April 10, 2022

• Hospitals in India are not reporting severe cases for some time now.
• Vaccination does not seem to have changed the game for Israel.
• South Korea and Singapore had a zero covid tolerance policy, but the last wave did not spare them.
• There are differing opinions about the fourth vaccine dose from reputed public health schools. The CDC and FDA have said that the current policy on boosting may not be sustainable.
• If we look at the reproduction rate of Covid-19 (till April 3, 2022), countries that still have  high case counts are still hovering around RR of 1. India is around 0.5 which means that the cases are going down.
• Data for daily new confirmed covid deaths per million people as on April 8, 2022 show that UK has had bad mortality rates in the earlier phase of the pandemic, but with Omicron the mortality rates are not so bad. The US is finally showing a downward trend.
• Vaccination, though protective against severe disease, is not the end game as it does not prevent the infection per se. Other measures, including a better lifestyle, also need to be implemented.
• In India, UK and the US, Omicron has almost completely replaced other strains including Delta.
• WHO figures for situation by WHO region show that Europe is higher than the rest of the world with 206,611,315 confirmed cases and seems to be still driving the pandemic.
• As per the WHO, the drivers of the global mortality are the Americas followed by Europe. Older demography, higher obesity rates, stressful lifestyle, poor vaccine acceptance could be the factors responsible for the high mortality.
• The UK has the highest share of people who have completed their initial vaccine protocol. 
• Africa is the least vaccinated part of the world. In terms of daily new confirmed covid cases per million people also as on April 8, 2022, Africa is the least affect part of the world.
• As on April 8, 2022, the US graph is finally inching towards the baseline though the daily new cases are still higher than the 7-day average. In the UK and South Africa, the daily cases are less than the 7-day average. Nearly 60% of cases in the UK now are incidentally discovered cases. In China, the new cases are more than the 7-day average despite the zero covid policy. South Korea reached a peak of nearly 200,000, but now the cases are declining and the new cases are less than the 7-day average.
• Zero Covid policy is definitely not the answer.
• In India, the new cases are slightly more than the 7-day average as on April 8, 2022.
• A study from Israel has shown that protection from the fourth dose of the Pfizer vaccine offers about 4 times protection versus the third dose. Maximum immunity is at the third week, by the sixth week, protection against severe disease is good and by the eighth week, despite the fourth dose, there is no protection. 
• As per Reuters, India is less than 1% of the peak and cases are falling. There have been 43, 034, 217 infections and 521, 656 coronavirus related deaths reported since the pandemic began. Countries reporting most new infections are South Korea, Germany, France, Vietnam and Italy. Countries reporting most deaths each day are UK, US, South Korea, Russia and Germany.
• India’s recovery rate is more than 97.8%. The active cases trajectory is constantly falling towards baseline and is currently less than 12,000. Likewise, the daily positivity rate is also falling and is at present 0.25%. The weekly positivity rate is reducing every week. India’s messaging has been very consistent and is being done in a very logical and phased manner keeping in view the logistics and capacity. Private hospitals have now opened up precaution dose for 18+. However, covid-appropriate behavior still needs to be adhered to.
• In Delhi, the new cases are little higher than the 7-day average. Cases are re-emerging. Though they are not causing severe disease, but we need to be watchful.
• T cell exhaustion seems to be a function of mitochondrial dysfunction. It is the reduced number or function of specific T cells in chronic persistent viral infections. Commonly seen in HIV, HBV and HCV including malignancies. It is often restricted to CD8+ cells, but sometimes also seen in CD4+ cells. 
• Mitochondrial function, exhaustion and altered metabolism are central to exhaustion and antioxidants seem to enhance recovery of the mitochondria.
• T cells are key players in adaptive, pathogen specific immune response. They are recognized by the antigen peptides and MHC complexes through T cells receptors, which activates them and they undergo differentiation over the next 1-2 weeks leading to proliferation, transcriptional, epigenetic metabolic changes to improve clearance of the recognised pathogens. There is massive clonal expansion, programmed tissue homing and development of tissue effector functions which eliminate the infected cells. Majority of the T cells die by apoptosis after antigenic clearance; 5-10% persist as central memory, effector memory and resident tissue memory cells. These persistent cells are the rapid responders in re-encounters with the antigen.
• Exhaustion is a sequential loss and it is possible to monitor and stop it at any of the sequenced steps. 
• Loss of IL2 is the first marker of exhaustion. This is followed by loss of TNFa and other cytokines. IFNg is depleted very late. The virus can persist because of these changes. The exhausted T cells fail to transit to quiescent stage or to acquire antigen-independent memory function. There is accelerated apoptosis hence the numbers are markedly reduced. The key molecule to look at is the programmed cell death molecule.
• These changes whether host mediated or pathogen mediated or a combination of both are still under study.
• T cell exhaustion may be driving long Covid; it makes severe Covid difficult to treat in the early stages. 
• Mild Covid-19 are more likely to suffer exhaustion.
• The macrophages do not have ACE2 receptors. They may be the link through antigen dependent enhancement towards T cell exhaustion.
• Pdcm 1 is the key marker of T cell exhaustion. IFNg prevents exhaustion. Hence inactivation of pdcm 1 is a useful treatment strategy to follow. Antioxidants like zinc, magnesium, vitamins C and E seem to work at the level of mitochondria.
• The percentage of SARS-CoV-2 specific T cells is least at the time of peak viral load.
• The balance between virus clearance and preservation of health is driven by some cytokines mainly IL-10, TGFb.
• Cytopathic viruses destroy the cells they enter, while the non-cytopathic viruses infect the neighboring cells and end up taking the inflammatory cascade.
• Loss of effector function reduces the ability to fight the virus at least for that virus.
• The anti-inflammatory and pro-inflammatory mechanisms are constantly undergoing homeostasis to preserve health.
• Natural immunity is not to be ignored; it has to be enhanced. This can be done via lifestyle changes, personal protection and population protection.

(Excerpts from the presentation by Dr Nidhi Dhawan)