Relevance of Antibody-Dependent Enhancement in COVID-19
Abstract
1. Introduction
2. Relationship Between the Antibody Response and COVID-19 Pathology
2.1. Antibody Response and COVID-19 Severity in Human Studies
Country | Year | Subjects | Time of Sampling | Main Finding | Reference |
---|---|---|---|---|---|
Saudi Arabia | 2020 | 87 | 4 to 70 days | Anti-N Abs correlated to severe disease; nAbs to ICU and death | [16] |
China | 2020 | 173 | 5 to 40 days | Total Abs two weeks after onset associated with disease severity | [23] |
Estonia | 2022 | 123 | 3, 6, 12 months | Severe disease had higher anti-RBD titers after 3 and 6 months | [17] |
Canada | 2025 | 938 | 1, 6 and 12 months | Anti-RBD, anti-N and nAbs higher in hospitalized at one month | [18] |
Thailand | 2024 | 110 | 14 days to 1 year | Anti-RBD levels associated with pneumonia at 14 days | [19] |
China | 2020 | 32 | 0 to 28 days | Higher anti-spike on days 14 and 21 | [28] |
China | 2020 | 87 | 4 to 41 days | Anti-RBD higher in severe and moderate cases on days 16 and 25 | [20] |
China | 2021 | 63 | 0 to 51 days | Anti-RBD, anti-N and nAbs higher in severe cases; correlated with IL1-β | [22] |
Turkey | 2023 | 208 | 0 to 15 days | Anti-spike and nAbs higher in severe and moderate cases | [21] |
México | 2022 | 111 | 5 to 50 days | Low probability of survival correlated to low neutralization | [29] |
2.2. Antibody Response and SARS-CoV-2 Infection in Animal Models
3. Antibody-Dependent Enhancement of SARS-CoV-2 Entry into Host Cells
3.1. FcγR-Mediated SARS-CoV-2-Antibody Complex Entry into Host Cells
3.2. Antibody-Dependent Enhancement of SARS-CoV-2 Entry into ACE2 Expressing Cells Independent of FcγRs
3.3. Impact of Antibodies on Virus Fusion
3.4. Enhancement of SARS-CoV-2 Entry by Antibodies Specific for Other Coronaviruses
4. Pathologic Mechanisms in COVID-19 Associated with Immune Complex-Mediated Cell Signaling
4.1. Enhancement of FcγR-Mediated Effector Mechanisms
4.2. Cytokine Secretion Induced by Immune Complexes
4.3. Impact of Antibody Glycosylation in Induction of Inflammation in COVID-19
5. Relevance of ADE in Vaccination Strategies
6. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
Abbreviations
ADE | Antibody-dependent enhancement |
DENV | Dengue virus |
SARS-CoV-2 | Severe acute respiratory syndrome coronavirus 2 |
COVID-19 | Coronavirus disease of 2019 |
ACE2 | Angiotensin converting enzyme 2 |
ARDS | Acute respiratory distress syndrome |
RBD | Receptor binding domain |
FcRs | Receptors for the Fc portion of antibodies |
FcγRs | Receptors for the Fc portion of IgG antibodies |
NTD | N-terminal domain |
SARS-CoV | Severe acute respiratory syndrome coronavirus |
MERS-CoV | Middle East respiratory syndrome coronavirus |
ADCP | Antibody-dependent cellular phagocytosis |
ADCC | Antibody-dependent cellular cytotoxicity |
ADCD | Antibody-dependent complement deposition |
nAbs | Neutralizing antibodies |
pDCs | Plasmacytoid dendritic cells |
IL | Interleukin |
TNF | Tumor necrosis factor |
TLR | Toll-like receptor |
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Rodriguez-Pinto, D.; Mendoza-Ruiz, M.S. Relevance of Antibody-Dependent Enhancement in COVID-19. Immuno 2025, 5, 20. https://doi.org/10.3390/immuno5020020
Rodriguez-Pinto D, Mendoza-Ruiz MS. Relevance of Antibody-Dependent Enhancement in COVID-19. Immuno. 2025; 5(2):20. https://doi.org/10.3390/immuno5020020
Chicago/Turabian StyleRodriguez-Pinto, Daniel, and María Sol Mendoza-Ruiz. 2025. "Relevance of Antibody-Dependent Enhancement in COVID-19" Immuno 5, no. 2: 20. https://doi.org/10.3390/immuno5020020
APA StyleRodriguez-Pinto, D., & Mendoza-Ruiz, M. S. (2025). Relevance of Antibody-Dependent Enhancement in COVID-19. Immuno, 5(2), 20. https://doi.org/10.3390/immuno5020020