Speaker: Dr Nidhi Dhawan

April 17, 2022, Sunday

• Australia, parts of Europe and Canada are high incidence areas. Asia, Far East and South American are medium to moderate incidence areas, while in Mexico, large parts of Asia and Africa, the case counts are low.
• Israel had its maximum number of cases around end of February and beginning of April, but cases are now on the decline.
• Vaccination does not seem to prevent infection, but does prevent severe disease and death.
• South Korea graph remained flat close to the baseline for the last two years, but climbed up in the beginning of April, but cases including deaths are now coming down. 
• In the United States, deaths have finally started to come down.
• In the UK, about 60-70% are incidentally found to be Covid. There is an increase in deaths. 
• Nearly 65% of the world population has received at least one dose of the vaccine and nearly 60% is fully vaccinated.
• Countries doing well in terms of vaccination like Singapore, China are not doing so well in terms of case count despite strict lockdown policy in China.
• In Israel, lockdown in some sectors in the economic framework of the country did not prevent surge in cases.
• In India, there are no lockdown measures, despite this, the omicron peak is lower than the delta peak. The number of new cases in India is slightly more than the 7-day average. This is a matter of concern and needs to be closely monitored. Majority of cases are in Delhi. There is an uptick in the number of cases in Delhi, this has to be carefully watched over the coming weeks.
• UK had a strict lockdown at the time of Omicron peak, but has now opened up fully.
• Mumbai is the only city, which has implemented a sewage screening program.
• India’s active case load is less than 15,000 after 700 days.
• As of April 16, there were 11,29,723 vaccinations;3,00,918 samples were tested on April 15,2022. There were 11,366 new cases across India.
• In Maharashtra, new cases are less than the 7-day average. Kerala recorded zero cases on April 14, 2022.

Revisiting IVM

• A review published in the journal Antiviral Research has called ivermectin as a broad-spectrum antiviral.
• IVM targets the host importin a/b1 heterodimer and dissociates it into a and b units so taht the viral genome dose not enter the nucleus.
• It inhibits both RNA and DNA viruses. It has been proven to be effective in inhibiting dengue virus, zika virus and West Nile virus.
• Ivermectin has antimicrobial, antiparasitics and antiviral activity.
• In addition to its action on importin a/b, it also clocks CD147 and ACE-2 attachment with the viral protein.
• It also has immunomodulatory effect in the host, inhibits proliferation of cancer cells and regulates glucose and cholesterol metabolism in the cells.
• Ivermectin works on several receptors such as CD 147, P2xX4-ATP gated cationic channels and NFkb mediated downstream proinflammatory cascade suppression.
• Ivermectin inhibits nuclear import of proteins of RNA virus, it also has a role as ionophore and exerts anti-inflammatory effect by reduction of immune cell recruitment and cytokine production.

Mitochondrial health

• SARS-CoV-2 has brought mitochondria into sharp focus.
• SARS-CoV-2 mortality is particularly higher in metabolic syndrome, diabetes because of association with altered immune response and cytokine storm. Apparently, there is a failure of resolution of inflammation in these patients and there is both an increase in innate immune response and failed or blunted adaptive response. This is called inflammaging characterized by T cell immunosenescence, thymic atrophy, T cell exhaustion and rise in inflammatory cytokines/chemokines.
• Physical and cardiorespiratory health and fitness might be a preventive/protective strategy.
• Sedentary lifestyle removes the body’s need to activate homeostasis. It is a proinflammatory lifestyle.
• Failure of hormesis also causes accelerated aging phenotype. This is associated with increase in altered macrophages and altered T cell homeostasis.
• Exercise is the adaptation response towards better hormetic control, anti-inflammation and decelerated aging.
• Mitochondrial adaptation is a key cellular link in the chain. 
• Mitochondrial stress improves mitochondrial function and improves longevity and muscle health.
• Improved muscle health releases myokines like irisin, which protect mitochondria, enhance anti-inflammatory adipocyte morphology and modulate macrophage reactive oxygen species.
• T cell exhaustion due to decreased oxidative phosphorylation leading to loss of mitochondrial function and increased aging. Increased ROS despite increased glycolysis, so there is altered glucose metabolism. This is reversible with antioxidants.
• T cells and monocytes both display altered mitochondrial markers.
• Mitochondrial health directly correlates with disease freedom and longevity.
• Aging is a function of rising intracellular oxidative stress rather than chronological time.
• Nick Lane double agent theory – pathogen and oxidative stress together seem to be causing the aging.
• It is possible to induce mitobiogenesis by moving even a little bit every day. Synthesis of new mitochondria rescue mitochondrial mass. This prevents shortening of telomere which is a sign of aging.
• The process is finely regulated by PGC1alpha and its interaction with transcription factors (NRF, ERR, PPAR), which further regulate mitochondrial DNA replication and transcription of mitochondrial protein genes.
• Deficiency of PGC gene is associated with inability to respond to stress and accelerated aging.
• Exercise reduces proinflammatory cytokines and increase anti-inflammatory cytokines. Contractility of blood vessels and angiogenesis with perfusion of the periphery is improved. With this mitochondrial biogenesis is improved. Oxidative stress is reduced and longevity is improved.
• A healthy human body produces their body weight in ATP at rest each day. At maximal exercise, this increases to 0.5-1kg per minute.
• ATP cannot be stored; thus, mitochondria are constantly working.
• Mitochondria occupy 25% of cellular volume. An average cell contains 1000-2500 mitochondria.
• Some nutrients are essential to ATP function and good mitochondrial health.
• Factors associated with mitochondrial damage include leakage of oxidants during ATP production, aging – cumulative oxidative damage to mtDNA, genomic susceptibility, toxic metals, organic pollutants, alcohol and some prescription drugs.
• Indirect measures of mitochondrial dysfunction are blood lactate and pyruvate levels. 8-hydroxy-2-deoxyguanosine (8-OHdG) in the urine measures degree of mitochondrial damage.
• Strategies to improve mitochondrial function are optimizing nutrition, decrease exposure to toxins, use antibiotics responsibly, avoid recreational drugs, antioxidants and exercise, supportive nutraceuticals. 
• Plant antioxidants and polyphenols and nutraceuticals improve mitochondrial reserve. Intermittent fasting and calorie restriction are very strong triggers for mitochondrial health. Redox optimized ROS balance is a measure of mitochondrial ATP generation maximized and ROS minimized with maximal respiratory rate.
• The more the respiratory rate is increased with activity, less is the oxidative damage.
• Mitochondria not only help you live a better and more energetic life but also improve energy uptake and insulin sensitivity.

Excerpts from presentation by Dr Nidhi Dhawan