REVIEW

published: 22 May 2020

doi: 10.3389/fped.2020.00294

SARS-CoV-2 Infection and the

Newborn
Fahri Ovalı*
Division of Neonatology, Department of Pediatrics, Istanbul Medeniyet University, Istanbul, Turkey

Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) affects people

at all ages and it may be encountered in pregnant women and newborns also. The
information about its clinical features, laboratory findings and prognosis in children
and newborns is scarce. All the reported cases in pregnant women were in the 2nd
or 3rd trimester and only 1% of them developed severe disease. Miscarriages are
rare. Materno-fetal transmission of the disease is controversial. Definitive diagnosis
can be made by a history of contact with a proven case, fever, pneumonia and
gastrointestinal disorder and a Polymerase chain reaction (PCR) test of nasopharyngeal
swabs. Lymphopenia as well as liver and renal dysfunctions may be seen. Suspected
or proven cases of newborns with symptoms should be quarantined in the neonatal
intensive care unit for at least 14 days with standart and droplet isolation precautions.
Asymptomatic infants may be quaratined at home. Transport of the neonates should be
performed in a dedicated transport incubator and ambulance with isolation precautions.
Edited by: There is no specific treatment for the disease, but hemodynamic stabilization of the
Manuela Zlamy,
infant, respiratory management and other daily care are essential. Drugs against cytokine
Innsbruck Medical University, Austria
storm syndrome such as corticosteroids or tocilizumab are under investigation. Routine
Reviewed by:
Piero Valentini, antibiotics are not recommended. No deaths have been reported so far in the neonatal
Università Cattolica del Sacro population. Families and healthcare staff should receive pyschological support. Since the
Cuore, Italy
Giovanni Battista Pajno,
infection is quite new and knowledge is constantly accumulating, following developments
University of Messina, Italy and continuous updates are crucial.
*Correspondence:
Keywords: newborn, COVID 19 infection, breast milk, pregnancy, SARS- CoV-2
Fahri Ovalı
[email protected]

Coronaviruses are single stranded RNA viruses with a diameter of 60–140 nm and a high rate
Specialty section: of genetic mutations and recombinations, rendering them capable of escaping from the immune
This article was submitted to
system and causing novel infections (1). They use the angiotensin-converting enzyme-2 (ACE2)
Pediatric Infectious Diseases,
a section of the journal
receptors on the cell surface to enter the cell. These receptors are abundant on the surfaces of type
Frontiers in Pediatrics II pneumocytes on the lung alveoli, esophageal endothelial cells and gut cells (2). They are highly
susceptible to inactivation with heat (56◦ C for 30 min), 75% ethanol, chlorinated disenfectants
Received: 13 April 2020
Accepted: 11 May 2020
or peracetic acid (1). Animals are reservoir for various types of Coronaviruses and humans may
Published: 22 May 2020 become infected through contact with bats, camels and cattle (3, 4). The new SARS-CoV-2 which
Citation:
appeared in Wuhan, China in December 2019 is a beta-Coronavirus which belongs to the same
Ovalı F (2020) SARS-CoV-2 Infection family with the previous Severe Acute Respiratory Syndrome (SARS) virus and Middle East
and the Newborn. Respiratory Syndrome (MERS) virus (5). The origin of this virus is thought to be the sea-food
Front. Pediatr. 8:294. market in Wuhan but now it spreads easily from human-to-human by aerosols or by close contact.
doi: 10.3389/fped.2020.00294 The disease which occurs with SARS-Co-2 is called COVID-19.

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Ovalı COVID-19 in Newborns

Infections with SARS-CoV-2 affects all age groups, and since findings. Lymphopenia was detected only in 3.5% of them (11).
most children may go unnoticed, they have the potential to Of the 171 infected children, only 3 children with co-morbidities
spread the virus to other people. It is calculated that a single required mechanical ventilation. There were a couple of children
patient with COVID-19 may infect 2.8 (1.5–6.6) other people with pulmonary findings but were asymptomatic at all (5). Most
(R0), but this rate depends on the attitute of people and on the of the children recover within 1–2 weeks after onset (25).
levels of precautions taken against its spread (6). The incubation Most infected children have mild clinical manifestations but
period is similar to that of SARS or MERS; i.e., usually between they may be contagious. The reason why SARS-CoV-2 infections
5 and 6 days but may reach up to 14 days in a small number of in children are mild remains elusive. The immune response
cases (7). As of May 8, 2020 there are over 3 950 000 confirmed of newborns to SARS-CoV-2 infections may be qualitatively
cases globally, with close to 272 000 fatalities so far (8). different with respect to adults. On the other hand, simultaneous
presence of other viruses in the lungs and upper airways of
children, which is quite common, may limit the growth of SARS-
SARS-CO-2 INFECTION IN CHILDREN CoV-2 by competition or viral interaction (17). Other reasons
include lack of smoking, less exposure to air pollution and fewer
Although the virus infects the entire population, infected underlying chronic conditions in children (12, 26).
children were 2% of cases in China, 1.2% of cases in Italy, 0.8% Since they are asymptomatic or mildly symptomatic, the
of cases in Spain, 1.7 % of cases in the USA and 1% of cases in majority of children do not undergo diagnostic investigations.
Turkey (9–12). Children under 10 years comprised only 1% of all Children who become infected with SARS-CoV-1 may have more
cases. In Korea, 6.3% of all cases that tested positive for SARS- upper respiratory tract than lower respiratory tract involvement
CoV-2−19 were children under 19 years (13). In a report which (27). However, extended shedding in nasal secretions and stool
studied 171 children, 31 (18.1%) were under 1 year, 60.8% were may have remarkable implications for community spread in
males and 64.9% had pneumonia whereas 41,5% had fever (14). kindergartens, schools and at home (27). Therefore, the role
As of April 2, 2020, there were 2572 pediatric cases in the USA. of children in community-based viral transmission should be
Fifteen percent of these cases (398 cases) occured in children < 1 carefully investigated to understand how much it can actually
year. There were 3 deaths among the pediatric cases (11). affect public health (28).
The data on the contamination route, susceptibility, clinical
findings, pathogenesis, pharmacological treatment and prognosis
of the COVID-19 disease in children are limited. The child may SARS-COV-2 INFECTION IN PREGNANT
acquire the virus through direct contact, as well as through WOMEN
droplets, aerosols or even fecal-oral route (15). Angiotensin-
converting enzyme 2 (ACE2) is the main host cell receptor of Viral pneumonia in pregnant women is generally associated with
SARS-CoV-2 and plays a crucial role in the entry of the virus premature rupture of membranes, preterm labor, intrauterine
into the cell (16). The expression of ACE2 in the epithelial fetal demise, intrauterine growth restriction and neonatal death
cells of the lung, intestine, kidney and blood vessels, may (29). Since SARS-CoV-2 is a new virus, there is scarce data
explain the high incidence of pneumonia and bronchitis with on the effects of infection in pregnant women; whether there
SARS-CoV-2 (17). SARS-CoV-2 spike protein binding to ACE2 is any difference with other adult infections, risk of vertical
downmodulates ACE2 expression and loss of ACE2 expression transmission to the fetus and the effects on the fetus, if any.
results in severe lung damage (18). Estrogens participate in The majority of pregnant women with COVID-19 disease
the upregulation of ACE2 expression and this may explain will have mild or moderate flu-like symptoms. Some women
the putative sex predisposition of the virus (19). ACE2 is also may have fever, cough and shortness of breath. Pneumonia and
protective in acute lung failure (20). Children have generally marked hypoxia are commonly described in older women, who
higher levels of ACE2 than adults and children with confirmed are immunosuppressed or have chronic diseases such as diabetes,
SARS-CoV infection have generally mild symptoms (21). ACE cancer and chronic lung disease. However, there can be a group
can pass through the placenta, enabling the mother to transfer to of asymptomatic women or those with minor symptoms carrying
baby her immunity and other kinds of protective soluble factors the virus; the incidence of such women is unknown (30).
(22). Soluble ACE2 may help children to better counteract the Experts from the World Health Organization (WHO) visited
virus. This could help them to contain the virus but also let various regions of China between 16 and 24 February 2020 and
them to be unrecognized carriers. Circulating levels of ACE2 analyzed 147 pregnant women. Eight percent of these women
might have prognostic significance and ACE2 polymorphisms had severe disease and 1% were in critical condition which led
might be a key element of individualized care for its prevention, the experts to conclude that the disease did not pose a high risk
diagnosis, treatment and monitoring (23). In 97% of cases, to pregnant women. Vertical transmission was not analyzed in
symptoms appear by the 10th day (24). Common symptoms this study (31). However, Hantoushzadeh et al. have reported
include fever, dry cough and fatigue with a few upper respiratory 7 pregnant women from Iran, presenting with severe COVID-
symptoms such as nasal congestion or runny nose and some 19 disease, and died in their latter second and third trimester.
patients may have gastrointestinal symptoms such as abdominal Three of the 7 women had stillbirth and 6 of their offspring
discomfort, nausea, vomiting, abdominal pain and diarrhea. (2 set of twins) died after birth (32). Recently, another infected
In 15.8% of children, there were no symptoms or radiologic pregnant woman had miscarriage at the 19th week of gestation.

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Ovalı COVID-19 in Newborns

She delivered 4 days after the onset of symptoms. Amniotic fluid during the first 16 days of life. Although decreased significantly,
and vaginal swabs were negative for SARS-CoV-2, as well as her IgM and IgG levels were still elevated at the 16th day.
fetal lung, liver and thymus biopsies. However, a placental biopsy Since IgM antibodies are elevated only after 3–7 days after the
obtained immediately after delivery under sterile conditions was infection, high IgM levels in the infant only at the 2nd h of
positive for SARS-CoV-2. Placental findings demonstrated mixed birth strongly suggested an intrauterine infection. PCR testing
inflammatory infiltrates in the subchorial space and increased of the amniotic fluid and placenta were not performed in this
intervillous fibrin deposits. Funisitis was also present. Any infant (42). Kimberlein and Stagno argued against this finding,
bacterial and fungal infections were ruled out (33). stating that “most congenital infections are not diagnosed based
Medical treatment of pregnant women is controversial. on IgM detection, because IgM assays can be prone to false
Hydroxychloroquine has been used widely in pregnant women positive and false negative results, along with cross reactivity
for the treatment of lupus erytematosus or malaria, without any and testing challenges.” (43). The sensitivity and specifity of IgM
significant side effects (34). Remdesivir is a nucleotide analog assays which are 70.2 and 96.2%, respectively, are lower than
which is active against all coronaviruses including SARS, MERS those of PCR testing (44). (Table 1) IgM testing in congenital
and SARS-CoV-2. Phase 3 trials for its efficacy in SARS-CoV- cytomegalovirus, toxoplasma, syphilis and Zikavirus infections is
2 positive pregnant women are under way (ClinicalTrials.gov not alone sufficient enough for definitive diagnosis of the relevant
number NCT04280705, NCT04252664, and NCT04257656). diseases. Furthermore, the rapid decay of IgM levels within 14
Lopinavir/ritonavir has proven to be a safe drug in HIV patients days lend support to the reasoning that high IgM levels might
without any increased risk of fetal anomalies, preterm birth or not represent a true infection.
low birthweight infants; it may be used in pregnant women, if On the other hand, there are some data that SARS-CoV-2 can
deemed necessary (35). be transmitted through the fecal-oral route (15). Transmission
of the virus is possible during vaginal delivery, by direct
contamination of the infant by vaginal secretions, as well as
MATERNO-FETAL VERTICAL through the droplets of the infected mother in the immediate
TRANSMISSION postpartum period, if no PPE is used.
It was not possible to prove the vertical transmission of the
Chinese National Health Commission issued a statement on 8 SARS virus during the SARS epidemic (53). Since SARS-CoV-
February 2020, which recommended that the pregnant women 2 shows 85% homology with the original SARS virus, it may be
should be cared carefully, infection control measures should be assumed that the new virus behaves similarly. However, although
taken at the delivery clinics including wearing PPE; and isolation PCR remains as the gold standard for the diagnosis, clinical
of suspected or proven cases of COVID-19 for 14 days. They findings and chest computed tomography (CT) findings should
also suggested to stop breastfeeding the infant and prevent close be investigated thoroughly (44). Since all the pregnant women
contact of the mother with the infant (36). However, it must be who had been infected were in their 2nd or 3rd trimester at the
underlined that this statement is not evidence-based, but rather time infection, it is impossible to have an idea on the transmission
reflects the opinions of an expert committee. dynamics of the infection during the whole pregnancy. It is well-
Transmission of SARS-CoV-2 from the infected pregnant known that the rate of transmission of rubella infection during
woman to the fetus is still controversial. Viremia is seen in pregnancy is higher in the first or second trimester, but not in
only 1% of COVID-19 cases, suggesting that placental and fetal the third trimester (54). On the other hand, fever is a common
seeding might be quite rare (37). However, if viremia is present, manifestation of SARS-CoV-2 infection and high temperature
the disease is more severe (38). The ACE2 receptor is widely may be a theoretical concern during the organogenesis period in
expressed in the placenta, with a similar receptor binding domain the first trimester and associated with increased risk of congenital
structure of SARS-CoV-2. However, until now, Polymerase Chain anomalies or miscarriage. Therefore, more information on the
Reaction (PCR) findings of suspected fetuses have been negative, transmission rates of the SARS-CoV-2 during the first and second
as well as negative amniotic fluid and placenta findings (39). trimester will be available after some months; i.e., when the
Zeng H et al. reported 6 infected mothers and their infants. women who got pregnant during the pandemic delivered 9
Although PCR results were negative both in mothers and infants, months later.
2 infants had elevated specific IgM and IgG levels, suggestive
of an intrauterine infection (40). Three other infants with
pneumonia on the 2nd day of life were reported by Zeng L. et al. OPTIMAL DELIVERY IN INFECTED
(41). Although they were delivered by cesarean section under MOTHERS
infection control procedures, they tested positive for SARS-CoV-
2 on nasopharyngeal and anal cultures. It is possible that early There is still a controversy on the optimal delivery method
infection might have occured by postnatal early contact with the of infected mothers (9, 55, 56). In pregnant women with
infected mother. In another report by Dong et al. a 37 week girl, SARS-CoV-2 infection, there is not any indication for routine
born to a SARS-CoV-2 positive mother in a negative pressure cesarean delivery except for obstetrical reasons. However, in
room, after taking all precautions, had high specific IgM levels many case reports, cesarean delivery was preferred most of the
at 2 h of age. Cytokines and white blood cell counts were also time, aiming for reducing hospital stay of mothers, minimizing
elevated. Her PCR results were negative for 5 consecutive swabs chance of cross-infection, reducing maternal physical exertion

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Ovalı COVID-19 in Newborns

TABLE 1 | Reports on infants with SARS-CoV-2 infection.

Author Infant Delivery route Clinical findings Outcome

Zeng et al. (45) 5 days male C/S* Fever, pneumonia Discharged well
2 days male C/S Fever, lethargy, vomiting, lymphopenia, pneumonia Discharged well
2 days male C/S 31 wks preterm, respiratory symptoms, bacterial sepsis, NIV** Discharged well
Dong (46) 2 h female C/S Asymptomatic infant, IgM(+) Discharged well
Zeng et al. (47) 17 days, male V*** Fever, cough, runny nose, vomiting Recovered well
Zhang et al. (48) 30 h male C/S Shortness of breath Discharged well
5 days male C/S Fever Discharged well
5 days female C/S Asymptomatic Discharged well
17 days male C/S Fever, cough, vomiting Discharged well
Aghdam et al. (49) 15 days male C/S Fever, mottling, tachycardia, mild retraction Discharged well
Wang et al. (50) 36 h male C/S Asymptomatic Clinically well
Buonsenso et al. (51) 15 days male C/S Asymptomatic Clinically well
Sinelli et al. (52) 5 days male V PCR (+) at 48 h, respiratory distress on day 5, chest x-ray: mild ground-glass opacities Discharged well

*C/S: Cesarean Section.

**NIV: Non-invasive ventilation.
***V: Vaginal delivery.

during delivery and ensuring safety of other people at the clinic DELIVERY ROOM MANAGEMENT
(57). Iqbal et al. have reported a 39 week infant, born through
vaginal route, and discharged home on the 6th day without Delivery should take place in a room with negative pressure and
any complications (58). In a systematic review of 8 studies, all staff should wear PPE including the pediatrician attending to
comprising 100 women, 85% of them had cesarean section, the delivery. If a room with negative pressure is not available,
29% had delivered a premature infant and 16% of the infants a separate room should be used. The number of staff attending
were low birthweight (59). If cesarean section is preferred, it to the delivery should be kept at the minimum. If needed,
should be performed by a senior physician in order to minimize neonatal resuscitation is performed according to the Neonatal
possible complications. Since general anesthesia is considered Resuscitation Program guidelines by an experienced person
as an aerosolizing procedure, personal protective equipment with PPE. Initial care of the newborn should not be delayed
(PPE) including N95 masks, long-sleeved scrub or jumpsuit, due to COVID-19, and should be done according to standard
goggles, face shields, two-layer gloves, should be worn by all procedures. If clinically stable, the newborn should be bathed
staff during the operation. Alternatively, epidural anesthesia may after birth in order to remove virus potentially present on the
be preferred. skin (62).
Although there is limited data, rupture of membranes does Some experts advocate refraining from delayed cord clamping
not pose an additional risk (59). However, since feces might but this recommendation is not evidence-based and American
contain virus, caution should be taken, especially during vaginal College of Obstetrics and Gynecology (ACOG) recommends no
birth (45). change in the practice of delayed cord clamping in COVID-19
Delivery is not indicated in a pregnant women with non- cases until there is sufficient evidence (46).
severe illness. Preterm delivery should be considered only by Obstetric and neonatology clinics should work in close
obstetric reasons. However, severely ill patients at least 32–34 collaboration for the management of these cases and the
weeks of gestation with SARS-CoV-2 pneumonia or patients neonatology team should be notified at least 30 min before
who do not improve by treatment may benefit from early delivery in order to make necessary preparations.
delivery even in the absence of obstetric indications (46, 57).
In critical cases, there is some evidence that early delivery
may improve maternal oxygenation, regardless of gestational SARS-COV-2 INFECTION IN THE
age (60). NEWBORNS
Antenatal corticosteroids for the prevention of respiratory
distress syndrome and other morbidities in the preterm infant Case reports or randomized controlled trials on SARS-CoV-2
is not contraindicated in women with confirmed SARS-CoV- infection in the neonates are limited and are summarized in
2 infection, although it is known that they accelerate the Table 1.
development of type 2 alveolar cells which are rich in angiotensin The first newborn in the World, infected with SARS-CoV-
converting enzyme 2, a co-receptor for SARS-CoV to enter the 2 was a 17 days old boy with fever, cough, runny nose and
cell (45). Moreover, antenatal corticosteroids have been used vomiting. He recovered with symptomatic treatment (47). Chen
safely in pregnant women with influenza and HIV infection (61). et al. reported 9 infants of positive mothers, all delivered by

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Ovalı COVID-19 in Newborns

cesarean section. Four of them were premature. None of the negative tests on day 1, 5, and 18. The father was feeding the
infants was positive for SARS-CoV-2, including amniotic fluid, baby with expressed breastmilk (51). Sinelli et al. reported a
umbilical cord blood, nasopharyngeal swab and breast milk (39). baby born to a mother with COVID-19. On the second day after
Liu et al. reported 3 infected women; their infants tested negative vaginal delivery, the infant tested positive for SARS-CoV-2. The
for SARS-CoV-2, and all of them were clinically well (45). Zhu mother and the infant were not separated, but isolated in the
et al. reported 10 infants from 9 mothers (1 twins). Seven same room. 48 h after isolation, the infant developed cyanosis,
mothers had delivered by cesarean section whereas 2 mothers respiratory distress and poor sucking. He was placed on 30%
had had vaginal birth. Although some of these infants were oxygen and high flow nasal cannula. Chest radiograph showed
symptomatic with respiratory symptoms, tachycardia, feeding mild bilateral ground-glass opacities. Respiratory support was
intolerance and fever, none of them tested positive for SARS- discontinued 50 h after NICU admission and he was discharged
CoV-2. In this group one preterm infant died at the 9th day of in good condition on day 18 of life (52).
life with multiple organ dysfunction, disseminated intravascular
coagulation and shock (63). Wang et al. reported an infant Clinical Manifestations in the Newborns
born at 30 weeks of gestational age with cesarean section to Neonatal infection with SARS-CoV-2 may begin insidiously.
an infected mother. The infant was negative for SARS-CoV-2 The most prominent characteristic of the infection in young
both on the first day and on the 9th day (64). Zhang et al. children is a history of contact with a proven case of COVID-
reported 4 newborn infants between 30 h and 17 days. All of 19 (commonly the mother) or travel history to an epicenter.
the mothers were infected with SARS-CoV, showing symtoms Diagnosis is confirmed by the demonstration of nucleic acids of
before and 1 week after delivery. Cesarean section was used the virus by real time PCR in the respiratory tract swabs (36).
for all of them. Two of the infants had fever, 1 had shortness There is no clinical finding specific to the newborns. The
of breath, 1 had cough and 1 had no symptoms. None of body temperature may be high, normal or low. S/he may have
them required intensive care and all of them were discharged respiratory symptoms such as cough, tachypnea, apnea, grunting,
well. Three of them were separated from their mothers and nasal flaring, and tachycardia as well as lethargy, vomiting,
were not breastfed (48). Another infant, who had had close diarrhea and abdominal distention (68, 69). In severe cases
contact with infected relatives presented at 55th day of life with and in cases with immune deficiency, congenital heart disease,
cough and runny nose and bilateral ground glass apperance on bronchopulmonary dysplasia, respiratory tract anomalies, severe
the lungs. There were slight elevations of liver function tests, malnutrition or anemia, the findings should be interpreted
myocardial enzymes; CD8 T-lymphocytes and serum IgM levels. more cautiously.
She was isolated and started on empirical antibiotics as well
as inhaled interferon α-1b (15 µg, bid), reduced glutathion,
ursodeoxycholic acid and traditional Chinese medicine lotus Laboratory Findings
qingwen. A feces sample at the 11th day proved positive for There are no specific laboratory findings. White blood cells
SARS-CoV-2 (65). Chen Y et al. reported 4 infants, 3 delivered may be normal or elevated and lymphocytes may be decreased.
by cesarean section and one by vaginal route. The infants tested Mild thrombocytopenia, mild elevations of creatine kinase,
negative for SARS-CoV-2. They were separated from the mother alkaline phosphatase, alanine aminotransferase, aspartate
after birth and fed with formula. They were discharged well (66). aminotransferase and lactate dehydrogenase may be seen.
In another case-control study, Li et al. reported 17 newborn The virus may be isolated from the upper respiratory tract,
infants born to SARS-CoV-2 positive mothers. Preterm birth endotrachaeal aspirate, blood or feces. Pneumonic infiltrations
rate was 23.5%, and low birthweight rate was 17.6%; both were may appear on chest radiography, lung ultrasonography or
higher than those of normal population, but was attributed computed tomography (CT) of the lung (70).
to pregnancy complications rather than COVID-19 itself (67).
In another case report, Aghdam et al. reported a 15-day old Suspected Newborns
newborn who presented with fever and mottling, accompanied All newborns born to a mother with confirmed COVID-19
by tachycardia, tachypnea and mild subcostal retraction without within 14 days before birth or 28 days after birth, or who had
cough, desaturation, runny nose or gastrointestinal symptoms. had direct contact with any person with confirmed infection
He was discharged 6 days later in good health (49). Wang S are accepted as suspected cases. All suspected newborns should
et al. reported an asymptomatic male infant diagnosed at 36 h be quarantined (70). This does not mean that all suspected
after birth (50). Recently, Buonsenso et al. reported 2 newborns newborns should be hospitalized; if they are clinically stable, they
born to mothers with COVID-19 in pregnancy. The first one was can be managed at home. Neonatal Intensive Care Unit (NICU)
delivered by cesarean section at 38 weeks. He tested negative on admission should be reserved for neonatal clinical reasons or
day 1 and day 5 of life, but became positive at day 15, although when close monitoring is indicated.
he was clinically well. The mother was breastfeeding the infant. In suspected cases, PCR testing should be done first at about
Milk samples tested negative and respiratory secretions were the 24 h of age. Repeat testing should be done about 48 h of age.
probable source of the infection. Maternal immunglobulin G and For well-newborns who will be discharged prior to 48 h, this
breastmilk antibodies might have protected the newborn from test may be omitted. However, in rare cases, the infant may test
symptomatic infection. The second newborn was delivered by negative in 24 h but positive in 48–72 h. Additional testing may be
cesarean section at 35 weeks and he was asymptomatic with considered for sick infants requiring prolonged hospial care (71).

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Ovalı COVID-19 in Newborns

Confirmed Newborns decide on which baby should be admitted to which section.

If any of the following is positive, the case is regarded as An algorithm for this purpose will be helpful. Suspected or
positive (36): confirmed cases should be kept in the NICU, in separate rooms,
in closed incubators. The decision on the separation of the
a) Positive PCR for SARS-CoV-2 in respiratory tract or
mother and infant depends on the clinical condition of the
blood samples
mother and infant, the physical configuration and infrastructure
b) High homology of viral gene sequences of the samples from
of the unit, the test results and the will of the mother to breastfeed
the respiratory tract or blood to the COVID-19 sequence.
her baby. Instruments such as stethescopes, thermometers,
Management of Asymptomatic Newborns laryngoscopes etc. should be private for each patient. If the
Whether suspected or confirmed, asymptomatic infants should neonatal unit is very busy, infants with similar findings may
have a complete blood count, C-Reactive Protein (CRP) and be cohorted in the same ward, all 2 meters apart from each
Real Time-PCR for SARS-CoV-2. It is preferable to take the other (70).
samples at least from 2 sites, including the upper respiratory All involved staff in the NICU should conform to the
tract, lower respiratory tract or blood. Feces may be obtained precautions which include but not limited to wearing hospital
and kept for further analysis (72). The infants should be kept scrubs, shaving facial hair, taking off accessories such as watches,
in an isolated room at least for 14 days. If deemed stable, the bracelets, rings, keeping nails short and long hair tied, wearing
infant may be discharged home, provided that s/he is kept in dedicated shoes at the hospital, wiping cell phones and other
an isolated room for 14 days. If the infant was kept with other personal accessories, notwithstanding putting on PPE (70, 71).
newborns in the same room previously, these infants should have It is noteworthy to state that COVID-19 disease may be spread
an SARS-CoV-2 test immediately and kept in quarantine until by non-symptomatic persons and is considered as Group-A
the tests are negative (73). Feeding of the infant depends on the infection, a category for highly infectious pathogens, such as
infectious status of the mother. Recent evidence suggests that cholera and plague (75). The order of donning and doffing of
even non-symptomatic individuals may spread COVID-19 and PPE should be observed by every personnel (76). Aerosolization
conventional measures of protection such as face masks provide should be minimized and during invasive procedures to the
insufficient protection. Therefore, healthcare staff should wear respiratory tract (endotracheal intubation, bagging, aspiration,
PPE while dealing with suspected cases (74). bronchoscopy or laboratory sampling, nasal cannula oxygen flow
> 2 Liter/min, or mechanical ventilation), additional water-
Management of Symptomatic Newborns resistant gowns, N95 masks, head shields and feet shields should
These infants require the above mentioned laboratory tests and be used. Intubation by the videolaryngoscopic technique may
an additional chest radiography and/or chest CT. Liver and reduce exposition to airborne particles. After the insertion of
kidney function tests and cardiac enzymes may be required. Since the endotracheal tube, the tube may be clamped, connected
young infants may have other respiratory tract viral infections, to the ventilator and the clamp is removed in order to to
viral pathogens may be sought. They should be quarantined and avoid aerosol and droplet spread (clamped intubation technique)
closely monitored until the results are negative. Feeding depends (77). The door of the room should be kept closed at all
on the infectious status of the mother. If RT-PCR for SARS-CoV- times and entrance to the room should be restricted to the
2 is negative, the infant should be treated according to the other minimum number of people. The equipment used for the
possible disease (69). The healthcare staff should wear PPE. patient should not be used concomitantly for another patient.
Infected infants may be discharged from the hospital if Visitation to the unit should be restricted. For parents or
father, a camera may be helpful. The air circulation in the unit
a) There is no fever for 3 consecutive days should be increased. Medical waste of infected patients should
b) Respiratory symptoms resolve be disposed of separately in double layer boxes. The linens
c) Severe lung radiological findings resolve and other textile should be treated with a chloride solution
d) Nasopharyngeal swabs taken 24 h apart are negative (62). at least for 10 min and then washed at 60–90◦ C, separately.
The room of the patient should be disinfected thoroughly after
Neonatal Transport discharge (78).
Newborns should be transported within the hospital and between
the hospitals in a closed, dedicated incubator and ambulance. The
ambulance should be equipped with a ventilator and necessary
drugs, surface disinfectants and hand disinfectants. Before and
TREATMENT
after the transport, the incubator and the ambulance should be Treatment is mainly symptomatic. Supportive treatment
disinfected. The transport personnel should wear a PPE (70). including fluid-electrolyte treatment, maintaining hemodynamic
stability of the infant, parenteral or enteral nutrition as well
NEONATAL INTENSIVE CARE UNIT as respiratory support are essential. Conventional mechanical
DESIGN AND PROCEDURES ventilation, high frequency ventilation or nitric oxide therapies
may be tried. In critical cases, continuous renal replacement
The NICU may be designed in 2 sections: a quarantine section therapy or extracorporeal membrane oxygenation (ECMO) may
and a non-infectious section. The attending neonatologist should be helpful.

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Ovalı COVID-19 in Newborns

Anti-viral treatment is not generally needed in newborns POST-DISCHARGE CARE

and there is no data on the efficacy of anti-viral drugs in the
newborn population (70). The recommendation by Zhejiang If the infant tests positive without any symptoms, s/he can
University School of Medicine comprises the use of nebulized be sent home, but should be followed up by outpatient visits,
interferon alpha-2b and oral lopinavir/ritonavir (79). In older telemedicine or telephone calls for 14 days. All caretakers at home
children and in children with severe pulmonary findings, should have hand hygiene, masks, and gloves. Uninfected persons
hydroxychloroquine, azithromycin and lopinavir+ritonavir older than 60 years of age or with co-morbid diseases should not
may be used. Hydroxychloroquine is an anti-malarial drug, provide care for these infants (91). If the infant is negative but
which is used in autoimmune diseases also. It increases the mother is positive, an uninfected person should take care of
the endosomal pH, inhibiting virus-cell fusion. It also the infant. These caretakers as well as the mother should stay at
inhibits the entry of SARS-CoV into the cells and interferes least 2 meters away from the infant and should use a mask and
with glycosylation of cellular receptors of SARS-CoV. practice hand hygiene when getting into contact with the infant.
Furthermore, it may have an immune-modulating effect In adults, viral shedding has been reported after nasopharyngeal
(80). Mechanism of action implies that hydroxychloroquine swabs become negative, because viral replication and clearance
needs to be given at the beginning of the infection. The are decided by the body defense mechanisms. How long an infant
possibility of drug toxicity including QT prolongation sheds the virus is currently unknown, but may be as long as 22
and retinal toxicity especially in individuals with epilepsy, days (92).
porphyria, myasthenia gravis and glucose-6-phosphate
dehydrogenase (G6PD) deficiency should be considered BREASTMILK
(81). Remdesivir is a nucleotide analog and acts on viral
RNA transcription after entering the cell by inhibiting RNA Breastmilk is generally considered safe against viral infections
polymerase and seems to be safe and effective in the adult because of its protective contents such as immunoglobulins and
population (82). other bioactive compounds. Breast milk may contain anti- SARS-
Cytokine storm syndrome, which appears at the final stage CoV-2 antibodies in infected mothers but there is no data yet on
of the disease is frequently related to extensive tissue damage this issue. On the other hand, various case reports have concluded
with lung involvement and multi-organ failure. The protagonist that breast milk does not contain the virus RNA (93, 94). If
of this storm is interleukin-6 (IL-6). In order to antagonize the PCR test is negative, the infant may be breastfed safely.
hyperinflammation, IL-6 blockade or immunosupression with However, if the mother tests positive, the recommendations for
corticosteroids can be hypothesized. Veronese et al. have breastfeeding becomes controversial. There is no data supporting
conducted a meta-analysis on the use of corticosteroids in the notion that these infants should not be breastfed. Academy of
COVID-19 patients (83). Four studies and 542 patients were Breastfeeding Medicine recommends breastfeeding after taking
included in this meta-analysis. Two studies reported negative all possible precautions (93). WHO recommends breastfeeding,
findings regarding the use of corticosteroids in COVID-19 after taking necessary precautions. The mothers should be
patients, one study did not report any benefit but one study encouraged for breastfeeding. They should put on appropriate
which included 201 participants with different stages of COVID- PPE, wash her hands before and after breastfeeding, and wash
19 pneumonia found that in severe forms, the administration clothes at 60◦ C, after the contact (95). However, since the
of standard doses of methylprednisolone significantly reduced infant and the mother are together, the possibility of airborne
the risk of death by 62% (84). Available literature does not fully transmission can not be ruled out. The mother should not hug
encourage the routine use of corticosteroids in COVID-19 (82). or kiss the infant. If the mother and infant is going to stay
There is one ongoing trial, pending results (85). Tocilizumab is together, there should be at least 2 meters between the beds. It
recombinant humanized monoclonal antibody which binds to should not be forgotten that with this practice, a person without
IL-6 seceptor and blocks its function (86). any PPE (i.e., the infant) gets into close contact without any
On the other hand, since ACE2 receptors play an important social distancing (i.e., sucks the breast) with another person with
role in the development of the disease, recombinant ACE2 suspected or confirmed infection (i.e., the mother). This type of
may be a treatment option for patients with severe COVID-19 contact is not allowed in adults, but it may be allowed between
(ClinicalTrials.gov NCT04287686) Lopinavir-ritonavir appears the mother and her child. Centers for Disease Control (CDC)
to have little role in the treatment of COVID-19 disease (87). recommends that, if the mother has suspected or confirmed
Drugs like remdesivir or lopinavir-ritonavir can be considered as COVID-19 infection, the option of separate management of the
compassionate treatment, after careful consideration of the risk- mother and child should be considered as the first choice and
benefit ratio and technical issues (88). Other treatment options the risks and benefits of this separation and consequences of
such as convalescent plasma and anakinra are under investigation not starting, continuing or suspending breastfeeding should be
(89, 90). shared with the family and documented (96). Guidelines issued
Antibiotics may be used if there is secondary bacterial by the Italian Society of Neonatology and endorsed by the Union
infection. Standard immunglobulins or hormonal treatments are of European Neonatal and Perinatal Societies (UENPS) suggest
not helpful. We do not have any information on the long-term that if a mother who is SARS-CoV-2 positive or is a person under
effects of COVID-19 acquired in the neonatal period. No deaths investigation, or who is asymptomatic or has few symptoms
have been reported so far among neonates. at delivery, rooming in is feasible and direct breastfeeding is

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Ovalı COVID-19 in Newborns

advisable but with strict infection control measures. If however, is separated from the mother, the mother and the whole
the mother is too sick to care for the newborn, the neonate family may suffer from anxiety and stress. Support from a
will be managed separately and fed fresh expressed breast milk, psychologist or a social worker may be sought. On the other hand,
with no need to pasteruize it, as human milk is not believed to health staff working with COVID-19 cases may develop various
be a vehicle of SARS-CoV-2 (97). Chinese Pediatrics COVID- pyschological manifestations due to heavy work load, shortage of
19 WorkingGroup also advocates formula or donor breast milk, equipment and guarded prognosis of the patients. Therefore, they
albeit without evidence (98). Therefore, the risks and benefits of may also need pyschological support.
breastfeeding should be balanced. If close contact is not preferred,
expressed breast milk may be preferred and given to the infant by CONCLUSION
an uninfected caregiver. This practice may have some drawbacks
also; such as preventing the bonding between the infant and SARS-CoV-2 infection is a new disease with many unknown
the mother. The benefits of breastfeeding outweigh any risk of issues. With emerging evidence, pathophysiology and
transmission of the virus through the breastmilk. This guidance management options change. The knowledge on vertical
may change as knowledge evolves. transmission of the disease and on clinical manifestations
Hydroxychloroquine is considered safe if used during in the newborns is expected to accumulate in the forseeable
lactation but nothing is known on the passage of remdesivir to future. There is a growing body of evidence on the subject
human milk (99). and continuous updates are important to implement current
knowledge in the management of COVID-19 in infants
PSYCHOLOGICAL SUPPORT and children.

Rising fears about the infection should be reduced and sound AUTHOR CONTRIBUTIONS
knowledge should be shared by the family. The information in
the social media should be interpreted cautiously. Education The author confirms being the sole contributor of this work and
and shared decision making empowers the family. If the infant has approved it for publication.

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March 24, 2020). absence of any commercial or financial relationships that could be construed as a
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Infection in the Perinatal Period of the Editorial Committee of Chinese
Journal of Contemporary Pediatrics. [Perinatal and neonatal management Copyright © 2020 Ovalı. This is an open-access article distributed under the terms
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