The COVID-19 Textbook

255

CHAPTER 8 • Antibodies in COVID-19

Longitudinal profile of COVID-19 antibody response

Incubation period

Disease

Convalescence

Live virus

IgG

Viral RNA via PCR

IgA

IgM

Serum antibody titer

Week 1

Week 2

Week 3

Week 4

Week 5

Weeks postinfection

FIGURE 8.3 Profile of COVID-19 antibody response. Ig, immunoglobulin; PCR, polymerase chain reaction.

antibodies, rather than quantitative levels, are likely key to control and clear infection. Dysfunctional Fc-effector functions have been linked to poor clinical outcome and have been associated with altered Fc-glycosylation. 99,100 Specifically, decreased Fc fucosylation and increased titers of proinflammatory but poorly functional IgG2 antibodies are observed in severely ill COVID-19 patients, especially in male patients that typically suffer from enhanced morbidity and mortality in COVID-19. 99 Collec tively, these data suggest that in natural infection, Fc-effector functions may play a critical role in the control and clearance of infection, resulting in milder disease. The majority of nAbs against SARS-CoV-2 target the RBD and work through steric hindrance, physically preventing the RBD from binding to its host angiotensin-converting enzyme 2 (ACE2) receptor, effectively preventing viral entry into the cell. Antibodies against the N-terminal domain (NTD) of the S protein can also have neutralizing activity, 101 either by preventing the structural rearrangement of S protein required for ACE2 binding or through other, poorly defined mecha nisms. 102,103 When induced by natural infection, the evolution of nAbs plays a critical role in con ferring transient immunity against that same viral strain, 104 but confer limited protection against additional strains. 105-110 Emerging data suggest that individuals that survive severe disease more rap idly evolve a higher proportion of nAbs to non-nAbs than those who ultimately pass away. 111 Sim ilarly, nAb potency, which is measured by the nAbs’ ability to outcompete ACE2 in binding to the RBD, is a predictor of survival in COVID-19 patients. 112 Thus, the production of nAbs, linked to Fc-effector function, likely enables antibodies to simultaneously block further rounds of viral repli cation while clearing the infection. ROLE OF ANTIBODIES FOLLOWING VACCINATION All current licensed vaccines demonstrated robust immunogenicity, inducing robust binding of the virus and nAbs, often at levels far superior to those induced by natural infection. 113-117 Antibodies induced by vector and messenger RNA (mRNA) vaccines are more durable than infection-induced antibodies, 118 and approved vaccines conferred 60% to 95% protection against severe disease and death, 114-116 providing the protection that was urgently required to curb the pandemic. Early phase 3

Copyright © 2023 Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited.