A pouch of convalescent plasma from a person who recovered from COVID-19. Photo: Lindsey Wasson/Reuters
When the number of COVID-19 cases began to surge in many parts of India from late April, the Centre’s and various state government’s failure to anticipate the second wave, and the inability of the Indian people at large to withstand it without additional protections, became glaringly obvious. A shortage of oxygen and antiviral and palliative drugs soon followed. With government help out of sight, people took to the social media to coordinate the verification, discovery and supply of oxygen and drugs by themselves.
There were many people in this informal arrangement who sought convalescent plasma to ‘treat’ their loved ones despite considerable evidence that this therapy doesn’t work as well as that it has some (relatively unknown) adverse effects. While others arranged for the transfer of convalescent, public health experts have been becoming more concerned about its continued use and the drain of resources it stands for. Some of them recently wrote a letter to the principal scientific adviser to the Government of India, K. VijayRaghavan. It is reproduced in full below.
§
To
The Principal Scientific Adviser,
Government of India
Copy to:
Director General, Indian Council of Medical Research (ICMR)
Director, All India Institute of Medical Sciences (AIIMS), New Delhi
Subject: Open letter expressing concerns about convalescent plasma for COVID-19
Dear Dr VijayRaghavan,
We are writing to you as concerned clinicians, public health professionals and scientists from India about the irrational and non-scientific use of convalescent plasma for COVID-19 in the country. This has stemmed from guidelines issued by government agencies, and we request
your urgent intervention to address the issue which can prevent harassment of COVID-19 patients, their families, their clinicians and COVID-19 survivors.
What treatments to offer, to which patients and at what stage of the disease are complex clinical decisions, but clinical guidelines provide recommendations to enable this process. You will also agree that clinical guidelines must necessarily be based on existing research evidence.
We therefore wish to bring to your attention the current evidence on plasma therapy in COVID-19 and how the ICMR guidelines are not based on the existing evidence:
* ICMR-PLACID Trial – The trial was the world’s first randomised controlled trial on convalescent plasma in 39 public and private hospitals across India which found “convalescent plasma was not associated with a reduction in progression to severe covid-19 or all-cause mortality. This trial has high generalisability and approximates convalescent plasma use in real life settings with limited laboratory capacity.”
* RECOVERY Trial – The large trial of 11,588 patients found no difference in death or proportion of patients discharged from hospital. Even for those patients who were not on ventilation initially, there was no difference “in the proportion meeting the composite endpoint of progression to invasive mechanical ventilation or death.”
* PlasmAr Trial – The trial from Argentina concluded that there is no significant difference in “clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo.”
Current research evidence unanimously indicates that there is no benefit offered by convalescent plasma for treatment of COVID-19. However, it continues to be prescribed rampantly in hospitals across India. Families of patients run from pillar-to-post for getting plasma, which is in short supply and reports of black-marketing is common. You might already be aware of these issues which have been widely reported in the media, and experiences shared by ordinary Indians in social media. The desperation of patients and their families is understandable because they did like to try the best for their loved ones, when a doctor has prescribed this.
We would also like to point out some very early evidence that indicates a possible association between emergence of variants with “lower susceptibility to neutralising antibodies in immunosuppressed” people given plasma therapy. This raises the possibility of more virulent strains developing due to irrational use of plasma therapy which can fuel the pandemic.
The problematic scenario arises because of guidelines issued by ICMR/AIIMS which currently recommends plasma therapy (April 2021 version) as “off label” use. This is rather unusual as off-label use by its very definition implies “unapproved use”. We would also like to point out that international guidelines such as those from the US National Institutes of Health and the IDSA guidelines also recommend against general use of plasma therapy for COVID-19.
We request you to urgently review the guidelines and remove this unnecessary therapy which has no benefit but is only causing harassment of patients, their families and even COVID-19 survivors who are being pressured to donate plasma. This should also be twinned with clear instructions to blood banks across the country on the same.
We are also willing to assist, if required, to appraise the evidence critically, conduct evidence synthesis and develop recommendations based on GRADE (which are global standards and followed by WHO), which can enable better clinical decision making.
We hope you will look into this as a matter of urgency and get the ICMR and AIIMS guidelines rectified so they reflect the current research and scientific consensus on plasma therapy.
Signatories (Signed in individual capacity, may not represent the views of their employers) in reverse alphabetical order:
1. Yogesh Jain, MBBS, MD (Paediatrics)
2. Vivekanand Jha, MD, DM, FRCP, FAMS
3. Soumyadeep Bhaumik, MBBS, MSc (International Public Health)
4. Soumitra Pathare, MD, MRCPsych, PhD
5. Shahid Jameel, MSc, PhD
6. Priti Meena, MBBS, MD, DNB
7. Prathap Tharyan, MD, MRCPsych
8. Prashanth N Srinivas, MBBS, MPH, PhD
9. Oommen John, MD, MBA
10. Kamna Kakkar, MBBS, MD
11. Jyoti Tyagi, BDS, PGDPHM, MPH
12. Gautam Menon, MSc, PhD
13. Gagandeep Kang, MBBS, MD, PhD
14. C.S. Pramesh, MS, FCRS
15. Ashrita Saran, MDS, MPH (epidemiology)
16. Aparna Ananthakrishnan, MSc (Development Planning), MSc (Public Health)
17. Anant Bhan, MBBS, PGDMLE, MHSc
18. Amar Jesani, Editor, Indian Journal of Medical Ethics