CME INDIA Presentation by Dr Basab Ghosh, Senior Diabetologist, Agartala, Tripura.

Just one year back

Just one year back, on 30th January 2020, World Health Organization (WHO) declared Public Health Emergency of international concern as the viral pneumonia like epidemic speeded in more than twenty countries in a short period since the first confirmed case of this highly contagious new viral infection was identified on 10th December 2019 and thereafter the world has experienced one of the worst health hazards of the humanity! Incidentally in India the first positive case was also reported on 30th January 2020.

Following the Crisis

If you follow the crisis of COVID-19 in China, as mentioned earlier, the first confirmed case was identified on 10 December 2019, in the pandemic epicentre Wuhan city, later on 14th March 2020, newspaper South China Morning Post reported that this 55 year old lady from Hubei province who could have been the first person might have contracted the disease on 17th November 2019 in Huanan Seafood Wholesale Market where they also sell live animals illegally, however in a short period of time the coronavirus infection took a critical shape of outbreak; during peak of the crisis when things were moving out of hand after 44 days at 10 am on 23rd January 2020, China implemented Lockdown in worst effected first epicentre of pandemic in Wuhan city of Hubei province, then gradually to other few more cities and ultimately massive quarantine of approximately 7 crore (70 Million) population was possible with Lockdown. Within eight weeks of Lockdown by 20 March 2020, new cases of the virus transmitting within the area dropped to zero.

New disease named

On 11th February 2020, World Health Organization (WHO) announced COrona VIrus Disease-2019 (COVID-19) as the name of this new disease caused by corona virus Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). The CoronaVirus (CoV) family is not new. They are certain type of zoonotic virus family that causes respiratory illnesses in animals and zoonotic diseases from animals to humans. The WHO considers bats the most likely natural reservoir of SARS-CoV-2, but some differences between the bat coronavirus and SARS-CoV-2 suggest that an intermediate reservoir such as a pangolin corona virus might be involved in its introduction to humans. Unfortunately, on 11th March 2020, WHO declared the rapidly spreading COVID-19 a pandemic, acknowledging the virus will likely spread to all countries on the globe.

Lockdown like this never seen on earth

‘Lockdown’ is the drastic step of ‘Social-distance’ including all social preventive medicine measures in infective disease control and it is implemented first time to mass quarantine by China during SARS outbreak in 2002-2003; China ‘locked down’ Beijing and closed more than 3500 public places in an effort to control community spread and got success immediately in community control of the SARS infection. Lockdown can limit movements or activities in a community while allowing most organizations to function normally, or limit movements or activities such that only organizations supplying basic needs and services can function normally.

Social Distancing – New mantra

In preventive and social medicine history ‘Social-distance’ was first exercised during 1916 New York City polio epidemic and thereafter during every infectious disease outbreak this protocol implemented successfully. The well-established protocols of social-distance are:

1. Personal level protection by facemask use, promoting personal hygiene by hand washing, regular cleaning of surfaces, etc.
2. Community level protection school closures, workplace closures, work at home policy of the offices, restriction of movement of people by controlling all transportation system including train and flights, cancelling mass gathering, closure of community recreational centers like, swimming pools, gymnasiums, etc.

When India reported first death

In India, first death from COVID-19 was on 12th March 2020 and on 31st March 2020, we had 49 deaths, however Prime Minister Narendra Modi asked 140 crores Indians to observe a strict lockdown of 21 days starting 24 March 2020, to slow down the spread of the deadly virus and subsequently lockdown was extended till 31st May 2020. WHO praised India’s initiation of lockdown as a “comprehensive and robust” response to breaking the vicious cycle of COVID-19 pandemic plaguing the world!

Strong Leadership comes forward

India is the world’s second most populous country and has large numbers of poor living in crowded, unsanitary conditions under a brittle public health infrastructure. So, if strict decisions like the one to lock it down by strong leadership were not taken and more importantly, executed properly it was impossible to control pandemic as on date!

This scenario in the beginning of pandemic led Ramanan Laxminarayan, founder and director of the Center for Disease Dynamics, Economics & Policy to make the following important remarks: “India is probably the first large developing country and democracy into which this pandemic will arrive. Many of the advantages of the Chinese [state] control and of having the health systems of Europe or the U.S. are not available to India. There will have to be a uniquely Indian response to COVID-19.”

World’s largest COVID-19 vaccination program in India

Rightly so, PM’s tough leadership went into full steam action mode to implement the most rigorous measure so far by any country in the world to put peoples’ health and safety before economic gains. Government gradually imposed all possible measures one by one under the guidelines of WHO and Indian Council of Medical Research (ICMR) and with all those efforts we could, not only come out from the worst situation, even launched the world`s largest vaccination programme, joining the ranks of wealthier nations where the effort is already underway too. On 16th January 2021, PM Narendra Modi launched the much awaited, world’s largest COVID-19 vaccination programme in India. Two vaccines have been approved for use in India, Covishield vaccine developed by Oxford/ AstraZeneca and manufactured by Serum Institute of India (SII) and Covaxin developed by Bharat Biotech.The initial phase of vaccination shall be for a priority group of 30 crore (300 million) people including Health care workers 1 crore, Frontline workers 2 crores, People above 50 years of age 26 crores, People below 50 years of age with chronic illnesses 1 crore.

More than 100 vaccines in trial

There are more than 100 COVID-19 vaccines in trial and 10 vaccines are already approved for use and they are mainly of four groups –

1) Whole virus: This group includes live attenuated and inactivated (killed) vaccines. Advantage: Well-established technology. Disadvantage: Live attenuated are unsuitable for immunocompromised individuals and killed vaccines require multiple doses. Eg: Covaxin by Bharat Biotech.

2) Nucleic acid vaccines: They use the viral genetic material either RNA or DNA to provide cells with instructions to make the antigen. Advantage: Easy to manufacture and cheap. Disadvantage: Have never been licensed for use in humans earlier to COVID. Eg: BioNTech/Pfizer and Moderna are both mRNA vaccines. Inovio – DNA vaccine (still in trials) – uses bacterial plasmids.

3) Viral vector vaccines: Various viruses like the adenovirus have been made into vectors by stripping them of any disease-causing genes and incorporating the genetic instructions for making the antigen from the target pathogen (corona virus in this case) Advantage: Strong immune response. Disadvantage: Previous exposure to the vector could reduce effectiveness’: Covishield by Oxford/ AstraZeneca and Gamaleya – Sputnik are both using the adenovirus.

4) Protein sub-unit vaccines: These consist of purified fragments of the virus with the ability to stimulate immune cells. They are of various types – protein subunits, polysaccharides, conjugate types. Advantage: Well-established process and relatively stable. Disadvantage: Relatively complex to manufacture and adjuvants and booster doses may be required. Eg: Novavax (still in trials) uses the protein subunit.

However, COVID-19 pandemic is not over yet!

Though less in number, new cases are still reporting alongside scare of new variant of SARS-COV-2, which carries a mutation identical to the UK strain and it is reported to be 70% more contagious than the usual COVID-19 virus.

Now it is well understood COVID-19 is a deadly pulmonary disease with peculiar characteristics, which include variable clinical course and thrombophilia. A thorough understanding of the pathological correlates of the disease is still missing. Also, as the global pandemic has progressed, evidence has emerged that some patients are experiencing prolonged multiorgan symptoms and complications beyond the initial period of acute infection and illness.

Ongoing Studies

Large ongoing studies in this field include PHOSP-COVID, an 18-month study that is assessing the long-term health outcomes for 10000 people who have been admitted to hospital with COVID-19. The Post-hospitalization COVID-19 study (PHOSP-COVID) is a grouping of leading researchers and clinicians from across the UK working together to understand and improve long-term health outcomes for patients who have been in hospital with confirmed or suspected COVID-19. Also preliminary pulmonary findings include an analysis of 41 post-mortem samples, and a scanning study of 40 patients who have persisting shortness of breath.

The analysis of 41 post-mortem samples by Rossana Bussani et.al (Department of Medical, Surgical and Health Sciences, University of Trieste, Italy) published on 3 November 2020, in EbioMedicine by The Lancet. They interpreted that COVID-19 is a unique disease characterized by extensive lung thrombosis, long-term persistence of viral RNA in pneumocytes and endothelial cells, along with the presence of infected cell syncytia. Several of COVID-19 features might be consequent to the persistence of virus-infected cells for the duration of the disease.

Early findings from the scanning study of 40 patients who have persisting shortness of breath into longer-term damage in patients recovering from COVID-19 suggest that cutting-edge scanning techniques may detect previously unseen lung damage. The research by the universities of Oxford and Sheffield is the first in Europe to use hyperpolarized Xenon gas with MRI scanning to identify the impact on lung function as patients recover from COVID-19, when standard MR and CT scans may be normal. The study is being supported by the NIHR Oxford Biomedical Research Centre. They are working with an initial group of 40 patients in Oxford and Sheffield over the next six months. So far, the hyperpolarized xenon MRI technique has identified weakened lung function in all patients who have taken part in the study – this damage to lungs from COVID-19 is not visible on a standard MRI or CT scan.

NICE Initiatives

On 18 December, 2020, the National Institute for Health and Care Excellence (NICE) in partnership with the Scottish Intercollegiate Guidelines Network and the Royal College of General Practitioners published a guideline for clinicians on the management and care of people with long-term effects of COVID-19. As COVID-19 and its consequences are still new conditions, the guideline is adaptive and is updated as new evidence becomes available from scientific and clinical studies. 

For easy understanding, COVID-19 NICE guideline clarified the following clinical definitions for the initial illness and long COVID at different times:

• Acute COVID-19: sign and symptoms for up to 4 weeks.
• Ongoing symptomatic COVID-19: sign and symptoms of COVID-19 from 4 weeks up to 12 weeks.
• Post-COVID-19 syndrome: sign and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks and are not explained by an alternative diagnosis. It usually presents with clusters of symptoms, often overlapping, which can fluctuate and change over time and can affect any system of the body. Post-COVID-19 syndrome may be considered before 12 weeks while the possibility of an alternative underlying disease is also being assessed.
• Long COVID: In addition to the clinical case definitions, the term ‘long-COVID’ is commonly used to describe signs and symptoms that continue or develop after acute COVID-19. It can be both ongoing symptomatic COVID-19 (from 4 to 12 weeks) and post-COVID syndrome (12 weeks or more).

The guideline makes recommendations for clinical investigations of patients presenting with new or ongoing symptoms 4 weeks or later after acute infection. The recommended investigations include a full blood count, kidney and liver function tests, a C-reactive protein test, and an exercise tolerance test (recording level of breathlessness, heart rate, and O₂ saturation). They also recommend that a chest x-ray should be offered to all patients by 12 weeks after acute infection if they have continuing respiratory symptoms.

Lastly

Clearly, a large number of resources will be needed further to help patients and clinicians understand and manage long-term COVID-19 sequelae. In the UK, many clinics have been set up so far by the National Health Service to assess long-term post-COVID-19 effects. If the vaccine works effectively, this could be the last chapter of the COVID pandemic. But the safety protocols against COVID -19 must be followed even after vaccination till WHO declares end of the pandemic.

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