A neonate born to mother with COVID-19 during Pregnancy & HELLP syndrome: A possible vertical transmission

Nirmal kumar Mohakud (  nirmal.mahakud@kims.ac.in ) Kalinga Institute of Medical Scinces https://orcid.org/0000-0002-4949-3585 Hari KrishnaYerru Kalinga Institute of Medical Scinces Monalisha Rajguru Kalinga Institute of Medical Scinces Shlok Saxena Kalinga Institute of Medical Scinces Srinitya Kollu Kalinga Institute of Medical Scinces Natasha Sharma Kalinga Institute of Medical Scinces Sushree Samiksha Naik Department of Obstetrics & Gyncology, Capital Hospital, Bhubaneswar


Introduction
The ongoing pandemic caused by a novel coronavirus disease 2019 (COVID-19) or severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has affected all age groups including the newborns [1]. There is a dearth of data on newborns with COVID-19 infection [2,3]. In addition, the published case reports and case series have shown con icts in the mode of transmission from infected mothers to their newborns. The con ict is because of some reports suggesting a possible vertical (in-utero) transmission in contrast to other reports refuting this mechanism [4][5][6][7][8]. According to the published reports, the lowest age of a newborn getting diagnosed with COVID-19 (testing of naso-pharyngeal sample by RT-PCR) is 16 hours. Here we report a preterm newborn who was born to a mother with HELLP syndrome with COVID-19 pneumonia, and was found to be COVID-19 positive (testing of tracheal aspirate by RT-PCR) at the age of 12 hours. HELLP syndrome is a serious complication in pregnancy characterized by haemolysis, elevated liver enzymes and low platelet count occurring in 0.5 to 0.9% of all pregnancies, and in 10 to 20% of cases with severe preeclampsia [9].

Case Presentation
A 30 year old primigravida with history of travel outside compianed of low-grade fever, and malaise. She was tested for COVID-19, and the nasopharyngeal sample was positive. She got admitted to a designated COVID-19 hospital in the Western part of Odisha state. After 2 days, she developed shortness of breath, lack of perception of fetal movement, facial pu ness, and diminished vision. She was referreed to our Institute. She had conceived spontaneously, was immunized and was taking iron-folic acid and calcium tablets regularly. No anomaly scan was done. She was noted to have hypertension during 2 nd month of pregnancy. Antenatal USG done at 33 weks of gestation had shown a single, live fetus with weight of 930 g, AFI of 9, and gestational age of 26±5 weeks. She was having hypothyroidism and was taking thyroxine tablet 25µg once daily. At admission, she was conscious and co-operative. Her vital parameters were as follows: temperature = 98.6 0 F, pulse rate = 112/min, respiratory rate = 30/min, blood pressure = 190/110 mmHg. Physical examination showed: facial pu ness +, pallor +, jaundice +, with urinary catheter in situ (50 ml of red coloured urine in urobag). Her last menstrualperiod (LMP) was on 25/10/19, and expected date of delivery (EDD) was on 1/9/2020. She underwent investigations, and nally a diagnosis of HELLP (haemolysis, elevated liver enzymes, and low platelet count) syndrome with hypothyroidism with COVID-19 pneumonia was made (Table 1). She received treatment as per our Institute protocol. She underwent a caesarean section, and a male baby with weight of 930 g (IUGR) was born (on 16/06/20 at 33+2 weeks). The baby did not cry immediately after birth (Apgar at 1 min = 3/10, and 5 min = 5/10). Resuscitation was done, and the baby was immediately put on mechanical ventilation (SIMV mode with FiO2 = 25%, PIP/PEEP = 12/5 cm of H2O, and rate of 30/min) without delayed cord clamping and skin-to-skin contact. Chest x ray was not suggestive of pneumonia ( Figure 1). The baby developed seizure after 2 hours, and was investigated ( Table 2). Injection phenobarbitone was started along with maintenance uids and antibiotics. Gradully the condition of the baby improved without any seizure recurenc. As the respiratory status and acivity improved, the baby was extubated to CPAP after 24 hrs. RT-PCR of tracheal aspirate taken after 12 hours came positive for COVID-19. Curently, the baby is in the COVID-19 neonatal ward, off respiratory support, tolerating feeds, and gaining weight.

Discussion
There is a dearth of data available on neonatal infection with COVID-19, limited to some case reports and case series. In one review, the authors could found 179 cases of newborns born to pregnant women infected in the third trimester of pregnancy, and getting tested for COVID-19 at birth [5]. These mothers were infected in late pregnancy, and the mean (range) time between delivery and infection was 3 (0 to 25) days. RT-PCRs performed on cord blood and amniotic uid were negative. However, COVID-19 was detected in naso-pharyngeal samples from 6 of 179 newborns at 16 hrs of life (n = 1), 36 hrs of life (n = 2), and 48 hrs of life (n = 3). As a result, it is di cult to determine the timing of transmission in them. However, the following possibilities are plausible: droplet inhalation or contact by infected parents or health-care professionals (transmission at birth), or via breast-feeding. But, the newborns were delivered by cesarean section, immediately separated from their mothers, and placed in isolation. These steps taken in the hospital makes the transmission from the mother unlikely. In addition, breast-milk has not been shown to transmit COVID-19 till date [10]. So, a vertical (transplacental/in-utero) transmission still remains a possibility that cannot be excluded completely [11]. In the index case also, the mother was infected in third trimester, the time between infection and delivery was 3 days, the newborn was delivered by cesarean section, and immediately shifted to ICU without getting contact with the mother.
There have been no clear criteria of what actually de nes a congenital COVID-19 infection. In one study, the authors described 3 newborns with positive antibodies (IgM and IgG) at birth who were born to mothers with COVID-19 infection [7,8]. Whether, these cases t into congenital COVID-19 due to vertical transmission is debated though IgM antibody is of fetal origin (as it can not cross placenta in contrast to IgG antibody) [5]. In a cohort study of 33 newborns, 3 were having severe pneumonia, and found to be positive for COVID-19 RT-PCR of naso-pharyngeal and anal swab samples, on day 2 and day 4 of life [8].
The authors were sceptical about the possibility of peri-natal or post-natal transmission, as these newborns were born by cesarean section like in the index case, and separated from mothers from birth. But the index case in this report was positive at 12 hours of life without severe COVID-19 infection or COVID-19 pneumonia, and is stable currently. It has been described that, maternal COVID-19 infection can cause premature deliveries, respiratory distress at birth, and even intra-uterine fetal death [3,5]. All these could be secondary to the effct of severe hypoxemia resulting from COVID-19 pneumonia in the mother. In the index case decreased fetal movement and resulting birth asphyxia could be due to these factors, as mother had severe COVID-19 pneumonia with underlying HELLP syndrome. Our report has some limitations. We did not evaluate the presence of virus in amniotic uid, cord blood, or placental tissue that could further clarify pathogenesis, and no antobody testing was done in the newborn.

Conclusion
The present report supports the fact that COVID-19 infection may get vertically transmitted from the mother to the fetus. More research in this area could throw light on the pathogenetic mechanism.

Consent to Publish
The patient consented to participate and publish both hers and her child's case report and accompanying image.

Con icts of interest
All authors have no example con icts of interest to disclose Funding Non funded Author contributions HKY, MR, and SS: conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. SK, NS, and SSN: designed the data collection instruments, collected data, carried out the initial analyses, and reviewed and revised the manuscript. NKM: conceptualized and designed the study, coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content. All authors approved the nal manuscript as submitted and agree to be accountable for all aspects of the work. NKM will act as guarantor. Chest X-ray of the newborn done at 1 hr of age