Management of an Early Onset Sepsis with COVID19 in a Premature Neonate - A Case Report

Background: neonates appear to be less affected by COVID-19 than adults. The overall challenge has been for all medical specialties, including neonatal intensive care. Unfortunately, current knowledge about severe acute respiratory distress syndrome of coronavirus 2 (SARS-CoV-2) infection is limited. Case presentation : In this report, we present an ill premature neonate who were born from mother with negative nasopharyngeal swab test for SARS-COV-2. On the 5th day of life, baby developed respiratory distress. Nasopharyngeal swab test for SARS-COV-2 was positive. Intubation and intratracheal surfactant was implemented. Patient was treated with Intravenous immunoglobulin and corticosteroid over a period of 14 days. Conclusion: The basis of treatment in neonatal covid19 is supportive care. Some studies have treated infants with various drugs such as Hydroxychloroquine, Favipiravir, and Remedsivir. In our case, we used corticosteroids and IVIg to treat a 5-day-old baby. We got good results after 2 weeks of treatment with dexamethasone 0.3 mg / kg per day and 2 g / kg IVIg (in three divided doses). It seems that these treatments, along with adjuvant ventilation and the use of endotracheal surfactants, can improve the patient's general condition.


Background
According to scienti c reports (at the time of writing), neonates appear to be less affected by COVID-19 than adults (1). The overall challenge has been for all medical specialties, including neonatal intensive care. Unfortunately, current knowledge about severe acute respiratory distress syndrome of coronavirus 2 (SARS-CoV-2) infection is limited. Based on studies and case series, most of newborn with this infection have an asymptomatic or mild illness, but a small percentage of patients require neonatal intensive care unit (NICU). Due to the lack of a global guideline at the beginning of the epidemic, many of these infected infants were admitted to the NICU, but as the experience of health workers gradually increased, several local guidelines were introduced. But in some cases, we have to take additional therapies to improve the babies. In the next section, we introduce an infant with COVID-19 infection in Iran. The baby's parents completed a written consent form regarding the patient's report.

Case Presentation
A preterm (gestational age = 34 weeks + 3days) infant boy was born via caesarian section on October 13, 2020, in Tehran Iran. His Apgar scores were 9 and 10 in 1 and 5 minute after birth, respectively. Moreover, the weight after birth was 1610 grams. His 45-years-old mother had 3 previous abortions (one in 8 weeks of gestational age, another one aborted medically due to Down syndrome in 18 weeks of gestational age and the last in 16 weeks of gestational age due to PPROM at 2015) and this pregnancy (gravid 4) was in the result of donated egg and IVF. She had no signs and symptoms since 14 days before delivery (also 14 days after delivery) and had negative nasopharyngeal swab test for SARS-COV-2 (by RT-PCR assay).

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At rst, the baby was well but gradually became ill during the rst day of his life. He got mild respiratory distress and sometimes needed oxygen hood, therefore the patient was transferred to NICU of Bahrami hospital. Laboratory tests and imaging (Fig. 1A) was performed and antibiotic therapy was started (Ampicillin + Cefotaxime).. The baby's respiratory distress gradually improved from the second day of birth and did not need oxygen, and low-volume feeding began.
With increasing daily feeding volume, the baby developed respiratory distress and mottling on the fth day of his life again. Subsequently, he was intubated due to progressive respiratory condition. After intubation and supportive cares, suddenly patient had status seizures that was not controlled with one loading dose of Levetiracetam and two loading doses of Phenobarbital infusion. Finally one Phenytoin loading dose infusion suppressed seizure clinically. Again Lab tests was performed and antibiotics were leveled up (Vancomycin + Meropenem). Patient had hypokalemia, hypocalcaemia, respiratory acidosis, lymphopenia, elevated LDH, thrombocytopenia and elevated INR (Table1). FFP and platelet was transfused and patient treated with more potassium and calcium supplementations. Chest X-ray showed a diffuse opacities in both lungs (Fig. 1B). He was injected by surfactant (4 cc Crossruff ®) twice through endotracheal tube. Therefore baby improved somewhat due to early intervention and ventilation support. Considering the Covid19 pandemic, nasopharyngeal swab was sampled for SARS-COV-2 that the result was positive thus we isolated him in a separate room. We also implemented strict protective protocols for his nurses. On the next day, sudden severe respiratory distress occurred and chest tube was inserted in regard of pneumothorax. Chest ultrasonography reported mild pleural effusion.
The patient was treated with daily oral Sildena l due to increased pulmonary artery hypertension (according to echocardiography). Lumbar puncture showed normal values and negative CSF culture so bacterial meningitis was ruled out. Both blood and urine culture tests results was negative. During the following weeks, according to neurological consultation, Phenytoin and Phenobarbital was discontinued but maintenance treatment with Levetiracetam was continued. His brain ultrasonography was normal.
Infectious disease specialist suggested treatment with corticosteroid and IVIG for Covid19 disease, so we treated him with Dexamethasone 0.3mg/kg/day interavenously (twice a day) for following 14 days and IVIG for 3 days(A total of 6 grams). After 4 days of Sildena l treatment (age: 10 days old), echocardiography reported normal pulmonary artery pressure. Repeated Chest X-ray had better aeration and some opacities was diminished (Fig. 1C).
During the following days, ventilator settings were reduced and we weaned the patient; then, he underwent NIPPV therapy and after 3 day we removed the chest tube (age: 19 days old). We repeated nasopharyngeal swab test for SARS-COV-2 that the result was negative. Serologic lab test result was negative (IgM an IgG against SARS-COV-2). Gradually we tapered Dexamethasone over 5 days. Then little by little, the patient began to be fed with breast milk. Finally patient discharged from hospital at age 30 days old. At age 28 days old, patient had ROP, stage I in Zone III. In follow up, ROP examination had normal report. Also ABR test was normal. at the present, he has a normal neurologic state, normal EEG and normal brain ultrasonography after 6 months and antiepileptic therapy(Levetiracetam) is tapering.

Discussion And Conclusions
There is no consensus on the vertical transmission of Covid19. Some studies have founded mother-tochild transmission of covid19 impossible. Furthermore, some studies claim that vertical transmission is possible(2). In our case, mother had no signs and symptoms of infection and his nasopharyngeal swab test was negative. Although there is some report of possible vertical transmission of coivd19 infection from mother that they had history of disease in 6 weeks before delivery (3). Also with epidemic condition of covid19, we could not exclude the transmission of covid19 from asymptomatic carrier mother to fetus.
There was several studies that reported diagnosis and management of covid19 early sepsis in neonates. Zeng  In our case, radiographic ndings were nonspeci c, also due to instability of the patient, we were not able to get chest CT scan (computed tomography). Some studies showed that radiographic ndings in neonates could be normal and may be show thickened lung texture, mild pulmonary infection, ground glass opacity, and patchy shadow under pleura, and in the chest CT scan, we may see subpleural lesions with localized in ammatory in ltration. (4,5) During this pandemic, there are few reports of neonatal early-onset infection of SARS-COV-2. Premature neonates maybe at risk of more severe signs and symptoms. Up to now, no valid guideline for the treatment of Covid19 disease in neonates has yet been published. Therefore, the management of Covid19 disease in neonates is usually different in each hospital (7) and in each country, medical groups have been developed guidelines for the neonatal COVID-19 disease (guideline models in Italy(8), United Kingdom(9), United State(10), Islamic Republic of Iran(11) addressed at reference). Undoubtedly, these are urgent steps against the pandemic, but due to constant updates and some controversial data, health systems have di culty in determining the best guidelines. In addition, it is clear that our knowledge about early onset infection of SARS-COV-2 is incomplete in many ways.
In this paper, we report our experience about use of corticosteroid and IVIg in covid19 pneumonia in one neonate. There is no speci c drug for COVID-19. The principle of care is supportive (including oxygen therapy, electrolyte maintenance, acid-base balance, nutritional support). Most of studies for newborns with severe acute respiratory distress syndrome implemented surfactant, nitric oxide, mechanical ventilation. According to some studies, recommended ventilation in neonates with COVID-19 is highfrequency oscillating ventilation (5). In our study, at rst we used intratracheal surfactant and Assist Control (A/C) mode ventilation then Synchronized intermittent mandatory ventilation (SIMV) mode ventilation until extubation.
some studies had different experience. Sagheb reported good outcome of using Hydroxychloroquine in treatment of covid19 pneumonia in two cases (12). Kamali used Oseltamivir in a 15 day old neonate and baby discharged with good condition(13) however, there is insu cient data to suggest any bene t of these medication. (14) Coronado et al used Hydroxychloroquine and azithromycin for a 3-week-old patient (14). Moolasart treated a 47-day-old male newborn with Favipiravir, Hydroxychloroquine, and Lopinavir/Ritonavir. He claimed that a Favipiravir-based regimen may be the drug of choice for coronavirus disease 2019 pneumonia in the newborn (15). Hopwood used Remdesivir and corticosteroid and plasma in a 4 day old neonate that had good outcome(16) in our case, we used corticosteroid and IVIG for treatment of 5 day old neonate. IVIG has been used in some pediatric with Covid19 in special conditions(17). We achieved good results after 2 week treatment of Dexametasone 0.3 mg/kg/day and 2 gr/kg IVIG (in three divided doses). It seems that this treatments, along with adjuvant ventilation and the use of intratracheal surfactants, was able to improve the patient's lung and pleural involvement. A: chest x-ray after NICU admission . B: chest x-ray after intubation . C : chest x-ray after 10 days