Discussion
Ketones are organized in the liver from free fatty acids. ketosis is a results of reduction in ketone consumption which can be clinically evident by elevated blood concentrations of ketone bodies (β- and hydroxybutyrate, acetone acetoacetate). Covid-19 might accelerate fat breakdown and induce ketosis, with further extension of ketoacidosis (1).
Euglycemic Dka is a rare and acute life-threatening metabolic emergency that the normal blood glucose may delay diagnosis and treatment. This problem is likely due to poor oral intake, treatment with insulin prior to arrival in the hospital, in pregnant women and with SGLT2 inhibitors consumption (5).
Dka must be distinguished from other causes of high anion gap metabolic acidosis including lactic acidosis (which can be associated with metformin consumption), aspirin or acetaminophen toxicity, methanol or ethylene glycol poisoning and chronic kidney disease. Although none of these disorders cause ketoacidosis, several types of acidosis may coexist, such as lactic acidosis and ketoacidosis (6, 7).
In this report, we introduced a patient who has been infected with Covid-19 virus in the context of a mild GDM and normal blood sugar with moderate pulmonary involvement and unexpectedly severe ketoacidosis. Euglycemic Dka is a rare extrapulmonary manifestation of Covid-19 that has been reported in both diabetic and non-diabetic patients, as well as in pregnant and non-pregnant women.
Our patient presented with shortness of breath, fatigue and productive coughs with intensification from two days ago. At the onset, the complaints were particularly ascribed to respiratory effects of Covid-19. Differential diagnosis was expanded when the blood gas analysis showed a high anion gap metabolic acidosis that was not due lactate or toxic agents. Urinalysis showed ketone bodies and lower limit normal blood glucose concentrations at admission. The remaining diagnosis was euglycemic Dka based on the high metabolic demand in pregnancy.
Due to the lack of proteinuria, high blood pressure, hemolysis and increased liver enzymes, preeclampsia also ruled out in this patient.
There are several facts about the physiopathology of ketoacidosis during infection with Covid-19. Like any other disease, these patients may not receive a proper intake due to gastrointestinal complaints which can lead to starvation or fasting Dka (8).
On the other hand, ketogenesis increases in pregnancy and the prevalence of ketoacidosis is higher in pregnant women than in non-pregnant women: 8.9% vs. 3.1%, respectively, due to the increase in the level of hormones secreted by the placenta such as placental lactogen and prolactin, which cause insulin resistance by the antagonistic effects of insulin, and by stimulating lipolysis, increase the production of free fatty acids as a substrate for the production of body ketones (9).
Ketoacidosis also occurs in pregnant women with diabetes in the presence of lower blood sugar, because pregnancy is associated with increased utilization by creating a hypermetabolic condition and reducing glucose production in the body (10).
Covid-19 virus has the ability to bind to the ACE2 receptor in the lungs and pancreas, and by inactivating it, it disrupts insulin secretion and hyperglycemia. Also, by increasing excessive fluid absorption through the RAAS system it can cause causes an irreversible state which can lead to underlying diseases occurrence (11).
Our patient, as in other cases reported from the third trimester of pregnancy has this complication, and is mild to moderate in terms of the severity of lung involvement, the rate of arterial blood oxygenation and biochemical factors associated with the severity of Covid-19 infection, as other cases reported from mild to medium. It seems that the metabolic acidosis of these patients is not consistent with the severity of Covid-19 (2, 12), and the association between Covid-19 infection and pregnancy is sufficient to cause severe metabolic acidosis.
With regard to the severity of pulmonary involvement with Covid-19 in this patient, it may be possible to suggest the patient’s blood type, which was O positive, as a protective factor (13). The patient was diagnosed with papillary thyroid carcinoma in the first trimester of pregnancy. Regarding the association between the patient with Covid-19 and ptc, although factors such as inflammation, immunity, obesity, and oxidative stress are involved, it is not yet clear whether Covid-19 infection could increase or decrease the risk of ptc (14).
Regarding the prognosis of Covid-19 infection in ptc patients, studies so far have shown that in addition to age and underlying disease effecting on the hospitalization process of ptc patients with Covid-19, the treatments and severity of Covid 19 disease in PTC patients were not correlated. Overall, the rate of hospitalization and mortality in ptc patients are lower compared to other cancers at the time of Covid-19 infection (15).