Although there are some data about the effects of COVID-19 during pregnancy, it is important to analyze these data in order to guide clinical practice. This includes early detection, detection, isolation of patients, epidemiological investigation and diagnosis, as well as early treatment. This is a report of three cases of COVID-19 confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) of nasopharyngeal secretions collected in swabs from pregnant women in the city of Vitoria, Espirito Santo State, Brazil. All three patients had fever, shortness of breath and diarrhea. Two others had abdominal pains, while two others had a cough. Three patients were diagnosed with COVID-19 and had a severe clinical evolution. The duration of stay in the intensive care unit was over 10 days. Two of the patients were able to recover, while one was left in ICU with irreversible and multiple organ failure. The method of delivery was determined based on the severity of the maternal infection and the obstetric indication. Cesarean was recommended in two cases of severe maternal COVID-19 that had improved. These babies were born prematurely and tested negative by RTPCR for COVID-19.

KEYWORDS:

COVID-19, SARS-CoV-2

INTRODUCTION

In 2019, a new coronavirus, the severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 (SARS-2 CoV-2) was identified. It is associated with pneumonia and has been named coronavirus disease COVID-19. This emergent infectious disease was first reported in Wuhan (China) by the World Health Organization (WHO). It has been declared a global emergency by the WHO and a pandemic 1 by WHO. Although studies on the effects of COVID-19 in pregnancy are limited, due to its transmissibility and potential development of severe acute respiratory symptoms, routine clinical practice of obstetrics must investigate COVID-19.

The pandemic is facing a significant challenge for pregnant women. Patients with pregnancies must attend monthly medical consultations for their prenatal care and delivery 2. Patients who miss these appointments are at greater risk of contracting COVID-19 either in the outpatient clinic or hospital environment. The impact of COVID-19 in pregnancy and infants is not yet known. One Chinese study, which tested amniotic fluid and cord blood as well as neonatal throat and swabs from mothers infected with COVID-19, found all samples were negative. Another study, however, determined that three of the placentas of COVID-19-infected women had been positive for the virus 3. The transmission rates of the virus from mother to child are unknown. The opportunity to protect pregnant women and their offspring, as well as the healthcare professionals involved in their care, will be provided by an assessment of clinical data.

This study reports on three cases of COVID-19 in pregnant women suffering from severe respiratory failure. It also evaluates the management of COVID-19 infections in obstetrical clinics in Vitoria and Espirito Santo States, Brazil.

CASE REPORTS

Case 1

A 28-year old woman was pregnant and worked as a nurse assistant. She had 31 weeks gestation. She sought emergency room treatment for fever and hyperemic lesion in her right lower limb. This could be indicative of a bacterial skin disease. The patient was not a smoker and did not have any previous history of asthma, tuberculosis, or pneumonia. The patient was treated with intravenous ceftriaxone (2 g) and 40 IU of heparin per day. However, after two days the symptoms began to worsen. Tactile hypotension and tachypnea were symptoms. The patient was given fifteen liters of oxygen per hour by the mask and transferred to an ICU at another public hospital. The patient was admitted to critical conditions that required immediate intubation and mechanical ventilation. She had a lactate dehydrogenase of 268 U/L, a D-dimer lower than 300 ng/mL (normally below 500 ng/mL), and 3,900 white blood cell (WBC). Computed tomography scans showed bilateral ground-glass opacities. The patient was suspected to have SARS-CoV-2 infection. Due to her CT findings and severe pregnancy evolution, the patient was given 500 mg azithromycin daily, 75 mg of oseltamivirphosphate twice daily, and 400 mg of hydroxychloroquine twice daily for five days. Specific diagnostic tests were used to exclude pulmonary embolism.

She tested negative for coronavirus by the real-time reverse transcription-polymerase chain reaction (RT-PCR) testing nasopharyngeal secretions swabs during the initial hospitalization. Due to severe medical conditions, a C-section was performed. A healthy, 31-week-old infant weighing 2,380g was born due to prematurity. He was then transferred to the neonatal unit. Apgar score of 8 in the first minute of life was acceptable for gestational age. It was 9 at the fifth minute. Due to her respiratory condition, the puerperal female was kept in hospital for 18 days. She received supportive care and continued treatment in the ICU. After being admitted, the patient was tested for COVID-19 using RT-PCR. After 5 days, the newborn was cleared of COVID-19 via RT-PCR. After 23 days, the puerperal woman showed positive signs and was released without complications.

Case 2

A 34-year old puerperal woman, who was a housewife during her second pregnancy and had previously delivered, went to the emergency room on the fifth day following delivery due to acute respiratory insufficiency. She didn’t report any abnormalities in antenatal care, nor was she admitted to hospital for delivery. She gave birth via C-section at 40 weeks gestational age to a girl newborn weighing in at 3,875g. Her Apgar scores were 8 and 9, respectively, in the first and fifth minutes. A severe dry cough, acute dyspnea and lower back pain with mild fever were reported by the mother 24 hours prior to her hospitalization. Although the chest CT scan suggested that the mother had viral pneumonia, the results did not support COVID-19. Angiotomograpy of thorax showed no evidence of pulmonary embolism. The oxygen saturation was 91%. LDH was 328 U/L, with D-dimer below 300 ng/mL. Initial leukograms showed 5,000 WBC.

Ceftriaxone (2g/day), azithromycin 500 mg/day, oseltamivir 75 mg twice daily and enoxaparin were administered to the patient (initially 40 mg daily, increasing in increments upto 80 mg/day). Three days after delivery, the RT-PCR test for SARS-CoV-2 showed positive results. 400 mg was given first, then 400 mg every five days for the next five days. Meropenem (500 mg three time a days) and vancomycin (1 g twice a daily) were also administered. Ceftriaxone has been discontinued.

The patient’s condition in her lungs worsened. The patient was kept in ICU with a persistent high temperature for 13 days. She received supportive care including oxygenation, ventilation and vasoactive medications. After this time, the patient was discharged from the ICU and transferred to the rehabilitation unit. Both her husband and the infant tested negative for COVID-19.

Case 3

A 25-year old pregnant woman in her third and final pregnancy, and having had two previous pregnancies, was referred by the hospital at 28 weeks six days gestational age. She complained of upper respiratory symptoms, fever, myalgia, diarrhea, and nausea for five days. The patient’s condition deteriorated to an intense fatigue and non-productive cough. Although she did not mention any comorbidities in her case, her husband was afflicted by fever for the past 24 hours. He also reported that he had been in contact with two COVID-19-positive coworkers. She was transferred to ICU. To accelerate the fetal lung maturation, corticosteroid therapy was initiated with 2 g hydrocortisone. Also, oseltamivir (zithromycin), ceftriaxone and enoxaparin were administered in standard doses. Mechanical ventilation was also required. The D-dimer levels were not abnormal (308 ng/mL), so pulmonary embolism could not be excluded by specific diagnostic tests. The oxygen saturation was 94%. Initial leukograms showed that there were 4,000 WBC and 11% lymphocytes.

The COVID-19 serological test resulted in negative results twice. However, the RTPCR on nasopharyngeal swab secretions showed positive results for SARS-CoV-2. 400 mg of hydroxychloroquine were administered twice daily, followed by 400 mg every day for five days. Due to severe oligohydramnios and the critical circumstances of the mother, a C-section was needed.

Delivered was a female infant weighing 1,255g. This is adequate for gestational age. Apgar scores were 6 and 7 respectively in the first minute and fifth minute. The newborn was negative for COVID-19 via RT-PCR, but she was referred to the neonatal ICU due to extreme prematurity. Due to right hemithorax, she received systemic antibiotic therapy. After 30 days, the neonate was released in good condition.

For 22 days, the mother was in ICU. The mother was given meropenem (500mg three times daily) along with vancomycin (1 mg twice daily) and polymyxin B, which required intubation and mechanical ventilation. During hospitalization, the LDH result increased from 226 to 524 U/L. . The patient survived the ICU stay, but her blood pressure dropped to 60/40 mmHg. Her condition progressed to irreversible shock, multiple organ failure, and ultimately death. All blood cultures came back negative.

DISCUSSION

The scientific evidence for mother-to-child transmission of COVID-19 (MTCT), is still not conclusive.

Current guidelines recommend that each case be evaluated according to the instructions of the obstetrician, and the severity of the maternal conditions. It is agreed that SARS-CoV-2 infection during pregnancy can increase maternal and fetal risk. COVID-19, an infectious disease, can lead to severe pneumonia, admissions to ICU, and possibly even the possibility of a premature delivery. In two cases of three, this occurred. All cases had fevers and patients’ clinical conditions rapidly worsened.

ICU hospitalizations lasted more than 10 days for all three patients. Two of the patients were able to recover, while one was still in ICU. The other suffered from refractory shock and eventually died.

Due to the necessity to perform C-sections, two of the three newborns were born prematurely. None of the newborns showed symptoms of infection and all three were negative for COVID-19 by RT-PCR, which tested nasopharyngeal secretions. Due to their prematurity, two of the newborns were admitted to the ICU. The three cases are summarized in Table 1.

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Table 1

Summary data from three pregnant women with COVID-19.

Brazil has other cases of maternal death from COVID-19 5. The conditions of women who were infected by SARS-CoV-2 during pregnancy have been observed to progress within a very short time after the incubation period and transmission. Case 1 was admitted for a suspected bacterial skin infection. Her condition quickly progressed into pneumonia within a few days. In China, 12.6% of COVID-19 patients were presymptomatic. They also found a mean time of 3.96 days between presymptoms and diagnosis. To identify these cases, it is crucial to be alert and to perform a thorough anamnesis.

Another Chinese study has shown that pneumonia in pregnant women infected with COVID-19 is not different from pneumonia in women who aren’t pregnant. A small number of pregnant women infected with COVID-19 showed no evidence of vertical transmission. Nine of these women developed pneumonia after they became pregnant. All patients had a cesarean and all newborns were tested negative for the virus. A second study, which included 43 pregnant COVID-19 women in New York City, reported a 4.7% incidence of critical illness. These data were comparable to those for adults not suffering from COVID-19 infection 7 Similar results were also found in a study that included pregnant Chinese women infected by COVID-19. There were no maternal deaths and no confirmed cases of intrauterine transmission to the fetuses 8. All three patients presented with fever in the cases reviewed here. One had shortness, one had diarrhea, two had abdominal pain and two had a cough. The clinical conditions of all three patients improved rapidly.

There are still questions regarding the MTCT or newborn infection. A case report was made of a pregnant lady with coronavirus and a newborn infected by SARS-CoV-2. It was reported that the newborn was infected 36 hours after delivery. However, it was not confirmed as MTCT 10. Although MTCT has been suspected in one case, the newborn’s RTPCR result was negative. COVID-19 is not a common condition, and many children with it are not recognized.

A placental morphological analysis of three cases of neonatal mothers infected by COVID-19 showed no evidence of infection. In our cases, RT-PCR was not performed on amniotic fluid or placenta. Two of the babies examined were born prematurely due to the need for a C-section. However, they didn’t show symptoms of SARS-CoV-2, which indicates that there was no MTCT. It is not known if the empiric administrations of hydroxychloroquine by our institution enabled patients to recover (cases 1 & 2). There is currently no recommendation for hydroxychloroquine or chloroquine in COVID-19 treatment. These drugs should not be used in pregnant women unless they have a greater benefit than the side effects.

This study revealed that case 1 was a medical professional. This highlights the need for extra security measures to protect front-line workers against contamination. Brazil’s only research on COVID-19 in pregnancy has been a review and analysis of the initial data. This study recommended that pregnancies be postponed 14. Because COVID-19 presents a new challenge to health professionals, its impact on mothers is not known. Therefore, it is important to conduct new studies to better understand its effects on mothers and their children.

CONCLUSION

There is no evidence to support the safety or timing of vaginal delivery for pregnant women with COVID-19. It is important to choose the right method of delivery based on the circumstances of each case. In severe cases, cesarean sections should also be indicated. This is the first publication to date on the deaths of pregnant Brazilian women who have had COVID-19 confirmed.

• ETHICS
• The women did not identify their identities as compromised. The study was approved by the university hospital’s ethical review board.
• FUNDING
• This research was not funded by any funding agencies from the commercial, not-for-profit, or public sectors.

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