ORIGINAL RESEARCH
published: 10 December 2020
doi: 10.3389/fped.2020.612627
Impact of COVID-19 Pandemic on
Pediatrics and Pediatric
Transplantation Programs
Steven Lobritto 1 , Lara Danziger-Isakov 2 , Marian G. Michaels 3 and George V. Mazariegos 4*
1
Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, NY, United States, 2 Division
of Infectious Diseases, Cincinnati Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, OH,
United States, 3 Division of Infectious Diseases, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, United States,
4
Hillman Center for Pediatric Transplantation, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, United States
Edited by:
Kyung-Yil Lee,
Catholic University of Korea,
South Korea
Reviewed by:
Roberta Angelico,
University of Rome Tor Vergata, Italy
William Werbel,
Johns Hopkins University,
United States
*Correspondence:
George V. Mazariegos
George.Mazariegos@chp.edu
Specialty section:
This article was submitted to
Pediatric Immunology,
a section of the journal
Frontiers in Pediatrics
Received: 30 September 2020
Accepted: 16 November 2020
Published: 10 December 2020
Citation:
Lobritto S, Danziger-Isakov L,
Michaels MG and Mazariegos GV
(2020) Impact of COVID-19 Pandemic
on Pediatrics and Pediatric
Transplantation Programs.
Front. Pediatr. 8:612627.
doi: 10.3389/fped.2020.612627
Frontiers in Pediatrics | www.frontiersin.org
COVID-19 has dramatically altered the health care landscape and disrupted global health
and world economics in ways that are still being measured. Its impact on children
with chronic conditions or those undergoing transplantation is evolving. The organ
specific manifestations in children will be reviewed and treatment strategies outlined.
The impact on pediatric transplantation in the United States over the initial 6 months of
the pandemic has shown significant regional variation and lags persist in resumption of
normal transplant activity, particularly for living related transplantation. Finally, guidelines
regarding return to school will be discussed.
Keywords: transplant volumes, treatment, telemedicine, comorbidities, return to school, resource utilization
INTRODUCTION
The novel coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2), continues to effect humans worldwide. Whether directly
infected or indirectly impacted by the economic implications, the psychosocial ramifications, the
disruption of normal everyday interactions, the way we educate our children or the trust we
have in our governmental representatives, our lives have all been impacted in some way. With
over 33 million infected worldwide and over 1 million reported deaths the healthcare system has
taken on the burden of reacting to this global health care crisis (https://www.worldometers.info/
coronavirus/). Although new cases continue to mount daily, children account for an estimated
2–7.6% of reported SARS-CoV-2 cases, with death being uncommon(<0.1%) (1, 2).
SARS-CoV-2 is a single, positive-stranded RNA virus that replicates using a virally encoded
RNA-dependent RNA polymerase. SARS-CoV-2 binds to, and is internalized into, target cells
through angiotensin-converting enzyme (ACE) 2, which acts as a functional receptor (3, 4). The
virus is transmitted on respiratory droplets via the mucosal surfaces of the eyes, nose or mouth
and activates antiviral immune responses that can lead to uncontrolled inflammatory reactions
characterized by marked pro-inflammatory cytokine release in patients severely affected leading to
lymphopenia, lymphocyte dysfunction, and granulocyte and monocyte abnormalities (5). This in
turn may lead to infections by microorganisms, septic shock, and severe multiple organ dysfunction
(6). Given the importance of the immune response to infection we will discuss the significant
impact on the transplant community.
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DISEASE MANIFESTATION IN CHILDREN
AND ORGAN SPECIFIC IMPACT WITH
SARS-COV-2/COVID-19
hemodialysis or home peritoneal dialysis are at significant risk for
experiencing infectious diseases such as COVID-19 because of
their compromised immune system and their frequent exposure
to the hospital setting. The factors potentially contributing
to the risk of SARS-CoV-2 infection in the pediatric chronic
kidney disease population include: (a) compromised immune
system (the result of long-term malnutrition, uremia, and/or
immunosuppressants); (b) close proximity to other patients
during treatment in a confined HD unit; (c) frequent contact with
healthcare workers, who may be asymptomatic but infected while
caring for a variety of other patients; (d) a need for the presence of
parents or other relatives during the treatment, which increases
the risk of cluster infection; and (e) non-adherence to, or a
break in implementation of recommended infection prevention
practices (18). Interestingly, early case reports of SARS-CoV2 infection outcomes in children with chronic kidney disease
conclude that affected patients have a similar clinical outcome as
in healthy children of the same age even if immunosuppressed;
however, special attention must be paid to fluid management and
drug dose adjustment (19).
Patients with advanced liver disease and those after liver
transplantation represent vulnerable populations with an
increased risk of infection and/or a potentially severe course
of COVID-19 (20). Given that the ACE2 receptor is present in
biliary and liver epithelial cells, the liver is a potential target
for SARS-CoV-2 infection. Fortunately, as noted above, severe
COVID-19 is uncommon in children (21, 22). Most children have
mild symptoms, though hepatic manifestations can be significant
(2, 23–27). Certainly, some children require hospitalization
for severe illness with over half having an underlying medical
condition, most commonly obesity (1, 15, 28–30). Likewise,
MIS-C can include significant hepatic injury and even acute
liver failure (9, 31–33). In these cases, liver disease may be
secondary to drug-induced liver injury, cytokine storm and/or
pneumonia-associated hypoxia.
One additional population at risk includes patients with
inborn metabolic diseases such as defects of amino acid, urea
cycle, organic acid, carbohydrate and energy metabolism, and
organelle disorders (lysosomal storage diseases and peroxisomal
diseases). Most of these patients require meticulous dietary and
therapy interventions as well as close monitoring of their clinical
status. Indeed, some patients are likely to be particularly fragile
and at risk of life-threatening acute metabolic decompensation
in case of SARS-CoV-2 infection. The conditions at greatest risk
include patients with defects of amino acid and organic acid
metabolism, urea cycle defects, and disorders of carbohydrate
and energy metabolism. Other patients, such as those with
substantial neuromuscular involvement, such as Pompe disease,
are likely susceptible to greater risks in case of respiratory
disease and need for ventilatory assistance. Fortunately, to date
single center reports show that through preventive measures and
adequate resource allocation major morbidity and mortality can
be avoided in this at-risk population (34). The common challenge
in the management of pediatric patients with chronic underlying
conditions is the shift in healthcare resource allocation necessary
to deal with the pandemic that may negatively impact the care of
patients that continue to require intensive medical attention.
While covered in more detail in other chapters, it is important
to transplantation to recognize that SARS-CoV-2 can impact
multiple organs. In general, pediatric patients have less
symptomatic disease compared to adults, but this is not always
the case. When symptomatic, COVID-19 primarily manifests
with respiratory symptoms and involvement of the pulmonary
tree. Early epidemiology of SARS-CoV-2 infection in children in
China showed that the vast majority were asymptomatic or had
only mild to moderate symptoms. When symptomatic, COVID19 was often indistinguishable from other acute respiratory
viruses with fever, fatigue, myalgia, pharyngitis with or without
fever (7, 8). Moderate symptoms included cough with or without
wheezing and evidence of pneumonia with less frequent episodes
of hypoxemia compared to adults. Severe disease occurred in
<10% of cases but when present, the dyspnea and hypoxemia
would generally develop around a week into the illness and
deterioration could follow quickly. Children with more severe
manifestation also were more likely to have gastrointestinal
involvement. Aside from the gastrointestinal manifestations,
extrapulmonary manifestations of COVID-19 have been noted
broadly including acute kidney injury, hepatitis, neurologic
manifestation and hematologic abnormalities.
Unique to children and young adults, a delayed illness
with inflammation involving multiple systems of the body is
recognized to occur and is called Multisystem Inflammatory
Syndrome in Children (MIS-C). It manifests with fever
and severe illness affecting at least two or more organ
systems. including cardiac, renal, respiratory, gastrointestinal,
neurological, dermatologic and/or hematologic (9–11). It was
noted initially to have some overlapping features of Kawasaki
Disease particularly including high fevers, rash, conjunctival
involvement and myocardial involvement including coronary
aneurysm. Ongoing research will help to clarify the immunologic
basis and treatment for this disorder but in severe cases it is
possible that some children may require transplantation if organ
dysfunction fails to recover.
THE IMPACT OF COMORBID DISEASE ON
SARS-COV-2
Metanalyses of the published literature in adults and pediatric
patients infected with SARS-CoV-2 have identified a number
of medical conditions correlating with disease severity and
being admitted to the intensive care setting (12–14). Some of
the factors identified include diabetes, hypertension, coronary
artery disease/cardiovascular disease, chronic pulmonary disease,
malignancy, chronic kidney disease, older age and male
gender although the heterogeneity between studies varied
substantially. The comorbidities leading to more severe disease
in children are less understood with obesity being reported
most commonly (15–17). In general, pediatric patients with
kidney failure (chronic kidney disease, stage 5) supported by
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SARS-COV-2 INFECTION IN CHILDREN
RECEIVING IMMUNOSUPPRESSIVE
TREATMENT
complement inhibitors) but the majority of studies focus on
adult patients and do not include pediatric solid organ transplant
(SOT) recipients.
As the pandemic continues the number of transplanted
patients, both children and adults and the number of patients
immunosuppressed for other autoimmune conditions or cancers
is steadily rising. Initial reports of outcomes in solid organ
transplant recipients suggested a more severe course, albeit
with limitations on testing of less severe cases (35, 36).
Immunosuppressive medications predispose to certain viral
pathogens including herpesviruses (CMV, EBV, HSV, and VZV)
BK virus, adenovirus, norovirus, influenza, and respiratory
syncytial virus (37, 38). This does not seem to be the case
for infections caused by the coronavirus family to date (22).
In fact, morbidity seems more related to exaggerated host
immune responses than to direct viral cytopathic injury (5).
Children seem to be less at risk of serious consequence than
adults but still pose an infectious risk to others. Although
there are no well-controlled randomized studies to support
general recommendations, experiences with other viral infections
(hepatitis C, cytomegalovirus) suggest that minimizing or
eliminating drugs that are associated with leukopenia may
be prudent (39). An analysis of various databases containing
immunosuppressed transplant recipients suggest that chronic
immunosuppression could exert a protective effect against the
most severe forms of COVID-19 and complete withdrawal
of immunosuppression may not be useful (40). A final point
regarding immunosuppression is the importance of recognizing
possible drug interactions, especially in the case of tacrolimus,
with some of the treatments with antiviral effect given in the
context of COVID-19 (lopinavir/ritonavir, azithromycin) (41).
IMPACT ON TRANSPLANT ACTIVITY
The global pandemic has wide-ranging implications to
transplantation programs beginning with the impact on
donor and recipients, health resource utilization and strategies
to mitigate risk during the pandemic. There is a ripple effect
on post-transplant life including return to school, routine
post-transplant follow-up, and vaccine development and
its implications.
Global recommendations continue to evolve but early on
demonstrated a staged approach to transplant activity based
on recipient illness and urgency as well as system resource
utilization requirements (46). Guidelines emerged quickly
regarding optimal donor screening based on nasopharyngeal
specimen NAT testing and were utilized in the United States
(U.S.) sporadically initially but almost universally by late
March 2020.
Initial impact on transplantation center practices and policies
have for the most part been focused on adult transplantation.
Boyarsky and colleagues surveyed U.S. centers between March
24- March 31, 2020 and demonstrated early impact of complete
suspension of living donor kidney transplantation in 71.8%
of centers and live donor liver transplantation in 67.7% of
respondents with restrictions being linked to regional incidences
of COVID-19 (47). Experience with resumption of activity have
been documented in several series including United Kingdom
(UK), U.S. and other centers (48). Recently, the US experience
with liver transplantation compared waitlist outcomes and
transplant activity between 3/15/2020 and 8/31/2020 to historical
trends. While new listings during the initial 6 weeks of the
pandemic were decreased by 11%, by August, waitlist outcomes
were occurring at expected rates and deceased donor transplants
were 13% more across all incidences (49).
United Network for Organ Sharing (UNOS) has continuously
updated transplant and waitlist data during the COVID-19
pandemic. Year-to-date transplants as of 9/10/2020 demonstrate
a total organ transplant count across all ages of 26,724 as
compared to 27,592 over the same time period in 2019, a decrease
of 3.4% (Figure 1A). This relatively small decrease demonstrates
a significant resiliency of the transplant enterprise in the U.S.
but also significant variation by geography and by transplant
type. For example, transplant activity in the Northeast and MidAtlantic regions has not caught up to 2019 levels whereas as of the
writing of this manuscript, transplant activity in the southeastern
U.S. is unchanged between 2019 and 2020.
Of concern, the impact on pediatric transplantation activity
has demonstrated some significant differences that demonstrate
both opportunities as well as challenges. Overall, pediatric
transplantation is down approximately 10% in 2020. Compared
to 1,375 pediatric transplants performed by early September
2019, as of 9/10/2020 there were only 1,202 pediatric transplants
(Figure 1B). The major decrease is seen with living donor
TREATMENT OF COVID IN CHILDREN
Limited data exist regarding effective treatment strategies for
SARS-CoV-2 in pediatric patients. Collaboratives of pediatric
providers, the National Institutes of Health (NIH) and the
Infectious Diseases Society of America (ISDA) have issued
treatment recommendations predominantly extrapolated from
adult studies (42–44). There are currently no FDA approved
therapeutic agents for the treatment of COVID-19 in pediatric
patients, although both remdesivir and SARS-CoV-2 rich
convalescent plasma are available through an emergency use
authorization. A recent report from a collaborative of pediatric
providers suggests administration of 5 days of remdesivir,
preferably as part of enrollment in a prospective clinical trial,
for pediatric patients requiring supplemental oxygen (43). The
NIH suggests consideration of remdesivir for pediatric patients
with severe disease and both the IDSA and NIH endorse
dexamethasone and remdesivir in adult patients with hypoxemia
(44, 45). Neither the NIH nor the IDSA suggest use of
convalescent plasma outside of the context of a clinical trial
(44, 45). Several additional therapies are under investigation
including antivirals (favipiravir) and immunomodulatory agents
(tocilizumab, IL-1 inhibitors, Janus kinase inhibitors and
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FIGURE 1 | (A) Impact on Total Transplant Activity in U.S. To Date. (B) Impact on Pediatric Transplant Activity in U.S. To Date. Adapted from: https://unos.org/covid.
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dramatically fell on the week of March 15 before beginning to
rebound in late April. Deceased donor transplants in children fell
earlier, on the week of March 8 and began to rebound earlier. As
shown in Figure 2, pediatric transplant activity by week is now
approaching pre-pandemic levels (50).
New wait list additions fell from a high of 1,435 additions
on the week of March 1–March 7, 2020 to a low in 2020 of
only 789 additions the week of May 3–May 9, 2020 before
rebounding back to 1,294 additions on the week of August
30–September 5, 2020 (Figure 3). March 22–March 28, 2020
showed the greatest number of “inactivations” due to COVID19 “precautions” during which time 72% of inactivations where
coded for this reason. Since May 24, 2020, inactivations due
to COVID-19 precautions have averaged approximately 2–
3% (50). A recent analysis in pediatric kidney transplantation
similarly emphasized a significant decrease in DDKT and
transplantation compared to deceased donor transplantation
which may reflect a step wise reduction in activity, beginning with
“elective” living donor transplants during the early phases of the
pandemic. Nonetheless, the curves demonstrated a persistent lag
in catchup activity through September 2020. However, in some
regions such as the mid-Atlantic, living donation has mitigated
the decrease of available deceased donors in the same region. The
regional differences are also impacted by the nearly simultaneous
advent of acuity circle distribution in the US which was instituted
on February 4, 2020.
The U.S. impact on transplantation in children began
to noticeably diverge from 2019 levels in mid-March, 2020,
corresponding with the March 11 declaration of the global
COVID-19 pandemic by the World Health Organization
(WHO) and the early regional outbreaks in the northeastern
and northwestern U.S. For example, living donor transplants
FIGURE 2 | Pediatric Transplants by Week (January–September 2020). Adapted from: https://unos.org/covid.
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FIGURE 3 | Waitlist Additions & Inactivations by Week. Adapted from: https://unos.org/covid.
dissemination and devices necessary to provide connected
care services (52). Several of the awardees including UPMC
Children’s Hospital of Pittsburgh, Children’s Hospital Colorado,
Mt. Sinai Hospital NY and Cincinnati Children’s Hospital
could continue to provide transplant follow-up to significant
pediatric populations.
In one adult-based survey of U.S. based adult transplant
programs by UNOS regions, a notable change between preand post -COVID telehealth utilization was documented. In
2019, of a total of 73 responding centers, 16% used telemedicine
as compared to in-person visits in outreach clinics. In 2020,
54 of the 55 (98%) originally surveyed programs across all 11
UNOS regions now used telemedicine. Telemedicine is now
being used by programs for transplant evaluations (65%), wait list
management (58%), and post-transplant care (98%). In addition,
LDKT of 47% and 82% compared to expected events.
However, by May 2020, the transplant activity was approaching
prepandemic levels (51).
TELEMEDICINE-NOW AND MOVING
FORWARD
One of the potentially enduring changes that the COVID
pandemic has actuated has been the institution of telehealth.
The COVID−19 Telehealth program provided $200 million in
funds as part of the Coronovirus Aid, Relief, and Economic
Security (CARES) Act. The program provided immediate
support to health care providers responding to the pandemic by
providing fully funded telecommunication services, information
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82% of centers used a combination of live video and phone
strategies (53) (Figure 4).
caution is still recommended. For example, an evaluation of the
UK Transplant Registry linked with the National Health Service
Digital Tracing Services identified only three cases of SARS-CoV2 among 1,703 pediatric SOT recipients (0.5%) and no deaths
occurred during a 4-month period during the height of the
first wave of the pandemic in the UK (60). Delineation of risk
for individual SOT recipients is proposed based on host factors
such as time from transplant, maintenance immunosuppressive
regimen, recent augmentation of immunosuppression and
developmental capability of participating in infection prevention
strategies to reduce risk, such as social distancing and mask
wearing. Community prevalence is a non-specific marker
of general risk that could be considered especially during
periods of high transmission rates within a community.
School-based infection prevention interventions support limiting
transmission, evidenced by the impact of mask-wearing, physical
distancing, hand hygiene, frequent disinfection and exclusion
of ill students and staff as suggested by the Centers for
Disease Control and Prevention and the American Academy
of Pediatrics (61–63). Certainly the balance between risk for
SARS-COV-2 AND SCHOOL IN SOT
RECIPIENTS
Recommendations around in-person school attendance for SOT
recipients in the era of SARS-CoV-2 remain challenging with
little definitive data for guidance. Best practice development
has focused on the epidemiology and impact of SARS-CoV2 in SOT patients, community penetrance of COVID-19
disease and school-specific infection prevention intervention
implementation in a consensus document recently published
(54). Although pediatric SOT recipients are at increased risk for
severe manifestations of common infections (55), case reports
and case series of SARS-CoV-2 infection in pediatric SOT
emerging thus far suggest pediatric SOT recipients are at similar
risk and present with a similar spectrum of infection as other
children (19, 56–59); however data are significantly limited and
FIGURE 4 | Telemedicine in Liver and Intestine Transplant: 2019 vs. 2020. Reprinted with permission: Liver Transplantation, First publisher: 09 August 2020,
doi: 10.1002/lt.25868.
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conducting virtual multidisciplinary rounds with dietary,
pharmacy, social work, and care coordination staff. Waiting
rooms for clinic visits, procedures, laboratory sampling and
radiologic procedures have been eliminated or adapted to
accommodate adequate patient spacing. Although initially
suspending non-urgent procedures and in some cases living
donor transplantations as above, centers should be able to
offer full services with adequate safety measures in place. One
of the greatest challenges lies with re-establishing patient and
family confidence in the implementation and effectiveness of
imposed safety measures. Nosocomial SARS-CoV-2 infection
that was once common is quite rare and practically non-existent.
Through the use of educational webinars, codified hospital
clinical policies and visibly apparent safety measures, we
can once again welcome patients back to the hospital when
deemed essential.
transmission, ability to limit exposure and the social and
emotional development of pediatric SOT recipients should be
weighed and decision-making will likely require flexibility and
fluidity depending on the individual, community and schoolbased factors as the pandemic continues (54).
SARS-COV-2 AND SAFETY MEASURES
NECESSARY FOR PROGRAM/CLINIC
REOPENING
In order to ensure patient and staff safety with the goal of
achieving pre-COVID clinical and transplant activity, centers
have adopted some general practices with the help of societal
guidance (41). These practices include healthcare staff and
patient training, body temperature monitoring, appropriate
use/availability of personal protective equipment, universal
masking and face shielding, frequent disinfection, spaced
scheduling, hand hygiene, remote medical care, limiting
accompanying persons, altering patient clinic flow through
and pre-procedural SARS-CoV-2 nasal or nasopharyngeal
PCR testing. Other prudent measures include conducting
medical and surgical transplant rounds with the minimum
number of personnel needed to provide care at a given
time, rotating in-person office/clinical staff, limiting the
number of team members who enter a patient’s room for
patient examinations, encounters and consultations and
DATA AVAILABILITY STATEMENT
The original contributions generated for this study are included
in the article/supplementary material, further inquiries can be
directed to the corresponding author/s.
AUTHOR CONTRIBUTIONS
All authors contributed equally to the content, design, and review
of the manuscript.
REFERENCES
10.
1. Kim L, Whitaker M, O’Halloran A, Kambhampati A, Chai SJ, Reingold A,
et al. Hospitalization rates and characteristics of children aged <18 years
hospitalized with laboratory-confirmed COVID-19 - COVID-NET, 14 States,
March 1-July 25, (2020). MMWR Morb Mortal Wkly Rep. (2020) 69:1081–
8. doi: 10.15585/mmwr.mm6932e3
2. Wu Z, McGoogan JM. Characteristics of and important lessons from the
coronavirus disease 2019 (COVID-19) outbreak in China: summary of a
report of 72314 cases from the Chinese Center for disease control and
prevention. JAMA. (2020) 323:1239–42. doi: 10.1001/jama.2020.2648
3. Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S, et al. Structure of the SARS-CoV-2
spike receptor-binding domain bound to the ACE2 receptor. Nature. (2020)
581:215–20. doi: 10.1038/s41586-020-2180-5
4. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al. Angiotensinconverting enzyme 2 is a functional receptor for the SARS coronavirus.
Nature. (2003) 426:450–4. doi: 10.1038/nature02145
5. Ovsyannikova IG, Haralambieva IH, Crooke SN, Poland GA, Kennedy
RB. The role of host genetics in the immune response to SARS-CoV-2
and COVID-19 susceptibility and severity. Immunol Rev. (2020) 296:205–
19. doi: 10.1111/imr.12897
6. Yang L, Liu S, Liu J, Zhang Z, Wan X, Huang B, et al. COVID-19:
immunopathogenesis and Immunotherapeutics. Signal Transduct Target
Ther. (2020) 5:128. doi: 10.1038/s41392-020-00243-2
7. Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, et al. Epidemiology
of COVID-19 among children in China. Pediatrics. (2020)
145:e20200702. doi: 10.1542/peds.2020-0702
8. Liguoro I, Pilotto C, Bonanni M, Ferrari ME, Pusiol A, Nocerino A,
et al. SARS-COV-2 infection in children and newborns: a systematic
review. Eur J Pediatr. (2020) 179:1029–46. doi: 10.1007/s00431020-03684-7
9. Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M,
et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre
Frontiers in Pediatrics | www.frontiersin.org
11.
12.
13.
14.
15.
16.
17.
8
of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. (2020)
395:1771–8. doi: 10.1016/S0140-6736(20)31103-X
Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P.
Hyperinflammatory shock in children during COVID-19 pandemic. Lancet.
(2020) 395:1607–8. doi: 10.1016/S0140-6736(20)31094-1
Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MBF, et al.
Multisystem inflammatory syndrome in children US, and adolescents. N Engl
J Med. (2020) 383:334–46. doi: 10.1056/NEJMoa2021680
Jutzeler CR, Bourguignon L, Weis CV, Tong B, Wong C, Rieck B, et al.
Comorbidities, clinical signs and symptoms, laboratory findings, imaging
features, treatment strategies, and outcomes in adult and pediatric patients
with COVID-19: a systematic review and meta-analysis. Travel Med Infect Dis.
(2020) 37:101825. doi: 10.1016/j.tmaid.2020.101825
Liu H, Chen S, Liu M, Nie H, Lu H. Comorbid chronic diseases
are strongly correlated with disease severity among COVID-19
patients: a systematic review and meta-analysis. Aging Dis. (2020)
11:668–78. doi: 10.14336/AD.2020.0502
Emami A, Javanmardi F, Pirbonyeh N, Akbari A. Prevalence of
underlying diseases in hospitalized patients with COVID-19: a
systematic review and meta-analysis. Arch Acad Emerg Med. (2020)
8:e35. doi: 10.1371/journal.pone.0241265
Zachariah P, Johnson CL, Halabi KC, Ahn D, Sen AI, Fischer
A, et al. Epidemiology, clinical features, and disease severity in
patients with coronavirus disease 2019 (COVID-19) in a children’s
hospital in New York City, New York. JAMA Pediatr. (2020)
174:e202430. doi: 10.1001/jamapediatrics.2020.2430
Gao F, Zheng KI, Wang XB, Sun QF, Pan KH, Wang TY, et al. Obesity is
a risk factor for greater COVID-19 severity. Diabetes Care. (2020) 43:e72–
4. doi: 10.2337/dc20-0682
Korakas E, Ikonomidis I, Kousathana F, Balampanis K, Kountouri A, Raptis
A, et al. Obesity and COVID-19: immune and metabolic derangement as a
possible link to adverse clinical outcomes. Am J Physiol Endocrinol Metab.
(2020) 319:E105–9. doi: 10.1152/ajpendo.00198.2020
December 2020 | Volume 8 | Article 612627
Lobritto et al.
COVID-19 Impact on Pediatrics and Transplantation
18. Shen Q, Wang M, Che R, Li Q, Zhou J, Wang F, et al. Consensus
recommendations for the care of children receiving chronic dialysis in
association with the COVID-19 epidemic. Pediatr Nephrol. (2020) 35:1351–
7. doi: 10.1007/s00467-020-04555-x
19. Melgosa M, Madrid A, Alvarez O, Lumbreras J, Nieto F, Parada E, et al. SARSCoV-2 infection in Spanish children with chronic kidney pathologies. Pediatr
Nephrol. (2020) 35:1521–4. doi: 10.1007/s00467-020-04597-1
20. Boettler T, Newsome PN, Mondelli MU, Maticic M, Cordero E,
Cornberg M, et al. Care of patients with liver disease during the
COVID-19 pandemic: EASL-ESCMID position paper. JHEP Rep. (2020)
2:100113. doi: 10.1016/j.jhepr.2020.100113
21. Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 infection in
children. N Engl J Med. (2020) 382:1663–5. doi: 10.1056/NEJMc2005073
22. D’Antiga L. Coronaviruses and immunosuppressed patients: the facts during
the third epidemic. Liver Transpl. (2020) 26:832–4. doi: 10.1002/lt.25756
23. Patel KP, Patel PA, Vunnam RR, Hewlett AT, Jain R, Jing R, et al.
Gastrointestinal, hepatobiliary, and pancreatic manifestations of COVID-19.
J Clin Virol. (2020) 128:104386. doi: 10.1016/j.jcv.2020.104386
24. Redd WD, Zhou JC, Hathorn KE, McCarty TR, Bazarbashi AN, Thompson
CC, et al. Prevalence and characteristics of gastrointestinal symptoms in
patients with severe acute respiratory syndrome Coronavirus 2 infection
in the United States: a multicenter cohort study. Gastroenterology. (2020)
159:765–7. doi: 10.1053/j.gastro.2020.04.045
25. Xu L, Liu J, Lu M, Yang D, Zheng X. Liver injury during highly
pathogenic human coronavirus infections. Liver Int. (2020) 40:998–
1004. doi: 10.1111/liv.14435
26. Zhang C, Shi L, Wang FS. Liver injury in COVID-19: management
and challenges. Lancet Gastroenterol Hepatol. (2020) 5:428–
30. doi: 10.1016/S2468-1253(20)30057-1
27. Henry BM, Benoit SW, de Oliveira MHS, Hsieh WC, Benoit J, Ballout RA,
et al. Laboratory abnormalities in children with mild and severe coronavirus
disease 2019 (COVID-19): a pooled analysis and review. Clin Biochem. (2020)
81:1–8. doi: 10.1016/j.clinbiochem.2020.05.012
28. Centers For Disease Control and Prevention. Demographic Trends of
COVID-19 cases and deaths in the US reported to CDC. (2020). Available
onlne at: https://www.cdc.gov/covid-data-tracker/index.html#demographics
(accessed September 29, 2020).
29. Shekerdemian LS, Mahmood NR, Wolfe KK, Riggs BJ, Ross CE,
McKiernan CA, et al. Characteristics and outcomes of children with
coronavirus disease 2019 (COVID-19) infection admitted to US
and Canadian pediatric intensive care units. JAMA Pediatr. (2020)
174:868–73. doi: 10.1001/jamapediatrics.2020.1948
30. Gotzinger F, Santiago-Garcia B, Noguera-Julian A, Lanaspa M, Lancella L,
Calo Carducci FI, et al. COVID-19 in children and adolescents in Europe: a
multinational, multicentre cohort study. Lancet Child Adolesc Health. (2020)
4:653–61. doi: 10.1016/S2352-4642(20)30177-2
31. Godfred-Cato S, Bryant B, Leung J, Oster ME, Conklin L, Abrams J, et al.
COVID-19-associated multisystem inflammatory syndrome in children United States, March-July 2020. MMWR Morb Mortal Wkly Rep. (2020)
69:1074–80. doi: 10.15585/mmwr.mm6932e2
32. Cantor A, Miller J, Zachariah P, DaSilva B, Margolis K, Martinez M. Acute
hepatitis is a prominent presentation of the multisystem inflammatory
syndrome in children: a single-center report. Hepatology. (2020) 72:1522–
27. doi: 10.1002/hep.31526
33. Centers For Disease Control and Prevention. Information for Healthcare
Providers about Multisystem Inflammatory Syndrome in Children (IMISC). (2020). Available online at: https://www.cdc.gov/mis-c/hcp/ (accessed
September 29, 2020).
34. Brunetti-Pierri N, Fecarotta S, Staiano A, Strisciuglio P, Parenti G. Ensuring
continuity of care for children with inherited metabolic diseases at the time
of COVID-19: the experience of a metabolic unit in Italy. Genet Med. (2020)
22:1178–80. doi: 10.1038/s41436-020-0831-4
35. Pereira MR, Mohan S, Cohen DJ, Husain SA, Dube GK, Ratner LE,
et al. COVID-19 in solid organ transplant recipients: initial report from
the US epicenter. Am J Transplant. (2020) 20:1800–8. doi: 10.1111/
ajt.15941
36. Lee BT, Perumalswami PV, Im GY, Florman S, Schiano TD,
Group CS. COVID-19 in liver transplant recipients: an initial
Frontiers in Pediatrics | www.frontiersin.org
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
9
experience from the US epicenter. Gastroenterology. (2020) 159:1176–8
e2. doi: 10.1053/j.gastro.2020.05.050
Kaltsas A, Sepkowitz K. Community acquired respiratory and gastrointestinal
viral infections: challenges in the immunocompromised host. Curr Opin Infect
Dis. (2012) 25:423–30. doi: 10.1097/QCO.0b013e328355660b
Memoli MJ, Athota R, Reed S, Czajkowski L, Bristol T, Proudfoot
K, et al. The natural history of influenza infection in the severely
immunocompromised vs nonimmunocompromised hosts. Clin Infect Dis.
(2014) 58:214–24. doi: 10.1093/cid/cit725
Forns
X,
Navasa
M.
Liver
transplant
immunosuppression
during the covid-19 pandemic. Gastroenterol Hepatol. (2020)
43:457–63. doi: 10.1016/j.gastre.2020.10.001
Rodriguez-Peralvarez M, Salcedo M, Colmenero J, Pons JA. Modulating
immunosuppression in liver transplant patients with COVID-19. Gut.
(2020). doi: 10.1136/gutjnl-2020-322620. [Epub ahead of print].
Fix OK, Hameed B, Fontana RJ, Kwok RM, McGuire BM, Mulligan DC, et al.
Clinical best practice advice for hepatology and liver transplant providers
during the COVID-19 pandemic: AASLD expert panel consensus statement.
Hepatology. (2020) 72:287–304. doi: 10.1002/hep.31281
Bhimraj A, Morgan RL, Shumaker AH, Lavergne V, Baden L, Cheng
VC, et al. Infectious diseases Society of America guidelines on the
treatment and management of patients with COVID-19. Clin Infect Dis.
(2020). doi: 10.1093/cid/ciaa478. [Epub ahead of print].
Chiotos K, Hayes M, Kimberlin DW, Jones SB, James SH, Pinninti SG, et al.
Multicenter interim guidance on use of antivirals for children with COVID19/SARS-CoV-2. J Pediatric Infect Dis Soc. (2020). doi: 10.1093/jpids/piaa115.
[Epub ahead of print].
National Institutes of Health. COVID-19 Treatment Guidelines. (2020).
Available online at: https://www.covid19treatmentguidelines.nih.gov/specialpopulations/children/ (accessed September 29, 2020).
Infectious Disease Society of America. Guidelines on the Treatment and
Management of Patients wtih COVID-19. (2020). Available online at: https://
www.idsociety.org/practice-guideline/covid-19-guideline-treatment-andmanagement/#toc-7 (accessed September 29, 2020).
Kumar D, Manuel O, Natori Y, Egawa H, Grossi P, Han SH, et al. COVID-19:
a global transplant perspective on successfully navigating a pandemic. Am J
Transplant. (2020) 20:1773–9. doi: 10.1111/ajt.15876
Boyarsky BJ, Po-Yu Chiang T, Werbel WA, Durand CM, Avery RK, Getsin SN,
et al. Early impact of COVID-19 on transplant center practices and policies in
the United States. Am J Transplant. (2020) 20:1809–18. doi: 10.1111/ajt.15915
Lembach H, Hann A, McKay SC, Hartog H, Vasanth S, El-Dalil P, et al.
Resuming liver transplantation amid the COVID-19 pandemic. Lancet
Gastroenterol Hepatol. (2020) 5:725–6. doi: 10.1016/S2468-1253(20)30187-4
Strauss AT, Boyarsky BJ, Garonzik-Wang JM, Werbel W, Durand CM,
Avery RK, et al. Liver transplantation in the United States during the
COVID-19 pandemic: National and center-level responses. Am J Transplant.
(2020). doi: 10.1111/ajt.16373. [Epub ahead of print].
UNOS. 700 North 4th Street, Richmond, VA 23219. Available online at: www.
unos.org (accessed September 29, 2020).
Charnaya O, Chiang TP, Wang R, Motter JD, Boyarsky BJ, King EA,
et al. Effects of COVID-19 pandemic on pediatric kidney transplant in the
United States. Pediatr Nephrol. (2020):1–9. doi: 10.1007/s00467-020-04764-4.
[Epub ahead of print].
Federal Communications Commission. FCC Approves First Set Of Covid-19
Telehealth Program Applications. Available online at: https://www.fcc.gov/
document/fcc-approves-first-set-covid-19-telehealth-program-applications
(accessed September 12, 2020).
Sherman CB, Said A, Kriss M, Potluri V, Levitsky J, Reese PP,
et al. In-person outreach and telemedicine in liver and intestinal
transplant: a survey of national practices, impact of COVID-19 and
areas of opportunity. Liver Transpl. (2020) 26:1354–8. doi: 10.1002/
lt.25868
Downes KJ, Danziger-Isakov LA, Cousino MK, Green M, Michaels
MG, Muller WJ, et al. Return to school for pediatric solid organ
transplant recipients in the United States during the COVID-19
pandemic: expert opinion on key considerations and best practices.
J Pediatric Infect Dis Soc. (2020) 9:551–63. doi: 10.1093/jpids/
piaa095
December 2020 | Volume 8 | Article 612627
Lobritto et al.
COVID-19 Impact on Pediatrics and Transplantation
Missouri, May (2020). MMWR Morb Mortal Wkly Rep. (2020)
69:930–2. doi: 10.15585/mmwr.mm6928e2
62. Centers For Disease Control and Prevention. Operating Schools during
COVID-19: CDC’s Considerations. (2020). Available online at: https://www.
cdc.gov/coronavirus/2019-ncov/community/schools-childcare/schools.html
(accessed September 29, 2020).
63. American Academy of Pediatrics. COVID-19 Planning Considerations:
Guidance for School Re-entry (2020). Available online at: https://
services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/
clinical-guidance/covid-19-planning-considerations-return-to-in-personeducation-in-schools/ (accessed September 12, 2020).
55. Feldman AG, Beaty BL, Curtis D, Juarez-Colunga E, Kempe A. Incidence
of hospitalization for vaccine-preventable infections in children following
solid organ transplant and associated morbidity, mortality, and costs. JAMA
Pediatr. (2019) 173:260–8. doi: 10.1001/jamapediatrics.2018.4954
56. Russell MR, Halnon NJ, Alejos JC, Salem MM, Reardon LC. COVID-19 in a
pediatric heart transplant recipient: emergence of donor-specific antibodies. J
Heart Lung Transplant. (2020) 39:732–3. doi: 10.1016/j.healun.2020.04.021
57. Heinz N, Griesemer A, Kinney J, Vittorio J, Lagana SM, Goldner D, et al. A
case of an infant with SARS-CoV-2 hepatitis early after liver transplantation.
Pediatr Transplant. (2020) 24:e13778. doi: 10.1111/petr.13778
58. Morand A, Roquelaure B, Colson P, Amrane S, Bosdure E, Raoult D, et al.
Child with liver transplant recovers from COVID-19 infection. A case report.
Arch Pediatr. (2020) 27:275–6. doi: 10.1016/j.arcped.2020.05.004
59. Bush R, Johns F, Acharya R, Upadhyay K. Mild COVID-19 in a
pediatric renal transplant recipient. Am J Transplant. (2020) 20:2942–
45. doi: 10.1111/ajt.16003
60. Ravanan R, Callaghan CJ, Mumford L, Ushiro-Lumb I, Thorburn D, Casey J,
et al. SARS-CoV-2 infection and early mortality of wait-listed and solid organ
transplant recipients in England: a national cohort study. Am J Transplant.
(2020) 20:3008–18.. doi: 10.1111/ajt.16247
61. Hendrix MJ, Walde C, Findley K, Trotman R. Absence of apparent
transmission of SARS-CoV-2 from two stylists after exposure at
a hair salon with a universal face covering policy - Springfield,
Frontiers in Pediatrics | www.frontiersin.org
Conflict of Interest: The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could be construed as a
potential conflict of interest.
Copyright © 2020 Lobritto, Danziger-Isakov, Michaels and Mazariegos. This is an
open-access article distributed under the terms of the Creative Commons Attribution
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December 2020 | Volume 8 | Article 612627