Sex: F
Vaccine: COVID19
Symptoms: Hyperglycinaemia, Influenza A virus test, Influenza B virus test, Insulin C-peptide, Mini mental status examination
Clinical narrative: type 2 diabetes melitis; nonketotic HHS without coma; This is a literature report from the Regulatory Authority : A case series and discussion.  In this case series, the authors present patient cases of hyperglycaemic emergencies triggered not by COVID-19 disease but likely by COVID-19 vaccination. The patient experienced symptoms within 48 hours of vaccination and ultimately presented with HHS and/or DKA after the first of 2 vaccinations. The patient tested negative, by polymerase chain reaction (PCR), for active SARS-CoV-2 infection. Within 2 months after hospital discharge, the patient has been completely titrated off insulin and required oral DM medications only. Data suggests that the immune dysregulation caused by the vaccine may worsen diabetes and supports the hypothesis that a similar mechanism underlies the association between COVID-19 infection and diabetes. Case 1: A 52-year-old woman with a history of hypertension presented with polyuria, polydipsia, light-headedness, and dysgeusia of 2 days duration. She reported no fever, myalgias, cough, dysuria, nausea, diarrhoea, decreased appetite, or chest pain. She denied prior positive testing for SARS-CoV-2 but stated that she had received the first of 2 Pfizer COVID-19 vaccination doses 3 days prior to admission. The onset of symptoms began within 48 hours after the vaccination. Upon arrival to the emergency room, her heart rate was 102 beats/min with a respiratory rate of 20/min; blood pressure was 137/88 mmHg, her oxygen saturation was 100% on room air, and the patient remained afebrile. The physical exam was notable for an alert mental status, dry oral mucosa, and body mass index (BMI) of 32.5 kg/m. The nasopharyngeal swab combined test (by the Cepheid Xpet Xpress real-time PCR assay) for SARS-CoV-2, Influenza A and B, and the respiratory syncytial virus (RSV) was negative. The initial labs were remarkable for a blood glucose of 1062 mg/dL, sodium of 154 mEg/L [reference range (RR) 135-145], bicarbonate of 27 mEd/L, blood urea nitrogen (BUN) of 39 mg/dL, and a creatinine of 2.87 mg/dL. The serum osmolality was elevated at 381 mOsm/Kg, the anion gap was 20 mEq/L (RR, 7-16 mEq/L) with an undetectable beta-hydroxybutyrate (in mmol/L; less than 0.2), and the pH was 7.33. The hemoglobin Alc (HbA1c) was 12.0%. The white blood cell (WBC) count was 13.1 K/ uL (RR, 4.8-10.8 K/uL) with a normal differential, the lactic acid dehydrogenase (LDH) was 230 U/L (RR, more than 240 U/L), and the D-dimer was 0.42 ug/mL (RR, 0.27- 0.5 ug/mL). Inflammatory markers including ferritin and C-reactive protein (CRP) were elevated at 752.5 ng/mL (RR, 10-150 ng/mL) and 1.3 mg/dL. (RR, more than 0.8 mg/dL), respectively. There were no signs of active infection nor evidence of an acute ischemic event. The patient was diagnosed with T2DM and nonketotic HHS without coma possibly triggered by the COVID-19 vaccination. Although family medical history was notable for T2DM in the mother, brother, and grandmother, she reported no prior history of diabetes despite regular visits to her primary care physician pre-pandemic. Previous HbA1c values, last checked in 2019, ranged 5.5 percent to 6.2 percent. Intravenous hydration and an insulin infusion were initiated. The polyuria, polydipsia, and dizziness resolved, and the patient was then transitioned to a subcutaneous basalbolus insulin regimen. She was subsequently discharged on insulin glargine 18 units once daily, insulin lispro 12 units with each meal, and metformin 500 mg twice daily. At an outpatient 7-week follow-up visit, her HbA1c had improved significantly to 6.7 percent and a C-peptide level was 1.45 ng/mL, indicating recovery from the prior acute hyperglycaemic emergency and insulin deficiency. Insulin glargine and lispro were discontinued and the regimen was modified to metformin 1000 mg twice daily and weekly dulaglutide 0.75 mg was prescribed. The patient has since continued her weight loss efforts and has reported controlled self-monitored blood glucoses within a range of 80 to 140 mg/ dL throughout the day. Discussion: All 3 cases presented with acute onset of classic hyperglycaemic symptoms and were diagnosed with HHS and/or DKA within 2 to 10 days of their first COVID-19 vaccination, albeit we cannot absolutely rule out that Case 3 had only HHS, without DKA, and another cause for the anion gap metabolic acidosis. The case series demonstrating that the COVID-19 vaccine may trigger hyperglycaemia supports the fourth hypothesis, namely that DM is potentiated by the systemic immune dysregulation and inflammatory response. Since both COVID-19 vaccine and COVID-19 infection trigger a robust systemic immune inflammatory response, it is likely that this is the common mechanism that explains both phenomena. The patient promptly experienced symptoms of malaise and weakness within 48 hours of the COVID-19 vaccination. And 2 patients developed acute onset of overt hyperglycaemic symptoms, including polyuria, polydipsia, and blurry vision within 48 hours. In conclusion, the authors describe here 3 rare cases of hyperglycaemic emergencies, HHS and DKA, developing after COVID-19 vaccinations. Clinicians should be aware of this potential rare complication of COVID-19 vaccinations. Future studies will hopefully pinpoint the underlying mechanisms.  No follow-up attempts are possible; information about the lot/batch number cannot be obtained. No further information is expected.; Sender's Comments: As there is limited information in the case provided, the causal association between the events type 2 diabetes mellitus and Hyperglycinaemia and the suspect drug BNT162B2 cannot be excluded. The case will be reassessed once new information is available.