A Pregnant Woman With COVID-19, Diabetic Ketoacidosis, and Pancreatitis

The novel coronavirus infection 2019 (COVID-19) is a pandemic viral disease officially named by World Health Organization (WHO) on March 11

Hormozgan Med J . Vol 25, No 4, 2021 199 Kheirandish et al hmj.hums.ac.ir http with lying down. She denied any history of anorexia, shortness of breath, chest pain, dysuria, discoloration of urine, and flank pain. Vital signs at the time of admission included blood pressure (BP) 110/80 mm Hg, pulse rate (PR) 120 beats per minute, respiratory rate (RR) 25 per minutes, oral temperature (T) 37ºC, and O 2 saturation of 100% in ambient air. On physical examination, the only positive point was mild epigastric tenderness. Fetal heart rate (FHR) was 164 beats per minute. The rest of the exam was normal. The laboratory evaluation showed, amylase 382 U/L, triglyceride (TG) 7664 mg/dL, cholesterol 979 mg/dL, and blood sugar (BS) 382 mg/dL. Venous blood gas (VBG) contained pH 7.2, HCO3 12, and Pco2 25. The rapid urinary test revealed the ketone body (Table 1).
Abdominal sonography showed evidence of pancreatitis such as pancreatic enlargement and inflammation, the presence of mild free fluid in the left pararenal space, and an incidentally discovered 4 mm gall stone. According to the laboratory and imaging findings, diagnosis of DKA and pancreatitis was considered. On the second day of hospitalization, she was intubated due to respiratory distress and referred to our center. Intravenous hydration and insulin infusion that had started in the first hospital were continued until acidosis was subsided and blood sugar controlled. Because of hypotension, despite good hydration, we prescribed hydrocortisone 50 mg three times a day for only one day and discontinued when her blood pressure returned to normal. Eventually, she underwent plasmapheresis three times at the intensive care unit (ICU) (Figure 1), and serum TG level dropped dramatically. On the fourth day, the polymerase change reaction (PCR) test for COVID-19 infection was positive, and antiviral therapy with remdesivir and Kaletra (lopinavir/ritonavir) was started, and she was transferred to COVID-19 ICU. Due to suitable oxygen saturation, relative contraindication in acute pancreatitis, and destructive effects on triglycerides and blood glucose, we did not start corticosteroids again. With improvement in the clinical situation, she was extubated and transferred to COVID ward on the seventh day of admission. Finally, the patient was discharged with a good general condition (RR: 18 and O2 saturation 98%) with no significant lung involvement on a chest CT scan ( Figure 2). Gemfibrozil 450 mg daily and omega-3 1000 mg two times a day were prescribed her after hospital discharge. She was completely well one month later during follow-up and eventually delivered a healthy baby without any complications.

Discussion
We presented the case of a young T1DM pregnant woman that was controlled by insulin therapy. She presented Pregnancy is an incomplete immune suppression status, making women more susceptible to infections, and disease-related morbidity is higher during pregnancy (9). COVID-19 might present in pregnancy with the atypical presentation of clinical symptoms other than respiratory ones (10). There are two case reports of COVID-19 associated pancreatitis during pregnancy until now. The first case was a T1DM patient who presented with gastrointestinal symptoms without any predisposing factors for pancreatitis. She had no respiratory distress. Although the symptoms our patient presented with were similar to the first patient, but the concomitant conditions, including DKA and elevated TG were only present in our patient. Another case report was about a pregnant woman with respiratory symptoms and pancreatitis without other causes of pancreatitis in contrast to our case (10,11). Though COVID-19 presents mainly with respiratory symptoms, the prevalence of gastrointestinal symptoms in patients with COVID-19 is estimated to be between 17% and 25% (12,13). On the other hand, pancreatitis is a relatively common disease with an increasing prevalence in hospitalized patients with various causes, including gallstones, alcohol consumption, drugs, and viruslike mumps (14,15). Currently, there is no conclusive evidence that COVID-19 is the cause of acute pancreatitis (16). However, the presence of ACE2 receptors in the pancreas, which are the binding site for the virus (16,17), and concomitant metabolic disorders in patients with COVID-19, such as hyperglycemia and dyslipidemia, suggests that it could lead to pancreatitis directly by binding to the ACE2 receptors or indirectly through hyperglycemia, DKA, and hypertriglyceridemia. While glycemia and lipid values were entirely under control on the second day of admission, it can be suggested that the virus-induced pancreatitis through various mechanisms illustrated previously. As a result, pregnancy is a high-risk condition, and metabolic disorders in COVID-19 during pregnancy should be considered and rapidly corrected. It is necessary to mention that we could not use imaging modalities to evaluate the pancreas because of pregnancy.

Conclusion
We reported a case of DKA with acute pancreatitis in the context of severe hypertriglyceridemia in a diabetic pregnant patient with PCR confirmed COVID-19. Although the concurrency of multiple illnesses in a patient is rare, our case had multiple potentially severe and fatal conditions. The pathophysiology of COVID-19 associated pancreatitis has not been well known yet; it could be explained by the direct binding of the virus to ACE2 receptors and indirectly with a trigger of dysglycemia and hypertriglyceridemia.

Availability of Data and Materials
The authors confirm that the data supporting this study's findings are available within the article.

Authors' contributions
Study concept and design: AR, Drafting of the manuscript: MK & FY, Acquisition of data: KS, Critical revision of the manuscript: MK, Study supervision: MKB. All authors have read and approved the manuscript and ensure that is the case.

Ethical approval
The study received ethics approval from the Ethical Committee of Hormozgan University of Medical Sciences under the ethics code: IR: HUMS.REC.1399.506, and it complies with the statements of the Declaration of Helsinki. Written informed consent for the publication of the article and any associated images were obtained from the patient.