COVID-19 and Convalescent Plasma: when compassion and ethics are in conflict.

 

“Integrity without knowledge is weak and useless, and knowledge without integrity is dangerous and dreadful.” – Samuel Johnson (1709 – 1784), English Author, Poet and Writer.

The current pandemic of COVID19 came upon the world suddenly. With little knowledge about SARS CoV2, armed with only with some selected data, extrapolated from SARS, MERS, the world tried to wage a war against this contagion, attempting to stop its rampage and treat people affected by this serious disease.

Since December 2019 the initial knowledge about spread, measures to be taken, have  proven to be incorrect. Now masks are mandatory (1). Our knowledge about human to human transmission (2), infection risk in confined spaces (3), spread from asymptomatic patients has been radically altered since the beginning of this pandemic (4). This clearly shows the dangers of inadequate or wrong data supporting decision making.

We now understand the pathology of the breathing problems and hypoxia (5,6) in patients and have altered the way we manage the disease from aggressive ventilation support to oxygen therapy and anti- coagulation. Many medications like choroquin/ hydroxychloroquin which were shown to have some in vitro activity have now been shown to be therapeutically ineffective (7).

The media hype related to every treatment option led to irrational and often dangerous consequences. Much of the fear and hype around COVID19 is gradually decreasing and the need for good scientific studies to support the interventions re-emerging, but we have not yet seen this normalization in regards to convalescent plasma therapy.

A planned randomized trial on convalescent plasma after completing all regulatory requirements started accrual. At our center we had slow enrollment as many families only wanted to participate if their patients would receive convalescent plasma. I received calls from families of patients on the control arm asking to receive the intervention, even though the patients were improving and stable.  On July 2, the first convalescent plasma bank opened in Delhi, with 10 apheresis machines and storage capacity of 200 units for use of any hospital (8). The accompanying news information highlighted the full recovery of patients within 1 to 3 days of treatment (8).

In India the media campaigns have pushed public opinion, leading the public to believe and demand this “life saving” intervention, all with little scientific evidence. The published case series have publication bias, selection bias and unfortunately other flaws. The only randomized trial on convalescent plasma did not show reduction in mortality or benefit in time to discharge (9). Even a meta-analysis of convalescent plasma therapy in other respiratory viruses did not show significant affect on mortality (one RCT uncertain, 3 RCT inconclusive evidence) (10).

With only low-quality medical evidence, but large media support and now hugely significant public demand for compassionate use of convalescent plasma, we now are faced with an ethical dilemma. The overwhelming public demand for compassionate use is causing huge and unavoidable pressures on doctors taking care of patients and the administration has had bow to these demands and commit to only compassionate use of convalescent plasma.

Compassion is important. But is it ethical to allow families who can pay a convalescent plasma donor (the grapevine suggests payments of up to Rs 50,000 (£525), or for families with patients in extremis, to insist on this “life saving” unproven treatment for their loved ones? These demands will interfere with or delay other interventions. This will also lead to decreased availability of convalescent plasma for the patients who may potentially benefit from this medical intervention. We also do not truly know if there is harm from this passive immunity therapy, as so much is unknown about the infection and its long term effects. The rampant demand has even led to some hospitals using convalescent plasma without testing for protective antibodies.

There is still so much we do not know. We need a balanced scientific way of evaluating treatments, for without knowledge we are weak and useless. Fortunately many patients recover from COVID-19, possibly by their own immune system .  Public sentiments are important to consider, but there is a collective amnesia on the earlier unfortunate missteps and mistakes made by the incomplete information in this crisis.

About the author

Tulika Seth is a clinical hematologist at a large tertiary care hospital in India.

Competing Interest

Tulika Seth is a co-investigator in a clinical trial to study convalescent plasma in COVID 19. She has no other competing interests.

 

References

  1. https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/cloth-face-cover-guidance.html (accessed 30 June, 2020)
  2. Preliminary investigations conducted by the Chinese authorities have found no clear evidence of human-to-human transmission of the novel #coronavirus (2019-nCoV) identified in #Wuhan, #China pic.twitter.com/Fnl5P877VG. World Health Organization (WHO) (@WHO) January 14, 2020
  3. Jayaweera M, Perera H, Gunawardana B, Manatunge J. Transmission of COVID-19 virus by droplets and aerosols: A critical review on the unresolved dichotomy [published online ahead of print, 2020 Jun 13]. Environ Res. 2020;188:109819. doi:10.1016/j.envres.2020.109819
  4. Bai Y, Yao L, Wei T, et al. Presumed Asymptomatic Carrier Transmission of COVID-19. JAMA. 2020;323(14):1406–1407. doi:10.1001/jama.2020.2565
  5. Spiezia L, Boscolo A, Poletto F, et al. COVID-19-Related Severe Hypercoagulability in Patients Admitted to Intensive Care Unit for Acute Respiratory Failure. Thromb Haemost. 2020;120(6):998-1000. doi:10.1055/s-0040-1710018
  6. Ciceri F, Beretta L, Scandroglio AM, et al. Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis [published online ahead of print, 2020 Apr 15]. Crit Care Resusc. 2020;.
  7. Katelyn A Pastick, Elizabeth C Okafor, Fan Wang et al. Hydroxychloroquine and Chloroquine for Treatment of SARS-CoV-2 (COVID-19), Open Forum Infectious Diseases, Volume 7, Issue 4, April 2020, ofaa130, https://doi.org/10.1093/ofid/ofaa130
  8. Covid-19: Delhi CM Arvind Kejriwal inaugurates India’s first convalescent plasma bank – delhi news – Hindustan Times. https://www.hindustantimes.com/india-news/covid-19-delhi-cm-arvind-kejriwal-inaugurates-india-s-first-convalescent-plasma-bank/story-WvGImjm5f4FLHP412cDaCN.html (accessed July 3, 2020).
  9. Li L, Zhang W, Hu Y, et al. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial. JAMA. Published online June 03, 2020. doi:10.1001/jama.2020.10044
  10. Niveditha Devasenapathy, Zhikang Ye, Mark Loeb, Fang Fang, Borna Tadayon Najafabadi, Yingqi Xiao, Rachel Couban, Philippe Bégin, Gordon Guyatt. Efficacy and safety of convalescent plasma for severe COVID-19 based on evidence in other severe respiratory viral infections: a systematic review and meta-analysis. CMAJ Jun 2020, cmaj.200642; DOI: 10.1503/cmaj.200642
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