Severe metabolic ketoacidosis- Unusual symptom of COVID-19 in non diabetic
The coronavirus (SARS-CoV-2) pandemic and the associated illness COVID-19 have presented a challenge to clinicians, partially due to the initial unfamiliarity with the natural course of COVID-19 and the lack of knowledge on optimal treatment strategies. Clinical manifestation is now known to vary from asymptomatic to respiratory failure and death.
Despite rise in scientific advancements on understanding the virus, it has been a challenge unfolding its pathophysiology in pregnant women.
A case report published by van Amesfoort JE et al. in BMJ cases and reports citing metabolic acidosis as a primary presenting finding in a pregnant patient.
A 21-year-old primigravida woman with a gestational age of 37+6 weeks presented at a hospital in the Netherlands with a fever of 38.0ºC, complaining of headache, fatigue, nausea and vomiting. Her medical history reported childhood asthma and an iron deficiency anaemia.
She had an otherwise uncomplicated pregnancy. Gestational diabetes was routinely ruled out. Having a temperature of 38.0ºC, Covid testing was done for the patient which came out positive.
Fetal well-being was confirmed.
Her vitals were stable including blood pressure, respiratory rate and other parameters thereby rendering her a low risk case of sepsis and was advised outpatient follow up.
Two days later, the patient was readmitted with increasing headache, nausea, vomiting, fever, shortness of breath and thoracic pain worsening on inspiration.
Vital parameters were a blood pressure of 117/76mm Hg, heart rate of 136 beats per minute, temperature of 38.1°C, oxygen saturation of 100% and a respiratory rate of 40 breaths per minute.
Prompted by this maternal deterioration, the patient agreed to insertion of a cervical Foley catheter, aimed at enabling induction of labour.
Pre-eclampsia was ruled out. An ECG did not show signs of ischaemia or arrhythmia.
D-dimer was elevated (2.39mg/L), and CT angiography (CTA) was performed to rule out a pulmonary embolism. The CTA showed no signs of pulmonary embolism or pneumonia. The COVID-19 reporting and data system (CO-RADS) score and CT Severity score were both 6.
CO-RADS 6 refers to evidence of any pulmonary findings on CT consistent with COVID19, in a patient with a positive SARS-CoV-2 test. A CT Severity score of 6 (maximum score of 25) refers to a limited proportion of the lungs being affected by COVID-19.
Infection parameters were partially increased (C reactive protein, 34.1mg/L); leucocyte count, (8.0×109 /L) . Urine and blood cultures were negative.
Arterial blood gas analysis revealed a high anion gap metabolic acidosis with respiratory compensation . Lactate levels, kidney function and liver function were normal . Urinary analysis was positive for ketone bodies.
The cardiotocogram trace and ultrasound did not show signs of fetal distress.
Ketoacidosis can be seen in non-diabetic patients during acute starvation.
Pregnancy is a hypermetabolic state, to which ongoing infection is likely to have added further metabolic demand, making patient more prone to starvation ketoacidosis. There have been reports indicating an association between COVID-19 and an increased risk of (non-diabetic) ketoacidosis.
Supportive management was started to correct the metabolic acidosis.
Treatment effects were monitored with blood gas analysis.
Patient's vitals as well as blood gas analysis improved responding to treatment.
After 48 hours, the Foley catheter was expelled, and labour started with spontaneous contractions.
An uncomplicated caesarean section was performed for fetal distress, under neuraxial anaesthesia. During surgery, maternal condition was stabilised, and after birth vital parameters and the blood gas improved.
A girl was born at a gestational age of 38+3 weeks with a birth weight of 2930g and an Apgar score of 7 and 8 after 1 and 5min.
Umbilical cord blood gas analysis showed an arterial pH of 7.09 with a base excess of −17 and venous pH of 7.29 with a base excess of −12.
After the caesarean section, the patient felt better. However, after 1 day, her condition worsened again with increasing dyspnoea and respiratory rate (23 breaths per minute), oxygen saturation (95% with 4L O2), tachycardia (130 beats per minute) and fever (39.0°C).
On physical examinations, bilateral decreased breathing sounds and crackles were heard.
A CTA showed a consolidation in the left lung suspect for a bacterial pneumonia and no signs of pulmonary embolism. The CT Severity score was 9.
The COVID-19 was defined as moderate to severe based on a bacterial pneumonia and hypoxaemia. Urine, blood and vaginal cultures were negative.
Corticosteroids, antiviral drugs (remdesivir) and antibiotics (moxifloxacin) were started. In the 4 following days, her clinical condition improved. Oxygen supplementation was discontinued after 3days. Treatment with remdesivir and corticosteroids was continued for 3days, and antibiotic treatment with moxifloxacin was continued for 10 days.
In this report, a term-pregnant woman's case with a nondiabetic ketoacidosis provoked by acute starvation as a result of gastrointestinal complaints due to COVID-19. This is another demonstration of the ability of SARS-CoV-2 to cause illness outside the respiratory tract. Furthermore, this illustrates the increased metabolic demand in pregnancy.
Pregnant women produce up to 2–4 times higher levels of ketone bodies in 12 hours of fasting compared with non-pregnant individuals. Furthermore, ketogenesis is increased in pregnancy as it is a state of relative insulinopenia and increased insulin resistance.
Pregnancy also limits the body's ability to compensate for acidosis, due to the fact that pregnant women have relative hypocapnia because of an increased minute alveolar ventilation, resulting in relative respiratory alkalosis. This is compensated by increased renal excretion of bicarbonate. The buffering capacity of bicarbonate is therefore reduced, an effect that is most prominent in term pregnancy.
However, the biggest initial threat to the patient was not respiratory compromise but rather the metabolic acidosis. Maternal acidosis can cause a fetal acidosis through different pathways.
"Induction of labour can contribute to a metabolic demand in pregnant women with a SARS-CoV-2 infection, leading to a severe metabolic acidosis."
There is accumulating evidence that a COVID-19 infection may play a role in the development of ketoacidosis.