The Intricacies of Convalescent Plasma Therapy: Will the Results Turn Promising?
Monday, 24 August 2020, 16:14 IST
Convalescent plasma, a treatment made from the blood of recovered COVID-19 patients has been gaining huge momentum over the recent times. As of August 17, 2020, convalescent plasma had reached 97,319 patients in India. This nationwide program to treat COVID-19 patients was initiated in search for an effective treatment to contain the pandemic. It is basically an old method of fighting infectious disease that involves transfusions with convalescent plasma wherein plasma is a component of blood and convalescence is the period in which the body recovers from a serious illness, injury or surgery. During this process of convalescence, the patients’ blood is extremely rich in antibodies which help them to recover from existing illness. In a nutshell, the treatment is known as convalescent plasma therapy, which was earlier deployed in multiple viral infections such as poliomyelitis, measles, mumps and influenza.
This convalescent plasma therapy or passive antibody therapy was introduced in 1898 when physiologist Emil Von Behring working with bacteriologist Shibasaburo Kitasto showed that injections of serum from an animal with tetanus could confer immunity to the disease in other animals and also that the same was true for diphtheria. Since then, the doctors have used passive antibody therapy to treat or prevent both bacterial and viral infections entailing forms of pneumonia, meningitis and measles. Earlier, convalescent plasma has been used with variable benefit in cases of H1 N1 influenza, SARS, and Ebola. After the outbreak of COVID-19, researches and healthcare professionals were looking into the possibility of using convalescent plasma therapy to treat people with COVID-19, the respiratory disease caused by SARS-CoV-2 virus.
In the US, Dr. Arturo Casadevail, Chair of Molecular Microbiology & Immunology Department at John Hopkins Bloomberg School of Public Health along with Dr. Liise-anne Pirofski, Professor of Infectious Diseases in the Department of Medicine at the Albert Einstein College of Medicine argued the potential merits of passive antibody therapy in COVID-19. Considering the lack of efficacious treatments for COVID-19 and the epidemic situation with high mortality rate, United States FDA (Food and Drugs Association) has approved convalescent plasma single patient emergency IND (Investigational New Drugs). This multi-centric, open label, randomized control trial has been planned to assess the efficacy and safety of convalescent plasma collected from recovered COVID-19 patients.
On May 4, 2020, top medical experts revealed that convalescent plasma therapy is no ‘magic bullet’ to deal with coronavirus and only large-scale controlled trials can ascertain its efficacy as part of the treatment strategy. Several states are now considering the use of the therapy to treat critically-ill COVID-19 patients. The health ministry recently warned against its use, saying that plasma therapy was at an experimental stage and has the potential to cause life-threatening complications. However, some state governments, including Rajasthan, Punjab, Maharashtra and Delhi, have shown keenness for plasma therapy treatment, and the Centre has permitted few states to perform it on a limited number of COVID-19 patients.
On May 6, 2020 the ICMR (Indian Council of Medical Research) had initiated a multi-centre clinical trial, titled ‘A Phase II, Open-Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease (PLACID Trial)’. The study has also received approval from the COVID-19 National Ethics Committee (CONEC). With the Ethics Committee approval in hand on May 8, 2020, the ICMR (Indian Council of Medical Research) cleared the hurdle to conduct a multi-centric phase 2 trial using Convalescent Plasma on COVID-19 with moderate illness. Its three feasibility studies in about 20 severely ill patients found the therapy to be safe and able to resolve illness or improve the clinical symptoms. As per ICMR guidelines, patients with moderate COVID-19 illness would be randomly assigned to receive either convalescent plasma (226 participants) or only standard of care (control group). The primary outcome of the trial in 21 hospitals would include prevention of illness from progressing to a severe form, and avoidance of deaths from all causes at 28 days after plasma infusion and secondary outcome would will include resolution of symptoms, reduction in hospital stay and respiratory support. Plasma is to be collected from donors 28 days after they make a complete recovery from illness or are symptom-free and have more than the required level of antibodies against the COVID-19. Molecular and other routine tests were the other requirements before plasma use.
This year, tens of thousands of people received plasma for COVID-19. It played out as a one-on-one decision between physicians and patients, not a population-scale experiment designed to elicit knowledge about its efficacy. A preprint from the expanded-access group, not yet peer-reviewed, recounts the outcomes of more than 35,000 of these recipients at hundreds of hospitals. It retroactively splits that population into groups based on when in their illness they got plasma, or how laden the plasma was with the antibodies that actually do the disease-fighting. But, as the researchers and outside experts both acknowledge, that’s not as good as a clinical trial in which people get randomly assigned to a group that gets a drug (or procedure or surgery or whatever) versus a group that doesn’t, and then someone compares the results.
Till date, there is no robust scientific proof to support that plasma therapy can be used as a treatment for COVID-19. The U.S. FDA and India have thus approved the use of plasma from recovered COVID-19 patients only for trial purposes. The ICMR’s insistence on an evidence-based approach to plasma therapy is in contrast to its earlier approval of the anti-malarial HCQ (hydroxychloroquine) without carrying out any trial and also when the risks were unknown. The apex health research body is yet to conclude its study and till such time plasma therapy is to be used only for research or trial purpose. Convalescent plasma (Off Label) may be considered in patients with moderate disease who are not improving (oxygen requirement is progressively increasing) despite use of steroids.
This convalescent plasma therapy or passive antibody therapy was introduced in 1898 when physiologist Emil Von Behring working with bacteriologist Shibasaburo Kitasto showed that injections of serum from an animal with tetanus could confer immunity to the disease in other animals and also that the same was true for diphtheria. Since then, the doctors have used passive antibody therapy to treat or prevent both bacterial and viral infections entailing forms of pneumonia, meningitis and measles. Earlier, convalescent plasma has been used with variable benefit in cases of H1 N1 influenza, SARS, and Ebola. After the outbreak of COVID-19, researches and healthcare professionals were looking into the possibility of using convalescent plasma therapy to treat people with COVID-19, the respiratory disease caused by SARS-CoV-2 virus.
In the US, Dr. Arturo Casadevail, Chair of Molecular Microbiology & Immunology Department at John Hopkins Bloomberg School of Public Health along with Dr. Liise-anne Pirofski, Professor of Infectious Diseases in the Department of Medicine at the Albert Einstein College of Medicine argued the potential merits of passive antibody therapy in COVID-19. Considering the lack of efficacious treatments for COVID-19 and the epidemic situation with high mortality rate, United States FDA (Food and Drugs Association) has approved convalescent plasma single patient emergency IND (Investigational New Drugs). This multi-centric, open label, randomized control trial has been planned to assess the efficacy and safety of convalescent plasma collected from recovered COVID-19 patients.
Top medical experts revealed that convalescent plasma therapy is no ‘magic bullet’ to deal with coronavirus and only large-scale controlled trials can ascertain its efficacy as part of the treatment strategy
On May 4, 2020, top medical experts revealed that convalescent plasma therapy is no ‘magic bullet’ to deal with coronavirus and only large-scale controlled trials can ascertain its efficacy as part of the treatment strategy. Several states are now considering the use of the therapy to treat critically-ill COVID-19 patients. The health ministry recently warned against its use, saying that plasma therapy was at an experimental stage and has the potential to cause life-threatening complications. However, some state governments, including Rajasthan, Punjab, Maharashtra and Delhi, have shown keenness for plasma therapy treatment, and the Centre has permitted few states to perform it on a limited number of COVID-19 patients.
On May 6, 2020 the ICMR (Indian Council of Medical Research) had initiated a multi-centre clinical trial, titled ‘A Phase II, Open-Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease (PLACID Trial)’. The study has also received approval from the COVID-19 National Ethics Committee (CONEC). With the Ethics Committee approval in hand on May 8, 2020, the ICMR (Indian Council of Medical Research) cleared the hurdle to conduct a multi-centric phase 2 trial using Convalescent Plasma on COVID-19 with moderate illness. Its three feasibility studies in about 20 severely ill patients found the therapy to be safe and able to resolve illness or improve the clinical symptoms. As per ICMR guidelines, patients with moderate COVID-19 illness would be randomly assigned to receive either convalescent plasma (226 participants) or only standard of care (control group). The primary outcome of the trial in 21 hospitals would include prevention of illness from progressing to a severe form, and avoidance of deaths from all causes at 28 days after plasma infusion and secondary outcome would will include resolution of symptoms, reduction in hospital stay and respiratory support. Plasma is to be collected from donors 28 days after they make a complete recovery from illness or are symptom-free and have more than the required level of antibodies against the COVID-19. Molecular and other routine tests were the other requirements before plasma use.
This year, tens of thousands of people received plasma for COVID-19. It played out as a one-on-one decision between physicians and patients, not a population-scale experiment designed to elicit knowledge about its efficacy. A preprint from the expanded-access group, not yet peer-reviewed, recounts the outcomes of more than 35,000 of these recipients at hundreds of hospitals. It retroactively splits that population into groups based on when in their illness they got plasma, or how laden the plasma was with the antibodies that actually do the disease-fighting. But, as the researchers and outside experts both acknowledge, that’s not as good as a clinical trial in which people get randomly assigned to a group that gets a drug (or procedure or surgery or whatever) versus a group that doesn’t, and then someone compares the results.
Till date, there is no robust scientific proof to support that plasma therapy can be used as a treatment for COVID-19. The U.S. FDA and India have thus approved the use of plasma from recovered COVID-19 patients only for trial purposes. The ICMR’s insistence on an evidence-based approach to plasma therapy is in contrast to its earlier approval of the anti-malarial HCQ (hydroxychloroquine) without carrying out any trial and also when the risks were unknown. The apex health research body is yet to conclude its study and till such time plasma therapy is to be used only for research or trial purpose. Convalescent plasma (Off Label) may be considered in patients with moderate disease who are not improving (oxygen requirement is progressively increasing) despite use of steroids.
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