COVID-19 (SARS-CoV2): FEW FACTS AND NEW DEVELOPMENTS

The Covid-19 virus belongs to the Corona virus family. Other members of this family include severe respiratory distress syndrome (SARS) and the middle east respiratory syndrome (MERS), previously involved for two major endemics, but NOT at the epidemic or pandemic scale. All these viruses occur naturally in wet-animals (reptiles, amphibians & variety of seafood). All Corona viruses have special affinity for respiratory epithelium.

Animals, mostly mammals (Bats & Humans), who consume these wet animals, could acquire the Corona virus. Infected Bats and Humans develop respiratory illness that could progress to severe respiratory distress with high risk of dying. The lung changes range from widespread bronchiolar and alveolar inflammation leading to pulmonary fibrosis. Survivors of this infection could become chronically oxygen dependent.

One of the key factors in tackling the spread of COVID-19 across the globe is testing. In South Korea, for example, mass testing has been used to try and quickly identify and isolate those with the disease. Testing is also vital to calculate accurate infection and survival rates – data that is critical for getting public safety measures right. And as this coronavirus continues to spread, people are being offered tests for sale, either at a high price from private clinics, or tests that are not officially approved, or perhaps even fake. So what tests are being used by health officials, how much do they really cost and what developments are there to come?

Two types of currently available tests for SARS-CoV2, the coronavirus that causes COVID-19 disease and the cause of 2020 pandemic.

  1. The first testing method is a very sensitive test that looks for the RNA of the virus using a technique called RT-PCR (reverse transcriptase polymerase chain reaction). This can detect as little as one virus particle in swabs taken from inside the mouth or nose.
  2. The second type of test measures the antibody responses to the virus in blood serum, similar to many other blood antibody tests for many other viral infections. There are
    many virus components that our bodies make many different antibodies against.

Development of antibody against any infection can either destroy the virus or stop the infection. A positive Covid-19 antibody test would simply mean exposure to SARS-CoV2 including other Corona family viruses. In other words it is NOT 100% specific; however, important for risk categorisation of people, particularly the front line Doctors, Nurses, key workers and carers.

The antibody test itself is very simple and cheap. The test requires purified virus components in a test tube to which a very diluted blood sample from the patient is added and let any antibodies bind to the test tube. Antibody typically takes a few weeks to develop against a new infection and lasts much longer in the bloodstream than the virus itself. The COVID-19 “serology” testing is a powerful tool to check if people have encountered the infection and as well as to assess the efficacy of vaccines. Rapid progress in being made for developing the vaccine against the SARS-CoV2 (Covid-19) strain. It is important to note that the current antibody tests for the novel coronavirus are yet to be validated for mass use, which is why WHO guidelines recommend RT-PCR testing. Prof. Chris Whitty, the UK Chief Medical Officer, said that a test that could reliably detect past infection would be “transformational”. The government recently announced that it had ordered 3.5 million home tests that could soon become available for NHS workers and some members of the public via Amazon once they were validated.

Most countries rely on RT-PCR method, as it is highly specific (low false positive cases) and very sensitive (low false negative cases). One of the Indian Genomic Laboratories has developed a kit using this method; others are fast developing. Most such tests will cost less than Rs. 2000 (just under £25). In the UK, the RT-PCR test remains the primary method, using a network of labs doing the same standardized test. Private labs in the UK are charging up to £375 for this test.

So far WHO or any other large Global agency, like Bill Gates Foundation, have not come forward to finance this test for poor or middle income countries. Most countries currently employ this test for identification and isolation of infected people, consistency in data collection and comparing useful statistics on the infection rate and outcomes.

There is no specific Covid-19 anti-viral therapy available yet. Claims made in India and other places on the therapeutic potential of combined chloroquine and anti-retroviral drugs should NOT BE TAKEN seriously. There is no evidence based on either double randomised trial or selected case-controlled study. It is anecdotal and unscientific. Surprisingly Indian Council of Medical Research (ICMR) has approved chloroquine for Covid-19, particularly in high-risk people and health workers.

In the USA, despite lots of hype for hydroxychloroquine (Plaquenil), the Food and Drug Administration is still undecided. WHO has yet to approve its use for treating the Covid-19 virus. Other countries have started case-based emergency clinical trials. The US President, Donald Trump, believes that it should be given ‘a try’! The chloroquine, a derivate of quinine, is very potent anti-malarial drug with anti-inflammatory qualities. Historically, it used to be good anti-inflammatory drug prior to the discovery of non-steroidal antiinflammatory drugs (Brufen, Naproxyn, Voltarol etc.). Doctors should not prescribe as chloroquine or hydroxychloroquine are very toxic with serious side effects. As the drug is cheap and widely available on the counter, risks of self-prescribing are very high.

Inevitably, many Doctors, Vaids and Hakims across India have claimed on the efficacy of several indigenous animal (Cow urine) and herbal medicine (usual combination of Ayurvedic products). Perhaps claims on beneficial effect of physical, behavioural and life-style modifications are justified and need to be explored, but on your own, as traditional group or community approach might be counterproductive due to risks of cross infection.

It is likely that some of the above contents might change as we come across and digest more information. However, the fact remains that Covid-19 (SARS-CoV2) is highly contagious spread by droplet aerosols and contact, however trivial that might be.

The key to prevention is isolation, social distancing, protection (self and others) by frequent hand washing or liberal use of alcohol gel and probably the use of facemasks.

Compiled by Professor Dhavendra Kumar, Cardiff / London, 29 March 2020

Seminar on “The Impact of Human Genomics in Current Medical Practice”

The Special Interest Group on Human Genomics and Rare Disorders (SIG-HGRD), JSS Medical College, JSS Academy of Higher Education & Research (JSSAHER) in association with ‘Indo-UK Genomic Education forum’ of the Genomic Medicine Foundation (UK) had organized one day seminar on “The Impact of Human Genomics in Current Medical Practice” on Thursday 31st October 2019 at Sri Rajendra Centenary Auditorium, JSS Hospital, Mysuru.

The one-day Seminar on “The Impact of Human Genomics in Current Medical Practice” being inaugurated by Dr. H. Basavanagowdappa, Vice chancellor, JSSAHER and Principal, JSS Medical College. Left to Right: Dr. Akila Prashant, Professor, Dept of Biochemistry, Dr. G.V. Manjunath & Dr. M.N. Suma, Vice Principals of JSS Medical College, Dr. Dhavendra Kumar, Head of Indo-UK Genomic Education Forum, Dr. H. Basavanagowdappa, Dr. (Col) M. Dayananda, Director, JSS Hospital, Dr. P.A. Kushalappa, Director (Academics), JSSAHER, Dr. M. Guruswamy, Medical Superintendent, JSS Hospital.

The event was inaugurated by Dr. H. Basavanagowdappa, Vice Chancellor, JSSAHER and Principal, JSS Medical College. The other guests present during the occasion were Dr. P.A. Kushalappa, Director (Academics), JSSAHER and Dr. (Col) M. Dayananda, Director, JSS Hospital, Dr. M. Guruswamy, Medical Superintendent, JSS Hospital, Dr. G.V. Manjunath and Dr. M.N. Suma, Vice Principals of JSS Medical College. The dignitaries released the seminar souvenir and also the brochure for the maternal serum screening for chromosomal abnormalities which has been recently initiated at JSS Hospital.

The dignitaries releasing the seminar souvenir

The current and future management of patients aims for evidence based precision and personalized medicine. Genomic medicine is the promising key to the development of precision and personalized medicine. The focus of one- day seminar was to enhance the skills and knowledge of general and specialist medical practitioners to bring about changes in their current clinical practice.

Eminent speakers from reputed institutes shared their immense knowledge with the delegates present. The sessions started with the introductory remarks by Dr. Akila Prashant, Professor Department of Biochemistry and Convener of Medical Genetics who emphasized the vast role genomics plays in the current medical practice. This was followed by the first session on “Neurogenetics” which was chaired by Dr. M.D. Ravi, Professor, Department of Pediatrics and Dr. Harsha S, Professor and Head, Department of Neurology, JSS Medical College. In this session Dr Sumita Danda, Professor and Head, Department of Clinical Genetics, Christian Medical College and Hospital, Vellore spoke about childhood neurodegenerative disorders and presented specific case scenarios to distinguish the types of neurodegenerative disorders and discussed the challenges faced in reaching the diagnosis. She also provided a background for the management and further research in this area. Second talk was by Dr. Meenakshi Bhat, Consultant Clinical Genetics, Centre for Human Genetics, Bangalore, Karnataka who spoke on Metabolic neuro-develop¬mental disorders- from diagnosis to treatment and discussed how genetic testing revealed that mutations in Indian cohorts of neurometabolic disorders were distinct from those seen in the Caucasian or the Jewish populations described elsewhere. She illustrated this by using the example of Gaucher disease the commonest treatable lysosomal storage disorder caused by a single gene. The final talk of the session was by Dr. Deepa Bhat, Associate Professor, Department of Anatomy and Genetic Counsellor, JSS Medical College who spoke on prenatal and newborn diagnosis. She laid emphasis on high degree of suspicion, pre and post-test genetic counselling for effective management of these cases.

The next session was on “Next Generation Genome Diagnosis” which was chaired by Dr. N.B. Ramachandra, Professor & Head, Department of Genetics and Genomics, University of Mysore and Dr. K.A. Raveesha Professor & Head, Faculty of Life sciences, JSS Academy of Higher education & Research. In this session Prof. Dhavendra Kumar, Director- The Genomic Medicine Foundation, Cardiff University, United Kingdom spoke on Genome diagnosis of disorders of genome architecture. He enlightened us about various genome technologies including array comparative genome hybridization (aCGH), targeted clinical exon (TES), whole exon (WES) or whole genome sequenc¬ing (WGS) and highlighted their benefits and limitations. Dr. Anju Shukla, Professor, Department of Medical Genetics, Kasturba Med¬ical College, Manipal Academy of Higher Education, Mani¬pal spoke on Genomic Techniques: Current applications for Diagnosis and Discovery of Rare Mendelian Disorders. She deliberated on how the advent of next generation sequencing based techniques have made it possible to increase the yield of diagnosing rare Mendelian dis¬orders in a much more timely and cost-effective manner. The next speaker was Dr. Meenakshi Bhat, who spoke on the clinical utility of genomic sequencing. She further emphasised with suitable examples that with better understanding of the human genome structure and organization and wide availability of next generation testing methodologies including array comparative genomic hybridization and exome sequenc¬ing, the ability to accurately diagnose genetic disorders has improved enormously.

The third session was on “Common Medical Diseases” which was chaired by Dr. Pratibha Pereira, Professor & Head, Department of Geriatrics and Dr. Premanath Raman, Professor, Department of Ophthalmology, JSS Hospital. In the first talk Dr. Radha Venkatesan, Executive Scientific Officer & Head, Department of Molecular Genetics, Madras Diabetes Research Foundation, Chennai, Tamilnadu spoke about “Genetic & Molecular approach to diabetes mellitus”. She highlighted the fact that genetic diagnosis is of great clinical importance for patients with monogenic diseases such as Maturity Onset Diabetes in Young (MODY) and Neonatal Diabetes to understand the pathophysiology of the disease, tailor the optimal anti-diabetic treatment, and define the prognosis for the entire family. Next Prof. Dhavendra Kumar spoke on Cardiovascular Genomic Medicine in Clinical Cardiology- Applications in chronic heart failure. He laid emphasis on the fact that how targeted genetic/ genomic testing provides evidence-based clinical protocols and pathways that can be used to guide the comprehensive healthcare for heart failure patients. Prof. Govindasamy Kumaramanickavel, Research Director, Narayana Nethralaya, Bangalore spoke on “Age Related Macular Degeneration: The Genetics and Biology”. He discussed how the challenge of treating Age Related Macular Degeneration can be overcome by complement pathway related drug discoveries that have become possible because of powerful genomic technologies.

The fourth session was on “Cancer Genetics and Genomics” which was chaired by Dr. MVSST Subbarao, Professor, Department of Biochemistry and Dr. Ravi Krishnappa, Assistant Professor, Department of Surgical Oncology, JSS Medical College. Prof. Dhavendra Kumar spoke about the role of genomics in clinical oncology and Targeted molecular cancer therapy. He discussed on how the next-generation sequencing has revolutionized our understanding of the genomic underpinnings of cancer development and progression. Also, he threw light on how recent advances in cancer molecular biology have led to identification of several cellular and molecular targets for new drug discovery and development. There is pipeline of candidate drugs with different molecular targets and modes of action in development.

At the end of all the sessions an online quiz competition was conducted for the student delegates on Kahoot App. About 75 students participated in the quiz and top three winners were duly awarded. More than 250 participants from different genetic laboratory, research institute, staff, research scholars and students from medical, dental and life science colleges had participated in the seminar and 18 of them presented posters during the event. The posters were evaluated during the lunch break and the two best posters were duly awarded. The day was closed with the valedictory function were in the prizes were distributed to the winners and feedback was collected from the participants to know about their learning experience. The participants felt that the knowledge acquired by them during the sessions will help them in their daily practice and future research. This event has marked the beginning of a long-term collaboration with the Indo-UK Genomic Alliance with which JSS Academy of Higher Education and Research will soon sign a Memorandum of Understanding.