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Treatment with tocilizumab does notinhibit induction of anti-COVID-19 antibodies in patients with severe SARS-CoV-2 infection
Clinical Cancer Research ; 26(18 SUPPL), 2020.
Article in English | EMBASE | ID: covidwho-992084
ABSTRACT
Tocilizumab (TCZ), an interleukin-6 (IL-6) receptor-blocking monoclonal antibody, is used to treat variousrheumatologic conditions and cytokine release syndrome in CAR-T cell therapy and has been repurposed to treatCOVID-19-related hyperinflammation. There are limited data available reporting how TCZ affects the immuneresponse in the context of COVID-19. To investigate this question, we recruited patients treated with TCZ as part ofa COVID-19 biobanking protocol (A-28063295) to study immune parameters that might be affected. We enrolled 19patients who were treated with a range of 40-200mg TCZ as part of a low-dose TCZ trial (COVIDOSE, reportedseparately as abstract A-94803796), and 11 patients who received 400mg TCZ on a standard-of-care expanded-access basis. As IL-6 acts as a stimulant of B-cell proliferation, plasma cell maturation, and antibody responses, weevaluated whether blocking the IL-6 receptor with TCZ therapy impairs antibody generation to SARS-CoV-2. Toevaluate antibody levels in these patients, we performed ELISAs against the SARS-CoV-2 spike glycoprotein and itsreceptor-binding domain (RBD). The spike glycoprotein, a structural protein of SARS-CoV-2, is a crucial componentin the recognition, attachment, and entry of the virus into host cells. Specifically, the RBD is responsible for bindingthe ACE2 receptor on human cells, and likely serves as a major target for neutralizing antibodies. To establish if theformation and persistence of antibodies was affected by TCZ treatment, we analyzed serum and plasma sampleslongitudinally from 29 patients treated with TCZ and 26 control patients. To account for potential variability betweenplates, the measured optical density (OD) values were normalized to the OD for COVID-19-negative control serumat 150 dilution, and the same negative control was tested on each plate. Titers were calculated as the linearinterpolation of the inverse dilution at which the normalized OD value crossed a threshold of 1, representing themaximum OD measured for the negative control. Anti-spike and anti-RBD antibodies increased significantly overtime in both TCZ-treated patients and controls (p < 0.005 for both). Increasing antibody titers throughout the diseasecourse followed a similar trajectory in TCZ-treated patients compared to control patients, suggesting that TCZtreatment does not impede the generation of antibodies to SARS-CoV-2. Additionally, TCZ-treated patients achievedcomparable maximal observed antibody titers to control patients (average maximal log10 (titer) of 5.42 and 4.96 forspike and of 4.39 and 4.44 for RBD, respectively). These data suggest that TCZ does not impair the induction ofanti-SARS-CoV-2 antibodies.

Full text: Available Collection: Databases of international organizations Database: EMBASE Language: English Journal: Clinical Cancer Research Year: 2020 Document Type: Article

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Full text: Available Collection: Databases of international organizations Database: EMBASE Language: English Journal: Clinical Cancer Research Year: 2020 Document Type: Article