Investigational Treatments for COVID-19 in Tertiary Care Hospital of Pakistan

1-1.5 plasma volume exchange, 2/3rd plasma should be replacing with FFP to avoid coagulopathy, adequate dieresis to prevent volume overload, 1-5 sessions in total, 1 session daily

"Convalescent plasma as part of replacement therapy (200-400ml) if reported within 14 days of illness. An IgG titer of \> 1.320 will be considered suitable for use. It will be Collected from person previously infected with Covid-19 and meet following criteria;~1. After 28 day of illness till 3 months~2. Symptom free 2 weeks prior to donation~3. Negative two consecutive PCRs any time between initial positivity and before donation~4. Anti SARS-CoV2 IgG positive, IgM negative~5. Fulfills healthy donor criteria as per WHO/AABB guidelines~6. Volume of plasma to be collected: 900-1200 ml through Apheresis OR plasma separated from phlebotomy donation"

A predefined number of patients having evidence of cytokine release storm with normal procalcitonin level for three consecutive days, a normal blood culture and IL-6 level \> 3 times ULN will be given 1-2 doses of Tocilizumab (80mg IV) . Following contraindications to Tocilizumab will be considered (Allergy to any monoclonal Ab, ANC \< 1000, Platelets \< 50, ALT or AST \> 5 times ULN, Pregnancy and breast feeding, Post TB lung). Some patients will receive it alone in addition to standard treatment whereas in few patients where indicated it will be given in combination with MSC or Remdesivir or both

It will be given to selected patients who have evidence of hypoxemia and presented with in 14 days of illness. For adults requiring invasive mechanical ventilation the dosage of remdesivir is a single loading dose of 200 mg sta on Day 1 followed by once daily maintenance doses of 100 mg IV for 9 days (days 2 through 10). For adults not requiring invasive mechanical ventilation 5 standard doses will be used. However, patients with known hypersensitivity to Remdesivir, multi organ failure, ALT \> 5 times ULN and GFR \< 30ml/minute will not be given Remdesivir. In some patients, where indicated other novel treatments including MSC therapy, Tocilizumab and therapeutic plasma exchange will be given.

Single Dose of 2 x 106 cells/kg will be administered either alone or in combination with other novel therapies. At Armed Forces Bone Marrow Transplant Centre (AFBMTC), MSCs will be isolated from bone marrow harvested cells. About 50ml bone marrow will be collected from iliac crest using aseptic technique in syringes primed with anticoagulant. The collected sample will be diluted with Phosphate Buffer Saline (PBS) and MSCs will be separated using density gradient centrifugation. After resuspension the cells will be seeded at a fixed concentration of 100,000 cells/cm2 in specially designed flasks and incubated at 37Oc in 5% CO2. Medium will be changed after every third day till harvesting of MSCs from the flasks. Once confluent (approximately day 20) the cells will be harvested with sterile techniques using Trypsin- EDTA solution.