Speaker: Dr Nidhi Dhawan

March 27, 2022

Covid Update - emerging variants

• The cumulative confirmed cases in the US are 78 million, India 42 million and UK 18 million as of February 16, 2022. If we look at the population of these countries, in the UK 11% are seropositive, in the US 25% population has been infected and in South Korea, 18% population has been infected.
• With regard to daily new cases, UK and Denmark are showing an upward trend. At least 50% of new cases are incidental cases.
• Countries with zero covid policy such as Australia, (52,000), New Zealand (17,000), Hong Kong (14,000), Singapore (nearly 10,000) have high numbers vis a vis India (1766) as on March 24, 2022.
• In countries with high vaccination rates such as Germany, UK, Singapore, Israel, China, the numbers are still not touching the baseline, whereas in India, the numbers are almost touching the baseline.
• In South Korea, despite high vaccination rate and zero covid, cases are not coming down. But in India, US, Israel, UK, the numbers are coming down.
• In UK, South Korea and Israel, it is 100% omicron, whereas in South Africa, there is some delta.
• Each country might have reached the peak at different times, but the shape of the graph for delta remains the same – a sharp rise reaching a plateau followed by a sharp decline.
• For omicron, there is again a sharp rise and then a flat plateau.
• In terms of Covid vaccine boosters, South Korea is at the top with 63.40 followed by UK at 56.77, Israel at 56.18, US at 29.24, South Africa at 3.30. India is lowest with 1.50.
• In a statement, the WHO has said, “For the Omicron variant, the mutational profile and preliminary data indicate that vaccine effectiveness will be reduced against symptomatic disease caused by the Omicron variant, but protection against severe disease is more likely to be preserved. However, more data on vaccine effectiveness, particularly against hospitalization, severe disease, and death are needed, including for each vaccine platform and for various vaccine dosing and product regimen.”
• The National Institutes of Health (NIH) has said, “Despite reduced antibody responses against the variants, T cells serve as a second line of defense. This may help to explain why omicron infections, while easily spread, are less likely to lead to severe disease in fully vaccinated people.”
• Before Omicron, the average seropositivity across the country ranged from 85-87% including children older than 5 years.
• The combination of natural infection and vaccination gives protection that is 30 times higher than vaccine alone.
• The R number for India is 0.5, for US and South Africa it is around 1 and for Israel and UK it is 1.5. R number less than 1 indicates that the pandemic is on its way out.
• In India, the new cases are less than the 7-day average (24^th March).
• People infected with Omicron pass it more to their close contacts compared to those infected with delta regardless of their vaccination status.
• Vaccines continue to be effective against delta, but not so much against Omicron, which is why it became the dominant strain globally.
• A person who has received three vaccine doses is less likely to spread the delta or Omicron variant to household members vs an unvaccinated person.
• The deltacron has retained the changes in the RBD and NTD, so it has the signatures of both delta and omicron.

CBC - WBCs

• Neutrophils have been called the soldiers. They are produced by the bone marrow and the major early responders and typically die in the process of fighting the infection. Humans are predominantly neutrophilic. Dogs are neutrophilic, while wolves are lymphocytic.
• Functions of neutrophils are phagocytosis, cytokine release, NETosis and degranulation.
• Early response is triggered by recognition of pathogen-associated molecular patterns (PAMPs), which is helped by opsonization.
• Classic phagocytosis is mediated by actin prime and useful for bacteria.
• Clathrin mediated endocytosis is used for viruses.
• Neutrophils release cytokines of almost every family, but these are in much lower amounts than the cytokines produced by the macrophages. They contribute to angiogenesis, hematopoiesis, wound healing, autoimmunity. Their major role is in local acute inflammation and in linking innate and adaptive immunity.
• Neutrophilic responses can go to nonresolving inflammation or to enhanced host defense leading to resolution of inflammation.
• The antimicrobial response of neutrophils is largely phagocytosis, release of antimicrobial polypeptides and NET (neutrophil extracellular traps) release.
• All mediators can target the endothelial cells and increase endothelial activation and vascular permeability.
• They work on monocytes and macrophages and increase their recruitment and secretion of chemokines and cytokines.
• Dendritic cells are also recruited by neutrophils.
• APC-like neutrophils cause T cell proliferation/suppression/recruitment and activation of Th1 and Th2 cells.
• The classic functions of neutrophils include degranulation, cytokine release, phagocytosis and oxidative burst. But new studies have shown that neutrophils have a far greater role to play in pathology and physiology. There is neutrophil heterogeneity in the form of CD177, which is increased under inflammatory conditions; OLFM4+, which is less effective in clearing bacteria, TAN (anti-tumor function) and PAN (MMP-mediated extracellular matrix remodeling).
• Markers of cytokine storm (ALT, ferritin, d-dimer, LDH, CRP, cytokines, ESR and NLR) are all raised.
• In Covid, the cut-off for ferritin is ≥400 mcg/L (normal 18=350 ng/ml), for d-dimer is ≥1000 ng/mL (250-500 ng/mL), CRP is ≥20 mg/dL (normal 0.3-1.0 mg/dL) and NLR is 6.6 (normal 1.0-3.0).
• PAMPs are recognised by PRR in APCs and activate them, which release cytokines and activate Th cells leading to release of cytokines from T cells.
• IL-1 is a marker of innate inflammatory response.
• IL-4 and 5 promote B cells, eosinophils and basophils. They are seen in helminths and allergic responses.
• There is a Red Queen hypothesis in immunology, which means that any biological entity evolves to beat what can eliminate it. Some bacteria have become intracellular such as chlamydia, salmonella; fungi and helminths secrete proteases that lyse cytokines and viruses and helminths have evolved to produce their own anti-inflammatory cytokines that deceive our cells to turn them off. Viruses mutate leading to immune memory failure.
• If neutrophils are very high with corona-like symptoms, think of Covid.
• In dehydration, hematocrit and ESR will change; if hematocrit is 3 times of hemoglobin, this is a sign of dehydration.
• If NLR is greater than 3, in Covid times, this is likely to be Covid. It is also a marker of septicemia and acute inflammatory conditions such as pancreatitis. It is a signature of cytokine storm and immune exhaustion.
• If lymphocytes are high and neutrophils are low with no apparent symptoms, think of chronic infection such as TB, HIV.
• If platelets are low (as in dengue) or exorbitantly high (in thalassemia, splenectomised patients), ask for a corrected report (manual count).
• Peripheral smear can release some form of anemia even with normal hemoglobin.

(Excerpts from a presentation by Dr Nidhi Dhawan)