A 26-year-old Somalian woman (Gravida 2, Para 1) who had been living in Sweden for a year presented at the Emergency Department of Skåne University Hospital in Malmö on April 17th, 2020 pregnant at 32+1 weeks of gestation. She was transferred to the Infectious Diseases Department with suspicion of COVID–19. A diagnostic test, based on quantitative real time polymerase chain reaction (qRT-PCR), from a nasopharyngeal swab, was positive for SARS-CoV–2.
She had recently moved from Stockholm to Malmö. In 2015 she had a normal vaginal delivery in Somalia. The patient had an appendectomy and a cholecystectomy in Somalia. Her medical history also included hypothyroidism, currently treated with 150 ug Levothyroxine daily. The body mass index (BMI) on admission to the prenatal care was 47 kg/m2 with length 163 centimetres (cm), weight 126 kilograms (kg). Apart from the obesity, her pregnancy had been without complications. She had received an intramuscular injection of Anti-D immunoglobulin at 28+5 weeks of gestation since she was Rhesus D (RhD) negative and the fetus was RhD positive.
At admission, the patient described a nine-day history of shortness of breath, dry cough, myalgia, nausea, abdominal pain and fever (Figure 1). She had significant abdominal pain on admission but the surgeon did not find any signs of an acute abdominal event. The patient had also noticed reduced fetal movements for the last two days. Obstetric examination including cardio-tocography (CTG) and an abdominal ultrasound showed no abnormalities.
The patient’s respiratory rate was 22 breaths/minute, oxygen saturation 95%, blood pressure 116/71, pulse 113 beats/minute and temperature 37.2 degrees Celsius (oC). The laboratory tests are shown in Table 1. The patient was given morphine, paracetamol and oxycodone for pain relief and also received thromboprophylaxis, Dalteparin 7500 units /day subcutaneously. No additional oxygen was needed.
Table 1: Maternal laboratory results during admission and readmission.
Variable
|
Reference Range
|
Admission Day 1
(17/4/2020)
|
Readmission Day 2
(22/4/2020)
Prior to Caesarean Section
|
Readmission Day 3
(23/4/2020)
|
Haemoglobin
(Hb) g/L
|
117-153
|
113
|
95
|
101
|
Platelet count
x109/L
|
165-387
|
209
|
122
|
179
|
White cell count
x109/L
|
3.5-8.8
|
5.1
|
4.4
|
7.0
|
Neutrophil count
x109/L
|
1.8 - 7.5
|
2.8
|
3.1
|
6.1
|
Lymphocyte count
x109/L
|
1.0 - 4.0
|
1.9
|
0.3
|
0.5
|
Reticulocyte
x109/L
|
28-120
|
-
|
38
|
53
|
Haptoglobin
g/L
|
0.24-1.90
|
-
|
2.02
|
-
|
|
Ferritin
µmol/L
|
13-148
|
-
|
875
|
370
|
C-reactive protein
(CRP) mg/L
|
<5
|
37
|
102
|
136
|
Interleukin-6
ng/L
|
<1.8
|
-
|
211
|
-
|
Procalcitonin
µg/L
|
< 0.05 μg/L
|
-
|
149
|
209
|
P-NT-pro-BNP
ng/L
|
< 150
|
-
|
71
|
-
|
Troponin-T
ng/L
|
<5
|
<5
|
-
|
-
|
Myoglobin
µg/L
|
25-58
|
<22
|
34
|
-
|
Glucose
mmol/L
|
4.2-6.0
|
-
|
4.3
|
4.4
|
|
Aspartate aminotransferase (ASAT) µkat/L
|
0.25-0.6
|
0.38
|
28
|
11
|
Alanine aminotransferase
(ALAT) µkat/L
|
0.15-0.75
|
0.84
|
5.8
|
3.5
|
Alkaline phosphatase
(ALP) µkat/L
|
0.70-1.9
|
-
|
4.6
|
3.9
|
Gamma-glutamyl transferase
(GGT) µkat/L
|
0.15-0.75
|
-
|
5.4
|
5.7
|
Bilirubin
µmol/L
|
5-25
|
-
|
21
|
21
|
Lactate Dehydrogenase
(LDH) µkat/L
|
1.8-3.4
|
-
|
34
|
9.9
|
Pancreatic amylase
µkat/L
|
0.15-1.1
|
0.30
|
0.15
|
0.12
|
-
|
Creatinine
µmol/L
|
45-90
|
50
|
59
|
63
|
Urea
mmol/L
|
2.6-6-4
|
-
|
1.3
|
1.0
|
Uric acid
µmol/L
|
155-350
|
-
|
312
|
267
|
Sodium
mmol/L
|
137-145
|
136
|
135
|
136
|
Potassium
mmol/L
|
3.5-4.4
|
3.5
|
2.8
|
3.6
|
Chloride
mmol/L
|
98-110
|
-
|
107
|
103
|
Calcium ion
mmol/L
|
1.15-1.33
|
-
|
1.10
|
1.06
|
Magnesium
mmol/L
|
0.70-0.95
|
-
|
0.62
|
0.73
|
Plasma Paracetamol concentration µmol/L
|
< 200 µmol/L
|
-
|
67
|
-
|
|
D-dimer
mg/L
|
<0.5
|
5.4
|
4.3
|
5.6
|
Prothrombin-complex International Normalized Ratio (P-INR)
|
0.9-1.2
|
0.9
|
1.0
|
1.0
|
Activated Partial Thromboplastin Time (APTT) in seconds (s)
|
26-33
|
39
|
46
|
45
|
Fibrinogen
g/L
|
2.0-4.0
|
-
|
2.7
|
2.2
|
Antithrombin (IIa)
kIE/L
|
0.8-1.2
|
-
|
-
|
0.66
|
Arterial blood gases
|
pH
|
7.35-7.45
|
-
|
7.43
|
7.40
|
Partial pressure of carbon dioxide
pCO2 in kPa
|
4.6-6.0
|
-
|
4.1
|
5.1
|
Partial pressure of oxygen
pO2 in kPa
|
10.0-13.0
|
-
|
8.6
|
9.9
|
Base Excess
mmol/l
|
22-27
|
-
|
22
|
23
|
Bicarbonate
HCO3- mmol/l
|
-3.0-3.0
|
-
|
-3.2
|
-1.7
|
Lactate
mmol/L
|
0.5-1.6
|
-
|
1.5
|
0.7
|
Saturation of oxygen
%
|
97-100
|
-
|
92
|
93
|
On day 2 (18/4/2020), the patient was relatively stable apart from two short episodes of fever up to 38.9 oC. Due to risk for preterm labour, the patient received 12 milligrams (mg) of Betamethasone intramuscularly to aid fetal lung maturity. Daily fetal monitoring using CTG showed no signs of fetal distress.
The patient was discharged on day 3 (19/4/2020) with a planned obstetric follow-up including fetal growth assessment after recovery. She was prescribed dalteparin for four weeks.
The patient returned to the Emergency Department the next day (20/4/2020) with a sore throat and severe difficulties in swallowing. Apart from tachypnoea (25–35 breaths/minute) and tachycardia (118 beats/minute), other vital signs were normal. After examination, she was discharged with a prescription of Betamethasone tablets for three days (6, 4 and 3 mg) for swallowing difficulties and potassium supplements for the hypokalaemia noted in the blood tests (Table 1).
The patient was readmitted to the Infectious Diseases Department the next day (21/4/2020) (Figure 1). Her COVID–19 symptoms (cough, myalgia, abdominal pain and fever) had worsened and she now presented with dyspnoea. At readmission, the patient’s respiratory rate 42 breaths/minute, blood pressure 114/61, pulse was 120 beats/minute and temperature 38.9 oC. During episodes of coughing, her oxygen saturation fell to 86%, but with 5 litres of oxygen on mask the saturation rose to 99%. Laboratory tests are shown in Table 1.
Her condition deteriorated on day 2 (22/4/2020) of the readmission. In addition to the generalized pain and tenderness, the pain in her right upper abdomen had worsened. Blood tests showed elevation of aspartate aminotransferase (ASAT), interleukin–6 (IL–6) and ferritin concentrations. There was impaired coagulation as shown by a prolonged activated partial thromboplastin time (APTT), high D-dimer, falling platelet count and decreased level of Anti-thrombin III (Table 1). Hemolysis was indicated by a fall in the hemoglobin concentration and rising lactate dehydrogenase levels although haptoglobin concentrations only were slightly elevated (Table 1). Despite her worsening condition, the patient felt active fetal movements and normal intermittent CTG controls were registered. Intravenous antibiotic treatment with Cefotaxime (2 grams, 3 times daily) was initiated due to suspicion of concomitant bacterial infection (Table 1). Blood and urine cultures were taken but since the general condition of the patient had worsened, a decision was made to deliver by Caesarean section (32+6 gestational weeks), on maternal indication. The operation was performed in spinal analgesia in an operating theatre with negative air ventilation. The local hospital guidelines were followed to prevent the spread of COVID–19 (9). An uncomplicated operation was completed within 40 minutes and the total blood loss was 200 millilitres (mL).
After two hours in the post-operative unit, the patient returned to the ward and received thromboprophylaxis, dalteparin at a total dose of 10.000 units divided in two doses. A computed tomography (CT) lung scan, performed later the same day, showed bilateral diffuse, ground-glass opacities with both peripheral and perihilar distribution, but no signs of pulmonary embolism (Figure 2).
Post-operative pain management
Due to deranged liver values, the patient was unable receive paracetamol and due to the COVID–19 infection not able the receive ibuprofen (10). The pain relief was managed by administering 2.5 mL of intravenous morphine as needed. However, the patient’s condition worsened during the night and on examination, the patient was somnolent and lethargic but answered adequately when woken up (Reaction Level Scale 2). The patient’s pain was mostly localized to the upper right quadrant of the abdomen and epigastrium. Her uterus was well contracted and there were no signs of postoperative complications such as bleedings and local infection. On examination, the patient had mitotic pupils that reacted poorly to light stimulation. Even though the patient only was given 7.5 mg of morphine over the course of 8 hours, a morphine over-dose was suspected, and intravenous morphine was replaced by a combination of orally administered Naloxone and Oxycodone. Post-operative mobilization was initiated one day after surgery where after the patient made a steady recovery.
Table 1 illustrates the drastic improvement in the patient’s blood tests on day 3 (23/4/2020) of the readmission. The patient was discharged in good health on the 30th of April, 2020 with thromboprophylaxis planned for 6 weeks postpartum and a follow-up visit to the Obstetrics Clinic.
The neonate
A male baby was delivered with birth weight 2085 grams (37th percentile), birth length 48 cm (99th percentile) and head circumference 33.5 cm (99th percentile). The cord was clamped immediately after birth and the baby was shown briefly to the mother before being taken to a neonatal resuscitation station. At 1-minute after delivery, the baby had a normal heart rate but was gasping and had absent tone and no spontaneous movements. Positive pressure ventilation by a T-piece (neopuff) was given with peak inspiratory pressure (PIP) 20 cmH2O and positive end expiratory pressure (PEEP) between 5 and 7 cmH2O intermittently during the first seven minutes of life. At ten minutes, the baby was spontaneously breathing, albeit grunting, through T-piece continuous positive airway pressure (CPAP) with preductal oxygen saturation between 90–95% at FiO2 (fraction of inspired oxygen) 0.4. Fine crackles could be heard on lung auscultation. Intermittent intercostal retractions were also seen. Skin colour, tone and reflex irritability improved gradually during the stabilisation process. Apgar score; 1 minute: 4 (appearance 1, pulse 2, reflex irritability 0, activity 1, respiration 0), 5 minutes: 6 (appearance 1, pulse 2, reflex irritability 1, activity 1, respiration 1), 10 minutes: 8 (appearance 2, pulse 2, reflex irritability 1, activity 1, respiration 2). Vitamin K was given intramuscularly and a nasogastric tube was inserted. Nasal CPAP with PEEP 6 cmH2O was started.
Arterial umbilical cord blood gas showed mild combined respiratory and metabolic acidosis with pH 7.28, partial pressure of oxygen (pO2) 3.45 (kilopascal) kPa, partial pressure of carbon dioxide (pCO2) 6.97 kPa and base excess –6.8.
The baby was put in an incubator and transferred to the neonatal intensive care unit (NICU) and placed in an airborne infection isolation room (AIIR) with negative pressure ventilation. It was given preterm formula supplemented with intravenous glucose infusion. Venous blood gas was analysed at 4 hours of age: pH 7.27, pO2 5 kPa, pCO2 7.3 kPa, BE –1.8, Hb 184 g/l and lactate 2.7 mmol/l.
After parental consent, formula was changed to donated breast milk. The mother was supplied with a breast pump and instructed in its use. After the initial need of breathing support and supplemental oxygen during day one of life the baby has enjoyed an uneventful clinical course. Nasopharyngeal swabs for SARS-CoV–2 detection were collected at 48 hours and 96 hours of life and were found to be negative in both instances.