A novel in-vitro model for COVID-19 virus propagation
Key Words: Placenta, COVID-19, Vertical Transmission, Organ
Culture, Virus Propagation, Vaccine Development, Culture Media, elution
of virus
Research is an integral part in response to COVID-19 outbreak to
indentify the loopholes in current available scientific knowledge.
COVID-19 was reported as a pandemic threat to the global public health
by World Health organization (WHO) because of its higher rate of
community spread, level of severity and mortality [1]. In response
to COVID-19 outbreak, there is an urgent need to speed up the
development of vaccines and novel therapeutics [1]. Number of
increased cases worldwide raised the anxiety about viral intrauterine
transmission from mother to her fetus. It has been confirmed that the
Angiotensin-Converting Enzyme 2 (ACE2) is cell surface receptor
responsible for SARS-CoV-2 entry, increasing infections and transmission
in humans; yet the capacity of vertical transmission of the virus is a
mystery [2,3].
Findings by Li et. al., 2020 suggested that ACE 2 receptor is
highly expressed in maternal-fetal interface including placenta cells
e.g. stromal cells, prevascular cells of deciduas, cytotrophoblast,
syncytotrophoblast [2]. Additionally, the findings reveals that the
elevated levels of ACE-2 might increase the threat of vertical
transmission of SARS-CoV-2 through placenta and increase the risk of
fetal infections. However, there are no reports till date that COVID-19
infections in new born occur through nCoV infected mothers, yet the
preeclampsia and fetal distress are predicted outcomes (Table 1).Lu Q. and Shi Y. 2020 study is also reported the zero threat of
transplacental transmission of SARS-CoV-2 from a COVID-19 positive
mother to fetus; however the pneumonia infections is one of the leading
cause of pregnancy deaths worldwide[4,5,6]. Current available
knowledge suggests that the SARS-CoV-2 may not be transmitted from
mother to her child due to some placenta barriers but may be replicating
inside the placenta. Here, we hypothesize that placenta could be carrier
/ reservoir for COVID-19. It will not transmit virus and may protect
fetus. Hence placenta could be an ideal for propagation of virus for
vaccine development.
Bhonde et.al. in 1985 shown that human placenta organ culture
supports the replication of Japanese Encephalitis(JE) virus indicating
their susceptibility and possibility to support propagation of other
viruses [7]. An organ culture retains the most of the in-vivohistological features. An organ culture method is used to preserve
tissue structure or functions; which allows the organ to still resemble
and retain the characteristics they would have in-vivo [6,7].
Our team at Dr. D.Y.Patil Vidyapeeth has established in-vitro human
placenta organ culture model, tested positive for pregnancy hormones HCG
and prolactin indicating its fictional state (figure1). These findings
may support our hypothesis. These human placenta organ cultures can
present better results than traditional 2D cultures. We can use this
human placenta organ culture as a virus reservoir and will see whether
this in-vitro model system is supportive of the hypothesis. If the human
placenta organ culture supports the viral propagation, this in-vitro
system can be used further to scale up the viral replication for vaccine
development in short term. Based on our previous experience and present
data we propose that human Placental organ culture will be an ideal in
vitro model for propagation of COVID-19 as it has the requisite
receptors and tissue architecture needed for virus replication. It is
also possible that virus will be eluted out into the culture medium
making the antigen collection easier for vaccine development.