key: cord-0733089-w2nz643v
authors: Hinojosa-Velasco, Alejandro; de Oca, Paloma V. Bobadilla-Montes; García-Sosa, Lidia E.; Mendoza-Durán, J. Gabriel; Pérez-Méndez, María J.; Dávila-González, Eduardo; Ramírez-Hernández, Dolores G.; García-Mena, Jaime; Zárate-Segura, Paola; Reyes-Ruiz, José Manuel; Bastida-González, Fernando
title: A Case Report of Newborn Infant with Severe COVID-19 in Mexico: Detection of SARS-CoV-2 in Human Breast Milk and Stool
date: 2020-08-27
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.08.055
sha: 2481785bbe7274f050e6102898c4dc36b735370f
doc_id: 733089
cord_uid: w2nz643v

Although COVID-19 in pregnant women and their neonates has been demonstrated, there is not enough evidence about how this vertical transmission occurs. This report describes SARS-CoV-2 infection in a 21-year-old mother-son duo at the time of birth, focusing on the viral RNA detection in the stool of both, and the human breast milk.

The coronavirus disease 2019 caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a global public health threat (X. . The dynamics of SARS-CoV-2 transmission occurs from human-tohuman through respiratory droplets , however, other routes of transmission have not been appropriately characterized.

The high-risk populations for COVID-19 include old-age individuals or people with severe comorbidity (Jordan et al., 2020) . Particularly, this novel coronavirus causes severe complications in pregnant women, which increases the risk of maternal morbidity (Schwartz and Graham, 2020) . Also, proper documentation of the source and potential for mother-to-infant vertical transmission of SARS-CoV-2 is required to prevent cases of severe COVID-19 in newborn infants. We described the case of a mother with confirmed COVID-19 and her neonate that was positive for SARS-CoV-2 at the time of birth. Since the neonate had central cyanosis, dyspnea, and oxygen saturation of 87%, she was defined as a severe case of COVID-19.

The infant´s stool was positive for SARS-CoV-2 on the fifth day but not on the thirteenth day after birth, as well as the nasopharyngeal and oropharyngeal swabs recollected on the same day. Additionally, viral RNA was detected in the stool, and milk of the infected mother actively breastfeeding the neonate. This report provided evidence of the risk of intrauterine infection and breastfeeding as mechanisms for vertical transmission of SARS-CoV-2.

At 38 weeks of gestation, a twenty-one years old female (gravida 1, para 1) with fever (39.5 °C) for the last two days was admitted to the Gynecology and Obstetrics In addition, the acute hypoxemic respiratory failure and atypical pneumonia were consistent with COVID-19. On day 1 at the hospital, she had painful and irregular contractions. Therefore, an emergency caesarian section was performed, and she delivered a female infant. The newborn weighed 3,075 g, the Apgar score was 8/9

and required only routine resuscitation. The infant´s body temperature was 36.5 °C, and her heart rate was 140 beats per minute, with a respiratory rate of 52 breaths per minute. The newborn was separated from her mother immediately after birth without skin-to-skin contact. Nasopharyngeal and oropharyngeal swabs samples were taken from the neonate during delivery and tested by real-time RT-PCR confirming the clinical diagnosis of SARS-CoV-2 infection with a low cycle threshold value (Orf1ab gene, 23), suggesting high viral load. Moreover, the neonate had newborn jaundice, tachypnea, hyponatremia, central cyanosis, dyspnea, and oxygen saturation of less than 92% (87%). Thus, this was defined as a severe case of COVID-19 (Yuanyuan . The neonate was kept in the intensive care unit with oxygen therapy which was withdrawn when the oxygen saturation level was greater than 90%. The infant´s clinical laboratory results (Table 1) revealed that basophils, hemoglobin, hematocrit, total bilirubin, indirect bilirubin, and lactate dehydrogenase were above the normal range during the first six days after birth. In contrast, prothrombin time, platelets, and urea were below the normal range.

On regard of the mother, she had severe respiratory depression and episodes of oxygen desaturation between 40-60% at the immediate postoperative period. Therefore, the patient received rapid sequence intubation and intensive care. After 24 h the extubation was performed when the mother showed adequate ventilation parameters. The mother was well and afebrile (37.3 °C) during the immediate postextubation period with vital signs stable, respiratory rate of 22 breaths per minute, blood pressure of 107/87 mm Hg, and blood oxygen saturation >90%. The patient J o u r n a l P r e -p r o o f was treated with anticoagulant therapy using Enoxaparin 40 mg/day via subcutaneous injection and antiviral therapy with Ivermectin 12 mg/single-dose oral administration. The mother´s clinical laboratory results (Table 1) indicated that lymphocytes ratio, hemoglobin, hematocrit, total protein, urea, and calcium were below the normal range. At the same time, triglycerides were still above the normal range as on first-day hospital admission. Even though the lymphocyte ratio was below the normal range, the absolute lymphocyte count within the reference interval was found, as previously reported (L. .

The newborn was feed with synthetic milk formula instead of human milk until she was confirmed with COVID-19, without any adverse effects. On day fourth after delivery (25 May), real-time RT-PCR analyses of the mother´s milk and stool samples were positive for SARS-CoV-2 RNA, similar result was obtained for the infant´s stool sample. On 3 June, after 13 days of delivery, the infant´s nasopharyngeal and oropharyngeal swabs and stool samples were negative for SARS-CoV-2 compared with the maternal samples which was remained positive.

The mother and infant were discharged from the hospital when they had a resolution of respiratory symptoms and an uneventful postpartum and neonatal course.

The written informed consent was obtained from the patient according to the 

SARS-CoV-2 is responsible for the epidemic of the COVID-19 in worldwide . Previous reports suggest the intrauterine vertical transmission potential of SARS-CoV-2 and its implications on newborn infants (H. Zhu et al., 2020) . Nevertheless, there is not enough evidence about how mother-to-infant vertical transmission occurs. Here, we reported the first case of SARS-CoV-2 infection in a neonate born to a woman with COVID-19 in Mexico.

SARS-CoV-2 infection in the newborn infant was described as a severe case of COVID-19 because she had central cyanosis, dyspnea, and oxygen saturation of 87% (Yuanyuan . Moreover, the newborn had thrombocytopenia accompanied by high lactate dehydrogenase levels, which suggested abnormal liver function (Y. Zhu et al., 2020) . Lymphopenia (lymphocyte count of less than 1.5x10 9 /L) is an indicator of the severity in COVID-19 patients , however, it was not observed in the mother and newborn like a previous study . Even though the mother was treated with Ivermectin, we do not recommend its use since there are no clinical trials suggesting its efficacy against SARS-CoV-2 infection.

The infant was born by emergency caesarian without the premature rupture of the membrane or placental abruption, and with airborne transmission precautions. Also, we did not observe that the newborn swallowed amniotic fluid. Thus, we rule out that these are the causes of SARS-CoV-2 detection in the newborn. Her nasopharyngeal J o u r n a l P r e -p r o o f and oropharyngeal swabs samples taken immediately after birth were positive for SARS-CoV-2, suggesting intrauterine vertical transmission. Nevertheless, no umbilical cord or placenta tests were performed, so whether the SARS-CoV-2 infection was acquired by intrauterine transmission cannot be confirmed. A recent report has demonstrated the transplacental transmission of SARS-CoV-2 with clinical manifestation in the neonate (Vivanti et al., 2020) , as in this case, which confirms that the mother-to-infant transmission is possible. Therefore, SARS-CoV-2 infection could be considered as a TORCH (Toxoplasmosis, Other (syphilis, varicella-zoster and parvovirus B19), Rubella, Cytomegalovirus, and Herpes simplex virus) infection (Muldoon et al., 2020) . The fact that this case is an intrauterine vertical transmission or not remains controversial, but this is not ruled out. Also, we rule out SARS-CoV-2 infection in the newborn infant as nosocomial. Since the risk of infection was reduced according to Management Guidelines for Obstetric Patients and Neonates Born to Mothers With Suspected or Probable SARS (Maxwell et al., 2017) .

On the other hand, the shedding of SARS-CoV-2 RNA in stool from both patients and breast milk was detected. Thus, human breast milk could be involved in SARS-CoV-2 transmission from mother to newborn infant during breastfeeding but not in this case. However, it is not yet known how SARS-CoV-2 shedding occurs in breast tissue, and whether this viral RNA represents infectious viral particles. We ruled out that the milk had been contaminated because the self-expression of human milk was performed with hand hygiene and after breast decontamination, and it was expressed directly into a sterile specimen container. Although SARS-CoV-2 RNA was not detected in breast milk thirteen days after delivery, it may contain a low viral load or even elevated IgM and IgA antibodies against virus , as has been reported (D. Yunzhu Dong et al., 2020) . Since human breast milk is essential for provide immunity to the infant, the monitoring of the human milk banks is required to prevent the risk of infection through breastfeeding. We recommend that whether SARS-CoV-2 RNA is detected in breast milk, the breastfeeding could be suspended but instead pump the milk to avoid mastitis. Nevertheless, the benefits of human milk could greatly outweigh the risk of vertical transmission of COVID-19 J o u r n a l P r e -p r o o f since it contains IgM and IgA antibodies to SARS-CoV-2 (Yunzhu , suggesting that breastfeeding might have a protective role in neonates. Further studies will determine whether breastfeeding is appropriate during maternal COVID-19 infection. In summary, this report provided evidence on the risk of SARS-CoV-2 infection during pregnancy and breastfeeding. 

Recurrence of positive SARS-CoV-2 RNA in COVID-19: A case report

Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records

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We thank the patient for cooperating with this report. Also, we acknowledge Brenda Yareth Vargas-Castañeda, Luis Ricardo Díaz-Hernández, Beatriz Gutiérrez-Escamilla, and Victor Ivan Rodriguez-Buendía by their technic assistance.

This study was non-funded.

The informed consent was obtained from the patient for publication of this case report.

The authors declare no conflicts of interest.