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

CMAAO Corona Facts And Myth COVID: Non COVID phase

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With input from Dr Monica Vasudev

1071:  Minutes of Virtual Meeting of CMAAO NMAs on “Covid-19 Update”

29th August, 2020, Saturday, 9.30am-10.30am

Participants: Member NMAs

Dr KK Aggarwal, President CMAAO, Dr Marthanda Pillai, Member World Medical Council, Dr Alvin Yee-Shing Chan, Hong Kong, Dr Prakash Budhathoky, Nepal

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

Key points from the discussion

  • Three acute phase reactants– C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR) and Interleukin-6 (IL-6). In a resource-limited country, CRP is the best choice amongst the three. It is an indicator of intensity of inflammation. CRP cannot rise without increase in IL-6. When CRP is raised, presume that the d-dimer is high.
  • We do not know how China with a higher population density than India has managed to control the disease. Mortality is 3 per million; new cases are 9.
  • Antigens of various diseases such as typhoid, malaria, chikungunya, and dengue are false positive in Covid-19.
  • All overseas players and support staff underwent two COVID-19 RT-PCR tests before flying into the UAE and could fly only if the tests were negative. If not, then the same 14-day quarantine period and two negative tests was needed to be able to fly to the UAE. The players and support staff will be tested on Day 1, Day 3 and Day 6 of their quarantine in the UAE and after clearing that, they will be tested every fifth day during the 53-day event.” Instead of three tests, pooled testing of the teams can be done daily.
  • Oxygen administered without anticoagulation has no significance. Aspirin/anticoagulation must be given. For cases under home care, rivaroxaban (10 mg prophylaxis) can be given in place of Low Molecular Weight Heparin (LMWH); it is cheaper, can be taken by the patient, onset of action is 10 hours.
  • According to a Times of India report, 87,000 healthcare workers in India are infected with COVID-19; there have been 573 deaths; 74% cases and over 86% deaths are from six states: Maharashtra, Tamil Nadu, Delhi, West Bengal, Gujarat and Karnataka. The numbers projected seem to be very high and need to be checked.
  • Doctors have a high viral load so have higher chances of developing hypercoagulable state. Should prophylactic anticoagulation be initiated on Day 1 of the illness itself for doctors/HCWs?
  • There are three phases of the illness: COVID (1-9 days, infectious phase), post-COVID (after 9 days, non-infectious, persistent inflammation) and non-COVID (after 3 months). After 3 months, the patient should be treated as non-COVID, instead of post-COVID. However, this comes laced with medicolegal aspects.
  • In Hong Kong, the third wave is partly controlled. There have been less than 20 cases per day for the last week or more. One-third of confirmed cases have no known source of origin; so the chain of spread of infection is not known. Universal community testing scheme will start from 1stSeptember to find out silent carriers. The Hong Kong government has agreed to expand to high risk group tracing and testing even with universal testing. With opening up of economy, better monitoring of industries is mandatory, to ensure there is no fourth wave. The third wave began with 9 cases with mutated virus strain (d614g). At that time, sailors coming to Hong Kong had been exempted from testing and quarantine; also restrictions of social distancing were relaxed. This created the third wave.
  • Reinfection: A person from Spain tested positive in March then became negative reached Hong Kong and tested positive again in July. This raises a question whether this virus can re-infect. It was a mutated virus with 24 gene differences. It formed antibodies quickly, caused no symptoms and no serious manifestations and disappeared early. We need to be vigilant about this. People in post-COVID phase getting recurrent corona-like illness may be getting re-infection with a different strain.
  • Another case of re-infection reported in the US; a young person who had severe symptoms and required oxygen and assisted breathing in the second infection.
  • A study from Mumbai has reconfirmed the US study that antibodies do not last for more than 3 months.

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA

CMAAO Coronavirus Facts and Myth Buster: Steroid and Diabetes

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With inputs from Dr Monica Vasudev

1048: New guidance from the UK National Diabetes COVID-19 Response Group [August 2 in Diabetic Medicine]

  1. Address the triple insult of dexamethasone-induced impaired glucose metabolism, COVID-19-induced insulin resistance, and COVID-19 impaired insulin production.
  2. Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial revealed that dexamethasone led to reduction in deaths in patients with COVID-19 on ventilators or receiving oxygen therapy. The dose used in the trial was 6 mg daily for 10 days, which is 5 to 6 times greater than the therapeutic glucocorticoid replacement dose.
  3. High glucocorticoid doses can result in exacerbation of hyperglycemia in those with established diabetes, can unmask undiagnosed diabetes, cause hyperglycemia or new-onset diabetes, and can also lead to hyperglycemic hyperosmolar state (HHS).
  4. The guidance recommends a target glucose of 108-180 mg/dL and further states that up to 216 mg/dL is acceptable.
  5. It recommends the use of once- or twice-daily NPH insulin for patients with glucose above 216, in certain cases with the addition of a long-acting analog.
  6. Patients already taking premixed insulin formulations can continue, while increasing the dose by 20% to 40%.
  7. Considering the risk of hypoglycemia associated with those formulations, many experts say that they would switch those patients to NPH during the time theyre being given dexamethasone. [Medscape Excerpts]

Comments

  1. Steroid induced high sugar is often post meals.
  2. Give repaglinide 1 mg or 2 mg sublingual before meals.
  3. Add 0.3 units insulin per kg in divided doses.
  4. In high-risk cases steroids may have to be started on day 1 itself so adjust dose accordingly.
  5. In post COVID illness, steroids may have to continue for weeks together like in any immunological illness.

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA

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