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• There was no reversal on convalescent plasma
  Nigel Paneth MD MPH, Michael Joyner MD and Arturo Casadevall
  Published on: 13 February 2025
• Eye-catching title re the COVID-19 pandemic
  Christina J. Niederstadt
  Published on: 30 January 2025

• Published on: 13 February 2025

  There was no reversal on convalescent plasma

  • Nigel Paneth MD MPH, University Distinguished Professor of Epidemiology and Pediatrics College of Human Medicine, Michigan State University
  • Other Contributors:
    • Michael Joyner MD, Caywood Professor of Anesthesiology
    • Arturo Casadevall, Bloomberg Distinguished Professor of Microbiology and Immunology

  To the editor:
  Kacew et al review “reversals” of therapeutic guidelines for COVID-19 disease issued by the National Institutes of Health (NIH) and authorizations granted by the Food and Drug Administration (FDA). However, the FDA issued only emergency use authorizations, which are based “on a reasonable belief that the product may be effective…without waiting for all the information that would be needed for an FDA approval.” This is a very different standard than used in NIH guidelines.
  In claiming a “reversal” in the case of CP, the authors rely on a single meta-analysis (Mihalek et al, ) that focused entirely on all-cause mortality, reviewing just 19 randomized controlled trials (RCTs). By contrast, the meta-analysis by Senefeld et al included 39 RCTs, finding a 13% reduction in mortality with CP, more than twice the reduction estimated by Mihalek et al.
  Some RCTs of CP used insufficient antibody or treated too late for therapeutic effectiveness. Mihalek et al echoed these concerns in the RCT’s they reviewed, asserting that “It is possible that in some of the trials in included in our meta-analysis the antibody titer was not high enough to lead to any clinical change” and adding that “we suspect that convalescent plasma may be more effective in reducing clinical progression when administered early in the clinical course.”
  The Senefeld et al meta-analysis found that mortality was 15% lower in recipients of plasma with high antibody conten...

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  To the editor:
  Kacew et al review “reversals” of therapeutic guidelines for COVID-19 disease issued by the National Institutes of Health (NIH) and authorizations granted by the Food and Drug Administration (FDA). However, the FDA issued only emergency use authorizations, which are based “on a reasonable belief that the product may be effective…without waiting for all the information that would be needed for an FDA approval.” This is a very different standard than used in NIH guidelines.
  In claiming a “reversal” in the case of CP, the authors rely on a single meta-analysis (Mihalek et al, ) that focused entirely on all-cause mortality, reviewing just 19 randomized controlled trials (RCTs). By contrast, the meta-analysis by Senefeld et al included 39 RCTs, finding a 13% reduction in mortality with CP, more than twice the reduction estimated by Mihalek et al.
  Some RCTs of CP used insufficient antibody or treated too late for therapeutic effectiveness. Mihalek et al echoed these concerns in the RCT’s they reviewed, asserting that “It is possible that in some of the trials in included in our meta-analysis the antibody titer was not high enough to lead to any clinical change” and adding that “we suspect that convalescent plasma may be more effective in reducing clinical progression when administered early in the clinical course.”
  The Senefeld et al meta-analysis found that mortality was 15% lower in recipients of plasma with high antibody content and - in RCTs, matched-cohort studies and case series - mortality was 37% lower when treatment was initiated early in the disease course. They further found that the six outpatient RCTs of CP (only two of which were reviewed by Mihalek et al) showed a 35% reduction in hospitalization.
  Kacew et al make no mention of patients who might especially benefit from CP, but Mihalek et al recognized that “patients with coexisting immunodeficiency…may benefit from convalescent plasma therapy.” The FDA’s EUA for CP was affirmed, not reversed, by the full approval it gave to high titer COVID-19 CP “in individuals who are immunocompromised” in 2024.
  It is a mistake to lump CP plasma with clearly ineffective treatments such as ivermectin and hydroxychloroquine, ignoring the fact that convalescent plasma almost certainly saved thousands of lives during the COVID pandemic, and failing to recognize that convalescent plasma will be the first available therapeutic option in any new pandemic.

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  Conflict of Interest:
  None declared.

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• Published on: 30 January 2025

  Eye-catching title re the COVID-19 pandemic

  • Christina J. Niederstadt, Medical doctor and consultant for the statutory German health insurances Sozidoc.org

  The title gives rise to the hope of finding some elucidation regarding the management of the COVID-19 pandemic.
  After reading, however, I am left with more questions than answers.
  The authors state that they found 329 recommendations and they also found that 25 of these were contradicted by the results of randomized controlled trials.
  It is unclear what conclusions should or could be drawn from this information.

  Is it a suggestion to start randomized controlled trials first thing when a pandemic hits - and apart from that, do nothing?
  Or do the authors just want to draw attention to the fact errors that were made? If so, what is to be concluded from this information? Is the implicit message that the pandemics management was faulty? And if so, what was ok and who was at fault?
  The authors do not state explicitly that any error amounts to wrongdoing. But the paper implies that any errors could or would have been averted by conducting randomized trials before the errors were ever made.
  This is not, however, how progress is achieved in real life - and in science and (scientific) medicine.
  In fact - if we would look back at the years of the pandemic and we would find that no errors occurred - that would imply that we did not learn a thing!
  Progress without the identification of former "errors" in medical treatment (or, indeed within any area of human endeavour) is not possible.
  The fact that medicine is a l...

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  The title gives rise to the hope of finding some elucidation regarding the management of the COVID-19 pandemic.
  After reading, however, I am left with more questions than answers.
  The authors state that they found 329 recommendations and they also found that 25 of these were contradicted by the results of randomized controlled trials.
  It is unclear what conclusions should or could be drawn from this information.

  Is it a suggestion to start randomized controlled trials first thing when a pandemic hits - and apart from that, do nothing?
  Or do the authors just want to draw attention to the fact errors that were made? If so, what is to be concluded from this information? Is the implicit message that the pandemics management was faulty? And if so, what was ok and who was at fault?
  The authors do not state explicitly that any error amounts to wrongdoing. But the paper implies that any errors could or would have been averted by conducting randomized trials before the errors were ever made.
  This is not, however, how progress is achieved in real life - and in science and (scientific) medicine.
  In fact - if we would look back at the years of the pandemic and we would find that no errors occurred - that would imply that we did not learn a thing!
  Progress without the identification of former "errors" in medical treatment (or, indeed within any area of human endeavour) is not possible.
  The fact that medicine is a learning profession and that the COVID-19 pandemic gave rise to some serious learning is, indeed, highlighted by the changes in quite a few of the NIH-recommendations.
  So, if this was the intended message of this article, the authors could have stated as much in clearer words.
  If they wanted to say something special regarding the COVID-19 pandemic, they article does not provide any clarifying details on how the process of knowledge-generation during the COVID-19 pandemic should have been different.
  The article title mentions experts. However, the article text doesn't contain any reference to expert opinions and the expert discussions about droplet versus airborne spread of particles. One can only suspect that the authors didn't want to get involved with "medical matters as such":
  Diving into such medical discussion topics would necessitate expert knowledge; in this case foremost from aerosol scientists, virologists and field-working epidemiologists, which is pretty inconvenient if any of said scientist is not at hand.
  The accumulation of numbers from the literature however, is quite convenient if one does know how to impress with numbers. It also does lend an aura of objectivity to anything said/written.
  If it is true that we live in an age where numbers are more important than meanings, this article provides a proper demonstration.

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  Conflict of Interest:
  None declared.

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