Hemofiltration with the Seraph® 100 Microbind® Affinity filter decreases SARS-CoV-2 nucleocapsid protein in critically ill COVID-19 patients
Critical Care volume 25, Article number: 190 (2021)
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 . 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 .
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 ultra-high 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 . The spike protein of SARS-CoV-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 . In addition to an anecdotal report  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%) .
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 continuous renal replacement therapy, N-protein concentration was consistently reduced when comparing pre- and post- Seraph treatment blood samples (Table 1). Calculating the Seraph whole blood clearance (CL) by the nucleocapsid concentration upstream (Cin) and downstream (Cout) of the Seraph and the blood flow (QB) by the formula: CL = (Cin / Cout) / Cin × QB, resulted in a measurable device clearance that was not observed with other proteins including total serum protein (Fig. 1).
In conclusion, treating critically ill COVID-19 patients with the Seraph® 100 Microbind® Affinity filter decreased SARS-CoV-2 nucleocapsid protein in blood. The effect of clinically relevant outcome parameters needs to be determined.
Availability of data and materials
The datasets during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Shan D, Johnson JM, Fernandes SC, Suib H, Hwang S, Wuelfing D, Mendes M, Holdridge M, Burke EM, Beauregard K, et al. N-protein presents early in blood, dried blood and saliva during asymptomatic and symptomatic SARS-CoV-2 infection. Nat Commun. 2021;12(1):1931.
Fajnzylber J, Regan J, Coxen K, Corry H, Wong C, Rosenthal A, Worrall D, Giguel F, Piechocka-Trocha A, Atyeo C, et al. SARS-CoV-2 viral load is associated with increased disease severity and mortality. Nat Commun. 2020;11(1):5493.
Seffer MT, Cottam D, Forni LG, Kielstein JT: Heparin 2.0: a new approach to the infection crisis. Blood Purif 2020:1–7.
Kim SY, Jin W, Sood A, Montgomery DW, Grant OC, Fuster MM, Fu L, Dordick JS, Woods RJ, Zhang F, et al. Characterization of heparin and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions. Antiviral Res. 2020;181:104873.
Pape A, Kielstein JT, Kruger T, Fuhner T, Brunkhorst R. Treatment of a critically Ill COVID-19 patient with the seraph 100 microbind affinity filter. TH Open. 2021;5(2):e134–8.
A Multicenter Evaluation of Blood Purification with Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19: A Preliminary Report [https://doi.org/10.1101/2021.04.20.21255810v1]
The authors thank Steve Winston from the CrisiScience Collaborative for his insightful advice.
The study was funded by intramural grants.
This study was approved by the Ethics Committee of the Medical School Hannover (9130_MPG_23b_2020).
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SH, DM, and AB are current employees of Quanterix Corporation. JK received research support from ExThera Medical and owns Quanterix stocks.
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Kielstein, J.T., Borchina, DN., Fühner, T. et al. Hemofiltration with the Seraph® 100 Microbind® Affinity filter decreases SARS-CoV-2 nucleocapsid protein in critically ill COVID-19 patients. Crit Care 25, 190 (2021). https://doi.org/10.1186/s13054-021-03597-3