Multifactorial Effects of Covid-19: A Review of Published Autopsy Reports

Introduction: SARS-CoV-2 is responsible for the current global pandemic. SARS-CoV-2 infection underlies the novel viral condition coronavirus disease 2019 (COVID-19). COVID-19 causes significant pulmonary sequelae contributing to serious morbidities. The pathogenesis of COVID-19 is complex with a multitude of factors leading to varying levels of injury numerous extrapulmonary organs. This review of 124 published articles documenting COVID- 19 autopsies included 1,142 patients. Method(s): A PubMed search was conducted for COVID-19 autopsy reports published before March 2021 utilizing the query COVID-19 Autopsy. There was no restriction regarding age, sex, or ethnicity of the patients. Duplicate cases were excluded. Findings were listed by organ system from articles that met selection criteria. Result(s): Pulmonary pathology (72% of articles;866/1142 patients): diffuse alveolar damage (563/866), alveolar edema (251/866), hyaline membrane formation (234/866), type II pneumocyte hyperplasia (165/866), alveolar hemorrhage (164/866), and lymphocytic infiltrate (87/866). Vascular pathology (41% of articles;771/1142 patients): vascular thrombi (439/771)-microvascular predominance (294/439)-and inflammatory cell infiltrates (116/771). Cardiac pathology (41% of articles;502/1142 patients): cardiac inflammation (186/502), fibrosis (131/502), cardiomegaly (100/502), hypertrophy (100/502), and dilation (35/502). Hepatic pathology (33% of articles;407/1142 patients): steatosis (106/402) and congestion (102/402). Renal pathology (30% of articles;427/1142 patients): renal arteries arteriosclerosis (111/427), sepsis-associated acute kidney injury (81/427) and acute tubular necrosis (77/427). Conclusion(s): This review revealed anticipated pulmonary pathology, along with significant extrapulmonary involvement secondary to COVID-19, indicating widespread viral tropism throughout the human body. These diverse effects require additional comprehensive longitudinal studies to characterize short-term and long-term COVID-19 sequelae and inform COVID-19 treatment.

Acute kidney injury in patient with severe SARS-CoV-2 infection.

Acute kidney injury (AKI) during SARS-CoV-2 infection is frequent and associated with mortality. Pathophysiology of AKI is multifactorial, and encompasses direct (viral invasion, endothelitis and thrombosis, renin-angiotensin-aldosteron system activation, cytokine elevation) and undirect mechanisms (hemodynamic instability, effect of mechanical ventilation, nephrotoxic medications). Acute tubular necrosis is the most frequent histological lesion identified, but glomerular disease can also be observed. To date, there is no specific treatment of SARS-CoV-2 induced AKI.Copyright © SRLF 2021.

Spectrum of Indication Kidney Biopsies in Community Acquired Aki

Introduction: Community acquired acute kidney injury (CA-AKI) in low income settings is different from that in the high income settings. Infections, poisoning, toxic envenomations and pregnancy related AKI are common. Kidney biopsy is seldom performed in these patients unless atypical clinical course or features are present. We have established a prospective cohort of patients with CA-AKI at the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh in India. We present the spectrum of kidney biopsies in patients who underwent kidney biopsy in this cohort. Method(s): The study is a single centre, prospective, observational cohort study of patients with CA-AKI at PGIMER. Patients aged >12 years and with a diagnosis of CA-AKI are eligible for enrolment. Patients with underlying CKD, urinary tract obstruction, COVID 19, malignancy or heart failure are excluded. Clinical and laboratory data are recorded at baseline. Follow up visits are scheduled at 1 and 4 months after hospital discharge. Kidney biopsies are done only in those patients who have atypical clinical course or features (e.g. persistent kidney dysfunction despite other clinical improvement, strong clinical suspicion of dominant glomerular involvement or interstitial nephritis etc.). We present the spectrum of histopathological diagnoses that were recorded in such patients till date. Result(s): Till now, 646 patients have been included in the cohort. The leading causes of CA-AKI are sepsis (52%), obstetric complications (14%), envenomation (8%), nephrotoxic drugs (6%) and poisons (3%) (figure 1). 18.4% patients had died after CA-AKI. At >=3 months after CA-AKI, 16.3% patients had not recovered completely with persistent eGFR <60 ml/min/1.73m2. 44 patients had undergone kidney biopsy in this cohort. Incomplete recovery, and clinical or diagnostic dilemmas were indications for doing kidney biopsy. The leading clinical diagnoses in this subgroup were sepsis (23%), nephrotoxic drugs (23%), envenomation (9%), obstetric causes (6.8%) and others (25%). Acute interstitial nephritis, acute tubular necrosis and acute cortical necrosis were most common histologic diagnoses (table 1). Combinations of various histologic features were not uncommon. Pigment casts were recorded in 13 patients. 4 patients had acute cortical necrosis, 2 being after post-partum AKI and one each due to acute gastroenteritis and unknown animal bite. Glomerular involvement were recorded in 8 patients (table 1). Thrombotic microangiopathy was present in 4 patients. In this subgroup of patients who underwent kidney biopsy, 3 (7%) had died and 8 (18%) had eGFR <60 ml/min/1.73m2 at >=3 months. Figure 1: Causes of CA-AKI in patients [Formula presented] Table 1: Histologic diagnoses in kidney biopsies in CA-AKI cohort. [Formula presented] Conclusion(s): Acute interstitial nephritis and acute tubular necrosis, alone or in combination with other findings, were the most common histologic diagnoses in indication kidney biopsies in CA-AKI. Adverse outcomes (mortality or progression to CKD) are common after CA-AKI. No conflict of interestCopyright © 2023

SARS-CoV2 Infection and Acute Kidney Injury - A Rare Presentation

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) is one of the most devastating and lethal pandemics in human history. The disease initially affected adults much more than children, but now pediatric patients are being more commonly affected. Symptoms are often mild in pediatric age and characterized by the occurrence of fever and gastroenteritis. Respiratory involvement is generally benign in this age group and improves with symptomatic treatment. Kidneys can be a target of the disease and several factors have been incriminated. We report the case of a 5-year-old patient hospitalized for acute kidney injury following an asymptomatic SARS-CoV2 infection. We aim to focus practitioners' attention on a different aspect of renal involvement in this disease.Copyright © 2023, Pakistan Pediatric Journal. All rights reserved.

Bilateral Cerebral Strokes and Adrenal Hemorrhage Associated with Mis-A

INTRODUCTION: Multisystem Inflammatory Syndrome in Adults (MIS-A) is an underrecognized post-infectious manifestation of COVID-19.We report a case of a 21-year-old male with MIS-A who presented with adrenal hemorrhages, acute kidney injury (AKI) and cerebral strokes leading to multiorgan system failure and death. DESCRIPTION: A 21-year-old, morbidly obese male presented at an outside hospital with COVID-19 and abdominal pain. His abdominal CT demonstrated bilateral adrenal hemorrhages, he was discharged home on hydrocortisone. A month later was readmitted with fever, diarrhea, thrombocytopenia and AKI. Laboratory work revealed creatinine 5.49mg/dL, ferritin 701ng/ml, BNP 3020 pg/ml and D-Dimer 17,650 ng/ml. He received hydrocortisone, intravenous immunoglobulin and enoxaparin. Fever subsided and renal function normalized. On day 7 he developed acute altered mental status and recurrent AKI. Head CTA showed multiple short stenotic segments in the anterior circulation, diminutive appearance of several intracranial arteries and basal ganglia hypodensities. Brain MRA demonstrated extensive bilateral acute/subacute strokes, no evidence of sinus thrombosis and markedly decreased caliber of internal carotid, left middle and anterior cerebral arteries without evidence of thrombus. He received aggressive neurocritical care management including decompressive craniectomy and pulse steroids for suspected vasculitis. Due to the severity of his neurological injury and poor neurologic prognosis family elected to withdraw support. His autopsy demonstrated hepatomegaly, acute tubular necrosis, bilateral adrenal hemorrhages and hypercellular bone marrow with myeloid predominance. Neuropathology showed severe segmental stenosis of the carotid arteries and bilateral vertebral arteries. DISCUSSION: Stroke is a potentially life-threatening complication of COVID-19 including large vessel occlusion and less frequently vasculitis-like phenotype with vessel wall enhancement. Despite initial improvement, our patient developed an acute extensive ischemic stroke leading to a devastating neurologic injury. The neuropathology findings suggest SARS-CoV-2 associated vasculitis. Stroke in the context of COVID-19 may have different pathogenetic mechanisms, clinical characteristics and complications that warrant further investigation.

Cholera in the Time of Covid

INTRODUCTION: Cholera is endemic to 50 countries with most US cases acquired during international travel. However, several cases have occurred from the ingestion of local oysters, crabs, and shrimp with resident Vibrio cholerae strains on the Gulf Coast. DESCRIPTION: A 52-year-old man with insulin dependent diabetes mellitus and well controlled HIV presented with hypovolemic shock. He reported 4 days of non-bloody diarrhea, poor oral intake, and oliguria. Before symptom onset, he ate crabs and tasted the water they were boiled in. He was prescribed azithromycin outpatient which mildly improved his diarrhea but presented to the hospital due to dizziness. He was initially hypotensive but this improved with 2 liters of normal saline without needing vasopressors. He had a blood glucose of 417 mg/dL, sodium bicarbonate of 13 mmol/L, anion gap of 29, creatinine of 10.5 mg/dL, calcium 8.3 mg/dL and corrected sodium of 124 mmol/L. Lactate and beta-hydroxybutyric acid levels were normal. Prior to admission, he took his insulin despite little oral intake. Given his glucose level and anion gap acidosis, he was placed on an insulin drip for concern of diabetic ketoacidosis (DKA). Stool PCR was positive for Vibrio cholerae and Salmonella enterica. Blood cultures were also positive for S. enterica. He received doxycycline for cholera and 14 days of ciprofloxacin for salmonella bacteremia. During his hospitalization, he got 14 liters of fluids with resolution of electrolyte abnormalities by discharge. DISCUSSION: In this patient, the anion gap acidosis was concerning for DKA but normal ketones made this diagnosis less likely. Cholera infection leads to "rice water" stool outputs up to 200cc/kg/hour in the first 2 days then ending after 4-6 days with profound electrolyte abnormalities. Due to rapid volume loss, patients present in hypovolemic shock with hyponatremia, hypocalcemia and hypoglycemia. Anion gap metabolic acidosis occurs due to acute tubular necrosis as in this patient. Stool culture is the gold standard for diagnosis. Treatment with doxycycline, ciprofloxacin or azithromycin decreases the duration of illness and reduces stool volume by 50%. Despite its rarity in the US, cholera should be considered and promptly treated in patients presenting with copious diarrhea, hypovolemia, and renal failure.

Multisystem Inflammatory Syndrome in Adults (Mis-a) after Covid-19 Infection

INTRODUCTION: Multisystem Inflammatory Syndrome was first described in children (MIS-C) after COVID-19 infection, it is characterized by gastrointestinal symptoms, shock, fevers, elevated inflammatory markers, and systolic dysfunction. A few similar presentations have also been reported in young adults designated as Multisystem Inflammatory Syndrome Adult type (MIS-A). Often, due to multi-organ involvement, extensive testing is undertaken with no yield of a clear etiological factor. We present a case of a 23-year-old male who was admitted into the Critical Care Unit for Encephalopathy with multi-organ dysfunction. DESCRIPTION: A 23-year-old male with a medical history of Williams-Campbell syndrome complicated by severe bronchiectasis and obstructive lung disease requiring 2 liters of oxygen at baseline, presented to the hospital with severe Encephalopathy, notably, he tested positive for COVID-19 one month before presentation with no increase in oxygen requirements until hospital presentation. Vitals were otherwise stable. Initial lab values were significant for an elevated AST of 6,620, ALT of 9,540, Creatinine of 4.71, Troponin-I of 3,913, CRP of 19.2, IL-6 of 22.1, and Ammonia of 171. Further investigative workup, including imaging, did not reveal a clear etiology for his presentation. An Echocardiogram however showed left ventricular dysfunction with an ejection fraction of 41%. Management included: broad-spectrum antibiotics which were discontinued after negative infectious workup, steroids for a suspected exacerbation of his lung condition, lactulose, and CRRT being initiated due to worsening renal function which was attributed to cardiac dysfunction leading to Acute Tubular Necrosis. MIS-A was eventually suspected as a diagnosis of exclusion considering the recent history of COVID-19 infection. Steroids were continued leading to gradual improvement of lab values. DISCUSSION: With COVID-19 continuing to make an impact, it is essential to be cognizant of various presentations and sequela. There have been multiple reports of different kinds of sequela, such is our case of MIS-A for which a long steroid taper is the mainstay of treatment. We want to raise awareness in the medical community of the possible consequences of COVID-19 infection such as MIS-A.

Anti-Glomerular Basement Membrane Disease Sans Kidney Involvement

Introduction: Anti-Glomerular Basement Membrane (anti-GBM) is an autoimmune disease involving glomerular and pulmonary capillaries diagnosed in 1 patient per million per year. Predominant lung involvement can be seen in 6% of patients most of which still demonstrate microscopic hematuria and biopsy with typical linear IgG immunofluorescence (99%). Case Description: We report a case of a 57-year-old man who presented with several weeks of dyspnea and myalgia, and was found to have acute kidney injury and multifocal tree-in-bud groundglass opacities throughout both lungs (Figure 1). His serum creatinine was elevated to 4.5 mg/dL from baseline of 0.8 mg/dL three months earlier but no proteinuria or hematuria. COVID19 was negative. Bronchoscopy showed blood throughout the tracheobronchial tree. Anti-GBM was elevated at 80 AU/mL. CRP was elevated at 17 mg/dL. Further work-up for other infectious or autoimmune causes was unremarkable. Kidney biopsy showed acute tubular necrosis (ATN), mixed interstitial inflammatory infiltrate, and one isolated fibrous cellular crescent. Immunofluorescence was negative. Due to the concern for progression of untreated anti-GBM disease, the patient was given high dose steroids, plasma exchange, and oral cyclophosphamide. His anti-GBM titer decreased to an undetectable level. Creatinine improved to 2.33 mg/dL. Discussion(s): This case brings to light a rare variant of anti-GBM with no detectable kidney involvement and presents a therapeutic dilemma. Two independent pathologists reviewed kidney biopsy and felt that crescent was a non-specific result of prior glomerular injury or pauci-immune focal glomerulonephritis. ANCA serologies were negative, and there were no other systemic manifestations. ATN was attributed to poor intake and Naproxen use. The patient received a typical anti-GBM treatment but more data are needed to support this approach in mild cases. (Figure Presented).

Cannabinoids May Be a Trigger or a Stop of Glomerular and Podocyte Injury From Parvovirus B-19 Infection

Introduction: Cannabinoids are widely distributed recreational substances and young patients with chronic epilepsy tend to use the substance even though harmful side effects such as acute tubular necrosis (ATN) and acute interstitial nephritis (AIN) have been reported. This is a rare case of glomerulopodocytopathy that might be triggered by Cannabinoids to raise awareness among clinicians and to emphasize on the need for patient education concerning the deleterious side effect of these substances. Case Description: A 21 years-old African American male was brought to the emergency room with seizure disorder and hypertension. Initial lab results showed a creatinine kinase of 233, serum creatinine of 1.13 mg/dL, it peaked at 7.6 in 72 hours. Upon nephrology consultation, obstructive nephropathy was ruled out. His renal ultrasound showed severe echogenicity. Urine microscopy showed granular cast with no WBC or RBC casts. His urine protein creatinine ratio was 1.3 gm. A physical examination showed mild lower extremity edema, he denies NSAIDs use. Serology was negative for ANA, Anti dsDNA, Anti Smith Ab, ANCA, COVID-19, HIV, HCV. Serology for Parvovirus B-19 (IgG) was positive while IgM was negative, APOL1 gene wasn't done due to lost follow up. 3 months earlier creatinine was 0.9 mg/dL, at time he was admitted for respiratory illness treated with steroid and antibiotics. Pathology revealed collapsing glomerulopathy in 4/22 glomeruli, no interstitial fibrosis and tubular atrophy and mild arterio- and arteriolosclerosis. His renal function responded well to pulsed steroids, He was maintained on 1 mg/kg daily prednisone taper, and his creatinine started trending down, while the edema resolved and the blood pressure normalized. The patient was discharged with nearly normal creatinine and a urine protein to creatinine ratio of 0.3. Discussion(s): Cannabinoids induced AKI with ATN or AIN are common. The renal injury related to delta-9-tetrahydrocannabinol (active ingredient in marijuana). The cannabinoid might trigger glomerulopathy and podocytopathy due to underlying viral illness could need further investigations, or it can be a protective substance for the glomerulus. Being vigilant with a high index of suspicions to any rapid progression of GN with a decline of renal functions, in order to take immediate actions with a diagnostic biopsy;prompting treatment to reverse salvaged renal functions.

Importance of Renal Biopsy in the Current COVID-19 Era: Acute Phosphate Nephropathy in a Patient With COVID-19 and New Systemic

Introduction: Lupus nephritis is a common manifestation of systemic lupus erythematosus. About 40-60% of patients with systemic lupus erythematosus will have renal involvement. We present a case of a young lady with SARS-CoV-2 pneumonia who additionally presented with alopecia, arthritis and acute renal injury. Initially, the consulting team presumed the diagnosis to be due to lupus nephritis. The patient was treated with IV methylprednisolone and oral prednisone. The renal biopsy revealed widespread calcium phosphate crystals within the tubular lumens, suggestive of acute phosphate nephropathy. Electron microscopy showed diffuse foot process effacement consistent with minimal change disease. Case Description: A 20-year-old lady with no past medical history presented with right-sided chest pain, myalgias, fever, and vomiting for 5-6 days. She had proteinuria and serum creatinine of 5 mg/dl. She was SARS-CoV-2 positive. She also had frontal alopecia and photosensitivity over the past five months, along with swelling/tenderness in her wrists and MCPs over the past year. The patient's mother had a diagnosis of lupus which was well controlled on Hydroxychloroquine. Further lab work revealed lymphopenia, positive for smith, coombs, cryoglobulins, RF, RNP, and SSA. Other pertinent work-up was negative. The patient was started on induction therapy for possible lupus nephritis of 1 g IV solumedrol daily for three days. The patient progressively became anuric, and creatinine peaked to 8 mg/dl. Dialysis was initiated. Her urine output improved after the third dialysis session, and dialysis was stopped. Her creatinine improved to 2.4 mg/dl. After the biopsy confirmed phosphate nephropathy, a focused history failed to reveal a cause. She denied sodium phosphate bowel preparations, consuming star fruit or ethylene glycol exposure. Discussion(s): This case shows the importance of biopsy even in a well-known condition such as lupus nephritis. The etiology of renal failure in SARS-CoV-2 is primarily acute tubular necrosis, with collapsing focal segmental glomerulosclerosis also reported. Calcium phosphate deposition is not a reported complication of COVID-19 or lupus nephritis. The tubuloreticular inclusions can be found with lupus nephritis and viral infection. The etiology of phosphate-induced nephropathy remains unclear.

ACUTE KIDNEY INJURY AS A PREDICTOR OF MORTALITY IN PATIENTS WITH COVID-19

SESSION TITLE: Late Breaking Posters in Critical Care SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: Multiple mechanisms may cause acute kidney injury (AKI) after mechanical ventilation. Cross-talk between the lung and kidney precipitates other complications such as fluid overload, electrolyte derangements and pro-inflammatory cytokine production. In this study, we compared hospital mortality rates in unvaccinated COVID-19 patients with respiratory failure (requiring mechanical ventilation) who developed oliguric AKI. METHODS: Using an observational database, we analyzed 3183 unvaccinated hospitalized COVID-19 PCR-positive patients at Methodist Health System (Dallas, TX) from March 2020 to December 2020. The primary endpoint was all-cause in-hospital mortality in patients with respiratory failure requiring mechanical ventilation who developed AKI (as defined by the kidney disease improving global outcomes (KDIGO) guidelines). We also counted the rate of kidney replacement therapy and degree of kidney recovery among the survivors who developed AKI. Chi-square (X2), Fischer’s exact test, and odds ratio tests were used to analyze observed variables. RESULTS: Of the 3183 COVID-19 patients, 351 (11%) developed respiratory failure requiring invasive mechanical ventilation. Of those, 313 (89%) had previously normal kidney function (no documented CKD). Of the 313 intubated patients, 186 (59.4%) developed AKI and 127 (40.5%) patients did not. Thirty-five (18.9%) of the patients who developed AKI survived hospital admission, while 54 (42.5%) patients without AKI survived (OR = 3.306, 95% CI = 1.98-5.51, P<0.001). Ischemic acute tubular necrosis from septic shock was the most common cause of AKI. Hyperkalemia and metabolic acidosis were the most common indication for kidney replacement therapy, and continuous kidney replacement therapy was the most common modality used. The mean age for the AKI vs no AKI groups were 63.5 (SD 14.5) vs 62 (SD 14.49) years old. Mean BMI was comparable between both groups 32 (SD 9.7) vs 32 (SD 9.64), while the BUN level 26 (SD 26.75) vs 19 (SD 9.9) mg/dl and Cr 1.15 (SD 1.59) vs 0.08 (SD 0.27) mg/dl were higher in the AKI group. In the AKI group, kidney replacement therapy was prescribed in 73(39.2%) patients, of which only 33 (17.7%) recovered meaningful kidney function. CONCLUSIONS: As the world emerged from the COVID-19 pandemic, there are innumerable lessons still to be learned. In our study, we demonstrated that AKI in COVID-19 patients with respiratory failure is associated with a higher incidence of mortality compared to patients without AKI. CLINICAL IMPLICATIONS: The risk of new SARS-CoV-2 variants and the possibility of future pandemics makes the recognition of high-risk medical complications of COVID-19 crucial to improve outcomes in acutely ill patients. A true multi-disciplinary team and an incredible amount of resources is required to identify and treat such patients. This study reminds us that kidney replacement therapy is only a means of supportive treatment rather than a cure to COVID-19-related kidney pathology. DISCLOSURES: No relevant relationships by Victor Canela No relevant relationships by Manavjot Sidhu No relevant relationships by Lucas Wang

A HARD PILL TO SWALLOW

SESSION TITLE: COVID-19 Case Report Posters 3 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Epiglottitis is an inflammation of the epiglottis which can be life-threatening in the absence of prompt intervention. Although primarily a pediatric condition, streptococcus pneumonia has been identified as a common pathogen in adults. SARS-CoV 2 has been known to affect a multitude of systems including the upper respiratory tract, but rarely the epiglottis. CASE PRESENTATION: A 66-year-old female with a past history of hypertension, and hypothyroidism presented with acute onset pharyngodynia and dysphagia with a feeling of throat closing up due to swelling and difficulty speaking. She had a recent COVID-19 diagnosis and was doing well except for mild fatigue. Upon presentation, she was hemodynamically stable. Physical exam revealed posterior pharyngeal edema without any exudate, mildly edematous uvula, and no stridor. Laboratory data was pristine except for elevated inflammatory markers. Rapid streptococcal test and MRSA swab were negative. Sputum culture showed usual respiratory flora and blood cultures were negative. A neck CT showed diffuse edema without any evidence of abscess. Laryngoscopy performed by the ENT surgeon revealed diffuse edema including epiglottitis. Emergent intubation revealed supra and epiglottis edema sparing the vocal cords. The patient was given Decadron and Benadryl to help with the edema along with clindamycin and subsequently transferred to ICU for further care. She was treated with Ceftriaxone for 7 days due to a chest X-ray finding of pneumonia. As for COVID 19 treatment, she received a course of Remdesivir and Decadron. Decadron was given at an increased interval to reduce edema around the epiglottis. Her ICU course was complicated with hypotension requiring intermittent vasopressor support, and acute kidney injury from ischemic acute tubular necrosis which slowly improved. Repeat CT chest showed bibasilar consolidations with peripheral ground-glass opacities. In view of hospital-acquired pneumonia, she was started on Ertapenem. Her clinical condition improved and she was successfully extubated. She was shifted to the floors from where she was discharged without any further complications. DISCUSSION: There are only two other reported cases of COVID 19 epiglottitis. The patient's advanced age and obesity were non-modifiable risk factors, but the COVID-19 infection played a role. The virus can lead to excessive upregulation of the host inflammatory response through repeat epithelial and endothelial damage leading to a cytokine storm, which may be responsible for this presentation. A great level of attention is to be maintained while attending to these patients given the multitude of systems that can be affected. CONCLUSIONS: COVID-19 is a potential cause of life-threatening acute epiglottitis. Early suspicion and direct visualization of the epiglottis is the key to success for early management. Reference #1: Emberey J, Velala SS, Marshall B, et al. Acute Epiglottitis Due to COVID-19 Infection. Eur J Case Rep Intern Med. 2021;8(3):002280. Published 2021 Mar 3. doi:10.12890/2021_002280 Reference #2: Smith C, Mobarakai O, Sahra S, Twito J, Mobarakai N. Case report: Epiglottitis in the setting of COVID-19. IDCases. 2021;24:e01116. doi: 10.1016/j.idcr.2021.e01116. Epub 2021 Apr 7. PMID: 33842206;PMCID: PMC8025537. DISCLOSURES: No relevant relationships by Arunava Saha

THE MONSTROSITY OF MAGNESIUM CITRATE

SESSION TITLE: Critical Gastrointestinal Case Reports SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Magnesium citrate is an osmotic laxative which is occasionally used in the intensive care unit (ICU) for refractory constipation. We present a patient in whom a bowel regimen containing magnesium citrate resulted in severe hypermagnesemia with paralytic ileus, requiring renal replacement therapy. CASE PRESENTATION: 70-year-old male was admitted to the ICU for COVID-19 associated acute hypoxic respiratory failure and suffered multi-day, refractory constipation, treated with one dose of 17 grams of magnesium citrate. Vital signs were remarkable for bradycardia and hypotension. On examination, patient was lethargic and the abdomen was soft and non-distended, but there were decreased bowel sounds throughout. Subsequently, laboratory findings were notable for a magnesium level of 8.8 mg/dL and serum creatinine of 2.3 mg/dL (estimated glomerular filtration rate 28mL/min/1.73m2), all of which were previously normal at admission. Computerized Tomography of the abdomen was performed showing dilated cecum, ascending and transverse colon and moderate to large amount of intraluminal rectal stool and air. Patient was started on intravenous fluids, loop diuretics, and calcium gluconate, however, the patient required renal replacement therapy for magnesium clearance. Patient clinically improved with normalization of kidney function and magnesium levels as well as resolution of ileus. DISCUSSION: Magnesium homeostasis is regulated by gastrointestinal absorption and renal excretion, for which the kidney maintains magnesium equilibrium until creatinine clearance falls below 20 ml/min [1]. Elevated magnesium levels can decrease bowel motility by blocking myenteric neurons and interfere with excitation - contraction coupling of smooth muscle cells as well as serve as a reservoir for continuous magnesium absorption [2]. Our patient suffered acute kidney injury, likely from COVID-19 pneumonia and acute tubular necrosis from shock, placing him at increased risk for hypermagnesemia. One retrospective study identified that patients with COVID-19 are more prone to the development of hypermagnesemia, which is associated with renal failure and increased risk of mortality [3]. The magnesium load from magnesium citrate in our patient created for a seemingly out of proportion effect of hypermagnesemia-induced paralytic ileus and presumably a magnesium reservoir, refractory to conservative measures. CONCLUSIONS: The use of magnesium containing bowel regimens should be considered with caution due to the possibility of hypermagnesemia in at-risk patients, which may result in paralytic ileus and other sequelae. Hypermagnesemia reduces colonic peristalsis and interferes with magnesium equilibrium, prolonging its effects. There are rare case reports in the literature discussing this phenomenon, but should be further evaluated for specific patient susceptibility and effects on morbidity and mortality. Reference #1: Cascella, M. (2022, February 5). Hypermagnesemia. StatPearls [Internet]. Retrieved March 16, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK549811/ Reference #2: Bokhari, S., Siriki, R., Teran, F., & Batuman, V. (2018, September 8). Fatal Hypermagnesemia due to laxative use. The American Journal of the Medical Sciences. Retrieved March 16, 2022, from https://www.amjmedsci.org/article/S0002-9629(17)30467-6/fulltext Reference #3: Stevens, J. S., Moses, A. A., Nickolas, T. L., Husain, S. A., & Mohan, S. (2021, July 29). Increased mortality associated with hypermagnesemia in severe covid-19 illness. American Society of Nephrology. Retrieved March 16, 2022, from https://kidney360.asnjournals.org/content/2/7/1087 DISCLOSURES: No relevant relationships by Adnan Abbasi No relevant relationships by Sarah Upson

IDIOPATHIC ISOLATED RIGHT VENTRICULAR DYSFUNCTION IN THE SETTING OF RECENT COVID-19 INFECTION: A CASE REPORT

CASE: We describe a case of isolated acute right ventricular (RV) strain not attributable to pulmonary embolism (PE) or Acute Respiratory Distress Syndrome (ARDS) in the setting of recent COVID-19 infection. A 77-year-old male with medical history notable for type 2 diabetes, obesity, chronic kidney disease, obstructive sleep apnea, and chronic hypoxemic respiratory insufficiency with a last known left ventricular ejection fraction (LVEF) of 77% on admission with preserved RV function, and recent COVID-19 infection was admitted for septic shock secondary to a post-viral MRSA pneumonia 12 days after diagnosis with COVID-19. On day 5 of admission, after completion of antibiotic therapy and resolved shock, the patient developed relative hypotension and an oliguric acute kidney injury with creatinine of 1.9 (previously 1.0) and urine microscopy findings consistent with acute tubular necrosis. EKG at the time showed new incomplete right bundle branch block. On day 8 of admission, relative hypotension continued with an uptrend in creatinine to 4.8 despite adequate fluid resuscitation. EKG showed new complete right bundle branch block with high-sensitivity troponin peaking at 550 (previously 15). A transthoracic echocardiogram showed enlarged RV and isolated severe hypokinesis of the RV mid-free wall consistent with “McConnel's sign” and acute right heart strain, with poorly visualized left ventricle, but without regional wall motion abnormalities. CTA Chest evaluating through the segmental arteries ruled out acute PE. Acute coronary syndrome was ruled out with traditional and right-sided EKG. Oxygen requirements remained unchanged throughout the course of his admission. The patient was transferred to the ICU for undifferentiated shock requiring triple pressor therapy and eventually died from acute renal failure and volume overload. IMPACT/DISCUSSION: While RV strain secondary to ARDS and PE has been implicated in COVID-19 and found to be an independent predictor of mortality, there is limited literature describing isolated RV dysfunction in their absence. Increasing reports showing cardiac microthrombi in autopsies of COVID-19 patients suggest alternate etiologies of RV injury and suggest potential utility of empiric therapeutic anticoagulation in all patients presenting with COVID-19. Alternatively, direct viral injury isolated to the RV may be unique in COVID19. Additionally, “McConnell's sign” combined with enlarged RV is traditionally considered a specific marker of PE, with reported specificity of 94% in the original report. However, there are increasing reports shedding doubt on the specificity of this finding. CONCLUSION: This case demonstrates the need to consider alternate etiologies for RV dysfunction in COVID-19, including microthrombi and direct viral injury. Additionally, this case adds to the growing literature demonstrating the limitation of “McConnell's sign,” even in patients with high suspicion for PE.

ACUTE RENAL FAILURE IN COVID-19 PATIENTS IN A LATIN AMERICAN HEALTH INSTITUTION

BACKGROUND AND AIMS: Acute renal failure in hospitalized patients for COVID- 19 occurs in 3%-28% and is a poor prognostic factor. The mechanisms of renal involvement are not completely clarified. However, it has been evaluated that the presentation of renal failure increases adverse outcomes. METHOD: Prospective observational study of all the cases that were admitted for COVID-19 between January and December 2021. Clinical and analytical data of kidney complications in patients with COVID-19 were collected. RESULTS: A total of 306 patients with a mean age of 70.2 years, 75.1% men and with previous chronic kidney disease in 29.7% were analyzed. A total of 50.8% had severe pneumonia or acute respiratory distress syndrome and 22.9% required admission to the ICU. Proteinuria was registered in 77.6% and hematuria in 67.6%. A total of 20.9% of the patients required renal replacement therapy. Renal failure was of prerenal etiology in 59.2%, acute tubular necrosis in the context of sepsis in 23.5%, glomerular in 8.1% and due to tubular toxicity in 9.2%. The median stay was 15 days, and 31.7% died. Patients who developed kidney failure during admission had higher C-reactive protein, LDH, and D-dimer values, more severe lung involvement, more need for ICU admission, and greater need for renal replacement therapy. CONCLUSION: Hypovolemia and dehydration are common causes of acute kidney injury in COVID-19 patients. Those who develop renal complications have a worse pulmonary, renal and systemic prognosis profile. We point out that monitoring an individualized management of blood volume can be decisive in preventing worse outcomes.

COVID-19 SEQUELS IN NEPHROLOGY CKD PATIENTS MORE PRONE TO FATALITY

BACKGROUND AND AIMS: This strange, prolonged, very exhausting and costly pandemic still is remaining in our world showing us that we are so weak, so unprotected, so fragile. It initiated and continued mostly like a respiratory syndrome but soon after it was seen that it has a systemic impact and consequences in our body. There were patients presented with hematuria, proteinuria and deteriorating of kidney function after the infection. Direct kidney involvement, cytokine storm, coagulopathy, rhabdomyolysis, antibiotic use, sepsis and haemodynamic instability then acute tubular necrosis, all of these factors contribute in this picture of kidney failure. Very difficult to treat and to rehabilitate a part of these patients are going through kidney replacement therapy and a part are dying. METHODS: We studied a population of 77 patients that had passed the COVID-19 infection, confirmed by RT PCR. Males 58% and females 42%. Mean age was 67.1 years old, the BMI 29.6. Comorbidities were present in our cohort in 59.7% only one comorbidity and in 31.1% of patients two comorbidities. Mean time from COVID-19 infection was 56 days. There were CKD 70% patients and 30% non-CKD. Diagnoses of CKD patients were: hypertensive nephrosclerosis 49%, diabetic nephropathy 32%, chronic glomerulonephritis 9%, ADPKD 8% and transplanted patients with CAN 1%. RESULTS: It resulted that our patients had higher D dimer (mean 3660 mcg/dL = 7-fold higher), PCR (mean 35 mg/dL, 7-fold higher) and ferritin (mean 634 ng/dL). Levels of lymphocytes remained lower (mean 13.9%). Proteinuria was found in 92% and hematuria was found in 88% of our patients. There were a significant correlation between need for KRT and diabetic nephropathy was p = 0.037 and also between need for KRT and proteinuria presence was P = 0.048. It was seen that higher the BUN levels lower the lymphocytes counts (P = 0.028) and lower the time post COVID lower the albumin levels (P = 0.007). It was seen that patients with CKD were more prone to need for haemodialysis treatment during the hospitalization and the mortality rate was higher in this group of patients. CONCLUSION: COVID-19 infection and its short term sequels play an important role on morbidity and mortality of CKD patients. It was a decisive factor for KRT in these patients. CKD patients with their immunosuppression, several drugs used, anemia, hypertension, diabetes are more prone for post COVID-19 complications, hospitalizations, dialysis and then death. Being aware of this dangerous infection and being vaccinated are the mainstay and crucial things for being healthy and being alive.

ACUTE RENAL FAILURE IN COVID-19: AETIOLOGY AND RENAL EVOLUTION. AKI-COVID REGISTRY OF THE SPANISH SOCIETY OF NEPHROLOGY

BACKGROUND AND AIMS: Acute kidney injury (AKI) has been described as a frequent complication in patients with COVID-19. The incidence of AKI is estimated to be around 5%-80% depending on the series;however, data characterizing the type of AKI and the evolution of renal function parameters in the medium-long term are still limited. METHOD: Based on the initial AKI-COVID Registry, we developed an extended registry where we registered retrospectively new variables that included clinical and demographic characteristics, infection severity parameters and data related to AKI (ethology, KDIGO classification, need of renal replacement therapy, analytic values: baseline creatinine, maximum creatinine during admission, creatinine at discharge or death, creatinine at 1 month after hospitalization and urinary parameters). Recovery of kidney function was defined as difference in at discharge or posthospitalization creatinine < 0.3 mg/dL with respect basal creatinine. RESULTS: Our analysis included 196 patients: 74% male, mean age 66 + 13 years;65% hypertensive, 33% diabetic and 22% chronic kidney disease. According to the KDIGO classification: 66% AKI KDIGO3, 17% KDIGO2 and 15% KDIGO1. Creatinine values are summarized in Table 1. We found significant differences in the baseline/high creatinine differential;these differences were lost after hospitalization. The main types of AKI were prerenal (35%) and acute tubular necrosis secondary to sepsis (ATN) (53%). 89% of patients with ATN presented AKI KDIGO 3, compared with 57% in the prerenal group (P < .001). Patients with prerenal AKI had greater comorbidity. On the other hand, patients with ATN AKI developed more serious COVID-19 infection: higher percentage of severe pneumonia, admission to the intensive care unit and need for orotracheal intubation. The analytical parameters were more extreme in patients with ATN AKI, except for creatinine and urea upon admission, which were higher in the prerenal AKI group. A total of 89 patients died during the study;65% of ATN AKI patients versus 31% of prerenal-AKI patients (P < .001). The ATN was a mortality risk factor, whit a hazard ratio 2.74 [95% confidence interval (95% CI )1.29-5.7] (P = .008) compared with the prerenal AKI. CONCLUSION: AKI in hospitalized patients with COVID19 presented with two different clinical patterns. Prerenal AKI more frequently affected older, more comorbid patients, and with a mild COVID19 infection. The NTA AKI affected younger patients, with criteria of severity of infection and multiplying mortality almost three times. In analytical control 1-month post-hospitalization, most of the patients recovered their kidney function. Although the implications of AKI associated with COVID-19 in the development of chronic kidney disease are still unclear, our data suggest that most patients will recover kidney function in a medium term. (Table Presented).

VITAMIN C NEPHROTOXICITY IN A COVID-19 PATIENT: A CASE REPORT

BACKGROUND AND AIMS: During the time of the COVID-19 pandemic, multiple treatment options have been investigated, even though their efficacy and secondary effects remain insufficiently known. We report the case of a vitamin C induced oxalate nephropathy in a COVID-19 patient with preexisting chronic kidney disease (CKD) resulting in irreversible acute renal failure. Vitamin C, also known as ascorbic acid, has been used as an anti-inflammatory therapy for COVID-19, but review of the literature shows similar cases of acute kidney injury (AKI), raising concern. METHOD: We report the case of a 73-year-old Caucasian woman admitted for hyperthermia and digestive disorders. She had recently started a first-line chemotherapy for multiple myeloma with partial response. She also displayed preexisting stage 4 CKD (eGFR 18.50 mL/min/1.73 m2 using CKD-EPI) of unknown aetiology. She was tested positive for SARS-CoV2 by nasopharyngeal swab and soon transferred to the intensive care unit. She received intravenous corticosteroids using dexamethasone 6 g/24 h for 10 days and a piperacillin + tazobactam probabilistic antibiotherapy. She also received high doses (15 g/24 h) of vitamin C for three consecutive days. No monoclonal antibodies were prescribed due to a previous vaccination with a positive serology upon admission. Although the patient recovered from respiratory tract infection, her kidney function progressively deteriorated with serum creatinine levels rising up to 8.06 g/dL, leading to her admission in our nephrology department. The patient was initially treated with high doses of diuretics for anasarca and an abdominal CT excluded urinary tract obstruction with normal kidney size and aspect. Urinary analysis showed protein to creatinine (p/c) ratio of 1348 g/g, and presence of urinary light chains. Her monoclonal spike was measured at 2.3 g/L and her kappa/lambda fraction was 1.74. Intermittent haemodialysis was initiated, and a kidney biopsy was performed. RESULTS: Histology revealed hundreds of intratubular calcium oxalate crystals, with severe and diffuse acute tubular necrosis and interstitial edema. There was no amyloidosis, no sign of active glomerular disease and no interstitial fibrosis. Immunofluorescence (IgA, IgG, IgM, C1Q, C3, kappa and lambda) was negative. We concluded to oxalate nephropathy. After a 2-month follow-up, the patient remains dialysis dependent. Vitamin C is a precursor of oxalate and has been shown to cause secondary oxaluria, particularly with high-dose regimens in patients with altered renal function. Given the histological findings evocative of acute oxalate nephropathy, the accountability of high doses of vitamin C should be considered. No other cause of hyperoxaluria was identified in our patient beside broad spectrum antibiotic use, which could decrease intestinal bacterial oxalate degradation. In particular, there was no malabsorption The limitation of our report is the unknown cause of preexisting CKD;therefore, we cannot rule out preexisting hyperoxaluria. Also, no dosage of serum vitamin C and oxalate levels were performed during follow-up. Finally, our patient had other possible causes AKI, such as recent SARS-CoV2 infection, or linked to multiple myeloma, but these were considered unlikely given the proper haematological response to treatment and non-evocative biopsy. The rationale for vitamin C use in COVID-19 is based on in vitro studies showing its antioxidant, anti-inflammatory, anticoagulant and immune modulatory properties. There lack large clinical studies, and the literature shows conflicting results. Multiple cases of acute oxalate nephropathy were described. CONCLUSION: Vitamin C is an anti-inflammatory treatment used in COVID-19 that can lead to secondary hyperoxaluria with significant and irreversible AKI. Due to the severity of AKI in patients with preexisting CKD, we believe renal function should be considered before using high doses of vitamin C. Larger controlled trials are needed both to establish the clinical benefit of vitamin C and further describe its potential ephrotoxicity.

COVID-19 causing myoglobinuria requiring hemodialysis in young adult

Introduction Cases of rhabdomyolysis causing myoglobinuria in post-COVID-19 patients have been seen occasionally, and exact mechanisms behind this seem multi-factorial. Some patients have severe myoglobinuria with highly elevated creatinine phosphokinase levels requiring urgent hemodialysis to keep creatinine and blood urea nitrogen levels under control and protect the kidneys from long-term damage. Case presentation We present a case of a 24-year-old man with autism who was admitted to the hospital for COVID-19 viral pneumonia and discharged without major complications. After 3 weeks, he came to the ER with a decreased mental status and asterixis, and labs indicated creatinine had increased from baseline 0.7 mg/dl to 2.9 mg/dl and eventually increased to 6.4 mg/dl despite IV hydration. Creatinine phosphokinase was ordered, and it was 289,500 mcg/L. The patient likely suffered acute tubular necrosis secondary to rhabdomyolysis. Urgent hemodialysis was initiated, and the patient showed clinical improvement after one week and was taken off dialysis in 2 weeks. During an outpatient Nephrology clinic visit, the creatinine level was close to baseline level at 0.9 mg/dl, and the patient was asymptomatic. Discussion Different viruses have been described to cause myositis and rhabdomyolysis. The list is long but not limited to influenza A and B, coxsackie, Epstein-Barr, herpes simplex, parainfluenza, adenovirus, cytomegalovirus, measles, varicellazoster, human immunodeficiency, and dengue. In addition, reports about myoglobinuria post-COVID-19 infection have been emerging. The mechanism is unclear, but one theory suggests muscular necrosis from the direct viral invasion of myocytes, and another one suggests a toxic effect on myocytes by the host response, i.e., cytokine release and other immunological factors. Hence, early clinical recognition of this entity can be lifesaving in some cases.