The plasma therapy debate

The plasma therapy debate

Context

• Recently published findings on convalescent plasma therapy on Covid-19 patients have triggered a debate over its efficacy.
• After the country’s largest such trial, known by the acronym PLACID, found that convalescent plasma was ineffective in arresting Covid-19, the Indian Council of Medical Research (ICMR) has been considering dropping this option from the national guidelines.

What is plasma therapy?

• Plasma is the liquid part of the blood.
• Convalescent plasma, extracted from the blood of patients recovering from an infection, is a source of antibodies against the infection.
• The therapy involves using their plasma to help others recover.
• For Covid-19, this has been one of the treatment options. The donor would have to be a documented case of Covid-19 and healthy for 28 days since the last symptoms.

What has happened to spark the debate?

• An ICMR study has found convalescent plasma was not associated with a reduction in progression to severe Covid-19 or all-cause mortality.

What are the trial findings?

• While use of convalescent plasma seemed to improve resolution of shortness of breath and fatigue in patients with moderate Covid-19, this did not translate into a reduction in 28-day mortality or progression to severe disease.
• PLACID was a randomised controlled trial in 39 hospitals spread across 14 states and Union Territories and representing 25 cities.
• It covered 464 adults admitted to hospital (screened April 22 to July 14) with confirmed moderate Covid-19, of whom 235 were assigned to convalescent plasma therapy while 229 were randomised to receive the best standard of care. The group of 235 received two doses of 200 ml convalescent plasma, 24 hours apart.
• Progression to severe disease or death at 28 days after enrolment occurred in 44 (19%) of the participants in the intervention arm as compared to 41 (18%) in the control arm .

Have there been such results elsewhere?

• In China, a controlled trial of 103 patients with severe Covid-19 reported no effect of convalescent plasma treatment in terms of time to clinical improvement.
• In the Netherlands, the ConCOVID trial, prematurely terminated after 86 patients had been enrolled, could not find any effect on mortality at 60 days, hospital stay, or disease severity at 15 days.

What happens if ICMR does remove the therapy from its guidelines?

• The ICMR has been cautious because of the trial findings. Experts said, however, that guidelines are not necessarily binding and it is too early to dismiss convalescent plasma therapy.
• But there are other issues.
• The authorisation of convalescent plasma as treatment for Covid-19 in India has led to questionable practices such as calls for donors on social media, and the sale of convalescent plasma on the black market.
•  Although convalescent plasma is a safe form of treatment when transfused in accordance to the regulations, it involves resource-intensive processes such as plasmapheresis, plasma storage, and measurement of neutralising antibodies.
• A limited number of institutes in India have the capacity to undertake these procedures in a quality-assured manner.

Way forward:

• This is a new virus, and around the world evidence is still emerging on the best therapeutic options.
  • For example, remdesivir has been sanctioned as a drug of choice by the US drug regulator, while the World Health Organization’s Solidarity Trial has found it had little or no effect on 28-day Covid mortality.
• And experts said use of convalescent therapy has saved some lives but concerns have been raised by the PLACID trial.