Dr. U S Vishal Rao shares deeper insights into the ICMR PLACID trial research on plasma therapy
- Post By : Kumar Jeetendra
- Source: Microbioz India
- Date: 11 Sep,2020
Bengaluru, 11th September 2020 – The recent study conducted by the Indian Council of Medical Research (ICMR) stated that using plasma therapy for COVID-19 claims that the therapy neither reduces the death risk nor does it slow down the disease’s progression from mild to severe stage. HealthCare Global Enterprises Limited (HCG) – largest cancer care hospital chain in the country – would like to keep its share its views on the study that has cast doubts on the plasma therapy’s potential benefits. Dr. U S Vishal Rao states that the convalescent plasma has been administered on 430 ICU patients by witnessing up to 60% recovery rate in our preliminary analysis. While this orphan drug has no pharma backing, it would need to survive the battle of medical evidence. Currently, it is indeed the only tangible option for severe and critically ill patients which is time tested, WHO & US FDA authorized, that must be attempted to save lives at this juncture.
This position is based on a WHO assessment that the potential benefit of providing antibodies that may neutralize infectivity of SARS-CoV-2 outweighs the risks of administration of these plasma products. Reports of a randomized controlled trial and several uncontrolled case series of use of COVID-19 convalescent plasma have suggested favorable patient outcomes.
Speaking on the ICMR study, Dr U S Vishal Rao, Associate Dean, Centre for Academics and Research, HCG Cancer Hospital Bengaluru said, “As per our current observations, up to 60% of the patients have recovered and nearly 90% of these patients were severe and critical patients in ICU at the time of plasma therapy. We have been closely monitoring all plasma transfusions to ensure good donor antibodies. The PLACID study did not check for plasma neutralizing antibodies prior to transfusion in the patients. In addition, the donors in the study comprised of mainly patients of mild diseases which could yield low or no antibodies.”
Other positive results of the ICMR study which haven’t received necessary highlight are:
1. CP therapy was associated with a higher resolution of symptoms like shortness of breath and fatigue on day 7.
2. CP use was also associated with reduction in FiO2 requirement on day 3 and 5.
3. There was a higher proportion of negative conversion of viral RNA on day 7 post enrolment in intervention arm.
HCG Cancer Hospital is conducting a phase 1 plasma trials in association with Victoria Hospital under the Bangalore Medical College and Research Institute since June 2020. Besides, HCG is jointly working with Emory University Atlanta.
The study conducted by the Emory University in India [Ref1 https://www.biorxiv.org/content/10.1101/2020.08.31.276675v1.full.pdf] has some very significant findings which prove that the methodology of the study and assessing the neutralizing antibody are incredibly critical. While a vast majority (38/42, 90.47%) of COVID-19 recovered individuals developed SARS-CoV-2 RBD-specific Immunoglobulin G (IgG) responses, only half of them had appreciable neutralizing antibody titers. RBD-specific IgG titers correlated with these neutralizing antibody titers as well as with RBD-specific memory B cell frequencies.
In contrast, IgG titers measured against SARS-CoV-2 whole virus preparation, which includes responses to additional viral proteins besides RBD, did not show robust correlation. Our results suggest that assessing RBD-specific IgG titers can serve as a surrogate assay to determine the neutralizing antibody response. These observations have timely implications for identifying potential plasma therapy donors based on RBD-specific IgG in resource-limited settings where routine performance of neutralization assays remains a challenge.
According to a recent study published in Lancet (by Zhou F and collogues from Wuhan, China), the median time to negative PCR is 20 days. However, in the ICMR PLACID trial, less than 54% patients have negative PCR by day 7. This means that patients have been infused plasma on a median of 14 days, which is conceptually late. Hence, it necessitates the clarification for the median day of infusion of CP since the onset of symptoms. As per the Mayo Clinic data, infusion within 3 days of admission is useful, and this stipulation has not been practiced uniformly in India.
If we carefully examine the existing global preliminary data, they indicate a positive outcome of CPT for management of severe and critically ill patients diagnosed with COVID-19. Hence, the need of the hour is to save lives with existing data while we continue to conduct further randomized controlled trials with larger sample sizes and homogeneity of data. The initial data of Mayo Clinic using CP on 55,000 patients provides robust evidence that transfusion of convalescent plasma is safe in hospitalized COVID-19 patients and credibly supports the notion that early administration within the clinical course is more likely to reduce mortality. CPT can hence be safely used as an effective adjuvant therapy against COVID-19 associated mortality.
(1) Zhou F, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054–1062.