Anti-SARS-CoV-2 IgG and IgA antibodies in COVID-19 convalescent plasma do not enhance viral infection

Abstract

The novel coronavirus, SARS-CoV-2 that causes COVID-19 has resulted in the death of nearly 4 million people within the last 18 months. While preventive vaccination, and monoclonal antibody therapies have been rapidly developed and deployed, early in the pandemic the use of COVID-19 convalescent plasma (CCP) was a common means of passive immunization with a theoretical risk of antibody-dependent enhancement (ADE) of viral infection. Though vaccines elicit a strong and protective immune response and transfusion of CCP with high titers of neutralization activity are correlated with better clinical outcomes, the question of whether antibodies in CCP can enhance infection of SARS-CoV-2 has not been directly addressed. In this study, we analyzed for and observed passive transfer of neutralization activity with CCP transfusion. Furthermore, to specifically understand if antibodies against the spike protein (S) enhance infection, we measured the anti-S IgG, IgA, and IgM responses and adapted retroviral-pseudotypes to measure virus neutralization with target cells expressing the ACE2 virus receptor and the Fc alpha receptor (FcαR) or Fc gamma receptor IIA (FcγRIIA). Whereas neutralizing activity of CCP correlated best with higher titers of anti-S IgG antibodies, the neutralizing titer was not affected when Fc receptors were present on target cells. These observations support the absence of antibody-dependent enhancement of infection (ADE) by IgG and IgA isotypes found in CCP. The results presented, therefore, not only supports the therapeutic use of currently available antibody-based treatment, including the continuation of CCP transfusion strategies, but also the use of various vaccine platforms in a prophylactic approach.

Theoretical Explanation for the Rarity of Antibody-Dependent Enhancement of Infection (ADE) in COVID-19

“…Altogether, the model results are in accordance with the data from [ 45 ], where it was shown that, in a cell culture, donor and patient plasma could induce ADE, but its probability did not differ between plasma samples from convalescent, mild, moderate and severe patients. In contrast to this data, a study on the transfer of neutralization activity with COVID-19 convalescent transfusion [ 46 ] demonstrated the absence of ADE upon transfusion. Based on our calculations, we speculate that convalescent plasma transfer is not likely to change the course of disease, but other plasma transfusion risks, such as hemolytic transfusion reactions, anaphylactic reactions, transfusion-related acute lung injury and allergic reactions, might occur [ 47 ].…”

Post-vaccination SARS-CoV-2 seroprevalence in children aged 3-11 years and the positivity in unvaccinated children: A retrospective, single-center study

“…In the early phase of the COVID-19 epidemic, transfusion of convalescent plasma from acute coronavirus infection was reported as an effective treatment for severe patients ( 32 ). Some studies demonstrated that the response of antibodies to the RBD of the spike protein was highly correlated with neutralization of SARS-CoV-2 ( 33 , 34 ).…”

Structural Dynamics of the SARS-CoV-2 Spike Protein: A 2-Year Retrospective Analysis of SARS-CoV-2 Variants (from Alpha to Omicron) Reveals an Early Divergence between Conserved and Variable Epitopes

“…A similar warning on vaccine safety due to potential risks of ADE was independently published by Shibo Jiang [19]. In contrast, several authors considered the risk to be null or minimal in the case of SARS-CoV-2 [20][21][22][23].…”