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935: Minutes of Virtual Meeting of CMAAO NMAs
Treatment protocols in different countries and their experience with remdesivir
30th May, 2020, Saturday, 9.30 am-10.30 am
Participants: Member NMAs: Dr KK Aggarwal, President CMAAO; Dr Yeh Woei Chong, Singapore Chair CMAAO; Dr Ravi Naidu, Past President CMAAO, Malaysia; Dr N Gnanabaskaran, President Malaysian Medical Association; Dr Thirunavukarasu Rajoo, Hon. General Secretary, Malaysian Medical Association; Dr Ashok Philip, Malaysia; Dr Alvin Yee-Shing Chan, Hong Kong; Dr Marie Uzawa Urabe, Japan; Dr Md Jamaluddin Chowdhary, Bangladesh
Invitees: Dr Russell D’Souza, UNESCO Chair in Bioethics, Australia; Dr Sanchita Sharma, Editor IJCP Group
- There is a discrepancy in the number of deaths. To get the actual number of deaths, multiply the number of deaths with 2. This will cover the false negatives, sudden deaths, etc.
- China conducted 6.5 million tests for coronavirus, where 6 new cases were detected two weeks ago; 200 cases were found, mostly people who showed no symptoms. The ratio of undocumented cases for each documented case in Wuhan is 1:33, i.e., there were 33 asymptomatic cases for every one new infection. This is a reliable study as the total population was studied and not a sample population.
- This ratio in New York City is 1:10, i.e., there were 10 asymptomatic patients for every positive patient. New York conducted an antibody testing study, while Wuhan did antigen test. The reliability of antibody test is unknown.
- Treatment for mild/pre-symptomatic/pauci-symptomatic/asymptomatic cases (Pauci-symptomatic patients have transient symptoms, e.g., mild fever or sore throat for 1-2 days): Paracetamol (for fever and myalgia), hydroxychloroquine (HCQ), azithromycin (this may have cardiac toxicity, so alternative is doxycycline), famotidine, ivermectin, ritonavir+lopinavir, nafamostat (anticoagulant), remdesivir.
- India is trying to make a biosimilar of remdesivir to reduce the cost; it should be recommended to the respective governments that Asian countries should be allowed to make biosimilars in this time of a pandemic.
- Management of COVID-19 is entirely in government hospitals by order of the government; no private hospital treats COVID patients.
- Treatment: Symptomatic treatment, combination of doxycycline and azithromycin, anti-HIV drug combination.
- The government had earlier stated that they would be participating in remdesivir trial, but there are no results of the trial.
- The cost of remdesivir is likely to be high in Malaysia.
- Remdesivir has been used by NCID only in clinical trial with NIH, not otherwise.
- Kaletra (lopinavir+ritonavir) and beta-interferon have been used. Following a feedback from NICD about their relative lack of usefulness, Kaletra and beta-interferon are not used now for treatment of patients.
- Basic supportive care is still paramount.
- HCQ has not been used at all, not even in clinical trials.
- A study has found that on Day 11, there is minimal viral load; it is noninfectious. Singapore has moved to time-based discharge, i.e., after Day 14, patient is deemed to be free of COVID and can go to work after Day 21.
Hong Kong protocol
- Combination of ritonavir+lopinavir has been mainly used.
- Supportive care is still the mainstay of treatment, for mild cases. All new cases are in people who have returned from overseas; they are mild or asymptomatic. No local cases for few weeks.
- Management of comorbid conditions such as diabetes is very important.
- Not tried remdesivir or HCQ.
- Bangladesh has been using HCQ and azithromycin; but has recently temporarily stopped use of HCQ after a directive from technical committee in line with the WHO guidelines on this and an analysis published in The Lancet.
- Plasma therapy is being used.
- Production of remdesivir has started but not come to the market yet.
COVID-19 has the following presentations. We should be able to differentiate patients according to their manifestations. All patients do not show all manifestations.
Hypothesis: If we choose the right patient for the drug, the results would be very different.
- It is a viral disorder and is self-limiting in 90% patients. The earlier you give antivirals (within 48 hours), the better it is. In India, Tamiflu (oseltamivir) is given on Day 1 before test results are available.
- The virus behaves like HIV in some patients; if there is lymphopenia or reduced CD4 cell count, give anti-HIV drugs.
- It produces hyperimmune inflammation, so if there are signs of hyperinflammation such as high ESR, CRP and ferritin, anti-inflammatory drugs such as HCQ, indomethacin become important.
- It behaves like bacteria, so azithromycin can be given; azithromycin may cause cardiotoxicity, so doxycycline may be given, which also covers atypical bacteria.
- It produces thrombo-inflammation; fibrinogen and D-dimer levels are raised; such patients have moderate/severe illness. Give anticoagulant – heparin, nafamostat.
- It produces silent hypoxia; oxygen supplementation with high flow nasal cannula, BiPAP (if required) and ventilator (last resort).
- Cytokine storm and ARDS: this is terminal illness and managed as per protocol for ARDS.
Hyperimmune inflammation is mainly seen in Europe and the US and not much seen in Asian countries, including India. Most CMAAO countries have not reported Kawasaki-like cases. There may be few scattered cases.
Use remdesivir early as studies with Tamiflu have shown that if used very early, the difference in morbidity is significant. Start antivirals when symptoms are primarily due to the viral infection. Don’t wait for symptoms due to body’s immune response.
The minimum space requirement for working in office, according to WHO, is 100 sq ft per person. In India, the standard is 75 sq ft per person for living. In countries with high population density, social distancing may not be possible. So masks should be compulsorily used at all places, at least for the next 3 months.
Take same precautions at home as followed outside the home.
Recommendations for re-opening of schools
- Individual countries can form their rules about use of masks by children as they do not sit facing each other.
- No cafeteria/canteens in schools.
- No mixing of classes.
- Not more than 20-25 students in one class.
- Break between classes will be divided.
- India recommends starting from 9thclass onwards, while Europe recommends starting primary school first.
- E-classes in high risk areas and for disabled.
- Only soap and water to wash hands; use of sanitizer must be done only under supervision.
- Teachers and staff to wear masks.
- Every school should have a written policy on how to handle the first positive case in their school to avoid any kneejerk reaction and/or media circus.
Dr KK Aggarwal
President CMAAO, HCFI and Past National President IMA