obat kumur povidone iodine sebagai tindakan pra-prosedural untuk mengurangi risiko penularan COVID 19. Metode dalam penelitian ini menggunakan metode studi pustaka yaitu data diperoleh dengan cara membaca, mempelajari dan memahami melalui media lain yang bersumber dari literature. Pencarian data dilakukan melalui database PubMed, Science Direct, dan Google Scholar. Hasil scoping review dari 15 artikel menyatakan bahwa adanya penurunan jumlah materi genetik virus yang ada setelah berkumur dengan povidone iodine. Kesimpulan dari scoping review ini bahwa penggunaan obat kumur povidone iodine sebelum tindakan pra-prosedural efektif untuk mengurangi risiko penularan COVID 19.Kata Kunci: Povidone iodine, COVID 19, perawatan gigi
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SARS-CoV-2 is the cause of COVID-19, which has a serious effect on the lower respiratory system. COVID-19 causes bilateral pneumonia and acute respiratory syndrome. Smell disorders are important diagnostic symptoms of COVID-19. This symptom is detected in about 90 % of cases. Anosmia may be the first or even the only symptom and may appear before other symptoms of SARS-CoV-2 infection. In the context of the COVID-19 epidemic, anosmia can be considered a clinical diagnostic criterion when laboratory tests are not available. The sense of smell is one of the most important senses needed to gain information about the environment. Anosmia can occur in both COVID-19 and allergic rhinitis (AR), which can make it difficult to detect the origin of these symptoms and make a diagnosis in the context of the COVID-19 pandemic. Research results indicate AR is not an aggravating factor for COVID-19. Comorbidity of AR does not affect the reduction of the sense of smell in patients with COVID-19. Patients with AR are recommended to use antihistamines and intranasal corticosteroids for relief of symptoms. Control of AR symptoms can help prevent the spread of SARS-CoV-2 infection. It can be assumed that both local and oral corticosteroids at COVID-19 can be regarded as effective in the treatment of olfactory dysfunction. To restore the sense of smell in patients with AR and COVID-19, experts recommend regular olfactory training, which, at the moment, is the only modern scientifically based therapy for restoring post-viral loss of smell. The use of face masks and respirators during a pandemic aims to minimize exposure to allergens and the SARS-CoV-2 virus. However, prolonged wearing of masks and respirators makes breathing even more difficult with rhinitis caused by AR or COVID-19, which reduces the quality of life and worsens the clinical picture.
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SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.
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Importance In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited. Objective To describe the epidemiological and clinical characteristics of NCIP. Design, Setting, and Participants Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020. Exposures Documented NCIP. Main Outcomes and Measures Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked. Results Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 10⁹/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0). Conclusions and Relevance In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.
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With reports of vancomycin-resistant enterococci recently emerging in hospital settings, renewed focus is turning to the importance of multifaceted infection prevention efforts. Careful compliance with established hygiene practices by healthcare workers together with effective antiseptic options is essential for the protection of patients from infectious agents. For over 60 years, povidone iodine (PVP-I) formulations have been shown to limit the impact and spread of infectious diseases with potent antiviral, antibacterial and antifungal effects. In addition to a lack of reported resistance, the benefits of PVP-I include an excellent safety profile and a broad spectrum of effect due to its multimodal action. Studies have shown that hand washing with PVP-I-based antiseptics is effective for the decontamination of skin, while PVP-I mouthwashes and gargles significantly reduce viral load in the oral cavity and the oropharynx. The importance of PVP-I has been emphasised by its inclusion in the World Health Organization’s list of essential medicines, and high potency for virucidal activity has been observed against viruses of significant global concern, including hepatitis A and influenza, as well as the Middle-East Respiratory Syndrome and Sudden Acute Respiratory Syndrome coronaviruses. Together with its diverse applications in antimicrobial control, broad accessibility across the globe, and outstanding safety and tolerability profile, PVP-I offers an affordable, potent, and widely available antiseptic option.
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Introduction: Recent virus epidemics and rising antibiotic resistance highlight the importance of hygiene measures to prevent and control outbreaks. We investigated the in vitro bactericidal and virucidal efficacy of povidone-iodine (PVP-I) 7% gargle/mouthwash at defined dilution against oral and respiratory tract pathogens. Methods: PVP-I was tested against Klebsiella pneumoniae and Streptococcus pneumoniae according to bactericidal quantitative suspension test EN13727 and against severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses (SARS-CoV and MERS-CoV), rotavirus strain Wa and influenza virus A subtype H1N1 according to virucidal quantitative suspension test EN14476. PVP-I 7% gargle/mouthwash was diluted 1:30 with water to a concentration of 0.23% (the recommended concentration for "real-life" use in Japan) and tested at room temperature under clean conditions [0.3 g/l bovine serum albumin (BSA), viruses only] and dirty conditions (3.0 g/l BSA + 3.0 ml/l erythrocytes) as an interfering substance for defined contact times (minimum 15 s). Rotavirus was tested without protein load. A ≥ 5 log10 (99.999%) decrease of bacteria and ≥ 4 log10 (99.99%) reduction in viral titre represented effective bactericidal and virucidal activity, respectively, per European standards. Results: PVP-I gargle/mouthwash diluted 1:30 (equivalent to a concentration of 0.23% PVP-I) showed effective bactericidal activity against Klebsiella pneumoniae and Streptococcus pneumoniae and rapidly inactivated SARS-CoV, MERS-CoV, influenza virus A (H1N1) and rotavirus after 15 s of exposure. Conclusion: PVP-I 7% gargle/mouthwash showed rapid bactericidal activity and virucidal efficacy in vitro at a concentration of 0.23% PVP-I and may provide a protective oropharyngeal hygiene measure for individuals at high risk of exposure to oral and respiratory pathogens. Funding: Mundipharma Research GmbH & Co. KG (MRG).
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Introduction Since the first case of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection was reported in 2012, the virus has infected more than 1300 individuals in 26 countries, and caused more than 480 deaths. Human-to-human transmission requires close contact, and has typically occurred in the healthcare setting. Improved global awareness, together with improved hygiene practices in healthcare facilities, has been highlighted as key strategies in controlling the spread of MERS-CoV. This study tested the in vitro efficacy of three formulations of povidone iodine (PVP-I: 4% PVP-I skin cleanser, 7.5% PVP-I surgical scrub, and 1% PVP-I gargle/mouthwash) against a reference virus (Modified vaccinia virus Ankara, MVA) and MERS-CoV. Methods According to EN14476, a standard suspension test was used to assess virucidal activity against MVA and large volume plating was used for MERS-CoV. All products were tested under clean (0.3 g/L bovine serum albumin, BSA) and dirty conditions (3.0 g/L BSA + 3.0 mL/L erythrocytes), with application times of 15, 30, and 60 s for MVA, and 15 s for MERS-CoV. The products were tested undiluted, 1:10 and 1:100 diluted against MVA, and undiluted against MERS-CoV. Results A reduction in virus titer of ≥4 log10 (corresponding to an inactivation of ≥99.99%) was regarded as evidence of virucidal activity. This was achieved versus MVA and MERS-CoV, under both clean and dirty conditions, within 15 s of application of each undiluted PVP-I product. Conclusion These data indicate that PVP-I-based hand wash products for potentially contaminated skin, and PVP-I gargle/mouthwash for reduction of viral load in the oral cavity and the oropharynx, may help to support hygiene measures to prevent transmission of MERS-CoV. Funding Mundipharma Research GmbH & Co.
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