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Currently available intravenous immunoglobulin (Gamunex®-C and Flebogamma® DIF) contains antibodies reacting against SARS-CoV-2 antigens

Our take —

Although the team concluded that several intravenous immunoglobulin preparations contained antibodies that cross-reacted with SARS-CoV-2, and thus may be clinically useful in neutralizing viral entry, in the absence of negative controls we have to conclude that their conclusion is premature. We do not know the test characteristics of the antibody tests used, nor do we know if these antibodies were neutralizing and thus effective against SARS-CoV-2.

Study design


Study population and setting

This is an in vitro study of two standard intravenous immunoglobulin products where the authors test for cross-reactivity against coronaviruses of medical significance, including human coronaviruses that cause upper respiratory infections, SARS-CoV-1, SARS-CoV-2, and MERS-CoV. The team uses commercial ELISA kits for various known or unknown viral antigens to test whether dilutions of several intravenous immunoglobulin preparations demonstrate reactivity to these antigens.

Summary of Main Findings

Found positive cross-reactivity in SARS-CoV, MERS-CoV, and SARS-CoV-2. For SARSCoV- 2, positive reactivity was observed at intravenous immunoglobulin concentrations ranging from 100 μg/mL with Gamunex-C to 1 mg/mL with Flebogamma 5% DIF.

Study Strengths

Testing a dynamic range of up to 10,000-fold dilutions of intravenous immunoglobulin is an exhaustive way of examining cross-reactivity. Dilutions tested seem to represent what might be achieved in patients: for example, the typical dose of Flebogamma 10% is 300-600 mg/kg or 3-6 mL/kg, which for a 70 kg individual would be 21-42g, which should be more than enough to see an effect in patients.


The most substantial problem is that the team does not show any negative controls (e.g., media alone, water). Thus, we cannot conclude that the apparent cross-reactivity is the result of assay performance. In addition, it would be helpful to see a positive control, i.e., something to which intravenous immunoglobulin products always react. The absence of the negative control makes the study uninterpretable. A minor point is that there were only 1-2 replicates for Flebogamma 5% DIF. It is strange that there are up to 500-fold differences in antibody responses between Flebogamma lots (up to 500 fold in the case of HCoV betacoronaviruses). We do not know the specificity of the Ab tests used in this study, nor do we know if the Ab found is neutralizing Ab—the authors suspect one of them may be, as it cross-reacts to a protein in SARS-CoV-2 thought to be responsible for neutralization.

Value added

An intriguing and potentially helpful in vitro finding, if the authors can demonstrate negative controls stay negative.

This review was posted on: 27 April 2020