Role of Povidone-iodine in COVID-19: Excerpts from Published Evidence

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Cases: 1M April 2, 2M April 15, 3M April 27, 4M May 8, 5M May 20, 6M May 30, 7M June 7, 8M June 15, 9M June 22, 10M June 29th, 11M July 4, 12M July 8, 13M July 13, 14M July 17, 15M July 23, 16M July 25, 17M July 29, 18M August 1, 19M August 6, 20M August 10, 21M August 16, 22M August 19, 23M August 21, 24M August 27, 25M August 30, 26M September 3, 27M September 7, 28M September 10, 29M September 14, 30M September 18, 31M September 21, 32M September 23

Ground Zero: Wuhan – in live animal market or cafeteria for animal pathogens: 10th January; Total cases are based on RT PCR, 67% sensitivity
The SARS-CoV-2, which causes COVID-19, is highly contagious. Human-to-human transmission of the disease is the primary route of spread and occurs through respiratory droplets expelled during coughing, sneezing and talking when a person is in close contact (within 1 m) with a person who has the infection. There is no cure for COVID-19 and till an actual vaccine is available, adherence to preventive measures (wearing face mask, hand washing, physical distancing), which protect against the infection, is critical.

The mouth is also a portal of entry for the virus. Throat is a reservoir for the transmission of the virus, as the virus mainly replicates here, even in asymptomatic or presymptomatic persons, who become potential sources of infection. Gargling therefore is another important preventive measure to reduce the viral load in the throat of the infected patients. Although it will not eliminate the virus, it may reduce spread of the virus into the community.

Excerpts from published evidence

Broad spectrum antimicrobial action

“Povidone‐iodine is considered to have the broadest spectrum of antimicrobial action compared with other common antiseptics such as chlorhexidine, octenidine, polyhexanide and hexetidine showing efficacy against Gram‐positive and Gram‐negative bacteria, bacteria spores, fungi, protozoa and several viruses.”1

Potent virucidal activity

“In addition to its broad antibacterial and antifungal activity, PVP-I has demonstrated in vitro activity against a range of viruses, including the related SARS-CoV and MERS-CoV.” 2
“Povidone‐iodine has been reported as having the highest virucidal activity profile among several antiseptics such as CHG, benzalkonium chloride (BAC), BEC and alkyldiaminoethyl‐glycine hydrochloride (AEG). Using a standardised in vitro approach, PVP‐I gargle was found to inactivate a panel of viruses that included adenovirus, mumps, rotavirus, poliovirus (types 1 and 3), coxsackie virus, rhinovirus, herpes simplex virus, rubella, measles, influenza and human immunodeficiency virus.” 1
“PVP-I gargle/mouthwash diluted 1:30 (equivalent to a concentration of 0.23% PVP-I) showed effective bactericidal activity against Klebsiella pneumoniaeand Streptococcus pneumoniae and rapidly inactivated SARS-CoV, MERS-CoV, influenza virus A (H1N1) and rotavirus after 15 s of exposure.” 3
“Viral infectious titers were reduced to levels below the detection limits by incubation for only 10 s with the PVP-I products used in this study. These results indicate that PVP-I products have virucidal activity against avian influenza A viruses.” 4
Virucidal activity against SARS-CoV-2 virus: In vitro evidence

“All four products [antiseptic solution (PVP-I 10%), skin cleanser (PVP-I 7.5%), gargle and mouth wash (PVP-I 1%) and throat spray (PVP-I 0.45%)] achieved ≥ 99.99% virucidal activity against SARS-CoV-2, corresponding to ≥ 4 log10 reduction of virus titre, within 30 s of contact. This study provides evidence of rapid and effective virucidal activity of PVP-I against SARS-CoV-2.” 2
In a Letter to Editor published in the British Dental Journal, Hassandarvish et al have given evidence of the in vitro virucidal activity of an oral PVP-I product against the SARS-CoV-2 virus. They write, “In our study, we present direct evidence of the virucidal activity of PVP-I gargle and mouthwash against SARS-CoV-2 in just 15 seconds. The study demonstrated that undiluted PVP-I achieved >5 log10 reduction in the virus titres at 15, 30 and 60 seconds treatment exposure under both clean and dirty conditions. In contrast, when PVP-I was tested at 1:2 dilution a >4 log10 kill at 15 seconds and >5 log10 kill at 30 and 60 seconds in comparison to control was seen in both clean and dirty.” 5
PVP-I mouthwash is included in the WHO R&D Blueprint for Experimental Therapies against COVID-19. 6

Rationale for throat gargling in COVID-19 pandemic

“SARS-CoV-2 shows tropism for the throat tissue, which is associated with disease transmission and severity.” 7
“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.” 8
“We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% (95% confidence interval, 30–57%) of secondary cases were infected during the index cases’ presymptomatic stage, in settings with substantial household clustering, active case finding and quarantine outside the home.” 9
“It is therefore imperative to reduce the viral load in oropharynx with adequate oral prophylactic measures.” 10
“Thus, throat gargling… might be potentially useful in controlling the COVID-19 pandemic.” 7 “This intervention is not intended to cure the disease but may significantly and dramatically reduce viral spread into the community and workplaces.” 11
Ricardo AP Persaud writes in an article in the Online Journal of Otolaryngology & Rhinology, “In my opinion, P-I is the new PPE and its topical usage in nose, oral cavity and pharynx is now one of the best ways to flatten the Curve of Covid-19, especially in countries like USA, India and Brazil.” 12
References

Kanagalingam J, et al. Practical use of povidone‐iodine antiseptic in the maintenance of oral health and in the prevention and treatment of common oropharyngeal infections. Int J Clin Pract. 2015;69:1247–56.
Anderson DE, et al. Povidone-iodine demonstrates rapid in vitro virucidal activity against SARS-CoV-2, the virus causing COVID-19 disease. Infect Dis Ther. 2020:1–7.
Eggers M, et al. In vitro bactericidal and virucidal efficacy of povidone-iodine gargle/mouthwash against respiratory and oral tract pathogens. Infect Dis Ther. 2018;7(2):249–59.
Ito H, et al. Outbreak of highly pathogenic avian influenza in Japan and ant-influenza virus activity of povidone-iodine products. Dermatology. 2006;212(Suppl 1):115–8.
Hassandarvish P, et al. Povidone iodine gargle and mouthwash. Br Dent J. 2020;228(12):900.
WHO R&D Blueprint COVID 19 Experimental Treatments: World Health Organisation. 2020. Available at: https://www.who.int/docs/default-source/coronaviruse/covid-classification-of-treatment-types-rev.pdf, Accessed 30.7.20.
Tsai C, et al. Possible beneficial role of throat gargling in the coronavirus disease pandemic. Public Health. 2020;185:45-6
Zhou L, et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med 2020;382:1177-9.
He X, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. Nat Med. 2020;26:672-5.
Pattanshetty S, et al. Povidone-iodine gargle as a prophylactic intervention to interrupt the transmission of SARS-CoV-2. Oral Dis. 2020;10.1111/odi.13378.
Mendoza L. Prevention of COVID-19 Infection with Povidone-Iodine (April 30, 2020). Available at SSRN: https://ssrn.com/abstract=3589404 or http://dx.doi.org/10.2139/ssrn.3589404
Ricardo AP Persaud. Povidone-Iodine may be the “Silver Bullet” in the Prevention and Control of Covid-19 Infection, Based on New Scientific Data. On J Otolaryngol & Rhinol. 3(1): 2020.

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA

Coronavirus Cases: 33,546,651

Deaths: 1,006,337

Recovered: 24,876,169

ACTIVE CASES 7,664,145

Currently Infected Patients7,598,798 (99%) in Mild Condition

65,347 (1%) Serious or Critical

CLOSED CASES 25,882,506

Cases which had an outcome: 24,876,169 (96%) Recovered / Discharged

1,006,337 (4%) Deaths

#

Country,Other

TotalCases

NewCases

TotalDeaths

NewDeaths

World

33,542,877

+229,710

1,006,121

+3,829

1

USA

7,361,611

+37,418

209,808

+355

2

India

6,143,019

+69,671

96,351

+777

3

Brazil

4,748,327

+16,018

142,161

+385

4

Russia

1,159,573

+8,135

20,385

+61

5

Colombia

818,203

+5,147

25,641

+153

India

India-USA New cases per day: 32253 difference

Total difference 1218592

With this speed and public behavior, India may cross USA by October end (38 Days), Deaths > 100,000 by 3rd October

Doubling time 37 days

28th September: New cases 69671, New Deaths 777, Total Cases 6143019, Total Deaths 96351

27th September: New Cases 82767, New Deaths 1040, Total Cases 6073348, Total Deaths 95574

26th September: New cases 89010, New Deaths 1124, Total Cases 5990581, Total Deaths 94534

25th September: New cases 85468, New Deaths 1093, Total Cases 5901571, Total Deaths 93410

24th September: New Cases 85919, New Deaths 1144, Total cases 5816103, Total Deaths 92317,

23rd September: New cases 89688, New Deaths 1152, Total Cases 5730184, Total Deaths 91173

22nd September: New cases 80391, New Deaths 1056, Total Cases 5640496, Total Deaths 90021

21st September: New Cases 74493, New Deaths 1056, Total Cases 5560105, Total Deaths 88965

20th September: New cases 87382, New deaths 1135, Total Cases 5485612, Total Deaths 87909

19th September: New cases 92755, New deaths 1149, Total cases 5398230, Total Deaths 86774

18th September: New cases 92789, New Deaths 122, Total Cases 5305475, Total Deaths 85625

17th September: New cases 96793, New Deaths 1174, Total cases 5212686, Total Deaths 84404

16th September: New cases 97859, New Deaths 1139, Total cases 5115893, Total Deaths 83230

15th September: New cases 91120, New Deaths 1283, Total Cases 5018-34, Total Deaths 82091

14th September: New cases 81911, New Deaths 1054, Total Cases 4926914, Total Deaths 80808

13th September: New cases 93215, New Deaths 1140, Total Cases 4845003, Total Deaths 79754

12th September: New cases 94409, New Deaths 1108, Total Cases 4751788, Total Deaths 78614

11th September: New cases 97654, New Deaths 1202, Total Cases 4657379, Total Deaths 77506

10th September: New cases 96760, New Deaths 1213, Total Cases 4559725, Total Deaths 76304

9th September: New cases 95529, New Deaths 1168, Total Cases 4462965, Total Deaths 75091

8th September: New cases 89852, New Deaths 1107, Total Cases 4367436, Total Deaths 73923

7th September: New Cases 75022, New Deaths 1129, Total cases 4277584, Total Deaths 72816

6th September: New cases 91723, New Deaths 1008, Total Cases 4202562, Total Deaths 71687

5th September: New cases 90600, New deaths 1044, Total Cases 4110839, Total Deaths 70679

4th September: New cases 87115, New deaths 1066, Total Cases 4020239, Total Deaths 69635

3rd September: New Cases 84156, New Deaths 1083, Total Cases 3933124, Total Deaths 68569

2nd September: New Cases 82860, New Deaths 1026, Total cases 3848968 Total Deaths 67486

1st September: New cases 78169, New Deaths 1025, Total cases 3766108, Total deaths 66460

31st August: New cases 68770, New Deaths 818, Total cases 3687939, Total deaths 65435

30th August: New cases 79457, New Deaths 960, Total cases 3619169, Total deaths 64617

29th August: New Cases 78472 New Deaths 944 Total cases 3539712 Total deaths 63657

28th August: New Cases 76665, New Deaths 1019, Total cases 3461240, Total deaths 62713

27th August: New Cases 76826, New Deaths 1065, Total cases 3384575, Total deaths 61694

26th August: New cases 75995, New Deaths 1017, Total cases 3307749, Total deaths 60629

25th August: New cases 66873, New Deaths 1066, Total cases 3231754, Total deaths 59612

24th August: New cases 59696, New Deaths 854, Total cases 3164881, Total deaths 58546

23rd August: New cases 61749, New Deaths 846, Total cases 3105185, Total deaths 57692

22nd August: New cases 70068; New Deaths 981; Total cases 3043436; Total Deaths 56846

India predictions

Death rate is deaths today vs number of cases today.
Corrected death rate is deaths today vs number of cases 14 days back.
For one symptomatic test positive case, there are 10-30 asymptomatic cases and 20 untested cases.
Estimated number of deaths = Reported deaths x 2.
Number of deaths today should be 15% of the serious patients present 14 days back.
Undocumented cases for each documented case – Iceland: 1: 2; Germany: 1: 5; New York City grocery store shoppers: 1: 10; California: 1.5%.
Amongst active cases, 2.37% are serious, 1.82% need oxygen, and 0.41% need ventilator support.
Facts

DENSITY: India: In states with average population density of 1185/sq km, the average number of cases were 2048. On the contrary, in states with population density of 909/sq km, the number of cases were 56. When Chandigarh and Pondicherry were taken out from this group, the Average Density of other states were 217 and the average number of cases were 35. [HCFI]

COVID Sutra: COVID-19 pandemic is due to SARS 2 Beta-coronaviruses (different from SARS 1 where spread was only in serious cases); with over eleven virus sequences floating; has affected up to 22.8% of Delhi population, Causes Mild or Atypical Illness in 82%, Moderate to Severe Illness in 15%, Critical Illness in 3% and Death in 2.3% cases (15% of admitted serious cases, 71% with comorbidity< Male > Females); affects all but Predominantly Males (56%, 87% aged 30-79, 10% Aged < 20, 3% aged > 80); with Variable Incubation Period days (2-14; mean 5.2 days); Mean Time to Symptoms 5 days; Mean Time to Pneumonia 9 days, Mean Time to Death 14 days, Mean Time to CT changes 4 Days, Reproductive Number R0 1.5 to 3 (Flu 1.2 and SARS 2), Epidemic Doubling Time 7.5 days; Origin Possibly from Bats (Mammal); Spreads via Human to Human Transmission via Large and Small Droplets and Surface to Human Transmission via Viruses on Surfaces for up to three days. Enters through MM of eyes, nose or mouth and the spike protein gets attached to the ACE2 receptors. ACE2 receptors make a great target because they are found in organs throughout our bodies (heart muscle, CNS, kidneys, blood vessels, liver). Once the virus enters, it turns the cell into a factory, making millions of copies of itself, which are then breathed or coughed out and infect others.

CMAAO Coronavirus Facts and Myth Buster: Human Challenge Trials

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With inputs from Dr Monica Vasudev

1047:  Human Challenge Trials for COVID-19 Vaccine and the Risk

Human challenge trials for the COVID-19 vaccine — These trials involve volunteering to receive an unproven vaccine, being exposed to the virus deliberately, instead of waiting to be exposed and for infection to occur naturally in the community.

The goal of such trials is to hasten vaccine development. Over 32,000 people from the United States and 139 other countries have signed up with an online registry, 1Day Sooner.

The trials could pave the way for delivering a vaccine and end the pandemic more quickly; however, there are several unknowns associated with this novel coronavirus, besides the lack of an effective treatment.The extra risk could come at a high cost – that of health, or potentially the life, of the volunteers.

These trials can be faster than conventional field trials, in part because fewer participants need to be exposed to provide early estimates of efficacy and safety.If one vaccine doesnt work, researchers can move on to other candidates. In challenge trials, volunteers are given the vaccine candidate or a placebo, just like conventional trials. After waiting for the vaccine to take effect, the volunteers are exposed to the virus.

While traditional vaccine trials may enrol 30,000 participants in phase 3 studies and have results in 6 months, challenge trials require only about 150 participants and obtain results in a period of 6 weeks. Several vaccine candidates can be compared at once through these trials and the most promising ones are subjected to larger studies.

Can a volunteer give informed consent when there are so many aspects that are unknown about COVID-19? According to clinicians, they would communicate the pros and cons if one of their patients ask about joining up.

According to the WHO, over the past 50 years, challenge studies have been safely conducted in thousands of consenting adult volunteers. The studies have helped ramp up the development of vaccines against cholera and typhoid and to assess immune protection against influenza.

Reducing even 1 day off vaccine development time could potentially save 7120 lives, according to estimates.

And reducing the development time by 3 months would go on to save more than a half million lives, according to estimates, considering that one sixth of the world would acquire COVID-19 annually and that a vaccine would prevent 0.2% of those people from dying.

Some experts note that the participants may include high-risk individuals who volunteer as they believe that the first vaccine attempts could prevent them from contracting COVID-19, a belief that may be termed “prevention misconception.” [Medscape Excerpts]

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA

CMAAO Coronavirus Facts and Myth Buster: COVID-19 Asian Countries Update

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1043: Minutes of Virtual Meeting of CMAAO NMAs on “Asian Countries Update – Part 1”

1st August, 2020, 9.30am-10.30am

Participants: Member NMAs

Dr KK Aggarwal, President CMAAO, Dr Yeh Woei Chong, Singapore Chair CMAAO, Dr Marthanda Pillai, Member World Medical Council. Dr Alvin Yee-Shing Chan, Hong Kong, Dr Subramaniam Muniandy, Malaysia, Dr Marie Uzawa Urabe, Japan, Dr Ashraf Nizami, Pakistan, Dr Prakash Budhathoky, Nepal

Invitees: Dr Russell D’Souza, UNESCO Chair in Bioethics, Australia, Dr S Sharma, Editor IJCP Group

Dr Marthanda Pillai spoke about COVID situation in the Gulf countries. Dr KK Aggarwal analyzed the COVID data in South Asia and Dr Yeh Woei Chong gave an update on COVID in China, South Korea and Singapore. Dr Alvin Yee-Shing Chan spoke on the current scenario of COVID in Hong Kong.

COVID in Gulf countries

Dr Marthanda Pillai

Many of the Gulf countries have been proactive in their response to COVID-19, launching tremendous efforts to control the infection prior to detecting the first case.
Iran was the first country to be affected; it continues to be a hotspot.
Saudi Arabia: Spread from Iran; disease detected in Jan/Feb, quick to implement measures to control the infection.
UAE reported four cases on 29th Subsequently, Bahrain, Kuwait, Oman, Iraq and Qatar reported their first case in late February. These cases were either Iranians or citizens of Gulf countries who had recently visited Iran.
Lockdown has been implemented, schools/religious places have been closed, no public transport in operation.
There is a good system of testing.
The entire treatment is free, especially COVID-19 treatment, for all citizens.
Overall, total cases are around 2.3 lakh; the cure rate is around 45-50%. Mortality is less than 1%, except in Iran, where mortality is 3.2%.
Non-COVID patients are restricted; e-prescriptions are being given, which has helped to control the infection.
Restrictions are in place; there is no international travel except chartered flights for people who wish to go back to their country of origin. Their status is checked.
The status of these countries has an indirect impact on the situation in our countries.
COVID-19 in South Asia

Dr KK Aggarwal

The south Asian region includes 8 countries: Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan andSri Lanka.
If the population density is more, the number of cases will be more in the first wave. If density is more than 1000, the number of cases is higher. Among the 5 countries, Bangladesh is the most densely populated at 1174/sq km. In all the rest, the density varies between 200 and 400.
India has the maximum number of cases in the South Asia region.
India, Pakistan and Bangladesh are almost the same in terms of total deaths per million population (20-25) and also same case fatality rate, which is around 2%. The total deaths per million population is 2 in Nepal; this may be because Nepal is yet to peak and spread is not yet seen.
The situation in Sri Lanka is; however, different, despite similar population density. The case fatality rate is low (1%) as is the total number of cases.
Analysis of the indicators of health infrastructure shows that all five countries have almost similar number of physicians per 1000 people. But in terms of hospital beds per 1000 population, Sri Lanka has the highest number (3.6); in India, Pakistan, Nepal and Bangladesh, this number if 0.5-0.8.
Sri Lanka and India reported their first case of COVID-19 at nearly the same time; 27thJanuary and 30th January, respectively.
All five countries implemented lockdown around the same time, but Sri Lanka extended the lockdown much longer.
More than 10% positive rate practically means community transmission and if less than 5%, then lockdown can be lifted. India, Pakistan and Bangladesh have more than 10% positivity rate.
Reasons for low mortality in Sri Lanka: First in the region to eliminate malaria, better hygiene index, educated population, better infrastructure, extended lockdown.
Kerala has similar mortality as that of Sri Lanka (0.3%); total cases are 23,000 cases and only 74 deaths. The seroprevalence is less than 10%. The seroprevalence in Delhi and Mumbai and Pakistan is around 20-30%. In Bangalore, seroprevalence is 10-12%.
COVID-19 in China, South Korea & Singapore

Dr Yeh Woei Chong

China:Confirmed cases 84,292 (discharged 78,974, deaths 4,634); cases have been rising from last one week. From 11th June to 23rd June, there were 256 cases in Beijing. Prior to this, there were no cases for 55 days. The trigger is a seafood market like in Wuhan and the source of infection apparently is contaminated chopping boards. China has a huge testing capacity; it is testing people in large numbers – half million tests daily. Outbreaks in Dalian and Xinjiang in the last week; the new outbreak in Dalian has been linked to a seafood company and contamination from packaging is suspected. On 30th July, there were 11 cases in Dalian and 112 in Xinjiang.
South Korea:There are more than 14,000 confirmed cases; 13,183 have been discharged and around 300 have died due to the infection. There is a second wave in South Korea. The number of cases is increasing. There were 113 cases on 30th July (Friday). South Korea has done 1,563,796 tests. Their clusters are nightclubs, door to door sales, churches, ports, and nursing homes.
Singapore:There are around 52,000 cases. Majority of cases in the country are in dormitories housing migrant workers (around 50,000), while the community has only around 2000 cases. Last week there were 400 cases in dormitories and 5 in the community. Around 5400 cases are in isolation. Since February, there are 128 ICU cases; this number has been zero since last 2 weeks. Number of tests performed is 1.23 million. There are 323,000 migrant workers in dormitories. Of these, 262,000 have recovered or cleared of the virus. Efforts are on to clear all the dormitories of COVID-19 by 7th August. Migrant workers are swabbed every month towards this end. 975 factory dorms + 64 blocks in 17 purpose-built dorms have been cleared. Everybody is swabbed and if there are any cases, swabbed again after a week. 13,000 swab tests are done in a day.
Hong Kong Update

Dr Alvin Yee-Shing Chan

Hong Kong is experiencing the third wave (July) with 3271 cases and 27 deaths, which is serious; up to end of June, there were 1200 cases and 8 deaths; in 2ndwave in April, the maximum number was only 65.
Origin of the third wave is from sea men and air crew who were exempted from quarantine and routine testing together with relaxation of rules of social gathering and fatigue set in.
No capacity for en massetesting; bottleneck of testing 13,000 daily; now screening started for high risk groups – people working in restaurants, catering, sellers, etc. No exemption now from testing and quarantine.
Manpower is adequate; 6219 doctors in public hospitals; only half of public hospital beds are occupied in the past two months as all elective surgeries have been postponed in public hospitals.
T614 gene mutation was found in cluster of sailors entering Hong Kong from Kazakhstan and Philippines; this DNA expression is similar to that seen in many people in Hong Kong infected in the third wave. Patients became more serious and more infectious.
Virology Dept in the University of Hong Kong is working on research to produce a vaccine against COVID-19.
Holiday homes/villages/resorts have been modified as isolation and quarantine centers for mild cases to prevent cross infection to family members.
Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA

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