Abstract
Patients with COVID-19 generally raise antibodies against SARS-CoV-2 following infection, and the antibody level is positively correlated to the severity of disease. Whether the viral antibodies exacerbate COVID-19 through antibody-dependent enhancement (ADE) is still not fully understood. Here, we conducted in vitro assessment of whether convalescent serum enhanced SARS-CoV-2 infection or induced excessive immune responses in immune cells. Our data revealed that SARS-CoV-2 infection of primary B cells, macrophages and monocytes, which express variable levels of FcγR, could be enhanced by convalescent serum from COVID-19 patients. We also determined the factors associated with ADE, and found which showed a time-dependent but not viral-dose dependent manner. Furthermore, the ADE effect is not associated with the neutralizing titer or RBD antibody level when testing serum samples collected from different patients. However, it is higher in a medium level than low or high dilutions in a given sample that showed ADE effect, which is similar to dengue. Finally, we demonstrated more viral genes or dysregulated host immune gene expression under ADE conditions compared to the no-serum infection group. Collectively, our study provides insight into the understanding of an association of high viral antibody titer and severe lung pathology in severe patients with COVID-19.
Highlights
COVID-19, which is caused by SARS-CoV-2, poses a great threat to public health and the global economy [1]
It was believed that antibodies, neutralizing antibodies played a pivotal role in inhibiting SARS-CoV-2 replication in patients, it has been argued that they may exacerbate COVID-19 through antibody-dependent enhancement (ADE) [3]
ADE has been documented to other viruses including dengue virus (DENV), respiratory syncytial virus (RSV), measles virus, and feline infectious peritonitis virus (FIPV) [4,5,6,7]
Summary
COVID-19, which is caused by SARS-CoV-2, poses a great threat to public health and the global economy [1]. ADE has been documented to other viruses including dengue virus (DENV), respiratory syncytial virus (RSV), measles virus, and feline infectious peritonitis virus (FIPV) [4,5,6,7] In these cases, ADE increased the severity of diseases either by enhanced antibodymediated virus uptake into Fc gamma receptor (FcγR)-expressing phagocytic cells, leading to increased viral infection and replication (type I ADE), or by excessive antibody Fcmediated effector functions or immune complex formation causing enhanced inflammation and immunopathology (type II ADE) [3]. Experimental infection of FIPV antibody positive cats resulted in more severe diseases, regardless of naturally acquired or vaccine acquired antibodies [6] This ADE is closely related to more viral replication and more inflammatory responses in viral target cells including monocytes and macrophages in an aminopeptidase N (APN)-independent, FcγRdependent manner [9,10]. Our results contributed to the understanding of the pathogenesis of SARS-CoV-2 in the context of viral treatment and control
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