When Shubham was told to get plasma for his COVID-positive father by the Sarvodaya Hospital in Faridabad, he had no option but to arrange it. "It may work, it may not work...but there are times when a family doesn’t have the strength to think scientifically. Every step appears to be the last chance to save your loved ones," says Shubham, who lost his father Raj Kumar Saxena (75) in April despite administering plasma therapy.
Erick Massey had arranged both Remdesivir and two units of plasma for his COVID-infected mother, Delphin Massey (61), admitted at the Jaipur Golden Hospital hoping that it would drag her out of the critical stage.
"There was no direct communication with the doctor; it only used to be the nurses who would call us in the morning to say plasma is needed, urgently, by evening. When we managed to provide both Remdesivir and plasma units, there was a ray of hope that things will get better. My mother had shown signs of improvement after the first unit of plasma was administered. But nothing helped ultimately," he recalls.
What, at times, frustrates Erick is the fact that the government has now decided to drop plasma therapy from the treatment protocol for COVID-19 after much damage had already happened in the national capital and across the country.
"When I think about those days or that restlessness… the hurdles we all had faced just to fetch these two products. It does boil my blood. Anger, resentment - words fall short to describe what families have gone through. If doctors knew that it won’t work, why did they administer plasma and made kin run post to pillar and spend lakhs," he asks.
Shubham, on the other hand, says he was aware of plasma's efficacy and how much it can help to save lives. "The doctor didn’t give us any false hope or raised expectations. The hospital had clearly told us that it may or may not work upon my father… But your brain doesn’t work that time. I was expecting that my father will improve with plasma. I was hoping for a miracle and that the theories over its efficacy may turn out to be false," he stated.
Erick recollects those days when people had spent lakh of rupees for drugs like Remdesivir and waited for hours in a queue at ILBS - the plasma bank set up by Delhi government last year. "It's not just the patient who is suffering but it also takes a huge toll, physically and mentally, on the families. Acquiring plasma and Remdesivir was the biggest challenge making the situation 100 times more complex. It seems all such efforts were futile ever since the efficacy of these two on corona patients was declared," he says.
When families were struggling to get even one unit of plasma or one vial of Remdesevir, many fell into trap of black-marketers who went on to demand as much as Rs 5-6 lakh. A family, who did not wish to be named, had sought help from this correspondent for plasma.
They narrated their harrowing experience: "As we had put up a request on social media for plasma, we were getting many calls. One of them said that he can provide two units of plasma for Rs 40,000. We decided to go for it as it was urgent. When we called back, the number was switched off. After a while, the same person called from another number but said that he would charge Rs 1.2 lakh for one unit now. We realised it was illegal and did not go further."
With the plasma therapy being dropped from the treatment protocol for COVID-19 by the Union Health Ministry, the blood donor groups and social media platforms are seeing a drop in the number of requests. Himanshu Verma, founder of CovidPlasmaIn (covidplasma.online) and a council member at TeamSOSIndia says that demands are definitely down both due to declining cases and ICMR guidelines.
"At peak, we at CovidPlasmaIn and TeamSOSIndia received requests in the range of 800-1000 from Twitter, Facebook, Telegram, and via calls. Currently, we’re getting most of the SOS calls from the southern regions of India. Nowadays, we’re getting roughly 150 daily requests on average. It had been a hard struggle but I could see a glimmer of light at the end of the tunnel," Verma says.
Arunesh Mishra from Blood Seva Parivar says that ICMR’s decision will put a check on unnecessary and overuse of plasma. "There was a huge gap between demand and donors available. It was very difficult to cater to so many requests. Demand has gone down, but not completely. Some demands came from patients who are already in a critical stage. Also, this decision will surely put a check on black-marketing," he says.
Verma says that in order to weed out black-marketing and plasma-related scams, the volunteer groups verified each request personally by validating the doctor’s prescription and other documents. “Upon verification, we amplified the request in our network, and our operations team tried its best to connect donors and recipients,” he adds.
STILL PUTTING HOPE IN PLASMA
While the Centre has decided to drop plasma therapy as a treatment for COVID-19, many - including the Delhi government - have a different view. Delhi Health Minister Satyendar Jain has said that it can still be initiated at the suggestion of doctors.
"It depends on a case-to-case basis and will be done only after the recommendation of the doctor. Nevertheless, we must know that there is no sure-shot specific medicine meant only for treatment against COVID-19," Jain noted.
The city hospitals too voiced a similar approach over usage of plasma therapy in further courses of treatment. "It is not a ban. It’s a recommendation that says plasma therapy is not beneficial. Also, there has not been any official communication from the Delhi government over its use. However, we will surely keep a cap on its usage. It doesn’t help in extreme critical cases. This year we did use it on some patients but only on those we knew will be beneficial," said an official from a state-run hospital.
Dr Suranjit Chatterjee, Senior Consultant, Internal Medicine from Indraprastha Apollo Hospitals said that selective usage of plasma in appropriate cases will be considered and "not using it irrationally, as has been".
"The Delhi government is right at this point as recommendations and guidelines are there to guide and not binding on the treating doctors. For an individual patient what might be useful may not be generalised to the population at large" says Dr Nikhil Bante, Consultant Pulmonology, Critical Care and Sleep Medicine from Fortis Hospital Vasant Kunj.
"We would continue to use plasma therapy as well as Remdesevir in carefully selected patients who fulfil the above-discussed criteria. These are extremely useful weapons in our fight against the coronavirus, at a time when our arsenal is limited and we are running out of options. There is no sense in giving up on something which we have already tried successfully in a large number of patients," Dr Bante added.
However, the experts acknowledge that plasma and Remdesevir have not worked on serious patients. According to Dr Chatterjee, while research-wise plasma and Remdesivir have both not sufficiently worked in serious patients, clinically marginal benefits have been observed in mild to moderate and earlier cases.
"When plasma therapy and Remdesivir are used together or simultaneously, it is difficult to pinpoint which drug worked-- there is no plasma vs Remdesivir clinical trial yet. With many patients on oxygen support this time, all we can say is that plasma therapy comes early in, during the first 3-4 days, as per the physician's discretion while Remdesivir is administered a little late in the course of the disease. Once the disease progresses to high oxygen demand, I don’t suppose plasma therapy has a role though antibody titer in plasma may be good," says Dr Vikramjeet Singh, Senior Consultant - Dept of Internal Medicine, Aakash Healthcare, Dwarka.
About the impact of plasma and Remdesivir in the second wave, Dr Bante noted that these new variants are showing an immune escaping phenomenon. “So the plasma therapy against these variants needs further research and study. Regarding Remdesivir, there is sufficient data recommendation to prove its efficacy against Covid-19 and the debate for its uses in my opinion are useless. The issue with Remdesivir is more logistic than scientific. The cost of medicine and limited availability in the current wave and intravenous route of administration requiring hospitalisation, when there is an acute shortage of beds have been the main reason for the government removing it from the recommendation,” he adds.
On the efficacy and success rate of plasma therapy on patients, Dr Bante says that his team has found that the use of high antibody titer plasma is quite useful in patients suffering from moderate diseases when used preferably within the first week or at best first 10 days of illness and no later than that.
"These riders have a strong scientific basis and make all the difference in the use of plasma being effective or not. The plasma therapy failed to show positive results when either the donor was not screened for the presence of high titers of neutralising antibodies as per the international recommendation or when used too late in the course of the disease," he informs further.
Dr Chatterjee states that since Covid-19 is still a new disease and its treatment is still evolving, it is natural that a few treatments would be dumped and new ones will be incorporated as evidence evolves.
Had the decision of dropping plasma from protocol been announced earlier, would that have made things better?
"Not at all... on the contrary I feel that this recommendation of dropping plasma therapy from the treatment protocol would in fact deprive the carefully selected patients of the potential benefit of this modality," states Dr Bante.
"These are not magic bullets. There is a frenzy created around Remdesirvir. It has been shown in various trials that it doesn’t have mortality benefits and is not needed for everyone. It is needed only for selected patients -- those who need early oxygen requirements. It may have a role in such circumstances and can be effective but that’s also a question mark. There's no need to rush for Remdesirvir. The same goes for plasma therapy. It is not required for everybody -- this message should be loud and clear," says Dr Neeraj Nischal, Associate Professor in the department of medicine, AIIMS Delhi.
Dr Anil Gurtoo, Director-Professor of Medicine at Lady Hardinge Hospital, says that for the past one and half year, he has never administered plasma therapy on any COVID patient. "Theoretically it is an interesting concept, however practically when it has been tested against scientifically designed randomized double-blinded controlled trials including one ICMR did," he said.
"The study is clear that it is of no use. However, there were concerns raised over specific antibodies where it might benefit. Plasma with sufficient antibodies given to patients within the first seven days should work. But new data shows it has not shown any benefit. Biological feasibility and everything in medicine is a ratio of benefit, harm and cost," Dr Anil Gurtoo said.
"Something which has no benefit then the question of harm and cost comes in. Plasma is the biological product of someone else, going into another body. It can cause so many other complications-- lungs damage, hepatitis, etc. The biggest risk of giving plasma is we are giving a fertile ground for mutants to develop," he added.
The New Indian Express made several attempts to get a comment from ILBS but got no response.
ICMR GUIDELINE ON PLASMA
The use of convalescent plasma was dropped from the recommended treatment guidelines for Covid-19, as per an advisory from the Indian Council of Medical Research (ICMR) last week
The National Task Force of the ICMR, along with experts from the Health Ministry, periodically updates guidelines on recommended modes of treatment. Registered doctors anywhere, however, aren’t bound by the Task Force recommendations.
A recent study by the Lancet published on May 14 suggests that high titer plasma did not improve survival or other prespecified clinical outcomes in patients hospitalised with COVID.
STERIODS &MUCORMYCOSIS
Mucormycosis, wrongly being referred as black fungus, was earlier commonly spotted in people suffering from diabetes mellitus, a condition where one’s blood sugar (glucose) levels are abnormally high, explained Dr. Randeep Guleria, Director AIIMS, recently
According to Dr Guleria, cancer patients undergoing chemotherapy, those who have had a transplant and people taking immunosuppressants (medications that weaken the immune system) also used to get Mucormycosis
Commenting on restricted use of steroids, Dr Guleria said that if a COVID-infected person’s oxygen saturation level is normal then steroids should be completely avoided. And those who are taking steroids need to keep a tab on their blood sugar levels
'Remdesivir, Plasma not magic bullets'
Plasma and Remdesivir are not magic bullets. Dr Neeraj Nischal, an Associate Professor at AIIMS Delhi, says there is a frenzy around Remdesivir. Trials show that it doesn't have mortality benefits and is not needed for everyone. There is no need to rush for Remdesivir. Same goes for plasma therapy.