To the Editor:
The Passive Immunity Trial for Our Nation (PassITON) investigators concluded in this issue of CHEST that treatment with COVID-19 convalescent plasma (CCP) did not improve clinical outcomes.1 However, this conclusion, which implies that CCP is ineffective, is potentially in error because it does not consider that approximately 80% of patients in both arms were receiving remdesivir, another antiviral therapy. Antibodies active against SARS-CoV-2 in CCP function as antivirals,2 which means that, for most patients in PassITON, CCP was assessed as an add-on combination therapy with another antiviral agent. Hence, the absence of a favorable effect for CCP in PassITON may simply reflect an non-significant incremental effect of combination therapy rather than a shortcoming for this antibody therapy. Indeed, the Convalescent Plasma to Limit COVID-19 Complications in Hospitalized Patients (CONTAIN COVID-19)3 and O’Donnell et al4 trials published in 2021 demonstrated CCP efficacy in the reduction of mortality rates for patients who were hospitalized early in the pandemic before remdesivir became part of standard clinical practice. It is notable that an analogous negative result for antibody-drug combination therapy was also observed in the early antibiotic era when physicians added sulfonamides to convalescent serum to try to improve the outcome of pneumococcal pneumonia.5 Because serum or sulfonamide monotherapy were each effective against pneumococcal pneumonia, there was likely no opportunity for improvement when they were combined.
We recognize that this trial was conducted at a time when therapeutic approaches were changing rapidly and remdesivir and corticosteroids were introduced as standard of care; investigators could not have controlled for these shifting variables while providing optimal patient care. Nevertheless, the results should be interpreted in the context of known biologic effects and published clinical experience. Given the concerns about concurrent remdesivir use, the current PassITON analyses on CCP efficacy are inconclusive.
Acknowledgments
Financial/nonfinancial disclosures: The authors have reported to CHEST the following: A. C. was one of the lead investigators on the Hopkins trial of convalescent plasma published in the New England Journal of Medicine and serves on the Scientific Advisory Board of SAB Therapeutics. J. P. H. serves on the COVID-19 Scientific Advisory Board of Immunome. A. C. and J. P. H. are in the leadership group of the COVID-19 Convalescent Plasma Project (ccpp19.org).
References
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