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EXPERI MENTAL AND THER APEUTIC M EDICINE 20: 296, 2020
Abstract. Severe acute respiratory syndrome coronavirus 2
(SARS‑CoV‑2) is a novel coronavirus, which causes coronavirus
disease 2019 (COVID‑19) and affects children less frequently
than adults. According to Professor Vana Papaevangelou,
Professor of Paediatrics at the University of Athens School of
Medicine, children comprise only 2‑6% of COVID‑19 cases,
worldwide, and they are not considered as super‑spreaders of
this infection. SARS‑CoV‑2 is transmitted through droplets,
fomites, aerosol and fecal‑oral route, while there is no strong
evidence as yet, supporting transplacental transmission.
Professor Papaevangelou highlights the epidemiological
differences between seasonal inuenza and COVID‑19 and
accepts that school closure had no direct impact since children
are not the main transmitters of SARS‑CoV‑2. On the other
hand, social distancing clearly limited the transmission of
SARS‑CoV‑2, while quarantine seemed necessary during the
rst wave of this pandemic. She refers to antivirals, as well as
other therapeutic agents able to diminish the immune response
producing multisystem inflammatory syndrome, which is
associated with increased mortality, and she notes that these
agents were rarely used in children with COVID‑19, while in
most cases supportive treatment sufced. She nishes with the
ongoing scientic efforts for the development of an effective
and safe vaccine against SARS‑CoV‑2 indicating that so far the
most promising vaccine developments include vaccines that
use viral vectors.
Contents
1. Introduction
2. Questions and Answers
1. Introduction
Born in Athens, Greece, Professor Vana Papaevangelou, MD,
PhD, Professor of Paediatrics at the University of Athens
School of Medicine, is a trained Greek paediatrician, with
a special interest in paediatric infectious diseases (PID).
She studied medicine at the University of Athens School of
Medicine, where she received her MD with honours. Her PhD
was performed at the Second Department of Paediatrics of
the University of Athens under the supervision of Professor of
Paediatrics Costas Sinaniotis focusing on the early diagnosis
of vertical human immunodeciency virus (HIV) infection
in infants (1). After completing her paediatric residency and
PID fellowship at the New York University (NYU) Medical
Centre, USA, she returned to Athens in Greece and has been
a full time clinical paediatrician in a tertiary teaching hospital
(‘P. & A. Kyriakou’ Children's Hospital and ‘Aghia Sophia’
Children's Hospital) since 1996. During this time, she has been
caring for general paediatric cases and children with infectious
diseases. Professor Papaevangelou has been actively involved
in the education of medical students and paediatric residents.
Since September 2013, she has been appointed Chairman
of the Third Department of Paediatrics of the University of
Athens, which is located at ‘ATTIKON’ Hospital, a tertiary
Correspondence to: Professor Demetrios A. Spandidos, Laboratory
of Clinical Virology, Medical School, University of Crete, 71003
Heraklion, Greece
E‑mail: spandidos@spandidos.gr
Key words: COVID‑19, SARS‑CoV‑2, paediatrics, children,
schools closure, quarantine, antivirals, therapeutic agents, vaccine
OPINION
COVID‑19 and paediatric challenges: An interview
with Professor of Paediatrics Vana Papaevangelou
(University of Athens School of Medicine)
IOANNIS N. MAMMAS1‑4, MARIA THEODORIDOU1,4 and DEMETRIOS A. SPANDIDOS1,3
1Institute of Paediatric Virology; 2Paediatric Clinic, Aliveri, 34500 Island of Euboea;
3Laboratory of Clinical Virology, Medical School, University of Crete, 71003 Heraklion;
4First Department of Paediatrics, University of Athens School of Medicine, 11527 Athens, Greece
Received July 31, 2020; Accepted October 24, 2020
DOI: 10.3892/etm.2020.9426
‘Catarrhs and coryza in very old people are not treated.’
[Βράγχοι καὶ κόρυζαι τοῐσι σφόδρα πρεσβύτῃσιν οὐ πεπαίνονται]
Hippocrates
MAMMAS et al: COVID‑19 AND PAEDIATRIC CHALLENGES
2
University Hospital in Chaidari, west Attica, Greece. Over
the past 20 years, Professor Papaevangelou has been actively
involved in multiple research projects. Her main interests have
involved the epidemiology of vaccine‑preventable diseases
(hepatitis A and B, varicella, measles) and vertical transmis‑
sion of viruses, such as hepatitis B virus (HBV), hepatitis C
virus (HCV) and cytomegalovirus (CMV). She is a member of
the National Advisory Board for Immunization Practices, the
National Hepatitis Board and the Viral Hepatitis Prevention
Board. Since May 2019, she is a Board member of the
European Society for Paediatric Infectious Diseases (ESPID).
Professor Papaevangelou has published more than 115 papers
in peer reviewed journals, with an H‑Index of 29 and more
than 2,500 citations ‑ see selected articles of her work in the
references list (2‑11).
Professor Papaevangelou has actively assisted the
Paediatric Virology Study Group (PVSG) (12) and since
August 2020, she is member of the Academic Advisory
Board (AAB) of the newly founded Institute of Paediatric
Virology (IPV). In the context of the forthcoming ‘6th work‑
shop on paediatric virology’, which will be organized by the
IPV on Saturday, October 24th, 2020, her plenary lecture will
focus on severe acute respiratory syndrome coronavirus 2
(SARS‑CoV‑2) vertical transmission in neonates. The aim
of this interview‑style article is to focus on the current coro‑
navirus disease 2019 (COVID‑19) pandemic threat and to
examine this novel viral outbreak under the paediatric point of
view. During the recent COVID‑19 pandemic threat, Professor
Papaevangelou is a member of the counseling committee of
the National Public Health Organisation (NPHO), which
constitutes the operational centre for the planning, measures'
implementation and surveillance of COVID‑19 in Greece.
2. Questions and Answers
Question: Professor Vana Papaevangelou, what is SARS‑CoV‑2,
what is COVID‑19 and how children are implicated in the
spread of this novel viral outbreak?
An swer: SARS‑CoV‑2 is a novel coronavirus, which causes
COVID‑19 disease and pandemic. Children do not seem to
play an important role in this pandemic. It is not clear as yet
why children are affected less than adults. Epidemiologic data
from China, Italy, other European countries, as well as USA
indicate that children comprise only 2‑6% of cases (1% in
Italy, 2% in China, 5‑6% in USA and Greece). It also appears
that children are not super‑spreaders of this infection, i.e., they
do not seem to be the source of major outbreaks in closed
communities.
Question: How is SARS‑CoV‑2 transmitted to children? Does
its transmission differ compared to other respiratory viruses?
What is the current evidence regarding perinatal transmission
of SARS‑CoV‑2?
An swer: SARS‑CoV‑2 is a respiratory virus mainly trans‑
mitted through droplets and fomites as inuenza and other
respiratory viruses. Additionally, this virus may also be
transmitted by aerosol and through fecal‑oral route. Regarding
potential vertical transmission, there is no evidence so far
supporting transplacental transmission. Some experts doubt
that such a transmission may occur and question whether
angiotensin‑converting enzyme 2 (ACE2) receptor is present
in placenta tissue. Perinatal transmission has been reported
mainly through maternal respiratory droplets and possible poor
hand hygiene.
Question: What are the most common underlying condi‑
tions that predispose children to become more vulnerable to
SA R S ‑ C oV‑2 ?
An swer: Although adults with diabetes mellitus and asthma
are considered at high risk, children with well controlled
type 1 diabetes and mild‑moderate asthma are not considered
at risk. Conversely, as with adults, children with underlying
malignancy (especially haematologic), immunosuppression
and chronic lung disease (such as cystic brosis) are consid‑
ered more vulnerable to SARS‑CoV‑2.
Question: What are the clinical symptoms of neonates and
children infected with SARS‑CoV‑2 and how do they differ
compared to the symptoms of children with inuenza and the
symptoms of elderly patients with COVID‑19?
An swer: In previously healthy children, COVID‑19 is usually
mild and indisti nguishable from other upper respiratory in fec‑
tions. Signs and symptoms are less severe when compared to
adults. Overall, while it has been estimated that 15% of adults
will be hospitalized due to severe infection, in children less
than 5% of infected children are admitted to hospital. Most
children are either asymptomatic or pauci‑symptomatic and
diagnosed through contact tracing. Main symptoms will
include fever, coryza, cough, sore throat, decreased PO
intake, fatigue as well as nausea, vomiting, diarrhea and
rash. Rash in children may be impressive and present as a
reddish‑purplish discoloration on toes. A minority (5‑10%)
will appear sick and or present with respiratory distress and
low oxygen saturation value <95%).
Figure 1. Professor Vana Papaevangelou, MD, PhD, Professor of Paediatr ics
at the University of Athens School of Medicine (Athens, Greece), plenary lec‑
turer at the ‘6th workshop on paediatr ic virology’ organised by the Institute
of Paediatric Virology (IPV) a nd recipient of the ‘2020 Paediatric Virology
Aw a r d’.
EXPERI MENTAL AND THER APEUTIC M EDICINE 20: 296, 2020 3
Question: How can we explain the decreased vulnerability of
neonates and children to SARS‑CoV‑2 infection?
An swer: Although there is no clear answer as yet, there have
been few reports suggesting that ACE2 receptor, the receptor
used by SARS‑CoV‑2 to enter human cells is signicantly less
expressed in children's respiratory system when compared to
adults.
Question: What is the prevalence of SARS‑CoV‑2 and
inuenza co‑infections and what is the estimating impact of
inuenza in the associated to SARS‑CoV‑2 mortality?
An swer: In the past, before SARS‑CoV‑2 pandemic, we paedia‑
tricians have faced many children with viral co‑infections. We
have been able to recognize them over the past decade with the
use of multiplex polymerase chain reaction (PCR) technique
able to confirm co‑infections. Data on viral co‑infections
suggest increased morbidity both in healthy and immuno‑
compromised children. We have not had the opportunity to
study SARS‑CoV‑2 and inuenza co‑infection as yet, since the
pandemic presented towards the end of the inuenza season in
2020 possibly due to school closure.
Question: How signicant was school closure in the limitation
of the transmission of the SARS‑CoV‑2 in the community?
How signicant is social distancing for the limitation of the
transmission of SARS‑CoV‑2? Could selected quarantine
(only conrmed patients and high‑risk populations) have been
alternatively used as a preventative tool against SARS‑CoV‑2
instead of general quarantine?
An swer: These are really challenging questions. Concerning
school closure and the limitation of transmission in the
community, we do have hard evidence for inuenza infec‑
tion where it has been evident that children are the driving
force of community spread. In the case of influenza,
therefore, one may strongly argue that school closure will
signicantly decrease community spread. In the case of
COVID‑19, there is no such evidence. Epidemiologic data
indeed support that school closure has decreased the Ro
in many areas. However, since children are not the main
transmitters in the case of SARS‑CoV‑2, one may postu‑
late that school closure had no direct impact, but had as
a consequence, parental work absence and fewer contacts
among adults as well. On the other hand, social distancing
clearly limits the transmission of SARS‑CoV‑2. Quarantine
seemed necessary during the rst wave of this pandemic.
Local lockdowns and selected quarantine may be optimal
over the next weeks and months.
Question: Immunization is an essential health interven‑
tion which is expected to be affected by the current
COVID‑19 pandemic, resulting in the increased likelihood of
outbreak‑prone vaccine preventable diseases. We would like
your comment on the necessity of the continuity of the current
immu n i zati on sc hedu le in Gr e e ce du r i ng the pa ndem i c per i od?
An swer: The importance of sustained high vaccination
coverage in any community cannot be stressed enough. It is
evident that no decrease in vaccination coverage, especially
in children is acceptable. In Greece, the advisory committee
for Immunization practices, responded to such a threat and
issued advice to both parents and pediatricians promoting the
continuity of uptake of immunizations for all children and
especially infants.
Question: To date, there have been several proposed manage‑
ment and therapeutic strategies for neonates, children and
adults with COVID‑19. Remdesivir vs. hydrochloroquine and
azathioprine vs. hydrochloroquine and lopinavir/r itonavi r,
etc. What is the reason of this diversity? Among the different
protocols already used in children, which one do you believe
is more effective and why? Which therapeutic protocol is
currently used or planned to be used in Greece in the paedi‑
atric patients with conrmed COVID‑19?
An swer: It is absolutely expected to have many clinical trials
running concurrently trying to identify best regimens to
face this new disease. Children rarely ever are treated with
antivirals, while in most cases supportive treatment sufces.
Although therapeutic algorithms suggested the use of hydro‑
choloquine and or lopinavir/ritonavir for severe cases, these
have been rarely if ever used. Remdesivir has not been admin‑
istered to any child in Greece so far.
Question: Based on your valuable clinical and research
paediatric experience, how possible do you consider the devel‑
opment of an effective vaccine or of novel targeted successful
therapeutic agents against SARS‑CoV‑19 in the next future?
An swer: At present more than 70 groups are working for
the development of a vaccine against SARS‑CoV‑2. Vaccine
development mainly aims to focus the spike glycoprotein (S),
which is the sole surface protein of the SARS‑CoV‑2 virion.
SARS‑CoV‑2 mediates viral entry into host cells via the
ACE2, which is expressed at high levels on the surface of
pulmonary epithelial cells. The virus enters human cells
through the conjunction of spike glycoprotein and more
specifically the receptor‑binding domain (RBD) of this
protein with the ACE2 receptor. So far the most promising
vaccine developments include vaccines that use viral vectors,
namely chimpanzee's adenoviruses (ChAd; Oxford group;
ChAdOx1 nCOV‑19). Other groups have been working with
novel platforms based on DNA or mRNA. Nucleic acid
vaccines are composed of DNA or RNA sequences encoding
the target antigen. These vaccines are delivered by viral
particles competent for entry in host cell, by formulation
with lipids or emulsions, or by means of electroporation.
They offer the ability to easily manipulate antigen and
most importantly have the advantage of producing candi‑
date vaccines faster. As per the therapeutic agents, current
clinical trials have two distinct targets. Agents targeting
the virus (hydrochloroquine, remdesivir, etc.) and most
importantly agents, such as dexamethasone, intravenous
immunoglobulin (IVIG) and monoclonal antibodies, able
to diminish the immune response elicited by humans and
producing multisystem inammatory syndrome associated
with increased mortality.
Question: We would like to thank you for this interview as
well as for your contribution and help to our PVSG. We look
forward to your plenary lecture entitled ‘vertical transmission
of SARS‑CoV‑2: Is there evidence supporting transplacental
transmission?’ in the forthcoming “6th workshop on paedi‑
atric virology”.
MAMMAS et al: COVID‑19 AND PAEDIATRIC CHALLENGES
4
Acknowledgements
This article is published in the context of the founda‑
tion of the Institute of Paediatric Virology (IPV; https://
paediatricvirology.org) based on the island of Euboea (Greece),
under the auspices of the World Academy of Sciences (WAS)
and the support of the Department of Clinical Virology of
the University of Crete School of Medicine and the First
Department of Paediatrics of the University of Athens School
of Medicine. We would like to thank all the members of the
IPV for their valuable comments and corrections.
Funding
No funding was received.
Availability of data and materials
Not applicable.
Authors' contributions
INM, MT and DAS contributed equally to the conception and
design of this manuscript, wrote the original draft, edited and
critically revised the manuscript, read and approved the nal
manuscript.
Ethics approval and consent to participate
Not applicable.
Patient consent for publication
Not applicable.
Competing interests
INM, MT and DAS are Co‑founders of the Institute of
Paediatric Virology (IPV). DAS is the Editor‑in‑Chief for
the journal, but had no personal involvement in the reviewing
process, or any inuence in terms of adjudicating on the nal
decision, for this article.
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