Combating Covid-19: The great hope of plasma therapy
With over 20 clinical trials for convalescent plasma therapy to treat coronavirus across the world, Lounge speaks to those geared up to begin trials in India, doctors and donors who are leading from the front
In 1890, physiologist Emile von Behring discovered that convalescent blood plasma from once- infected rabbits could be used to treat diptheria in humans. Soon whole blood or serum from recovered donors was identified as a possible source of specific antibodies of human origin.
More than a century and several clinical trials later, it is this same therapy that is showing promise as the world deals with a pandemic caused by a new virus.
On 11 March, Lucknow’s first covid-19 patient tested positive—a medical professional herself, she had come from Canada and had to be tested owing to her travel history. Tauseef H. Khan, 30, a resident doctor at King George Medical University (KGMU), Lucknow, was in charge of screening, testing and evaluating her. He did so in full protective gear (PPE, or personal protective equipment).
“I suppose the 2-3% chance one has even with PPE kits is what happened with me," he says. A few days later, on 17 March, when he started showing mild symptoms, he was tested for the novel coronavirus. Dr Khan, one of the many healthcare workers to have tested positive for covid-19 in India and around the world, spent 21 days in the ward reserved for infected patients at his institution.
By 25 April, the first day of Ramzan, the KGMU had received permission from the Indian Council of Medical Research (ICMR) to use convalescent plasma therapy on covid-19 patients—this entailed transfusing the plasma, rich in antibodies against the virus, from a recovered patient into the body of a sick patient.
“The nodal officer for infectious diseases, Dr D. Himanshu, and other seniors encouraged me. If I had come forward to donate plasma, as a healthcare worker myself, it would send out a good message, since people may be afraid," says Dr Khan. “That’s exactly what I did." He became the first plasma donor at KGMU.
LOOKING FOR A TREATMENT
As the number of those infected with the novel coronavirus rises across the world—with over 3.5 million infected so far, more than 50,000 of them in India—there is as yet no proven standard procedure for treatment. HCQ (hydroxychloroquine), antivirals such as remdesivir and therapies such as the use of plasma, or passive immunization, are being attempted.
The limited administration on patients across the world have shown promise but given the absence of data from a randomized clinical trial, it’s difficult to take a call on the effectiveness of plasma therapy. In the most recent study, 10 critically ill covid-19 patients from China were treated with convalescent plasma therapy and their condition improved. “No severe adverse effects were observed. This study showed CP (convalescent plasma) therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia (the presence of viruses in the blood) in severe covid-19 cases," noted the scientists.
Another study, published in the Journal Of The American Medical Association, reported “improvement in (the) clinical status" of five critically ill covid-19 patients using plasma therapy.
Worldwide, over 20 clinical trials are testing the use of convalescent blood plasma or serum, including a large-scale trial at the Mayo Clinic, US. In India, as Tulika Chandra, professor and head of the transfusion medicine department at KGMU, points out, the DCGI (Drug Controller General of India) is “allowing hospitals to use plasma therapy on patients who need it as long as they follow the ICMR protocol".
But the country is set to begin its own trials soon. On 12 April, the ICMR asked institutions to show intent for a study titled “A Phase II, Open Label, Randomized Controlled Study To Assess The Safety And Efficacy Of Convalescent Plasma To Limit COVID-19 Associated Complications".
Over 99 institutions responded. One of them is the Kasturba Hospital in Mumbai. “We have joined ICMR’s trials. All our paperwork is done, we are waiting on a few approvals. But we will probably wind up having one of the largest data sets in the world when we are done with this trial. just looking at the number of cases in Mumbai," says Swapneil Parikh, a research associate at the hospital’s molecular lab. Dr Parikh is also the co-founder of the health startup DIY.health and author of the recently published book The Coronavirus: What You Need To Know About The Global Pandemic (Penguin Random House)
“Recently, for SARS and MERS, plasma therapy was effective. But when we say effective, there too it’s based on small, poorly powered studies. Nothing in the form of widespread clinical trials. But there are two concerns. The first, immunity against SARS-CoV-2 may not be just related to antibodies but might be due to special white blood cells called T-cells; plasma therapy is based on the assumption that immunity is mainly due to antibodies. Secondly, some laboratory evidence with SARS has shown immune enhancement of infection. While this is speculative, it does cause concern of potential harm of plasma therapy," says Dr Parikh.
Two weeks after she became the first covid-positive patient to be discharged in Ahmedabad, Sumiti Singh, 34, went back to visit her doctors at Sardar Vallabhbhai Patel (SVP) Hospital. “I had been reading about plasma therapy and I would send the articles to my doctor, Meemansa Buch. I was like, ‘When will you call me back for this—when will I be useful?’ She used to laugh it off at the time."
Eventually, however, the call came. The doctors explained the procedure, patiently answered her questions and after consulting with her family, Singh agreed to donate plasma.
On 22 April, at the Indian Red Cross premises in Ahmedabad, 5ml of blood was drawn from her to check for infections through regular tests and for antibodies through the rapid test kit. “You have to be able-bodied, no pre-existing ailment, no medications for chronic ailments for six months. Of course they do blood tests to see that your blood is infection-free. But most importantly, you have to be willing to go through this. No pressure from anyone," says Singh. Once she got the all-clear, she spent around 40 minutes as a machine drew blood, separated close to 500ml of plasma and returned the blood to her body.
Singh said she felt slightly light-headed and nauseous, but only fleetingly. Her parents and she are proud, even more so since she learnt that her plasma has been transfused into a patient at the SVP Hospital. “They said they gave it to a patient who was stable and they will monitor on Day 0, 3 and 7 to see how the patient is doing. I want to know if it is working," says Singh. “Not just my plasma, but in general whether this line of treatment as well as others being tested across the world are working or not."
Dr Chandra explains the science. With covid-19, the body develops immunoglobulin M, a diagnostic antibody marker that signifies an acute phase of the disease. Eventually, if a patient develops the antibody immunoglobulin G, it signifies that the body is going into the recovery phase—it is protective since it is formed to fight the virus and can destroy the antigen.
“The purpose is to take the plasma of these people by a procedure called plasmapheresis. Before saying this is standard care of treatment, it has to be researched. The ICMR has planned a research model in which we have a number of persons and according to randomization—50% patients will receive that therapy and 50% will not and then we compare," she says. Dr Chandra points out that the timing of plasma collection is important—research suggests the antibodies are at their highest 28 days after recovery, which makes it the ideal time for donation.
“The ICMR hasn’t started the trial but they have given the protocol and the DCGI has given over-the-counter no-objection for doing it if it is done with strict compliance to these protocols because obviously this is not a normal situation, so we are using it for the patients who need it—according to the protocols in place in the system," says Dr Chandra.
She is hopeful. A covid-positive patient at the KGMU who was given plasma therapy did not go into a cytokine storm crisis and has stabilized. Across the country, hospitals have been using the therapy to help critically ill patients, and, in several cases, plasma therapy seems to have been effective. In Max Hospital, Saket, in Delhi too, a 49-year-old patient on ventilator support was given plasma therapy along with other medication. He was discharged after testing negative twice for covid-19.
In Mumbai’s Lilavati Hospital, however, a 53-year-old patient did not survive even after plasma therapy. “A patient came in fairly late after the virus had infected him. He was already on the ventilator and only after plasma therapy there was a marginal improvement—what we call the PO2, the partial pressure of oxygen, improved. The FiO2, which is the amount of oxygen that the ventilator gives, was 100%. We managed to bring it down to about 80%. He pulled through for three-four days but the lungs just didn’t improve and eventually he succumbed to the illness," says V. Ravishankar, CEO, Lilavati Hospital.
“Plasma therapy is not to be written off, it is here to stay, but it is in the research and experimental stage. It is showing promise—in Delhi at least three cases showed improvement. Plasma is like a ready-made vaccine, it has got antibodies. And we are pushed to the wall," says Dr Ravishankar.
For the therapy to be tested further, and indeed to save lives, people who have recovered must be encouraged to donate plasma. Last week, several members of the Tablighi Jamaat, who were termed “superspreaders" by various media outlets in early April, came forward to donate their plasma —in Karnataka, Delhi, Tamil Nadu and elsewhere.
One such donor is Farooq Basha, 42, who came to Delhi from his home-town Chennai for the Jamaat’s congregation in March. After he recovered and was discharged from the Rajiv Gandhi Super Speciality Hospital, Basha donated plasma on 25 April, after he broke his Ramzan fast. “People maligned us everywhere but we really want to help. It feels good to be able to become a medium through which others can be helped—there is no bhed bhaav when it comes to plasma and we really hope this can help save lives," says Basha, who is waiting to go back home to his family in Chennai.
Even as they wait for final approvals, Dr Parikh says they are ready. Getting approvals for a trial that involves humans is a long-drawn process but they are prepared with their ethical procedures, the team is prepped, the processes and data collection systems are in place. He says there is huge scope for plasma donation given the high percentage of young people in India.
“I think right now everyone wants to feel like they are doing something to help fight covid-19. And I think that’s important to recognize," he says. “Those who have recovered know they are the lucky few. They could have very easily drawn the other straw. I think that is the motivation for a lot of people, at least in my experience of talking to people. They genuinely want to help."
FIRST PUBLISHED08.05.2020 | 11:50 AM IST