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Perinatal SARS-CoV-2 Infection and Neonatal COVID-19
May 6, 2021 at 3:30 AM
by Dr.Rajesh Bariker, MDS
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This detailed infographic explains in detail: a) perinatal management approaches for pregnant women to improve the outcomes in mothers and neonates. b) Summarizes the clinical presentation and management of neonatal SARS-CoV-2 infection c) Describe the neonatal multisystem inflammatory syndrome in children.

A) Understanding SARS-CoV-2

· Coronaviruses are positive sense–enveloped, single-stranded RNA viruses.

· Serotypes from the α and β coronavirus genera can cause human disease.

· The novel SARS-CoV-2 is a α-coronavirus

· 80% homology to SARS-CoV-1 (the agent causing severe acute respiratory syndrome, or SARS)

· Even greater homology to some bat coronaviruses, suggesting a zoonotic origin.

· Like other coronaviruses, SARS-CoV-2 has a “crown” appearance on electron microscopy caused by projections of the spike (S) glycoprotein from the envelope

B) HOW Transmissible

· SARS-CoV-2 is more transmissible than SARS-CoV-1,

· *Maybe due to stronger binding to the ACE-2 receptor and more effective transmission of virus from asymptomatic and presymptomatic hosts.

· Transmission primarily occurs via respiratory droplets, though airborne and contact transmission may occur to a lesser extent.

· Disease caused by SARS-CoV-2 tends to occur in a biphasic manner, with the

· 1)Initial illness: the result of direct viral infection

· 2)Subsequent phase: immune-mediated.

· In addition, SARS-CoV-2 infection is known to cause coagulopathy, which may contribute to organ dysfunction as well.


In the United States, pregnant women with COVID-19 are significantly more likely to be admitted to an ICU and receive invasive ventilation and extracorporeal membrane oxygenation (ECMO) compared with nonpregnant women

Mortality is also higher among pregnant women infected with COVID-19.

These findings may be related to

a) physiologic changes of pregnancy, such as increased heart rate and oxygen consumption,

b) shift in cell-mediated immunity,

c) reduced lung capacity secondary to upward diaphragmatic shift, and

d) increased risk for thromboembolism.

Similar to nonpregnant women, pregnant women with COVID-19 present with

a) cough (50%)

b) fever (32%)

c) myalgia (37%)

d) and shortness of breath.

In addition to respiratory symptoms, the placenta may be affected in COVID-19.

D) Measures to prevent COVID-19 during pregnancy

a) wearing a proper mask,

b) frequent handwashing, and most importantly,

c) avoiding crowded areas and parties (including baby showers).

Vaccination during pregnancy is a controversial topic as to date, pregnant and lactating women have been excluded from vaccine studies.

However, the American College of Obstetricians and Gynaecologists and the Society of Maternal-Fetal Medicine have issued statements suggest

pregnant and lactating women should be given a choice to receive the vaccine after discussing individual risks (including the possibility of fever following vaccination)

E) AAP section Statement

Recommend shared decision-making regarding vaccination during pregnancy and lactation.

The risk of transmission of the vaccine (i.e., COVID-19 messenger RNA [mRNA]) across the placenta is unlikely but,

maternal immunoglobulin (Ig) G antibodies in response to the vaccine are likely to be transmitted.

Antibodies to COVID-19 are found in infants born to mothers with COVID-19 and in the breast milk of mothers with COVID-19.

Active immunization with other vaccines has been shown to increase specific IgA levels in breast milk.


Three potential mechanisms of maternal transfer of SARS CoV-2 to the infant

1. Intrauterine transmission through transplacental hematogenous spread or viral particles in amniotic fluid that are ingested or inhaled by the fetus. This mode appears less likely but there are anecdotal reports suggesting that this is possible.

2. Intrapartum transmission after exposure to maternal infected secretions or feces around the time of birth.

3. Postpartum transmission from an infected mother, family member, or health care worker (probably the most likely mode of prevaccine transmission).

Transmission from an infected mother is more likely from respiratory secretions and less likely from breast milk.

Pregnant women with suspected COVID-19 (symptomatic or recent positive household contact) must be prioritized for SARS-CoV-2 testing, while universal screening may be used in areas with high prevalence.

The timing and mode of delivery and anesthesia in pregnant women with suspected/confirmed SARS-CoV-2 infection is dependent on obstetrical indications.

A cesarean section rate of 24% to 41% has been reported in pregnant women infected with COVID-19 from hospitals in the United States.

Antenatal steroids may be administered to infected pregnant women at risk for preterm delivery (including 34–36 6/7 weeks) until more evidence is available because of the potential benefits of promoting fetal lung maturity and decreasing maternal mortality.

If a pregnant woman has significant COVID-19–related illness and requires invasive mechanical ventilation, delivery may need to be conducted in the intensive care unit setting.

Cesarean section has been reported in a pregnant woman with COVID-19 who was receiving ECMO.


No current compelling evidence suggesting that SARS-CoV-2 can be transmitted from an infected mother to her neonate via breast milk; rather, breast milk may be beneficial by providing protective antibodies against SARS-CoV-2 infection.

The nutritional, immunologic, and developmental benefits of breastfeeding, if permitted by the mother’s health, outweigh the potential transmission risk, given that infants typically have mild illness.

Newborns are more likely to acquire infection via horizontal transmission from an infected mother or another care provider; thus, the importance of maintaining appropriate respiratory hygiene when an infected person is in contact with a newborn cannot be overemphasized.

An infected mother should wear a surgical mask, wash her hands and breasts with soap and water before feedings, and breastfeed the infant.

Alternatively, the infant can be fed expressed breast milk by a healthy care provider. Between feedings, the infant’s crib (or incubator) should be placed at least 6 feet from an infected mother’s bed, preferably behind a physical barrier (such as a curtain).

Both international and national societies, including the WHO and AAP, support protecting breastfeeding during this pandemic.

It is worth mentioning that although the passage of remdesivir (an antiviral medication used for the treatment of moderate to severe SARS-CoV-2 disease) to an infant via breast milk is unknown, no adverse events were reported in a newborn whose mother received remdesivir therapy for Ebola infection.

The Academy of Breastfeeding Medicine does not recommend cessation of breastfeeding when lactating mothers receive an mRNA-based liposomal vaccine.


Vertical transmission of SARS-CoV-2 appears to be uncommon because of lack of viremia and nonoverlapping expression of ACE-2 and transmembrane serine protease 2.

Neonatal infection was reported in 1% to 3% of births to US mothers with COVID-19, with lower chances of infection if the mother tested positive more than 14 days before delivery.

Preterm birth, low birth weight, cesarean section, and NICU admissions were frequently observed among COVID-19 deliveries.

Contrary to initial beliefs, the rate of neonatal infection was not increased with vaginal delivery, rooming-in, or breastfeeding.


Infants should be monitored closely for symptoms and signs of SARS-CoV-2 infection, which may include fever, cough, rhinorrhea, respiratory distress, poor feeding, lethargy, vomiting, diarrhea, rash, and edema.

Testing for SARS-CoV-2 RNA RT-PCR is recommended for all neonates born to mothers with suspected or confirmed COVID-19 at 24 and 48 hours after birth (or a single test at 24–48 h) using a nasopharyngeal, oropharyngeal, or nasal swab.

Asymptomatic SARS-CoV-2–positive neonates can be discharged from the hospital after ensuring close follow-up.

An infected mother who has been afebrile for 24 hours without antipyretics and is improving is not likely to be contagious 10 days after the onset of symptoms and can safely care for her infant.


The immature immune system, passive transfer of maternal IgG antibodies, and lower ACE-2 expression may result in less inflammation, milder illness, and hastened recovery in infants and children compared to adults.

Neonates, however, have been reported to have more severe illness compared to older children (3% of older children required intensive care unit care) in a systematic review.

SARS-CoV-2–positive neonates should be clinically monitored and isolated.

Early-onset neonatal COVID-19 (onset of illness between 2 and 7 days after birth) is likely caused by perinatal transmission.

Most infected neonates are either asymptomatic (20%) or have mild symptoms such as

a) rhinorrhea and cough (40%–50%) and

b) fever (15%–45%)

Moderate to severe symptoms such as

a) respiratory distress (12%–40%),

b) poor feeding,

c) lethargy,

d) vomiting and diarrhea (30%), and clinical evidence of multiorgan failure have been observed as well.

Laboratory evidence of COVID-19 infection in a neonate may include

a) leukocytosis,

b) lymphopenia,

c) thrombocytopenia, and

d) nonspecific findings of elevated inflammatory markers.

Management for symptomatic COVID-19–positive neonates is mostly supportive.

Appropriate respiratory support, such as CPAP, is recommended for respiratory distress.

Endotracheal intubation is more likely to be indicated if there is neonate-specific lung pathology.


The majority of symptomatic SARS-CoV-2 infections in neonates are diagnosed beyond 5 to 7 days after birth (late-onset neonatal COVID-19).

Postnatal transmission by neonatal exposure to maternal respiratory secretions or exposure to infected health care workers or household contacts probably plays a major role in late-onset neonatal COVID-19 infection.

For neonates with COVID-19, management remains supportive and includes

a) supplemental oxygen,

b) respiratory support,

c) fluid resuscitation and

d) temperature control.

Currently, evidence for the use of antiviral medications and steroids in neonatal COVID-19 is lacking.

Use of remdesivir has been reported in 2 new-borns: a 22-day old with severe late-onset COVID-19 who clinically improved and tolerated the treatment well and a 4-day old who continued to deteriorate and received dexamethasone and convalescent plasma, required invasive ventilation until 13 days of age and ultimately improved.


Multisystem inflammatory syndrome in children (MIS-C) is a novel condition following COVID-19 infection in children, and is characterized by fever, elevated inflammatory markers, and high levels of both pro- and anti-inflammatory cytokines.

Children with MIS-C frequently present with symptoms related to the

a) cardiovascular system

-shock, left ventricular dysfunction, elevated cardiac enzymes, coronary artery abnormalities.

b) gastrointestinal system (nausea, vomiting and diarrhea mimicking gastroenteritis, or inflammatory bowel disease), or with mucocutaneous symptoms resembling Kawasaki disease.

The median age of children with MIS-C has been reported to be 5 to 9 years, as opposed to Kawasaki disease which is typically seen between 6 months and 5 years of age.

MIS-C is infrequent in infants, with the Centers for Disease Control and Prevention reporting only 4% of MIS-C cases occurring in children younger than 1 year.


Practices such as

a) mother-infant separation

b) caesarean section

c)early cord clamping and

d)avoidance of breastfeeding to err on the side of caution, could alter

1)neonatal colonization with maternal microbiota, hamper mother-infant bonding and breastfeeding, and

2) predispose the infant to

a) iron-deficiency anemia and

b) increased frequency of respiratory and gastrointestinal infections in infancy.

Infected neonates with no or mild symptoms may possibly remain hypoxemic for a variable period before becoming overtly symptomatic similar to what has been observed in infected adults.

Indeed, neonates may be silent carriers of the virus in their airway epithelia with prolonged asymptomatic shedding of the virus.

We speculate that chronic airway inflammation could result in airway remodelling and thickening, predisposing neonates to childhood asthma.

Reference: Sankaran D, Nakra N, Cheema R, et al. Perinatal SARS-CoV-2 Infection and Neonatal COVID-19: A 2021 Update. NeoReviews. May 2021. 22(5). 10.1542/neo.22-5-e1001