Dear Colleague

HCFI and MAMC are making a white paper on current status of coronavirus. Mentioned below are some of the deliberations discussed. Inputs are invited before a final document is made. The names of the persons adding inputs will be added to the round table expert’s group.

CMAAO Update 12^th February on novel coronavirus 2019

Namaste: Let’s not shake hands

Good News: Total cases increasing, deaths increasing BUT total daily cases declining

  Confirmed cases:  45166; Countries 28; Deaths 1115

Active cases: 39267 (currently infected), 31025 (79%) mild cases; 8242 (21%) serious cases; 12 serious cases outside China

Closed cases: 5899 (no outcome), 4784 (81%)

Pattern: 82% mild, 15% severe, 3% critical, 2% deaths

Serious or critical mortality: 15%

More than 136 cases have been confirmed on a ship quarantined in Japan

Secondary cases: Thailand, Taiwan, Germany, Vietnam, Japan, France, US

Deaths outside China: Philippines on Feb 2 (44-year-old Chinese man) and 2^nd in Hong Kong (39 M, local) on February 4; both had co-morbid conditions. Both acquired infection from Wuhan.

Likely deaths: 1115 +1236 = 2351, with the present trend and available treatment

Summary

The virus possibly behaves like SARS with <2 % case fatality (15% of admitted serious cases),  mean time to death 14 days,  mean time to pneumonia 9 days, mean time to symptoms 5 days, 3-4 reproductive number R0, incubation period 2-14 days, mean 5.5 days, has origin possibly from bats, spreads through large droplets and predominantly from people having lower respiratory infections and hence, standard droplet precautions are the answer for the public and airborne precautions for the healthcare workers. [So: RT Experts meet HCFI and MAMC]

 CDC Case Definition

1. Fever (subjective or confirmed)

OR signs/symptoms of lower respiratory illness (cough or shortness of breath)

PLUS, any person (including health care workers) who has had close contact with a laboratory-confirmed novel coronavirus patient within 14 days of symptom onset.

Contact refers to: Being within nearly 6 feet (2 meters) or within the room or care area of a 2019-nCoV case for a prolonged time while not wearing recommended personal protective equipment (gowns, gloves, NIOSH-certified disposable N95 respirator, eye protection); close contact may involve caring for, living with, visiting, or sharing a health care waiting area or room with a 2019-nCoV case OR having direct contact with infectious secretions of a 2019-nCoV case (such as being coughed on) while not wearing recommended personal protective equipment.

1. Fever andsigns/symptoms of lower respiratory illness (cough or shortness of breath) PLUS a history of travel from Hubei Province, China within 14 days of symptom onset
2. Feverand signs/symptoms of lower respiratory illness (cough or shortness of breath) requiring hospitalization PLUS a history of travel from mainland China within 14 days of symptom onset.

Continue asking patients with suspected flu or diarrhea if they, or someone they have been in contact with, recently returned from coronavirus-affected area. [In US, in a confirmed case, 2019-nCoV RNA has been identified in a stool specimen collected on day 7 of the patient’s illness.]

 Public Health Emergency of International Concern 30^th January, 2020

Mandatory to report to WHO each human and animal case.

Prior 5 PHEIC’s: 

 26^th April 2009 Swine flu: 10 August 2010, WHO announced that the H1N1 influenza virus has moved into the post-pandemic period. However, localized outbreaks of various magnitudes are likely to continue.

May 2014 Polio: resurgence of wild polio. October 2019 - continuing cases of wild polio in Pakistan and Afghanistan, in addition to new vaccine-derived cases in Africa and Asia; the status was reviewed and it remains a PHEIC. It was extended on 11 December, 2019.

August 2014 Ebola: It was the first PHEIC in a resource-poor setting.

Feb 1, 2016 Zika: link with microcephaly and Guillain–Barré syndrome. This was the first time a PHEIC was declared for a mosquito‐borne disease. This declaration was lifted on 18 November, 2016.

2018–20 Kivu Ebola: A review of the PHEIC had been planned at the fifth meeting of the EC on 10 October, 2019^[ and as of 18 October, 2019, it continues to be a PHEIC.

Kerala: State public health emergency. Three primary cases have been reported in North, South and Central Kerala (Kasaragod district in north Kerala, Thrissur in central Kerala and Alappuzha in South Kerala). Four Karnataka districts bordering Kerala — Kodagu, Mangaluru, Chamarajanagar and Mysuru - have been put on high alert.

 Help line India:  +91-11-23978046, ncov2019@gmaildotcom, mohfw.gov.in/node/4904

Virus

Single-strand, positive-sense RNA genome ranging from 26 to 32 kilobases in length, Beta coronavirus from Corona family.

 ‘Corona’ means crown or the halo surrounding the sun. Heart is considered crown and hence the arteries that supply oxygen to the heart are also called coronary arteries. Under an electron microscope, the virus appears round with spikes poking out from its periphery.

Origin: Wuhan, China; December 2019

1^st case informed to the world by Dr. Li Wenliang; died on Feb 6^th

 Virus is likely killed by sunlight, temperature, humidity. The virus can remain intact at 4 degrees or 10 degrees for a longer time. At 30 degrees; however, there is inactivation. The virus cannot also tolerate high humidity. SARS stopped around May and June in 2003 probably due to more sunlight and more humidity. Alive on surface: 3-12 hours

Link to ACE: 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans.

Three deadly human respiratory coronaviruses: Severe acute respiratory syndrome coronavirus [SARS-CoV], Middle East respiratory syndrome coronavirus [MERS-CoV]) and 2019-nCoV: The virus is 75-80% identical to the SARS-CoV.

 Pathogenesis

High viral load: Detection of 2019-nCoV RNA in specimens from the upper respiratory tract with low Ct values on day 4 and day 7 of illness suggests high viral loads and potential for transmissibility. [NEJM]

 2019-nCoV uses the same cellular receptor as SARS-CoV (human angiotensin-converting enzyme 2 [hACE2]), so transmission is expected only after signs of lower respiratory tract disease develop.

SARS is high [unintelligible] kind of inducer. This means that when it infects the lower part of the lung, the body develops a very severe reaction against it and leads to lots of inflammation and scarring. In SARS, after the first 10 to 15 days, it wasn’t the virus killing the patients it was the body’s reaction. Is this virus in the MERS or SARS kind picture or is this the other type of virus which is a milder coronavirus like the NL63 or the 229? It may be the mild (unintelligible) kind of inducer. [Dr John Nicholls University of Hong Kong]

Infectiousness to humans: This new virus seems to thrive better in primary human airway epithelial cells as compared to standard tissue-culture cells, unlike SARS-CoV or MERS-CoV. The 2019-nCoV will likely behave more like the SARS-CoV.

SARS-CoV and MERS-CoV affect the intrapulmonary epithelial cells more than the upper airway cells. Transmission thus occurs primarily from patients with recognized illness and not from patients with mild, nonspecific signs. However NEJM has reported a case of 2019-nCoV infection acquired outside of Asia wherein transmission seems to have taken place during the incubation period in the index patient but the same has been challenged now.

2019-nCoV seems to employ the same cellular receptor as SARS-CoV (human angiotensin-converting enzyme 2 [hACE2]). Transmission is expected to occur only after signs of lower respiratory tract disease develop.

 No sore throat: This new virus attacks the lungs as well, and not just the throat. Patients so far have not presented with a sore throat, because the 2019-nCoV attacks the intraepithelial cells of lung tissue.

 Transmission

Types: Droplet (droplet, contact, fomites) Corona; aerosol, nuclei or airborne, e.g. TB

Kissing scenes banned in movies in China

Air crew exempted from breath analyser tests: Kerala

Burial:  China has banned death ceremonies, people gathering together Lockdown: 50 million people in China

Asymptomatic transmission: A report of a small cluster of five cases indicated transmission from asymptomatic individuals during the incubation period; all patients in this cluster had mild illness. Another person got infected while using gown, but the eyes were not covered. NEJM reported a transmission from asymptomatic case but the same has been challenged.

 Link to Huanan Seafood Wholesale Market: 55% with onset before January 1, 2020 and 8.6% of the subsequent cases. The Chinese government has banned the wildlife trade until the epidemic passes. 

 Zoonotic but unlikely to spread through seafood: This new coronavirus is closely related to bat coronaviruses. Bats seem to be the likely primary reservoir for the virus. While SARS-CoV was transmitted to humans from exotic animals in wet markets, MERS-CoV transmitted from camels. The ancestral hosts were probably bats; however.

The virus has been traced to snakes in China. Snakes often hunt for bats. According to reports, snakes were sold in the local seafood market in Wuhan, thus raising the likelihood that the 2019-nCoV might have moved from the host species, i.e., bats, to snakes and then to humans. It is still not understood as to how the virus could adapt to both the cold-blooded and warm-blooded hosts. 

 Risk to other Asian countries: It is less likely to have serious illness in other countries, as patients with breathlessness are unlikely to board and patients will mild illness or asymptomatic illness are less likely to transmit infections.

Legal Implications India: Section 270 in The Indian Penal Code: 270. Malignant act likely to spread infection of disease danger­ous to life.—Whoever malignantly does any act which is, and which he knows or has reason to believe to be, likely to spread the infection of any disease dangerous to life, shall be punished with imprisonment of either description for a term which may extend to two years, or with fine, or with both.

 Clinical Features (Current trend)

Median age: 59 years (2-74 years); Male to female ratio: 56% male

Mean incubation period: 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days.

Epidemic doubling time: In its early stages, every 7.4 days, with a mean serial interval of 7.5 days (95% CI, 5.3 to 19)

Contagiousness or Basic reproductive number: 2.2 (95% CI, 1.4 to 3.9).  The reproduction number, referred to as R0 or “r naught” is the number of additional people that an infected person can infect. An outbreak with a reproductive number of below 1 will gradually disappear. The R0 for the common flu is 1.3 and for SARS it was 2.0.

Comorbid conditions: 71%, deaths in comorbid cases; SARS affected people in their 30 or 50 years. MERS affected people with co-morbidity. The China data indicate that it’s those with the co-morbidity that are most at risk like seasonal influenza.

0-15 years age: Just like SARS, it mostly does not affect children 15 years of age or less

ICU need: 20% need ICU care, with 15% mortality

Fever: In all (no fever, no corona)

Cough: 75% cases

Weakness or muscle ache: 50%

Shortness of breath: 50%

TLC: low

Liver transaminase levels: raised

Case fatality: 2% [Dr John Nicholls, University of Hong Kong] China is only reporting those who come for test; there are stricter guidelines for a case to be considered positive; actual mortality may be 0.8%-1%, like outside China

Healthcare Workers: In Hong Kong, with SARS, there was a lot of infection of healthcare workers since they were close to patients and did invasive procedures. But now, there is not much evidence of the healthcare workers getting sick or dying (unless China is not reporting it).  This may suggest that it is not being spread by close aerosol contact but more likely by the fecal-oral route or with droplets. So, it may not be as contagious within hospitals. Makeshift hospitals will help.

Lab precautions: BSL 2 (3 for viral culture labs)

Human to human contact period: Requires prolonged contact (possibly ten minutes or more), within three to six feet

 Travel restrictions

Travel preferable seat: Choosing a window seat and staying there lowers the risk

Travel advisory:  Level 1 in all countries (Exercise normal standard hygiene precautions), Level 2 in all  affected countries and states including Kerala ( Exercise a high degree of caution), Level 3 in all countries with secondary cases (Reconsider your need to travel) done by India and Level 4 ( Do not travel) done by US. Hong Kong has imposed 14 days quarantine on people arriving from China. The Karnataka government has ordered that anybody arriving from the 23 coronavirus affected countries must stay in isolation at home for 28 days. The home isolation requirement is irrespective of the virus symptoms. To date, 72 countries have implemented travel restrictions.

Travel and trade restrictions: WHO says no to countries

Leave china all together: UK, condemned by many countries

Entry to India not allowed: foreigners who went to China on or after January 15

Visas Suspended: All visas issued to Chinese nationals before February 5 (not applicable to aircrew)

Flight suspended: IndiGo and Air India have suspended all of their flights between the two countries. SpiceJet continues to fly on Delhi-Hong Kong route.Mass Quarantine May Spark Irrational Fear, Anxiety, Stigma

 Evacuation Many countries including US, Japan, India have evacuated their citizens.

 Case fatality

Current Coronavirus 2%

MERS 34% (2012, killed 858 people out of the 2,494 infected)

SARS 10% (Nov. 2002 - Jul. 2003, originated from Beijing, spread to 29 countries, with 8,096 people infected and 774 deaths) 

Ebola 50%

Smallpox 30-40%

Measles 10-15% developing countries

Polio 2-5% children and 15-30% adults

Diphtheria 5-10%

Whooping cough 4% infants < 1yr, 1% children < 4 years

Swine flu < 0.1-4 %

Seasonal flu 0.01%.

Current virus in Wuhan 4.9%.

Current virus in Hubei Province 3.1%.

Current virus in Nationwide 2.1%.

Current virus in other provinces 0.16%.

Number of flu deaths every year: 290,000 to 650,000 (795 to 1,781 deaths per day)

 Lab tests

There are two ways to detect a virus: through the genetic material DNA or RNA and to detect the protein of the virus. The rapid tests look at the protein. It takes 8-12 weeks to make commercial antibodies. Currently, for the diagnostics tests, PCR is being used which gives  a turnaround in 1-2 hours.

Treatment

No proven antiviral treatment.

With SARS, in 6 months the virus was gone and it never came back.

Pharmaceutical companies may not spend millions to develop a vaccine for something which may never come back.

Secondary infection, E.coli, is most likely the cause of deaths of the patients in the Philippines and Hong Kong.

A combination of lopinavir and ritonavir showed promise in lab in SARS

Combination of lopinavir, ritonavir and recombinant interferon beta-1b was tried in MERS

Scientists in Australia have reportedly recreated a lab-grown version of coronavirus.

Chloroquine had potent antiviral activity against the SARS-CoV, has been shown to have similar activity against HCoV-229E in cultured cells and against HCoV-OC43 both in cultured cells and in a mouse model.

Thailand: Oseltamivir along with lopinavir and ritonavir, both HIV drugs.

Experimental drug: From Gilead Sciences Inc., called remdesevir (started on 6^th Feb as a trial)

Russia and China drug: Arbidol, an antiviral drug used in Russia and China for treating influenza, could be combined with Darunavir, the anti-H.I.V. drug, for treating patients with the coronavirus. (The corona virus shares some similarity to HIV virus also)

PVP-I mouthwashes and gargles are known to reduce viral load in the oral cavity and the oropharynx. PVP-I has high potency for viricidal activity against hepatitis A and influenza, MERS and SARS

The Drug Controller General of India has approved the "restricted use" of a combination of drugs (Lopinavir and ritonavir) used widely for controlling HIV infection in public health emergency for treating those affected by novel coronavirus.

In SARS, people were put on long-term steroids ending with immunosuppression and late complications and death. The current protocol is short-term treatment.

 Standard Respiratory droplets precautions

Self-quarantine if sick with flu-like illness: 2 weeks

Adherence: Strict

Soap and water: Wash your hands often and for at least 20 seconds.

Alcohol-based hand sanitizer: if soap and water are not available

Avoid touching:  Eyes, nose, and mouth with unwashed hands.

Avoid close contact:  (3-6 feet) with people who are sick with cough or breathlessness

Cover your cough or sneeze with a tissue, then throw the tissue in the trash.

Clean and disinfect frequently touched objects and surfaces.

Surgical 3 layered Masks: For patients

N 95 Masks: For health care providers and close contacts

 Common Myths

1. People receiving packages from China are not at risk of contracting the new coronavirus as the virus does not survive long on objects, such as letters or packages.
2. There is no evidence that animals/pets such as dogs or cats can get infected with the new coronavirus. However, it is always in your best interests to wash your hands with soap and water after contact with pets to prevent transmission of common bacteria such as E. coli and Salmonella.
3. Pneumococcal vaccine and Haemophilus influenza type B (Hib) vaccine, do protection no against the new coronavirus.
4. Regularly rinsing the nose with saline does not protect people from infection with the new coronavirus or respiratory infections although it can hasten recovery from the common cold.
5. There is no evidence that using mouthwash protects from infection with the new coronavirus although some brands of mouthwash can eliminate certain microbes for a few minutes in the saliva in your mouth.
6. Garlic may have some antimicrobial properties, however, there is no evidence that eating garlic protects people from the new coronavirus.
7. Sesame oil does not kill the new coronavirus. Chemical disinfectants that can kill the 2019-nCoV on surfaces are bleach/chlorine-based disinfectants, either solvents, 75% ethanol, peracetic acid and chloroform. However, they have little to no impact on the virus if you put them on the skin or under your nose. It can even be dangerous to put these chemicals on your skin.
8. People of all ages can be infected by the new coronavirus (2019-nCoV). Older people, and people with pre-existing medical conditions (such as asthma, diabetes, heart disease) have increased odds of becoming severely ill with the virus.  People of all ages are advised to take steps to protect themselves from the virus, for example by following good hand hygiene and good respiratory hygiene?
9. Antibiotics do not work against viruses.  Hence, antibiotics should not be used to prevent or treat new coronavirus unless you suspect bacterial co-infection.
10. To date, there is no specific medicine recommended to prevent or treat the new coronavirus (2019-nCoV).

Trolls and conspiracy theories: Not validated and are fake news

1. The virus is linked to Donald Trump,and US intelligence agencies or pharmaceutical companies are behind it.
2. That eating snakes, wild animals or drinking bat soup cases coronavirus infection.
3. Keep your throat moist, avoid spicy food and load up on vitamin C.
4. Avoiding cold or preserved food and drinks, such as ice cream and milkshakes, for "at least 90 days".
5. Experts have been aware of the virus for years.
6. The virus was part of Chinas "covert biological weapons programme" and may have leaked from the Wuhan Institute of Virology.
7. Linked to the suspension of a researcher at Canadas National Microbiology Laboratory.
8. China wants to kill 20,000 coronavirus patients is totally false. The site is linked to a sex website.

Role of CMAAO and other Medical Associations

Get prepared for containment, including active surveillance, early detection, isolation and case management, contact tracing and prevention of spread of the virus and to share full data with WHO.   All countries should emphasize on reducing human infection, prevention of secondary transmission and international spread. Intensify IEC activities.

Confirmed Cases and Deaths

 Total Cases of Novel Coronavirus (2019-nCoV)

Daily Cases of Novel Coronavirus (2019-nCoV)

Total Deaths of Novel Coronavirus (2019-nCoV)

Daily Deaths of Novel Coronavirus (2019-nCoV)

CMAAO Suggestions so far

1. 7^th Jan: CMAAO Alert: WHO to monitor Chinas mysterious pneumonia of unknown virus outbreak
2. 8^th Jan: CMAAO warns Asian citizens travelling China over mystery pneumonia outbreak
3. 10^th Jan: Editorial: Coronavirus strain causing pneumonia in Wuhan, China, It’s a new strain of coronavirus in the China pneumonia
4. 13^th Jan: China Virus Outbreak Linked to Seafood Market
5. 15^th Jan: First Case of China Pneumonia Virus Found Outside China in Thailand
6. 17^th Jan: WHO issues warning after mysterious Chinese corona virus spreads to Japan
7. 17^th Jan: India at threat of Coronavirus. CMAAO urges travel advisory on coronavirus: http://www.drugtodayonline.com/medical-news/nation/10379-cmaao-urges-travel-advisory-on-coronavirus.html  (18^th Jan: Indian govt issues travel advisory as Chinas mysterious Coronavirus spread in other countries)
8. 18^th Jan: WHO issues warning after mysterious Chinese Coronavirus spreads to Japan [http://blogs.kkaggarwal.com/tag/who/]
9. 18-20 Jan: Three countries CMAAO meet, also discussed Coronavirus
10. 22^nd Jan: Still not being declared to be a notifiable disease; N 95 to be included in the list of essential drugs and price-capped; Oseltamivirshould also be price-capped; flights should have masks available for all passengers; not declaring flu-like symptoms while boarding or landing should be a punishable offence (23^rd Jan: India issues advisory to airports)
11. 24^th: Inter Ministerial Committee needs to be formed on Corona Virus (PMO took a meeting on 24^th evening)
12. 25^th Jan: Indian government should pay for Indians affected with the virus in China
13.  26^th Jan: Need of National Droplet Infection Control Program; Policy to ban export of face masks; policy to evacuate Indians and people of  neighboring countries from China’s affected areas; Time to collaborate on Nosode therapy (Exports of masks banned on 31^st January by Indian Government)

Action:  Feb 1^st: Ibrahim Mohamed Solih thanked India for the evacuation of seven Maldivian nationals from the coronavirus-hit Chinese city of Wuhan. India evacuated 647 people

 [On 30^th Jan, India banned gloves, PEP and masks but on 8^th lifted the ban on surgical masks/disposable masks and all gloves except NBR gloves. All other personal protection equipment, including N-95 and equipment accompanying masks and gloves shall remin banned.] 

27^th Jan: History of anti-fever drugs at airports should be taken

14. 27^th Jan: History of anti-fever drugs at airports should be taken
15. 28^th Jan: Do research on Nosodes
16. 29^th Jan: Closure of live markets all over the world, India should take a lead
17. 30^th Jan: Paid flu leave, surgical mask at public places, N 95 for health care providers
18. 31^st Jan: Respiratory hygiene advisory to schools, Pan-India task force to be made 
19. 1^st Feb: Disaster Budget is the need of the hour
20. 3^rd Feb: 100 crore budget for Coronavirus; Private labs to be recognized; one dedicated corona National help line; MTNL, BSNL to have a line of advisory in their bills; isolation wards to be single rooms or two beds separated with six feet distance; national insurance to cover cost of treatment;  Sea ports to have same precautions; price caps for masks, and gloves; National Droplet Control Program; clarification that import of goods is not risky And suspend AI flights to China and Hong Kong

[Feb 4 - Air India suspended flight services to Hong Kong from Friday until March 28. Earlier, Air India had cancelled its flight to Shanghai from January 31 to February 14; and 5^th Feb - The Ministry of Defence is setting up 10 new laboratories across the country, primarily to conduct research on viruses]

21. 4^th Feb: Kerala travel advisory needed [The Union Ministry of Health and Family Welfare issued a fresh travel advisory on Monday urging people to refrain from visiting China]
22. 5^th Feb: PM should talk about Coronavirus in Man Ki Baat or a special address
23. 6^th Feb: Time to have makeshift bed policy to tackle deaths in Kota, Muzaffarpur and Coronavirus cases [Uttarakhand to set up two dedicated hospitals to tackle coronavirus : https://www.hindustantimes.com/india-news/uttarakhand-to-set-up-two-dedicated-hospitals-to-tackle-coronavirus/story-NYxBOw6XHTbugznTWa3CXK.html]
24. 7^th Feb: IPC 269 should be applicable to coronavirus
25. 8^th Feb: Teleconsultation should be allowed to flu and coronavirus consultation

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA