Therapeutic Plasma Exchange–Neutralizing Antibody Combination Therapy for Severe Coronavirus Disease 2019

TO THE EDITOR––Zeng et al [1] describe discouraging effects of convalescent plasma therapy on survival in patients with coronavirus disease 2019 (COVID-19). This contrasts with quite opposite results of a pilot study [2] published earlier. The fundamental difference between these 2 studies is that the presence of virus-neutralizing antibodies (nAbs) in convalescent plasma was not assessed by Zeng et al [1], whereas convalescent plasma in the earlier and very encouraging study [2] was selected to contain substantial amounts of nAbs. These findings highlight the importance of assessing the presence of nAbs in convalescent plasma used therapeutically in patients with COVID-19.

Zeng et al [1] also describe a 30-year-old severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)–positive woman with bilateral pneumonia, in whom a sepsislike syndrome progressively developed. This progression was not affected by 2 convalescent plasma transfusions (400 and 200 mL, with unknown amounts of nAbs, administered 2 days apart), ultimately resulting in a fatal outcome. Indeed, in many patients with COVID-19, sepsislike syndromes develop, in which therapeutic plasma exchange (TPE) may significantly reduce the levels of key proinflammatory cytokines and permeability factors [3, 4] elevated owing to inappropriate inflammatory responses [5]. TPE is an effective treatment in many clinical situations, and a typical single TPE treatment takes about 2 hours and replaces 1–1.5 blood volumes; the plasma is discarded and replaced by an isotonic solution of approximately 5% human albumin, which typically does not induce any detectable hypersensitivity or toxic reactions.

TPE may be complemented by replacing 400 mL of the isotonic human albumin solution with 400 mL of ABO-matched convalescent plasma [1, 2] containing high titers of anti-SARS-CoV-2 nAbs. Significantly higher nAb titers are present in elderly and middle-aged patients than in young recovered patients [6]. Many hospitals probably cannot perform the SARS-CoV-2-neutralization assay, which requires a high-containment (biosafety level 3 or 4) facility. Therefore, plasma with high titers of antibodies binding to the S1 receptor binding domain, S1-N-terminal domain (NTD) and S2 should be selected. Testing with enzyme-linked immunosorbent assay (or another suitable assay) can replace the virus neutralization assay, because practically all known nAbs bind to 1 of these 3 SARS-CoV-2 regions and interfere with binding to angiotensin-converting enzyme 2 or with S2-mediated membrane fusion [7]. Alternatively, nAbs-containing allogeneic plasma could be replaced by cross-neutralizing SARS-CoV receptor binding domain–specific (human or “humanized”) antibodies [8] or SARS-CoV-2–specific monoclonal nAbs [9].

Note

Potential conflicts of interest. Author certifies no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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