ELEVATED ANION GAP AS A MARKER OF SEVERE SARS-COV-2 INFECTION IN PREGNANT PATIENTS WITHOUT DIABETES: A CASE SERIES

SESSION TITLE: Biological Markers in Patients with COVID-19 Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: In December 2019, a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in a global pandemic. The literature has been slowly growing in the subgroup of pregnant women but the metabolic derangements of pregnancy and SARS-CoV-2 have not been well described. METHODS: In this case series, we review 9 patients with severe SARS-CoV-2 infections admitted to the medical ICU at a single institution between 2020-2022, during the delta variant wave. RESULTS: Of the nine critically ill patients, the mean age was 32 ± 6.4 years with fetal age on admission of 27 ±2.81 weeks and 29 ±2.91 weeks at delivery. Average CRP of 114 ± 25 mg/L. In eight of 9 patients (89%), there was an anion gap metabolic acidosis (AGMA) on admission. The average albumin-corrected anion gap was 18±1.93. 75% of patients had mild ketonuria based on urinalysis. However, 50% had documented symptoms of nausea, vomiting, or diarrhea. While betahydroxybutyrate was checked in 2 patients, neither were abnormal. One had lactic acidosis, but none required vasopressors at time of identification. No renal failure or diabetes was noted and only two had abnormal glucose tolerance tests. At delivery, average PEEP was 10± 4 cmH2O with an average respiratory rate of 28 ± 4 breaths per minute. All patients with AGMA delivered early resulting in preterm delivery. 75% of the fetuses showed signs of distress at the time of delivery, which was the primary indication for delivery in 37.5% of deliveries. 37.5% of deliveries were due to significant maternal hypoxia. The only patient without AGMA did not deliver early. CONCLUSIONS: After excluding renal failure, toxin ingestion, and lactic acidosis, only ketosis can weakly explain the AGMA. There have been several studies that highlighted the association between COVID and ketone production. In pregnancy, placental production of glucagon and human placental lactogen and subsequent insulin resistance increases susceptibility to ketosis. A recent study posited that COVID could cause placental abnormalities. Therefore, pregnant women may be more susceptible to significant ketosis because of COVID infection. In one of our cases, the combination of hypoxia and acidosis could not be managed safely by the ventilator and resulted in early delivery. CLINICAL IMPLICATIONS: Ketosis and an elevated anion gap could be a marker for more severe outcomes in pregnant patients with COVID. This case series highlights the challenges of managing the metabolic demands of critically ill pregnant patients infected with SARS-CoV-2. DISCLOSURES: No relevant relationships by Calli Bertschy no disclosure on file for Joey Carlin;No relevant relationships by Jessica Ehrig No relevant relationships by Shekhar Ghamande no disclosure on file for Jordan Gray;No relevant relationships by Abirami Subramanian

ATYPICAL PRESENTATION OF MUCORMYCOSIS IN A NONSEVERE COVID-19 PATIENT

SESSION TITLE: COVID-19 Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Coronavirus Disease 2019 (COVID-19) infection ranges from asymptomatic to severe disease as defined by WHO. Emerging fungal infections such as mucormycosis and aspergillosis have been described in critically ill patients, most notably in India, when treated with steroids due to severe COVID-19 [1]. We present a unique case of an atypical presentation of mucormycosis in a non-severe COVID-19 patient not treated with corticosteroids. CASE PRESENTATION: A 19-year-old male with type 1 diabetes mellitus presented to the emergency room for evaluation of shortness of breath, nausea and fatigue. History was significant for insulin noncompliance with home blood glucose in the 300s and a positive COVID-19 test one day prior to arrival. Initial vitals positive for tachycardia, tachypnea and hypertension while on room air. Labs showed leukocytosis 14,000 cells/uL, bicarbonate 7.2 mmol/L, anion gap 24.8, glucose 428 mg/dL, beta-hydroxybutyrate 58 mg/dL and nucleic acid amplification COVID-19 positive. Physical exam showed left eyelid and facial swelling, nasal congestion without sinus tenderness or other deformity, and kussmaul breathing pattern. CT face confirmed left periorbital cellulitis. Transfer to tertiary center for Ophthalmology evaluation was attempted but refused due to capacity. He was started on diabetic ketoacidosis treatment as well as broad spectrum antibiotics with the assistance of Infectious Disease, however COVID-19 treatments were held due to mild illness. Despite these interventions, he became stuporous and amphotericin was started. MR Brain showed findings suggestive of cavernous sinus thrombosis, acute ischemia and local mass effect. ENT then performed an endoscopic antrostomy with ethmoidectomy and biopsies were taken. Pathology resulted as invasive fungal sinusitis with 90° branching hyphae confirming mucormycosis and a lumbar drain was placed with intrathecal amphotericin started for concern of mucormycosis meningitis. The patient was ultimately transferred to a tertiary care center where he expired. DISCUSSION: Mucormycosis, an angioinvasive fungal infection affecting the immunocompromised and diabetics, is rare but deadly. The estimated prevalence in the United States is 0.16 per 10,000 hospital discharges [2] and bears a mortality rate of 46%. Recent systematic reviews report 275 cases of COVID associated mucormycosis with 233 in India [1] with 76.3% receiving corticosteroids prior to diagnosis [3], likely contributing to an immunocompromised state. Our case demonstrates that despite not receiving corticosteroids, even those with mild COVID-19 are at risk for this disease. CONCLUSIONS: Patients with diabetes, immunocompromised states, and now COVID-19, presenting with orbital symptoms warrant consideration of mucormycosis. Prompt management of the underlying condition, IV amphotericin, and possible debridement may increase survival. Reference #1: John TM, Jacob CN, Kontoyiannis DP. When Uncontrolled Diabetes Mellitus and Severe COVID-19 Converge: The Perfect Storm for Mucormycosis. J Fungi (Basel). 2021 Apr 15;7(4):298. doi: 10.3390/jof7040298. PMID: 33920755;PMCID: PMC8071133. Reference #2: Kontoyiannis DP, Yang H, Song J, et al. Prevalence, clinical and economic burden of mucormycosis-related hospitalizations in the United States: a retrospective study. BMC Infect Dis. 2016;16(1):730. Published 2016 Dec 1. doi:10.1186/s12879-016-2023-z Reference #3: Singh AK, Singh R, Joshi SR, Misra A. Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India. Diabetes Metab Syndr. 2021 Jul-Aug;15(4):102146. doi: 10.1016/j.dsx.2021.05.019. Epub 2021 May 21. PMID: 34192610;PMCID: PMC8137376 DISCLOSURES: No relevant relationships by james abraham No relevant relationships by christian ALMANZAR ZORRILLA No relevant relationships by Grace Johnson No relevant relationships by Thanuja Neerukonda No relevant relationships by Blake Spain No relevant re ationships by Michael Su No relevant relationships by Steven Tran No relevant relationships by Margarita Vanegas No relevant relationships by Alexandra Witt

An Unusual Case of Autoantibody-Negative KetosisProne Diabetes (KPD) Secondary to Marked Insulin Resistance

KPD is classically regarded as an atypical form of diabetes caused by near-complete beta-cell failure. A 37-year-old Egyptian man (BMI: 27.7 Kg/m2) presented with hyperglycemia (362 mg/dL) and DKA (arterial pH 7.20, ketonemia 5.0 mmol/L, ketonuria 80 mg/dL) . He was afebrile, with recent polyuria, polydipsia and weight loss. HbA1c was 107 mmol/mol (11.9%) and blood tests excluded diabetes secondary to endocrinopathies. SARS-CoV-2 RT-PCR test was negative. IV insulin infusion (0.1 IU/kg/h) and IV fluid therapy were started. He was shortly transitioned to a sc basal-bolus insulin regimen (0.7 IU/kg/day) . Mixed-meal tolerance test (MMTT) revealed a peak 120-min stimulated C-peptide of 12.3 ng/mL, suggesting marked insulin resistance. Islet autoantibodies (ICA, IAA, GADA, IA-2A, ZnT8A) and insulin receptor autoantibodies (IgG/IgM) were negative. HLA genotyping detected the following haplotypes: DRB1∗01, ∗04;DQA1∗01:01P, ∗03:01P;DQB1∗03:02P, ∗05:01P. Insulin dose was gradually reduced and insulin therapy was discontinued after 4 months in favor of metformin (2550 mg/day) plus sc semaglutide (up to 1 mg/week) . After one year, MMTT revealed a peak 60-min stimulated C-peptide of 8.25 ng/mL. During the 18-month follow-up period, fasting capillary beta-hydroxybutyrate values were <0.2 mmol/L and HbA1c remained <48 mmol/mol (<6.5%) , indicating disease remission. This case suggests the existence of an autoantibody-negative KPD subtype driven by marked insulin resistance rather than by insulinopenia.

Starvation Ketoacidosis in the Third Trimester of Pregnancy

Introduction: Starvation ketoacidosis represents one of the three metabolic acidoses caused by the accumulation of ketone bodies within the bloodstream. Outside of late pregnancy, it is a relatively rare condition. In late pregnancy, the placental production of the hormones estrogen, cortisol, and human placental lactogen combined with increased lipolysis causes greater insulin resistance and an overall catabolic state which improves nutrient availability for vital fetal growth. However, this also allows for a magnified response to fasting that results in increased ketone production and in rare cases “accelerated starvation.” In this case, we present a 25-year-old pregnant patient who presented with nausea, vomiting, and poor oral intake, who was found to be in starvation ketoacidosis. Case Description: A 25-year-old G2P1001 cis female with a previous medical history of migraines presented at 33 weeks gestation with nausea, vomiting, and poor oral intake for four days prior to admission in the setting of COVID-19 infection. Patient presented hemodynamically stable and in no acute distress. Fetal non stress test on admission was reactive. Initial lab work revealed a glucose of 95, anion gap of 21, and a bicarbonate level of 7. A beta hydroxybutyrate (BHB) level was elevated at 5.26. Arterial blood gas showed a pH of 7.2 and a PCO2 of 23, consistent with an anion gap metabolic acidosis. Urinalysis revealed 3+ ketones. Overall labs were consistent with starvation ketoacidosis and the patient was immediately resuscitated with dextrose containing intravenous fluids and an insulin drip to help shunt away from ketoacidosis. Her BHB rapidly downtrended to 1.28 within 12 hours and within 24 hours it normalized. Her metabolic acidosis continued to improve throughout her hospitalization. She was able to tolerate a regular diet prior to being discharged home. A few weeks later, she had an uncomplicated full term delivery of a healthy baby. Discussion: Starvation ketoacidosis outside of pregnancy is rare and takes at least two weeks to manifest as a mild ketoacidosis. In pregnancy, patients are in an insulin resistant state which increases with gestational age, making them prone to ketoacidosis particularly in the second and third trimesters. Ketoacidosis in pregnancy is not only harmful for the pregnant individual, but for the developing fetus as well. Ketones can cross the placental barrier, leading to neurological impairment and even fetal demise if the acidosis is not addressed quickly. Prompt treatment with IV fluids, dextrose, and insulin is imperative to prevent neurodevelopmental compromise. Patients with appropriate and timely treatment can continue on to have uncomplicated pregnancies and deliveries.

New Onset Autoimmune Diabetes Associated with Acute SARS-COV-2 Infection

Introduction: Infection with SARS-CoV-2 has been shown to cause complications affecting nearly all organ systems of the human body. Here, we outline a case of SARS-COV-2 associated with new onset of autoimmune diabetes. Case Description: A 62-year-old female with past medical history of class III obesity, primary hypothyroidism, obstructive sleep apnea, and endometrial cancer established care with a multidisciplinary bariatric team in March 2021. This team included a dietician and psychologist to promote healthful lifestyle intervention with the intent to undergo bariatric surgery in December 2021. At a follow up visit in September 2021 her HbA1c was 6.7% (normal < 5.7 %) and she was diagnosed with type 2 diabetes treated with healthful lifestyle. After lifestyle modification the patient successfully lost 40 pounds. In December 2021, she presented to the ED (Emergency Department) complaining of fatigue and neuropathy. She was found to be hyperglycemic with glucose 369 mg/dL (normal 70-100 mg/dL). β-hydroxybutyrate was 32.1 mg/dL (normal 0.20-2.81 mg/dL) and anion gap was 10 mmol/L (normal 3-13 mmol/L). She was resuscitated with fluid and referred urgently to Endocrinology. One week later, she was seen in the office by her endocrinologist for initial consultation. She was acutely complaining of anosmia and ageusia and found to be positive for acute SARS-COV-2 infection. Bloodwork revealed an increase in HbA1c to 13.9 %, fasting glucose 303 mg/dL (normal 70-100 mg/dL), normal C-peptide 1.6 ng/dL (normal 0.5-3.3 ng/dL), elevated GAD antibody 154.3 IU/mL (normal 0-5 IU/mL), elevated anti-Islet Cell antibody IgG ratio 1:64 (normal < 1: 4), elevated anti-Islet Antigen 2 antibody >120 U/mL (normal 0–7.4U/mL), and elevated anti-Zinc Transporter 8 antibody 500 U/mL (normal 0–15 U/mL). Patient was diagnosed with autoimmune diabetes associated with acute SARS-COV-2 infection and was started on basal-bolus insulin with improvement in her hyperglycemia. She did not require hospital admission or steroid treatment for SARS-COV-2 infection. Discussion: Although viral infections are associated with type I diabetes related autoimmunity in children, this case study is unique regarding its mechanism in association with SARS-CoV-2 infection. Potential mechanisms underlying onset of diabetes in patients with SARS-COV-2 infection are still under investigation. One potential mechanism involves pancreatic beta cell dysfunction with diminished insulin secretion due to a systemic inflammatory cascade. This case is unique in as the patient’s C-peptide was still detectable indicating intact beta cell function. Furthermore, the patient’s diabetes paradoxically worsened after a more healthful lifestyle and 40-pound weight loss. This patient’s case of autoimmune diabetes illustrates the need for further research into the mechanisms underlying the onset of diabetes after SARS-COV-2 infection.

Euglycemic diabetic ketoacidosis in a patient with COVID-19 case report

Purpose of The Study Awareness of Covid-19 virus infection can precipitate decompensation of chronic diseases such as type 2 diabetes Mellitus. Euglycemic diabetic ketoacidosis (eu- DKA) has been seen in patients using sodium-glucose co-transporter 2 inhibitor (SGLT2i) and with COVID-19 infection. Methodology Authors identified the case while providing clinical care of a 61-year-old man with medical history of Diabetes Mellitus Type II using SGLT2i and hypertension presented to the Emergency Room with chief complaint of fever, chills, dry cough, watery diarrhea and general malaise 5 days prior arrival to the hospital. Summary of Results A 61-year-old man Puerto Rican male with medical history of Diabetes Mellitus Type II using sodium-glucose co-transporter 2 inhibitor (SGLT2i), and hypertension, already vaccinated against COVID-19, who presented to the Emergency Room with chief complaint of fever, chills, dry cough, watery diarrhea and general malaise 5 days prior arrival to the hospital after returning from a recent family trip to Florida. Home medications include Empagliflozin. Patient referred he had a recent travel to Florida (United States) and was in contact with a family member infected with COVID-19 infection. Physical examination was remarkable for dry oral mucosa and laboratories showed a metabolic acidosis with a high anion gap of 20 mEq/L with a marked increase in plasma b-hydroxybutyrate of 57.8 mg/dL and a central glucose <300 g/dL. Patient tested positive for COVID- 19 infection. Chest X-ray showed bilateral scattered peripheral hazy groundglass opacities. Considering mentioned findings patient placed on airborne isolation precautions and was admitted to Medical Intensive Care Unit where he was started on DKA protocol with continuous intravenous regular, D5W and aggressive hydration. Medical therapy also included Remdesivir and Dexamethasone. Patient improved after 2 days with resolved eu-DKA. Patient transferred to Internal Medicine Ward. Conclusion Eu-DKA has been seen in patients using SGLT2i and with COVID-19 infection;several cases described in literature are suggestive of a specific association between these factors. Our case also highlights the importance of early recognition and management of euglycemic DKA in patients using SGLT2i infected with COVID-19, both increase the risk of dehydration. Physicians must be aware and identify this patients earlier in outpatient setting and be more aggressive in hydration, maintaining euvolemic status to avoid admission to Intensive Care Unit.