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

  1. José-María Díez
  2. Carolina Romero
  3. JĂșlia Vergara-Alert
  4. Melissa BellĂł-Perez
  5. Jordi Rodon
  6. José Manuel Honrubia
  7. Joaquim Segalés
  8. Isabel Sola
  9. Luis Enjuanes
  10. Rodrigo Gajardo
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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 log10dilution 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 PRNT50titers 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 PRNT50values 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.

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