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

Abstract

The novel coronavirus SARS-CoV2, which 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 the theoretical risk of antibody-dependent enhancement (ADE) of viral infection remaining undetermined. 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-CoV2 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 (FcaR) or Fc gamma receptor IIA (FcgRIIA). 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, support the clinical use of currently available antibody-based treatment including the continued study of CCP transfusion strategies.

Immunogenicity and immune-persistence of the CoronaVac or Covilo inactivated COVID-19 Vaccine: a 6-month population-based cohort study

“…The titers of SARS-CoV-2 antibody measured indicates that most antibodies generated against S protein and N protein belonged to subtype IgG; there were only low levels of antibodies with subtype IgM (21). This is not surprising; IgG antibody is typically produced for several weeks and lasts for a long time (more than 13 weeks), whereas IgM antibody is transiently expressed (22).…”

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).…”

Adverse effects of vaccinations and potential therapies against COVID-19

“…Na kanwie rozważań o ADE pojawia się również pytanie, czy terapia surowicą ozdrowieńców lub wyprodukowane przeciwciała są i do którego dnia mogą być skuteczne, co znajduje odzwierciedlenie w publikacjach. W tym aspekcie przeważają jednak doniesienia o tym, że takie zjawisko, jak ADE nawet w czasie choroby nie występuje [27,28]. Od początku logiczne wydawało się, że surowica ozdrowieńców może być skuteczna, jeśli zastosuje się ją bardzo wcześnie (dopóki istnieją wiriony, a nie ich remnanty), co okazało się być nierealne w warunkach szpitalnych.…”