Case report: The first COVID-19 case among pregnant women at 21-week in Vietnam

Introduction

In December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China [1] and since then it has spread worldwide, causing the coronavirus disease (COVID-19) pandemic as being declared by the World Health Organization on March 11th, 2020 [2]. Pregnant women are considered as the vulnerable group that has increased risk of hospitalization and intensive care unit admission [3]. Therefore, these patients have been prioritized for special care when getting the disease. In this report, we presented the clinical characteristics of a Vietnamese woman having SARS-CoV-2 infection at 21 weeks of gestation. We observed an increase of serum D-dimer and fibrinogen levels from admission day to day 5. We also discussed the hypercoagulability risk in pregnancy and how COVID-19 could potentially increase the risk of having coagulopathy.

Case presentation

A 34-year-old-woman at 21 weeks of gestation was the first confirmed case of COVID-19 in a pregnant woman in Vietnam. She had lived in Russia and then returned to Vietnam on March 25th, 2020. During the required centralized quarantine, her nasopharyngeal swab was tested positive for SARS-CoV-2 by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) on April 5th. One day later, she was transferred to the National Hospital for Tropical Diseases in Hanoi and hospitalized for 21 days. Although she had a history of chronic sinusitis and urinary tract infection, no complications were observed during admission.

On admission, she was asymptomatic with normal vital signs. Three days later, she experienced a productive cough, which was then resolved on day 5. Her cardiovascular, neurological, and gastroenterological exams were within normal limits during hospitalization. Abdominal ultrasound revealed a 21-week-old fetus with a fetal heart rate (FHR) of 154 bpm. Her echocardiography, chest X-ray, and lung pleural ultrasound showed no abnormalities. Her white blood cell, red blood cell, platelet, hemoglobin, hematocrit (Hct), complete blood count along with liver function test (serum glutamic pyruvic transaminase [SGPT], serum glutamic oxaloacetic transaminase [SGOT], and prothrombin time [PT]) and renal function test (Na⁺, K⁺, Cl⁻, BUN, and creatinine) were all within normal limits. During the first three days of admission, her D-dimer level increased from 937 ug/mL to 1,116 ug/mL and then gradually decreased from day 3 to day 21. In addition, the fibrinogen level was at 5.24 g/L on day 1 and fluctuated between 4.2 g/L and 5 g/L during hospitalization. Her CD4 count was 368 cells/mm³ (39.59%) on day 1, which was lower than the normal range. The CD4 count gradually increased and came back to the normal range at 603 cells/mm³ (38.4%) on day 7. Gram-positive bacteria were detected in her sputum smear, whereas other viruses, including hepatitis B virus and human immunodeficiency virus (HIV), were not detected. She was tested positive again for SARS-CoV-2 on April 6th. The RT-PCR test for SARS-CoV-2 was repeated every three days and the result was negative on April 9th, 12th, and 15th. However, her SARS-CoV-2 IgM test was positive on April 15th. The SARS-CoV-2 IgM test was performed for the first time in the hospital due to the limited number of kits and this pregnant woman was given priority.

The patient underwent a computed tomography (CT) of chest on day 1 and peripheral ground-glass opacities indicative of pneumonia were observed. The CT scan was repeated on day 7 to examine the progression of pneumonia and effects of the treatment Aluvia™ (Lopinavir/Ritonavir, AbbVie Deutschaland GmbH & Co. KG, Germany), and the result indicated that pneumonia was resolved. Aluvia that contains lopinavir and ritonavir substances is an anti-retrovirus medicine used to treat HIV and COVID-19. The repeat abdominal ultrasound scan test (USG) on day 10 revealed a normal FHR of 145 bpm in the 22-week-old fetus. No major derangement of laboratory parameters was observed after day 10. The patient was treated with lopinavir 800 mg/ritonavir 200 mg and ampicillin 4 g/sulbactam 2 g starting on day 1. Lovenox^® (Enoxaparin, Sanofi-Aventis, France) 40 mg/SC was added from day 5 because her coagulation profile showed a high level of D-dimer since admission day. Lovenox was discontinued from day 13, whereas lopinavir/ritonavir was continued until day 15. Her HBsAg and anti-HIV antibody test were negative on April 9th. None of the laboratory parameters, including blood pressure, body temperature, and full blood count, were deranged on the following repeated tests. The Doppler echocardiography was done to assess the heart, heart valves, and blood flow of the patient. All cardiac ultrasound parameters, including the ventricular systolic and diastolic pressure, left ventricular ejection fraction, atrial and ventricular volume, and E and A wave velocities, were within normal limits since admission day.

Discussion and conclusions

Distinct characteristics of the obstetric population warrant added consideration during a pandemic. Infectious diseases, such as COVID-19, potentially lead to poor outcomes in susceptible populations, such as pregnant women [4]. Our patient experienced mild symptoms with most laboratory parameters were within normal range. Although the patient had pneumonia until day 7, there was no complication exhibited in this case. Moreover, oxygen therapy and mechanical ventilation was not needed. Importantly, despite not experiencing severe illness, the patient had high D-dimer and fibrinogen level for 15 days, which was the indicator of coagulopathy [5]. As a result, careful examination of dynamic changes in coagulation factors should be considered in COVID-19 patients, especially the pregnant ones.

According to the COVID-19 Treatment Guidelines Panel of the National Institutes of Health, lopinavir/ritonavir or other HIV protease inhibitors are not recommended except in clinical trials [6]. During the hospitalization time of this patient, only Aluvia, which is considered safe for both mothers and fetuses, was available at our hospital. Therefore, the medication was used as the COVID-19 treatment for this patient. More studies such as randomized control trials are needed to determine the efficacy of lopinavir/ritonavir in treating COVID-19 patients, especially pregnant women. In addition, the co-chairs of the American Thoracic Society and Infectious Diseases Society of America (ATS/IDSA) Guideline for Treatment of Adults with Community-Acquired Pneumonia suggested that ampicillin/sulbactam could be used as a combination therapy for low-risk patients and our treatment selection followed this guideline [7]. Furthermore, studies have shown that the severity of COVID-19 was positively associated with coagulopathy indicated by an elevation of D-dimer level [8], [9], [10]. Therefore, anticoagulant medications, such as Lovenox, should be considered if D-dimer level is above the normal range [11]. Since our patient experienced an elevated level of D-dimer, Lovenox was prescribed from day 5 to day 12. With the use of a combination of different medications, our patient recovered and was discharged from the hospital on April 25th.

The clinical manifestations and severity degree of our case were similar to most COVID-19 pregnant cases reported. A systematic review about clinical characteristics and outcomes of pregnant women and their neonates having COVID-19 infection showed that the majority of pregnant cases had mild symptoms [12]. Interestingly, other studies mainly reported COVID-19 pregnant women in their third trimester, while our patient was in the second trimester of gestation. In addition, comorbidities such as diabetes, chronic hypertension, and cardiovascular diseases, have been known to result in severe COVID-19 infection [13]. The fact that our patient did not have these conditions could explain why she had mild symptoms and did not develop complications related to COVID-19, such as acute respiratory distress syndrome. Different from most COVID-19 pregnant cases reported [12], [13], our patient had a medical history of chronic sinusitis and urinary tract infection. In our case, however, no severe symptoms resulting from these two conditions were observed. The association between inflammation of the respiratory and urinary tract and COVID-19 complications remains elusive and future studies are needed to investigate this association.

Our case report has some limitations. Since the patient was in the second trimester of pregnancy and was discharged from the hospital after 21 days of admission, the vertical transmission potential of COVID-19 was not examined. Additionally, real-time RT-PCR was performed for only nasopharyngeal swab, but not other types of specimen, such as serum, urine, and stool. Moreover, the epidemiologic history, including linkage to endemic areas and contact with infected cases, was not investigated.

In conclusion, we presented the clinical picture of the first COVID-19 pregnant case in Vietnam. This case report highlighted the increased risk of developing coagulopathy even in mild and asymptomatic patients. Knowledge of clinical features and outcomes of pregnant women having COVID-19 in their second trimester is limited. Therefore, our findings have important implications in examining and treating COVID-19 infection for this vulnerable population.