Hemofiltration with the Seraph® 100 Microbind® Affinity filter decreases SARS-CoV-2 nucleocapsid protein in critically ill COVID-19 patients

Abstract

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. The nucleocapsid protein (N-protein) of SARS-CoV-2 is a structural protein that oligomerizes to form a complex surrounding viral RNA, thus protecting it from the host cell environment. It is abundantly expressed within infected cells, where it facilitates viral RNA transcription, an essential step for viral replication Recently an ultrasensitive Simoa® immunoassay has been described that robustly measures SARS-CoV-2 N-protein in venous blood, dried blood microsamples, and saliva [1]. This study measured N-protein in longitudinal blood samples of COVID-19 patients and demonstrated readily detectable viral antigen two weeks after initial positive PCR testing, with concentrations gradually decreasing, inversely correlated with anti-SARS-CoV2 adaptive immune response. This study supports observations reported elsewhere that viral load in blood correlates with disease severity [2]. The Seraph® 100 Microbind® Affinity adsorber (Exthera Medical, CA, USA) is an extracorporeal treatment currently being explored as an approach to improve the clinical course and outcome of critically ill patients with COVID-19. On April 17, 2020, the FDA granted emergency use authorization for the Seraph® 100 for use in the context of severe and critical disease, for which effective treatment options are limited. Bacteria and viruses bind to the immobilized heparin on the ultrahigh molecular weight polyethylene beads of the Seraph® device in a manner similar to the interaction with heparan sulfate on the cell surface and are thereby removed from the bloodstream [3]. The spike protein of SARSCoV-2 has been shown to bind to cellular heparan sulfate (and heparin) through its receptor-binding domain, and recent studies suggest the heparin binding of the spike protein is much more pronounced in SARS-CoV-2 than in other coronaviruses [4]. In addition to an anecdotal report [5] a recent multicenter study showed that mortality of COVID-19 patients was much lower (37.7%) in the Seraph 100 treated group compared to a control group (67.4%) [6]. Here, we report the effect of the Seraph treatment on the concentration of the N-protein in critically ill COVID-19 patients as part of an ongoing biomarker study, approved by the IRB of the Hannover Medical School (9130_MPG_23b_2020). Six out of seven COVID-19 patients exhibited measurable concentrations of the N-protein prior to treatment with the Seraph® device, that seemed to be related to the severity of the disease and the duration of the disease (Table 1). While hemoperfusion with the Seraph® was executed either alone or in combination with a wide range of supportive treatments, including intermittent hemodialysis and Open Access