What is convalescent plasma therapy (passive antibody treatment)?

Blood is drawn from a person who has recovered from COVID-19 infection. Their blood is screened for virus-neutralizing antibodies with the help of various serological and viral assays such as ELISA. Then, the serum containing a high amount of virus-neutralizing antibodies is separated from the blood.

This convalescent serum is then injected into the body of a high-risk patient - this could be someone with an underlying medical condition and COVID-19, medical professionals, someone with confirmed COVID-19 infection or someone in close contact with a confirmed COVID-19 patient.

The virus-neutralizing antibodies are usually derived from the blood of people who have recovered from SARS-CoV-2 infection. The convalescent serum can also be prepared in certain animal hosts, such as genetically modified cows that produce human antibodies.

As more individuals recover from COVID-19, the number of potential donors for the convalescent serum will continue to increase.

Read more: Why COVID-19 was declared a pandemic

So far, doctors have seen that passive antibody therapy has been more effective when used as a preventive measure rather than for the treatment of the disease.

If the serum is used for the treatment of the disease, it has to be delivered soon after the symptoms start to appear. Scientists believe that antibodies work by fighting off inflammation in the body - this is easier to achieve during the initial stages of infection when the inflammation load is low and the person is usually asymptomatic.

Similar application of passive antibody therapy was seen in the treatment of pneumococcal pneumonia where most of the benefit was seen when the antibody was administered shortly after the onset of symptoms. 

Similar results were also seen in a study involving 80 patients affected by the Severe Acute Respiratory Syndrome (SARS) in the year 2003 in Hong Kong. The results of the study showed that patients who were treated within 14 days after contracting the virus improved drastically and were discharged from the hospital before day 22.

However, scientists believe that convalescent sera (antibodies from the blood of recovered patients) should be used in a therapeutic mode only for those individuals who have a pulmonary disease or those who cannot be given plasma as they have a risk of getting a transfusion-related acute lung injury.

Though passive antibody therapy is usually used for prophylactic purposes; in some cases, doctors have also used the convalescent serum in seriously ill individuals.

Doctors in China have used the convalescent serum for the treatment of five critically ill patients with confirmed COVID-19 and acute respiratory distress syndrome (ARDS). The serum was donated by five donors between the ages of 18 and 60 years. After the administration of convalescent serum which contained neutralizing antibody, the patients showed an improvement in their clinical status. 

This was not the first time that convalescent serum was used for critically ill patients: in 2003, three seriously ill patients in Taiwan with SARS were treated with 500 mL convalescent serum which resulted in a decrease in their viral load and all three of them survived.

Passive antibody therapy can only be given if these conditions are fulfilled:

• There is a sufficient number of donors available who have completely recovered from the disease and can donate the antibody-rich serum.
• The blood banks have the facility to remove serum from the donated blood. 
• There is an availability of different tests like serological assays (required to detect SARS-CoV-2 in serum) and virological assays (required to measure viral neutralization antibodies).
• There are virology labs in the area to perform these assays.
• Randomized clinical trials have been done to assess the effectiveness of the serum and to measure the response of the immune system after delivering the serum.

Most of the risks associated with passive antibody therapy are similar to those seen in the case of a blood transfusion. The possible side effects of passive antibody therapy are:

• There is a risk of getting another infection due to negligence during the transfusion of the sera.
• There can be allergic reactions like itching and hives in the body due to the constituents of the serum transfused in the body.
• Immunological reactions such as serum sickness may occur in some patients after serum transfusion. The symptoms include fever, skin rash, polyarthritis or polyarthralgia (multiple joint pains).
• In some rare cases, passive antibody therapy can also lead to antibody-dependent enhancement of infection (ADE). This is an adverse side effect where the neutralizing antibodies aid the entry of more viruses into the body.

On 12th April 2020, the Indian Council of Medical Research announced that they would be starting off with the trials of plasma therapy for the critically ill patients of COVID-19 infection. ICMR has asked all the medical institutions of India, including those under the state government, to register themselves with the clinical trial ethics committee, and the Drug Controller of India in order to participate in the trial. This would be India’s first official clinical trial in towards finding a cure for the infectious disease, COVID-19.