Coronavirus: ‘Gold standard’ research finds plasma therapy has ‘low‐certainty evidence on effectiveness and safety’

A masked boy rides a bike in Kirklareli, Turkey. (Getty Images)

Many were optimistic plasma therapy could “cure” patients critically ill with the coronavirus.

People who have overcome the infection have been invited to donate their plasma, the liquid part of blood, in the UK and US.

Scientists hope to harness coronavirus-specific antibodies; immune-fighting proteins that circulate in the blood, preventing the infection taking hold again.

Doctors were cautiously optimistic the therapy could have some benefit, with a similar approach being adopted more than 100 years ago during the 1918/19 Spanish flu pandemic.

Transfusing plasma from a recovered coronavirus patient was thought to reduce the risk of death, speed up recovery or even be a preventative treatment for vulnerable people.

A Cochrane study – considered the gold-standard of research – reported scientists were “very uncertain” about the effectiveness of plasma therapy for hospitalised patients with COVID-19, the respiratory disease that can be triggered by the coronavirus.

Studies carried out so far were deemed “low quality” and “at high risk of bias”, as well as throwing up “inconsistent” results.

A teacher wears a mask in Antwerp, Belgium. (Getty Images)

Coronavirus: Scientists ‘very uncertain’ if plasma therapy is effective

Tom Hanks and his wife Rita Wilson posted pictures on Instagram of them donating their plasma to Californian scientists after beating the coronavirus.

On 20 April, NHS Blood and Transplant asked people who have recovered from the infection to give blood for research.

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Plasma transfusions are an experimental, unapproved approach to fighting the coronavirus outbreak.

To learn more about their effectiveness, scientists from all over the world looked at eight studies with a total of 32 patients.

None of the participants were randomly assigned to a “treatment group”, with these studies “producing the best evidence”.

In addition, none of the studies included a comparison group, where a treatment is held up against another drug or placebo.

All of the participants were alive at the end of their follow-up, but not all had been discharged from hospital.

Six studies measured the level of breathing support the participants required as a measure of their recovery.

Breathing support included oxygen therapy, mechanical ventilation and the need for a special machine that oxygenates the blood.

All six studies reported improvement in at least some of the participants, but it is uncertain whether this was related to the plasma therapy, another treatment or the natural progression of the disease.

Six of the eight studies were made up of people with severe COVID‐19.

Most saw improvement at follow‐up, however, this again could have been due to other factors.

Two participants reported side effects related to the plasma therapy, with one suffering a fever and the other anaphylactic shock.

“We are very uncertain whether plasma [therapy] is effective for people admitted to hospital with COVID‐19 as studies reported results inconsistently, making it difficult to compare results and to draw conclusions,” wrote the scientists.

“We identified very low‐certainty evidence on the effectiveness and safety of convalescent plasma therapy for people with COVID‐19; all studies were at high risk of bias and reporting quality was low”.

The scientists added better studies are being carried out and they will update their review accordingly.

“This Cochrane rapid review of the evidence shows there is only very limited evidence on the benefits and safety of convalescent plasma,” said Dr Lise Estcourt, head of NHS Blood and Transplant’s clinical trials unit, which is running the plasma study in England. 

“This is why it is so important to perform large randomised controlled trials that are powered to detect a difference in outcomes that are important to patients such as decreasing mortality or the need for mechanical ventilation. 

“In England we have opened a trial of plasma for adults admitted to intensive care and hope to open a trial in all hospitalised patients in collaboration with the [initial] trial for people of all ages”.

Coronavirus: Plasma therapy is ‘not a silver bullet solution’

Despite the limited evidence, experts have previously expressed cautious optimism about plasma therapy.

“We know survivors of COVID-19 will have antibodies which can block the virus from entering human cells in their blood serum,” said Professor Sir Robert Lechler, from the Academy of Medical Sciences.

“If these ‘neutralising antibodies’ can be donated to patients with COVID-19, then recovery and chances of survival should be much higher than without this treatment.

“The concept is very simple: you take blood plasma from a person who has recovered from the virus which will contain antibodies their body has made in the process of clearing the virus, and you put this into the patient who is grappling with the virus – transferring immunity (for a transient amount of time).

“There are several potential uses for this treatment: it could be used to treat critically ill patients (patients on ventilation) to reduce the risk of death and increase chance of survival, it could also be given to people who are ill with the virus but not yet needing ventilation to try to accelerate the immune response to prevent the patient from getting to the stage where they need ventilation. 

“Another way this could be used would be to go into care homes and give it to people who have been tested positive for COVID-19 to try to halt the development of a serious form of the disease by providing transient immunity”.

Professor Lechler added plasma transfusions were beneficial during the severe acute respiratory syndrome (Sars) epidemic of 2002/3, as well as in China amid the ongoing pandemic.

Both Sars and the circulating coronavirus are strains of the same virus class.

“Although it is much too soon to know the results, anecdotally it seems to have helped patients recover”, said Professor Lechler.

He stressed plasma transfusions are not a miracle cure, with any transferred immunity being “transient”.

“Convalescent plasma transfusions are not a silver bullet solution for the coronavirus health crisis, however, they do have the potential to be hugely beneficial,” said Professor Lechler.

“This is not a vaccine because a vaccine uses a virus or viral proteins to provoke immunity and here you are transferring immunity transiently from someone who has made an immune response.”

Scientists around the world are racing to develop a jab against the coronavirus, however, many were honest from the beginning one will not be ready for this outbreak.

A vaccine could be useful in the future, however, if the infection becomes seasonal.

In the absence of a jab, Professor Lechler added: “There is an urgent need for this kind of [blood plasma] intervention”.

Professor Michael Joyner from the Mayo Clinic in the US told the BBC: “Sometimes, as a physician, you just have to try to take a shot on goal when you have a shot.”

Safety concerns around plasma therapy have also been flagged.

These include “transmission of other agents (including transmissible spongiform encephalopathy) and antibody enhancement of disease”, said Professor Sir Munir Pirmohamed, from the British Pharmacological Society.

Spongiform encephalopathy is a rare progressive neurodegenerative disorder. It is caused by proteins called prions that can be transferred between individuals.

Antibody enhancement occurs when non-neutralising proteins facilitate virus entry into cells, leading to increased infectivity.

“Even if shown to work, scalability to treat large numbers of patients may become an issue,” added Professor Pirmohamed.

What is the coronavirus?

The coronavirus is one of seven strains of a virus class that are known to infect humans.

Since the coronavirus outbreak was identified, more than 4.4 million cases have been confirmed worldwide, according to Johns Hopkins University.

Of these cases, over 1.5 million are known to have “recovered”.

Globally, the death toll has exceeded 302,400.

The coronavirus mainly spreads face to face via infected droplets expelled in a cough or sneeze.

There is also evidence it is transmitted in faeces and can survive on surfaces.

Symptoms include fever, cough and slight breathlessness.

The coronavirus has no “set” treatment, with most patients naturally fighting off the infection.

Those requiring hospitalisation are given “supportive care”, like ventilation, while their immune system gets to work.

Officials urge people ward off infection by washing their hands regularly and maintaining social distancing.