Promising a “ray of hope” in the fight against COVID-19, Delhi chief minister Arvind Kejriwal on Friday said the results from convalescent plasma therapy from patients of COVID-19 were “encouraging”. The US FDA recently approved convalescent plasma from patients recovered from COVID 19 for the treatment of severe or life-threatening COVID-19 infections.
Kejriwal said that the Delhi government had received permission to conduct the therapy on a limited number of patients, and by next week, would be seeking permission to expand the trial to all severe and critically-ill patients in the national capital. Recovered patients should now come forward to donate their plasma antibodies and the Delhi government would be soon contacting them over the phone.
“Plasma therapy might have a role to play in critically-ill patients who have not reached the stage of organ failure,” said Dr S.K. Sarin, director of Indian Institute of Liver and Biliary Sciences (ILBS), an autonomous institute under Delhi government. Sarin said the disease progressed in three stages--stage one, where the virus multiplied in the body; stage 2, defined as the pulmonary phase where lung injuries start to appear;and late stage, where the patient starts to develop organ failure due to a cytokine storm that is unleashed in the body. Cytokines are small proteins released by several different cells in the body, including those in the immune system. Their job is to coordinate the body’s response against infection and trigger inflammation. However, when they are released in excess, they can cause harm and result in death.
“So, if the patient reaches the hospital while in stage 2, in about 7-15 days [from when they first caught the infection], then we can use plasma therapy to prevent complications,” Sarin said. While the therapy is safe, and has no side effects, sometimes, there may be some reaction in the body, and so, ILBS and MAMC (Maulana Azad Medical College) had started a “careful” trial on the four patients in Delhi’s LNJP Hospital. “If we have more patients that show similar benefits, we can take the lead on this,” Sarin said. “This is also inexpensive. Compare this to other therapies such as remdesivir [a Gilead drug that is currently under trial], which is very expensive, and we can’t afford it,” he said.
On April 20, Max hospital also reported that the first patient, a 49-year-old man, who was being given the plasma therapy on “compassionate grounds” had shown positive results and had been weaned off ventilator support. However, Dr Sandeep Buddhiraja, group medical director, Max Hospital, said the therapy was “no magic bullet” and that other factors pertaining to clinical management of the patient were important, too.
Though in this case, the family had arranged for the donors themselves; in other cases, donors had to step forward, too, Budhhiraja had told The WEEK. “Plasma from one donor (400 ml) can save two lives,” he added. Sarin said for a donor the procedure for plasma donation was similar to that of platelet donation in dengue--where the plasma [instead of platelets in dengue] would be separated from the blood, and the blood would be routed back to the donor's body.
In Bengaluru, HCG Cancer Hospital, too, has received permission to conduct trials on COVID-19 patients. Dr Vishal Rao, Associate Dean, Centre of Academics and Research, HCG Cancer Centre said: “The idea behind this therapy is that immunity can be transferred from a healthy person to a sick patient using convalescent plasma. This therapy uses antibodies from the blood of a recovered coronavirus patient to treat another critical patient. The recovered COVID-19 patient's blood develops antibodies to battle against COVID-19. Once the blood of the first patient is infused to the second patient, those antibodies will start fighting against coronavirus in the second person.” Rao said they had submitted three protocols to the DCGI and ICMR for expedited review. These three include Cell-derived Cytokine Therapy Trial for Early stage COVID patients, Mesenchymal Cell therapy clinical trial-Moderate Stage and Convalescent plasma therapy Clinical Trial-Severe stage.
On April 17, the drug regulator also issued a “no objection” order for conducting plasma therapy trials in conjunction with ICMR–the medical body has received 99 applications for the trials since--subject to certain rules and regulations. According to the ICMR protocol for trials, in a small case series [in China], five critically ill COVID-19 patients with ARDS were treated with convalescent plasma containing neutralising antibodies. “Infusion of plasma was followed by improvement in clinical status in all five patients, with no deaths and the study reported that three patients were discharged, while two continued to be stable on mechanical ventilation. In another small case, a series of four patients [also in China], including one pregnant woman, it was seen that all four recovered eventually,” the protocol states.
In another feasibility study of convalescent plasma therapy, 10 severely ill patients were transfused with 200 ml of convalescent plasma. “It was well tolerated with significant increase in neutralising antibodies and disappearance of viremia in seven days. Clinical symptoms rapidly improved in three days,” the protocol says.
The therapy is not new, say experts. “Historically, it has been used in viral diseases such as poliomyelitis, measles, mumps and influenza before vaccines became available. A meta-analysis of 1,703 patients with H1N1 influenza during the Spanish Flu of 1918 suggested that patients who received convalescent plasma had lower mortality,” the ICMR pointed out in its trials.
Convalescent plasma was also studied during the previous coronavirus outbreak of SARS in 2002 –2004 and better outcomes in patients were reported. However, in a double blind, randomised, placebo-controlled trial, convalescent plasma was not found to be superior to placebo in patients infected with Influenza A. “Furthermore, 84 patients with Ebola virus disease who were transfused with convalescent plasma without known levels of neutralising antibodies did not have a survival benefit,” the protocol says. Majority of the adverse effects associated with plasma transfusion are non-lethal, it adds.
