Study: Is convalescent plasma actually effective on COVID-19

Plasma therapy emerges as COVID-19 treatment option with cases reported from China and Korea

Medical experts raise issues over clinical limitations in efficacy

Following the case reported in China, Korea has published a case study of effective plasma therapy on COVID-19 patients.

 

As the Korean infectious disease control authority has announced its plan to establish a plasma therapy guideline for the COVID-19 patients, the public’s interest on the therapeutic mechanism and effect has heightened.

 

Following is a discussion over the issues regarding the plasma therapy’s mechanism of action and efficacy.

 

▲Plasma therapy using recovered patient’s antibody to fight against the virus A vaccine has a preventive effect but does not treat the disease after the viral infection.

 

Antiviral remdesivir, currently used to treat COVID-19 patients, relies on inhibition of viral replication and symptomatic therapy relieving the symptoms.

 

On the other hand, plasma therapy uses immune system of a patient who has completely recovered from the viral infection.

 

In the recovered patient’s blood, plasma containing antibody is generated during the process of post-viral infection recovery.

 

And if the convalescent plasma is extracted from the donor and transfused to another patient with severe symptoms, the antibody from the plasma fights against the virus in the patient.

 

Theoretically, the antibody that experienced a specific virus can easily detect the antigen or can mass produce antibody.

 

In such case, the time to alleviation of symptoms and treatment against the virus could be shortened.

 

This is usually the reason why the plasma therapy is a last resort for patients in a critical state of a novel infectious disease without a treatment or vaccine.

 

The U.S.

 

Food and Drug Administration (FDA) on Mar.

 

24 and Korean health authority on Apr.

 

1 have respectively approved of using blood product extracted from people who have cured from COVID-19 for treatment purpose.

 

After China has published a clinical study result confirming the therapeutic benefit on five people, Korea has also reported cases cured from blood product.

 

▲Effect of plasma therapy?

 

“All cured” On Apr.

 

6, Journal of Korean Medical Science (doi.org/10.3346/jkms.2020.35.e149) has published a study on the use of convalescent plasma therapy in two COVID-19 patients led by Professor Choi Jun Yong (Department of Internal Medicine, Severance Hospital, Seoul) and his research team.

 

This is a first report of using convalescent plasma extracted from recovered patients to treat COVID-19 cases in Korea.

 

The first case, a 71-year-old man, has been treated with antimalarial and HIV drug, but his symptoms worsened.

 

The respiratory rate was over 30 times per minute (normally under 20 times per minute) and chest radiographs showed critical pneumonic symptoms in both of his lungs.

 

C-reactive protein (CRP) was up at 172.6 mg/ L (normally less than 8 mg/ L).

 

When the second case, a 67-year-old woman, was hospitalized, her respiratory rate was at 24 times per minute and oxygen saturation was at 93 percent (normally over 95 percent), while her CRP elevated up to 314 mg/ L with signs of lymphopenia.

 

Regardless of using corticosteroid on top of administering antimalarial and HIV drugs, the female patient sustained lymphopenia and the viral titer was increased.

 

The researchers administered 500 ml of convalescent plasma, obtained from a recovered donor, twice in 12-hour interval and initiated corticosteroid treatment simultaneously.

 

The patients were discharged from hospital after seeing lymphopenia recovery, reduction in viral titer, and recovery of CRP level.

 

A plasma therapy study on critically ill patient with COVID-19 in China, led by Professor Chenguang Shen (National Clinical Research Center for Infectious Disease), has also demonstrated similar outcome.

 

Five patients with COVID-19 and acute respiratory distress syndrome (ARDS) have recovered normal body temperature in three days after receiving convalescent plasma, and showed increase in oxygenation capacity and decrease in viral titer.

 

Three out of five patients were discharged (hospitalized for 53, 51 and 55 days, respectively) and two patients stabilized on day 37 after the plasma therapy.

 

▲Plasma therapy with positive outcomes, but why the negative issue?

 

The problem is the effect.

 

One says the effect has been confirmed, but the others say it has not been fully confirmed.

 

So why are there contrasting claims?

 

The dispute has sparked due to the limitations in the clinical environment the plasma therapy was conducted.

 

As the studies were conducted in critically ill and desperate patients with novel infectious disease, the variables were not properly controlled in all cases.

 

To appropriately prove the efficacy of the plasma therapy, the infected patients should be divided into three groups.

 

A large-scale long-term clinical study with patient groups receiving plasma therapy only, plasma therapy plus antiviral agent (symptomatic therapy), and placebo should be conducted to test the clinical efficacy.

 

However, the studies published so far had five or two subjects and combined therapy or prior therapies were given to the patients, which makes it difficult to conclude the correlation of plasma therapy and ‘full recovery.’ Professor Choi Jun Yong of Department of Internal Medicine at Severance Hospital commented, “As corticosteroids were used besides convalescent plasma, the research cannot claim the recovered cases were a direct and sole result of the plasma therapy.

 

Such study is leaves limitations in confirming the effect of each therapy type as various antibodies were administered to the patient due to their severity.” “However, the study in Korea has witnessed the drop in viral load, which could be assessed as an effect of transfusing convalescent plasma, as using systemic corticosteroids can only relieve inflammatory response but does not block viral replication,” the professor emphasized.

 

▲Korean disease control authority setting convalescent plasma use guideline, what to look out for?

 

The limitations still exist because plasma therapy is not the only option and is definitely not the fully proven option.

 

The government guideline should take account of limited convalescent plasma from a donor, prioritization of administrated subject and different level of effect depending on the donor’s condition.

 

But also the authority should keep in mind that the therapy lacks sufficient medical evidences.

 

Medical experts stress that confusion in clinical scene and waste in resources would be minimized if only the health authority clarifies detailed guideline of convalescent plasma use.

 

Professor Choi Jun Yong highlighted, “As for the guideline, the Korean Society for Laboratory Medicine has a lot to contribute.

 

More than anything, it would have to recommend standard of prioritizing the subject for limited convalescent plasma transfusion considering the efficiency and benefit.” And he added, “Depending on the donor’s health condition, the convalescent plasma’s effect and outcome could differ.

 

Future studies should follow to evaluate adequacy of donor and recipient.” The professor also suggested, “The level of neutralizing antibody related to the plasma therapy needs more research.

 

The guideline should consider testing the donor’s neutralizing antibody titer prior to the transfusion, as the young age of a donor does not guarantee high level of the antibody.”