CMAAO Coronavirus Facts and Myth Buster: Understanding Cytokine Crisis

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With input from Dr Monica Vasudev

1082:   Minutes of Virtual Meeting of CMAAO NMAs on “Understanding Immuno-inflammation”

12th September, 2020, Saturday, 9.30am-10.30am

Participants: Member NMAs: Dr KK Aggarwal, President CMAAO; Dr Marthanda Pillai, Member World Medical Council; Dr Ravi Naidu, Malaysia, Immediate Past President, CMAAO; Dr Alvin Yee-Shing Chan, Hong Kong; Dr Marie Uzawa Urabe, Japan; Dr Debora Cavalcanti, Brazil; Dr Prakash Budhathoky, Nepal; Dr Qaisar Sajjad, Pakistan

Invitees: Dr Russell D’Souza, UNESCO Chair in Bioethics, Australia; Dr S Sharma, Editor IJCP Group

Key points of discussion

  • When virus enters the cell (naso oropharyngeal), different scenarios can result.
  • One, it is taken up and is killed by the macrophages. No antibodies are formed, the patient is asymptomatic.
  • In some persons, the virus enters the blood → dendritic cells in thymus →T cells and then to B cells and produces IgG and IgM. The patient is asymptomatic, but antibodies are formed.
  • In a third scenario, the cells produce IFN-1 on Day 1, which initiates neutrophils, NK cells and monocytes. The NK cells and monocytes produce IFN-γ, which kills the virus, as do the neutrophils. The patient remains asymptomatic because of adequate immunity.
  • Another scenario – the IFN-γ will produce TNF-α, which causes inflammation. The person will be symptomatic on Day 1 (fever, diarrhea, headache, rash, loss of smell/taste).
  • If the immunity is inadequate, the virus is not killed. The cells do not form IFN-1 in such a situation, alternate pathway opens up on Day 3. Macrophages produce NLRP3, which produces IL-1β and IL-18. IL-1β increases ferritin levels, glucuronidase causing tissue damage. IL-18 adds to the inflammation. Cells through the cellular dendritic cells produce Th1 cells, which produce IL-6 (formed on Day 3), TNF-α and IL-8. IL-6 causes clot formation, TNF-α (formed on Day 1), IL-8 and IL-1β (formed on Day 3), cause inflammation.
  • Clot formation will be seen as rising D-dimer and fibrinogen, inflammation presents as high CRP, tissue damage as raised LDH and ESR.
  • Transverse myelitis and Guillain-Barre syndrome have also been reported with coronavirus.
  • Transverse myelitis (one per million) and Guillain-Barre syndrome are known complications of a vaccine.
  • The post-vaccine transverse myelitis – can be due to the virus in the spinal cord or due to inflammatory reaction? We do not know. Or unrelated to the vaccine.
  • Drugs act at different levels: mefenamic acid (NLRP3, PLA2 and ILs), steroids (PLA2), tocilizumab (IL-6), infliximab (TNF-a), methylene blue (bradykinin).
  • The four vaccines (masking, physical distancing, hand hygiene and povidone iodine oral wash) are much more important than the fifth actual vaccine.
  • The vaccine may not protect from inflammation occurring anywhere in the body.
  • The virus does not kill the person directly; it is the hyperinflammation caused by the cytokine storm and the immunity of the person reacting to the viral invasion that kills the person or causes the morbidity.
  • Aerosol generating behaviors are shouting, speaking loudly; aerosol generating sounds are those where diaphragm movement is involved.

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA