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Amid the Covid-19 pandemic, more than 6,000 people in the United States who have recovered from the disease have donated their plasma. This convalescent plasma was transfused into more than 3,000 patients with the disease.
Convalescent plasma has previously been used against viral diseases such as rabies, hepatitis B, polio, measles, influenza, and Ebola. It has also been used in recent outbreaks of MERS and SARS-1, where faster viral clearance has been documented after convalescent plasma administration.
The researchers say that the convalescent plasma of a patient who has recovered from Covid-19 could contain antibodies developed by the individual against the disease. As a consequence, convalescent plasma could provide short-term immunity against disease by providing antibodies that neutralize the virus and prevent further damage.
On April 26, Max Hospital in Delhi had announced that a Covid-19 patient had shown “progressive improvement” after receiving convalescent plasma therapy. However, on April 28, the Union’s health ministry warned against its use. At a press conference, Joint Secretary Lav Agarwal said the Indian Council for Medical Research had launched an experimental study on the efficacy of plasma therapy. “Until the study is approved, no one should use it,” said Agarwal.
In a confused signal from the authorities, Delhi Prime Minister Arvind Kejriwal said on May 1 that a Covid-19 patient had recovered in a state-run hospital after receiving plasma therapy.
Antibody therapy
Convalescent plasma is one of the crudest forms of antibody therapy, which was widely used to treat infectious diseases a century ago. Starting in the 1890s, antibodies obtained from immunized human or animal donors were used to fight disease. With the invention of the first antibiotic in 1928, the use of this “serum therapy” rapidly decreased.
In the present case, a patient who has recovered from Covid-19 and meets the criteria of the donor donates blood as in a routine blood donation. Plasma is drawn from the blood. Two patients with Covid-19 can be transfused, each with 200 ml. Some patients have been transfused with 300 ml, 900 ml and even a total of 2,400 ml for eight days.
There are some caveats to consider regarding this method of treatment.
1. In donors, the level of antibodies varies from one individual to another.
2. The amount of antibodies in, for example, 200 ml of transfused plasma depends on several factors, such as how long before the donor was infected, if the donor had a severe or mild infection, if the donor had other underlying diseases that compromised immunity and how long the plasma had been stored.
3. High specificity means that the antibody will probably not work against a mutant or different version of the virus.
Previous studies in Lassa fever and SARS-1 have indicated that convalescent plasma works best as a prophylaxis to prevent disease (before and after exposure to the virus). This is a form of passive immunization, but it is short-lived, unlike a vaccine, which produces active immunity. It makes sense to have antibodies against the virus before it enters the body (before exposure) or against a limited number of viruses (immediately after exposure).
There are several advantages to using convalescent plasma for a new disease like Covid-19.
1. It is readily available, unlike specific drugs or vaccines that take time to develop, test, and produce.
2. It is cheap. The only cost involved is in extraction and storage.
3. Antibodies are highly specific against the virus.
4. Antibodies can have a potential immunomodulatory effect, reducing damage to the inflammatory response as the body mounts a severe response to the virus. Plasma treatment could help attenuate the high immune response, resulting in damage to normal tissue such as the lungs, leading to lung injury and requiring the patient to be put on a respirator.
5. It is generally safe and well tolerated. It is as safe as a blood transfusion.
There are some potential risks with convalescent plasma transfusion.
1. Risk of non-Covid-19 infections due to contamination and inadequate detection of plasma.
2. Risks associated with blood transfusion. The most common reactions are generalized itching and a rash, which develops in 1% -3% of patients. A fever-like reaction can occur in 0.1% -1% of patients. Transfusion-associated circulatory overload, which is due to the volume of transfused plasma that overwhelms the system, occurs in less than 1% of patients. Transfusion-related acute lung injury or TRALI occurs in less than 0.01% of patients.
3. These are not large available data on the risks of convalescent plasma in patients with Covid-19, although there is concern about TRALI in patients who already have lung injury. Convalescent plasma safety was previously observed in the Ebola and SARS-1 case series.
4. Theoretical concern about worsening immune damage, such as lung injury.
Is there clinical evidence that convalescent plasma works in Covid-19?
There is the evidence-based medicine pyramid. When someone mentions that a drug has weak evidence, minimal evidence, or doubtful evidence, it indicates that the data published so far falls at the bottom of the pyramid.
When a doctor says that convalescent plasma worked in his patient, this is just anecdotal evidence.
The evidence for convalescent plasma is mainly case series (description of a limited number of patients).
1. Five critically ill Covid-19 patients in Shenzhen, China, between January and March, three of the five who have been discharged, and the other two in stable condition.
2. Four critically ill Covid-19 patients in hospitals at different hospitals in China in February (including a pregnant woman), all of whom recovered
3. Ten severe Covid-19 patients at three hospitals in Wuhan, China in February all tolerated well.
These are from peer-reviewed magazines. There are other preprint reports as well as several anecdotal reports.
The United States Department of Food and Drug Administration approved the use of convalescent plasma for Covid-19 only in serious or immediately life-threatening cases. It makes sense because convalescent plasma is a limited resource and would be inappropriate to use extensively in asymptomatic / pre-symptomatic or prophylaxis.
Pharmaceutical companies are beginning to develop purification procedures and immunize large animals such as horses and cows to extract antisera. Biotechnology companies are competing to develop monoclonal antibodies or highly specific antibodies created in a laboratory that can be mass produced. But clinical trials are in the best of months. Meanwhile, the results of trials conducted in the United States are eagerly awaited.
Dr. Amith Viswanath’s Twitter account is @avstmd.
