Antibody-dependent enhancement effect as a potential threat
induced by COVID-19
Chen Hu, Yong He*
Department of Pulmonary and Critical Care Medicine, Daping Hospital,
Army Medical University, Chongqing, 400042, China
To the Editor,
Corona Virus Disease 2019 (COVID-19) induced by the Severe Acute
Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become a major
concern all over the world.
Until
now, there is no effective treatment strategy for COVID-19.
In viral infections, there exists a group of phenomena in
which secondary infection develops more severe clinical diseases than
primary infection, known as Antibody-dependent enhancement of infection
(ADE) effect. ADE of viral infection has been noted and researched
extensively in many viruses. The complex of dengue virus and antibody
can enter the immune cells through FcR and attenuate the
inhibitory effect of the immune cells on the virus
replication1. Wan Y and colleagues revealed the
molecular mechanism of ADE induced by MERS-COV, indicating that the
receptor-binding domain (RBD)-specific neutralizing monoclonal antibody
may mediate ADE of MERS-COV by mimicking the functions of viral
receptors2. The 1918 influenza pandemic known as the
”Spanish Flu” has been the most serious infectious conditions in recent
history3. The first wave of Spanish Flu was just like
a common cold, while the second wave was much more contagious and
deadlier than the first wave. ADE may be responsible for the large
number of deaths among young adults during the Spanish pandemic.
It is not yet clear whether SARS-CoV-2 infection causes ADE effects.
However, there is evidence that ADE may be found in COVID-19.
Researchers found that seriously ill patients not only had a stronger
IgG response but also a higher titre of total antibodies, which indicate
the poorer prognosis4-5. Based on these results,Cao X
summarized
that it was suggestive of possible ADE of SARS-CoV-2
infection6. One of the most perplexing questions
regarding the current COVID-19 coronavirus epidemic is the discrepancy
between the severity of cases observed in different countries, which
arouse increasing attention and still appear to defy explanation.
SARS-CoV-2 infection was more likely to affect older males with
comorbidities 7. While according to the Centers for
Disease Control and Prevention of the United States, young adults make
up a large portion of those infected and hospitalized. One probable
answer is ADE of SARS-CoV-2 due to prior exposure to other
coronaviruses.
If ADE has been confirmed in SARS-CoV-2 infection, patients who may
appear to have staged a full recovery would be exposed to the risk of
COVID-19 reinfection. WHO had already warned that ”There is currently no
evidence that people who have recovered from COVID-19 and have
antibodies are protected from a second infection”. Under threat of ADE
effect,
herd
immunity strategy should be considered more fully to battle against
the possible second wave of the COVID-19, in which new virus variants or
the secondary infection may aggravates the epidemics. ADE may also be a
significant obstacle to developing effective vaccines for SARS-CoV-2,
since virus-specific antibodies conferred by vaccination of
inappropriate concentration may enhance the ability of the virus to
entry into target cells, leading to increased severity of the
disease8. So all virus subtypes and antibody levels
must be taken into account for the vaccine development and
antibody-based therapies.