Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins

Abstract

Background: There is a crucial need for effective therapies that are immediately available to counteract COVID-19 disease. Recently, ELISA binding cross-reactivity against components of human epidemic coronaviruses with currently available intravenous immunoglobulins (IVIG) Gamunex-C and Flebogamma DIF (5% and 10%) have been reported. In this study, the same products were tested for neutralization activity against SARS-CoV-2, SARS-CoV and MERS-CoV and their potential as an antiviral therapy. Methods: The neutralization capacity of six selected lots of IVIG was assessed against SARS-CoV-2 (two different isolates), SARS-CoV and MERS-CoV in cell cultures. Infectivity neutralization was measured by determining the percent reduction in plaque-forming units (PFU) and by cytopathic effects for two IVIG lots in one of the SARS-CoV-2 isolates. Neutralization was quantified using the plaque reduction neutralization test 50 (PRNT50) in the PFU assay and the half maximal inhibitory concentration (IC50) in the cytopathic/cytotoxic method (calculated as the minus log10 dilution which reduced the viral titer by 50%). Results: All IVIG preparations showed neutralization of both SARS-CoV-2 isolates, ranging from 79 to 89.5% with PRNT50 titers from 4.5 to >5 for the PFU method and ranging from 47.0%-64.7% with an IC50 ~1 for the cytopathic method. All IVIG lots produced neutralization of SARS-CoV ranging from 39.5 to 55.1 % and PRNT50 values ranging from 2.0 to 3.3. No IVIG preparation showed significant neutralizing activity against MERS-CoV. Conclusion: In cell culture neutralization assays, the tested IVIG products contain antibodies with significant cross-neutralization capacity against SARS-CoV-2 and SARS-CoV. However, no neutralization capacity was demonstrated against MERS-CoV. These preparations are currently available and may be immediately useful for COVID-19 management.

Disease‐Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

“…With respect to the association with treatment duration, it has been shown that long‐term anti‐CD20 treatment is associated with the risk of hypogammaglobulinemia in neuromyelitis optica‐spectrum disorder 20 . A protracted treatment may impact on the protective, anti–SARS‐CoV‐2 humoral response 21 and on a pre‐existing humoral and cellular immune repertoire, recently described in unexposed individuals 22,23 …”

SARS-CoV-2 infection associated with hepatitis in an infant with X-linked severe combined immunodeficiency

“…A recent Cochrane systematic review indicated uncertainty as to whether convalescent plasma reduces COVID-19 disease mortality, although noted that it may increase improvement in symptoms at 15–30 days post-infusion [ 28 ]. In our patient's case we may have provided additional passive neutralizing anti-SARS-CoV-2 IgG through his IVIG infusions [ 29 ]. We were able to confirm the presence in the patient's circulation of broad IgG binding activity against SARS-CoV-2 viral proteins at several timepoints after plasma transfusion.…”

No SARS-CoV-2 cross-neutralization by intravenous immunoglobulins produced from plasma collected before the 2020 pandemic

“…al. published the detection of cross-reactive [12] as well as crossneutralizing Abs in 5 of 6 tested IVIG lots (Flebogamma and Gamunex C) [13]. This is in contrast to an earlier study which tested 21 IVIG lots (9 Gamunex C, 10 Gammagard Liquid, 2 other) with a SARS-CoV-2-specific ELISA (RBD or spike protein) that was shown to correlate well with a neutralization test, and revealed the absence of cross-reactive antibodies [14], as well as the current study.…”

“…of[13]). As two experimentally robust studies have not found SARS-CoV-2 nAbs in IVIG lots produced from pre-pandemic plasma, currently available IVIGs cannot be expected to afford protection from SARS-CoV-2 infection.No SARS-CoV-2 neutralization by IVIGs11With increasing numbers of human infections, also in the plasma donor community, it is interesting to follow the development of antibodies against SARS-CoV-2 in plasma donations and, after the several months production cycle time between plasma donation and IVIG lot release, also in IVIG lots, a longitudinal study currently in progress.…”