8^th May, 2021, Saturday, 9.30am-10.30am

Participants: Member NMAs: Dr KK Aggarwal, President CMAAO, Dr Yeh Woei Chong, Singapore Chair CMAAO, Dr Alvin Yee-Shing Chan, Hong Kong, Treasurer, CMAAO, Dr Angelique Coetzee, President South African Medical Association, Dr Debora Cavalcanti, Brazil, Dr Marthanda Pillai, India, Member World Medical Council, Dr Marie Uzawa Urabe, Japan Medical Association, Dr Md Jamaluddin Chowdhury, Bangladesh Medical Association, Dr Qaiser Sajjad, Secretary General, Pakistan Medical Association, Dr Akhtar Husain, South African Medical Association, Dr Prakash

Invitees: Dr Monica Vasudev, Allergist Immunologist, Advocate Aurora Health, WI, USA, Dr S Sharma, Editor IJCP Group, Dr Meenakshi Soni Bamalwa

Key points from the discussion

• Mild disease means fever, malaise, cough, URI in the absence of dyspnea. Presence of dyspnea means moderate or severe disease.
• Severe disease is characterized by hypoxia (SpO2 <9%) and the need for oxygenation or ventilator support.
• Management recommendations are rapidly evolving. Local protocols and guidance should be followed.
• Monitoring: CBC with differential, complete metabolic panel, creatine kinase, CRP, ferritin, procalcitonin, PT, D-dimer, IL-6 (marker of cytokine storm), LDH, troponin, EKG, chest X-ray, CT scan and sputum culture sensitivity (to look for secondary infection).
• Oxygen target is 92-96%; if the patient retains CO2 then the target is 88-92%. The target is >92-95% in pregnant patients and >94% during resuscitation and >90% once stable for children.
• A nasal cannula, Venturi or non-rebreather mask can be used. High flow nasal cannula oxygen can be used if no relief. Noninvasive ventilation (BiPAP) and endotracheal intubation (strict airborne protection precautions), if needed.
• Avoid fans and nebulized therapy due to the risk of aerosolization.
• Low flow devices: nasal cannula (first step for mild hypoxia), shovel mask, simple face mask, non-rebreather mask (good next step for hypoxia).
• High flow devices: high flow nasal cannula (risk of aerosolization), Venturi mask (good next choice for hypoxia).
• Prone positioning with moderate to severe ARDS; avoid in patients with pacemaker, facial trauma.
• Dexamethasone: moderate to severe patients; 6mg daily x 10 days or until discharge (hydrocortisone 150mg, methylprednisolone 32 mg, prednisone 40mg).
• Thrombosis is a major feature of COVID-19. Up to 30% COVID-19 patients develop thrombosis (arterial and venous). Microthrombosis is the key mediator of COVID-19 related morbidity and mortality and organ dysfunction. Hence, D-dimer is measured.
• Approved therapies: dexamethasone, remdesivir, monoclonal antibodies, baricitinib, tocilizumab.
• Therapies undergoing trials: convalescent plasma, inhaled interferon, full dose anticoagulation,  colchicine, ASA, vitamin D, ivermectin, molnupiravir, bevacizumab.
• Therapies with no benefit: hydroxychloroquine, lopinavir+ ritonavir.
• Remdesivir: RdRp inhibitor; RdRp is essential for replication of the virus. Dose: 200mg on Day 1, 100 mg daily from Day 2 administered only via IV infusion x 5 days (can be used for additional 5 days). It is recommended for use in patients in early stages of severe disease. Should not be used in patients on chloroquine or hydroxychloroquine.
• Baricitinib: Oral JAK inhibitor used to treat rheumatoid arthritis. Dose: 4mg once daily x14 days of total treatment or until hospital discharge, whichever is first.
• Clinical trials have shown that baricitinib + remdesivir was superior to remdesivir alone in reducing recovery time and hastening improvement in clinical status in hospitalized COVID-19 patients, especially those on high flow oxygen (NEJM).
• Tocilizumab: IL-6 receptor antagonist. Dose: 8mg/kg IV as a single dose (max 800mg) in combination with steroids within 14 days of onset. IDSA recommends that tocilizumab should be used in addition to standard care and should be used early in hospitalized severe/critical patients in ICU and raised inflammatory marker. Avoid if other bacterial/viral/fungal infection is suspected, thrombocytopenia (<50,000), AST/ALT >5 upper limits of normal, latent TB, history of diverticulitis or bowel perforation and pregnancy.
• Monoclonal antibodies (bamlanivimab-etesevimab) have been given emergency use authorization in the US for non hospitalized adults (≥65 years or who have certain chronic medical conditions) and pediatric patients (≥12 years weighing at least 40 kg). Not recommended for hospitalized patients or those who require oxygen therapy. It should be given as early as possible after a positive test and within 10 days of symptom onset and administered together as a single IV infusion.
• Favipiravir: Antiviral, in mild to moderate infection, 1800 mg orally twice daily on 1^st day followed by 800mg orally twice daily up to maximum of 14 days. Used extensively across the world, including India.
• Convalescent plasma gives passive immunity. It is perhaps beneficial if used earlier in the disease; no benefit in severe disease.
• Hydroxychloroquine/chloroquine: Lack of benefit in hospitalized patients, toxicity (QTc prolongation, arrhythmia), EUA revoked in the US in June 2020.
• Lopinavir-ritonavir: Trials have failed to show efficacy; no benefit in hospitalized adult patients with severe COVID-19 beyond standard care (NEJM).
• Ivermectin: US FDA has not approved ivermectin for use in treating or preventing COVID-19.

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA