Severe Coronavirus Disease 2019 Infection Research Articles

Survival and outcomes for co-infection of chronic hepatitis C with and without cirrhosis and COVID-19: A multicenter retrospective study.

BACKGROUNDChronic liver disease, particularly cirrhosis, is associated with worse outcomes in patients infected with coronavirus disease 2019 (COVID-19).AIMTo assess outcomes of COVID-19 infection among patients with pre-existing hepatitis C with or without liver cirrhosis.METHODSThis multicenter, retrospective cohort study included all cases of confirmed co-infection of severe acute respiratory syndrome coronavirus 2 and chronic hepatitis C with or without liver cirrhosis who were admitted to six hospitals (Al-Sahel Hospital, Al-Matareya Hospital, Al-Ahrar Hospital, Ahmed Maher Teaching Hospital, Al-Gomhoreya Hospital, and the National Hepatology and Tropical Medicine Research Institute) affiliated with the General Organization for Teaching Hospitals and Institutes in Egypt. Patients were recruited from May 1, 2020, to July 31, 2020. Demographic, laboratory, imaging features, and outcomes were collected. Multivariate regression analysis was performed to detect factors affecting mortality.RESULTSThis retrospective cohort study included 125 patients with chronic hepatitis C and COVID-19 co-infection, of which 64 (51.20%) had liver cirrhosis and 40 (32.00%) died. Fever, cough, dyspnea, and fatigue were the most frequent symptoms in patients with liver cirrhosis. Cough, sore throat, fatigue, myalgia, and diarrhea were significantly more common in patients with liver cirrhosis than in non-cirrhotic patients. There was no difference between patients with and without cirrhosis regarding comorbidities. Fifteen patients (23.40%) with liver cirrhosis presented with hepatic encephalopathy. Patients with liver cirrhosis were more likely than non-cirrhotic patients to have combined ground-glass opacities and consolidations in CT chest scans: 28 (43.75%) vs 4 (6.55%), respectively (P value < 0.001). These patients also were more likely to have severe COVID-19 infection, compared to patients without liver cirrhosis: 29 (45.31%) vs 11 (18.04%), respectively (P value < 0.003). Mortality was higher in patients with liver cirrhosis, compared to those with no cirrhosis: 33 (51.56%) vs 9 (14.75%), respectively (P value < 0.001). All patients in Child-Pugh class A recovered and were discharged. Cirrhotic mortality occurred among decompensated patients only. A multivariate regression analysis revealed the following independent factors affecting mortality: Male gender (OR 7.17, 95%CI: 2.19–23.51; P value = 0.001), diabetes mellitus (OR 4.03, 95%CI: 1.49–10.91; P value = 0.006), and liver cirrhosis (OR 1.103, 95%CI: 1.037–1.282; P value < 0.0001). We found no differences in liver function, COVID-19 disease severity, or outcomes between patients who previously received direct-acting antiviral therapy (and achieved sustained virological response) and patients who did not receive this therapy.CONCLUSIONPatients with liver cirrhosis are susceptible to higher severity and mortality if infected with COVID-19. Male gender, diabetes mellitus, and liver cirrhosis are independent factors associated with increased mortality risk.

Acute Mesenteric Ischemia in Severe Coronavirus (COVID19): Cases Report of 3 Patients

Background Coronavirus disease 2019 (COVID-19) is a respiratory disease with pulmonary infection, but some patients experiment gastrointestinal symptoms, in the literature only few cases of mesenteric ischemia in patients with severe COVID-19 infections have been described. Cases We present 3 cases of patient with severe COVID-19, with gastrointestinal manifestation in which bowel lesion was observed and which took benefits from bowel resections. No evidence available conclusively demonstrated a thrombotic or embolic event in our cases, therefore a precise knowledge of the mechanism of bowel lesion in COVID-19 patients is essential. Clinical managing patients with COVID-19 whom manifest gastrointestinal symptomatology should be aware of the mesenteric ischemia involvement. Conclusion In conclusion, patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may show atypical presentations, such as gastrointestinal symptoms, precise knowledge of the mechanism of bowel lesion in COVID-19 patients are essential.

COVID-19-Associated Pulmonary Aspergillosis: A Single-Center Experience in Central Valley, California, January 2020-March 2021.

Reports of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) have been widely published across the world since the onset of the pandemic with varying incidence rates. We retrospectively studied all patients with severe COVID-19 infection who were admitted to our tertiary care center′s intensive care units between January 2020 and March 2021, who also had respiratory cultures positive for Aspergillus species. Among a large cohort of 970 patients admitted to the ICU with severe COVID-19 infections during our study period, 48 patients had Aspergillus species growing in respiratory cultures. Based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology (ECMM/ISHAM) consensus criteria, 2 patients in the study had proven CAPA, 9 had probable CAPA, and 37 had possible CAPA. The incidence of CAPA was 5%. The mean duration from a positive COVID-19 test to Aspergillus spp. being recovered from the respiratory cultures was 16 days, and more than half of the patients had preceding fever or worsening respiratory failure despite adequate support and management. Antifungals were given for treatment in 44% of the patients for a mean duration of 13 days. The overall mortality rate in our study population was extremely high with death occurring in 40/48 patients (83%).

Intensive care unit hospitalizations and outcomes in patients with severe COVID-19 during summer and fall surges in Georgia

BACKGROUNDThere is limited data on the difference in the clinical characteristics and outcomes of patients with severe coronavirus disease 2019 (COVID-19) infection in the summer compared to the fall surge.AIMTo compare the sociodemographic, clinical characteristics, and outcomes among mechanically ventilated patients with severe COVID-19 infection admitted to the intensive care unit (ICU) during the summer and fall surges in the year 2020.METHODSWe included patients admitted to the ICU and treated with invasive mechanical ventilation for COVID-19 associated respiratory failure between April 1 and December 31, 2020. Patients were categorized into summer surge for ICU admissions between June 15, 2020, and August 15, 2020, and fall surge between October 15, 2020, and December 31, 2020. We compared patients' characteristics and outcomes using descriptive and inferential statistics.RESULTSA total of 220 patients were admitted to the Grady Memorial Hospital ICU and mechanically ventilated for COVID-19 associated hypoxemic respiratory failure during the period considered (125 during the summer surge and 95 during the fall surge). More women were admitted in the fall compared to summer (41.1% vs 36.8%, difference, 4.3%; 95%CI: 1.2, 7.5). Patients admitted in the fall had fewer comorbidities (chronic obstructive pulmonary disease, stroke, diabetes mellitus, obstructive sleep apnea and body mass index ≥ 35 kg/m2). Overall, patients in the fall had a lower ICU mortality rate (27.4% vs 38.4%, difference, -11.0; 95%CI: -6.4, -18.2), shorter length of stay on the mechanical ventilator (7 d vs 11 d, difference, 4 d; 95%CI: 2.1, 6.6) and shorter ICU length of stay (9 d vs 14 d, difference, 5 d; 95%CI: 2.7, 9.4).CONCLUSIONPatients admitted with severe COVID-19 infection requiring mechanical ventilation had better outcomes in the fall than summer. This difference observed is likely attributable to a better understanding of the condition and advances in treatment strategies.

Clinical and Immunological Assessment of Patients with Sars-Cov-2 Infections

▪Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induced coronavirus disease-2019 (COVID-19) has presented humanity with unprecedented challenges. Severe disease is associated with acute respiratory distress syndrome (ARDS), use of mechanical ventilation, ICU stay and prolonged hospitalization, The role of the immune system in the pathogenesis of COVID-19 disease is still unclear, which imposes limitations on identifying potential immunotherapy that can improve care for acute and chronic phases of COVID-19 in conjunction with current therapies. Research efforts are ongoing for more than 1 year to identify key immunological mechanisms involved in the disease process. While insightful, this knowledge is still incomplete and can be complemented with the assessment of immune response kinetics. Such assessment will help with the identification of early interventional modalities of immune cell regulation. With these considerations in mind, we aimed to assess several parameters of immune system regulation during the current medical care of patients with COVID-19.Methods: This is a pre-clinical prospective cohort study which involved laboratory-based assessments of blood samples obtained from COVID-19 patients and healthy volunteers. The study population was divided into three cohorts. Our first cohort included 18 years and older COVID-19 patients with respiratory complaints, oxygen (O2) saturations of less than or equal to 92 and pulmonary infiltrates on an imaging study or who were critically ill and required ventilatory support. Second cohort included 18 years and older COVID-19 patients who were hospitalized and did not require ventilatory support. Third cohort included participants with no prior diagnosis of COVID-19, or any recent viral respiratory symptoms including fever, cough or shortness of breath for the last 2 weeks. Patients with an established diagnosis of cancer or immunologic disorders were excluded. Blood specimens were collected over the period of hospitalization: specimen number 1 on day 1-3 of hospitalization, specimen number 2 on days 3-4 of hospitalization, specimen number 3 on days 5-7 of hospitalization, and specimen number 4 on 7-30 days after discharge. We performed capillary electrophoresis for serology and automated ELISA for cytokine measurement. We collected clinical data on patient demographic, clinical characteristics such as presence of any acute and chronic comorbidities and serum inflammatory markers C-Reactive Protein, D-Dimer and Ferritin.Results: We had 15 patients in cohort 1, 10 in cohort 2 and 15 in cohort 3. Patients in cohort 1 were older and had higher comorbidities. Males constituted a substantially high percentage of patients in cohort 1 and 2 (60% and 70% respectively). Patients had similar BMI in cohort 1 and 2. Total antibody levels were highest in cohort 1 but an upward trend over the course of hospitalization was noted in all cohorts. Most interesting pattern was noted in the context of antibodies against spike protein S1 receptor-binding domain (S1RBD) where patients in cohort 2 developed minimal S1RBD antibodies. Cohort 1 on average had higher levels of Interleukin 6(IL-6), Interleukin 8(IL-8), C-X-C motif chemokine ligand 10 (CXCL10) and other inflammatory cytokines except Interferon gamma (IFN-gamma) compared to Cohort 2. Remarkable difference in CXCL-10 levels was noted between the groups and healthy volunteers had the lowest levels. No significant difference in IFN-gamma was noted between cohorts and the levels quickly depleted over the course of the infection.Conclusion: Our analysis confirms that neutralizing antibodies do not correlate with lessened COVID-19 disease severity. Severe COVID-19 infection is secondary to ineffective innate immunity associated with immune overshoot. CXCL10 serves as a major component in triggering the cytokine storm that is a hallmark of SARS-CoV-2 infections. Our findings show an association between high levels of CXCL10 and more severe COVID-19 infection. There does not seem to be any significant correlation with disease severity and IFN-gamma levels. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Optimal Anticoagulant Dosing in Patients with COVID-19, a Retrospective Review

BackgroundHospitalized patients with coronavirus disease 2019 (COVID-19) infection have higher rates of venous thromboembolism (VTE).Higher mortality rates have been reported in severe cases of COVID-19 including those who have elevated D-dimer levels and have thromboembolic phenomena.ObjectiveThe objective of this retrospective and observational study was to ascertain which type and dosages of anticoagulation provide a mortality benefit and decrease the risk of developing VTE.MethodsWe evaluated the risk factors for VTEs in patients with a confirmed polymerase chain reaction test positive for COVID-19 who were admitted to our facility from April 1 to July 1, 2020. In addition, we performed a logistic regression to examine the relationship between mortality and intensive care unit (ICU) admission, specific risk factors outlined in the study, D-dimer, ferritin, prothrombin time (PT) and international normalized ratio (INR). Patients with a history of VTE, those already on anticoagulation (AC) prior to hospitalization, and patients on comfort care were excluded from study.ResultsThere were originally 331 patients in the data set. Of those, 111 patients were excluded based on exclusion criteria and 4 additional patients were removed as they were the only individual patients in their specific AC covariant group. The analysis was performed on the remaining 216 patients. We divided the AC medications administered to the patients into five separate covariates: 1. enoxaparin 40 mg subcutaneous (sq) daily, 2. enoxaparin 40 mg sq every 12 hours (q12h), 3. heparin 5000 mg sq q12h, 4. heparin 5000 mg sq every 8 hours (q8h), 5. Patients taking multiple AC or deep venous thrombosis (DVT) prophylaxis medications. 6. No AC and examined them via logistic regression for mortality at 28 days and 60 days (Table 1). Patients in enoxaparin 40 mg daily group had statistically significant lower 28 day mortality. There was no statistically significant relationship between the use of enoxaparin 40 mg q12h and 28 day mortality rate. Patients in both heparin groups did not have significantly lower 28 day mortality rates. Patients in groups 5 & 6 had significantly higher 28 day mortality rates (Table 1). It is important to note that 33 patients underwent a pulmonary computed tomography angiography due to concern for pulmonary embolism and 38 patients underwent an ultrasound of their lower extremities to rule out the development of DVT.For patients with additional risk factors defined as chronic kidney disease, chronic obstructive pulmonary disease, organ transplant recipient, obesity (BMI > 30), cardiac disease (heart failure, coronary artery disease or cardiomyopathy), sickle cell disease, diabetes mellitus and smoking history, the odds of death at 28 days increased by a factor of 1.71, at 60 days by a factor of 1.63 and being admitted to the ICU by a factor of 1.41. Patients with 3-5 risk factors are 2.48 times more likely to be admitted to the ICU than patients with 0-2 risk factors. Patients with 4 or 5 risk factors are 3.56 times more likely to be admitted to the ICU than patients with 0-3 risk factors (Table 2). Predictably, patients that were admitted to the ICU had a significantly increased rate of mortality compared to those who were not (Table 3).Per our analysis, there was no relationship between PT or INR and mortality. At 28 days and 2 months, the D-dimer > 4000 was indicative of a higher odds of death versus patients with a D-dimer < 4000. An increased ferritin was also indicative of a higher mortality rate (Table 4).ConclusionPatients receiving enoxaparin 40 mg daily benefited more than any other AC regimen with respect to the development of VTE at both 28 days and 2 months. Increasing the dosing to twice daily did not decrease mortality. Additionally, patients receiving heparin did not have a decreased mortality. It is important to note that there was no standard protocol used to determine which patients received daily or twice daily dosing. The type and dose of AC was determined based on the clinical judgment of intensivists in each case. It is also possible that patients with severe COVID-19 infection were more likely to be given twice daily dosing which could account for the lack of mortality benefit with more frequent dosing. We did not report bleeding rates in AC groups in our study and this can be a possible reason for no mortality benefit among higher dose AC groups. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Comparison Between Kidney and Liver Transplant Recipients Admitted to a Referral Center Regarding Coronavirus-2019 Manifestations in the Northeast of Iran During Three Peaks of Pandemic

Background: Transplant recipients are at high risk for severe Coronavirus disease-2019 (COVID-19). Transplant recipients are immune-compromised individuals at high risk for severe infection. This study aimed to compare the presentations and outcomes of liver and kidney transplant recipients who were infected with COVID-19 in the Iranian population. Methods: This cross-sectional study was conducted at Imam Reza and Montaserieh Hospitals affiliated with Mashhad University of Medical Sciences, Mashhad, Iran, between 2020 and 2021. In general, 52 patients were selected and divided into two groups of the kidney (n=28) and liver (n=24) transplantation. Two groups were compared in terms of demographic characteristics and clinical findings. Results: Of the 52 patients, severe COVID-19 infection was reported in 61% of the patients. There was no significant difference between the two groups in terms of symptoms, except for cough (χ2=8.09; P=0.004), clinical condition, and laboratory symptoms, except for creatinine (Z=14; P&lt;0.005), alkaline phosphatase (Z=4.55; P=0.03), total bilirubin (Z=8.93; P=0.03), and partial thromboplastin time (Z=5.97; P=0.01). There was no relationship between the outcome and the use of immunosuppressive medications (P&gt;0.05). All patients with kidney transplantation survived, while two cases in the liver transplantation group failed to survive (χ2=2.42; P=0.11). Conclusion: The mortality rate was higher in the liver transplant recipients, compared to the patients who underwent kidney transplantation.

Potential benefit of vitamin D supplementation in people with respiratory illnesses, during the COVID-19 pandemic.

This review describes the evidence for the potential benefit of vitamin D supplementation in people with respiratory diseases who may have a higher susceptibility to coronavirus disease 2019 (COVID‐19) infection and its consequences. Clinical evidence indicates that vitamin D may reduce the risk of both upper and lower respiratory tract infections and offers benefit particularly in people with vitamin D deficiency. Some evidence exists for a higher incidence of active tuberculosis (TB) in patients who are deficient in vitamin D. An association between low levels of 25(OH)D (the active form of vitamin D) and COVID‐19 severity of illness and mortality has also been reported. In addition, low 25(OH)D levels are associated with poor outcomes in acute respiratory distress syndrome (ARDS). The cytokine storm experienced in severe COVID‐19 infections results from excessive release of pro‐inflammatory cytokines. Due to its immunomodulatory effects, adequate vitamin D levels may cause a decrease in the pro‐inflammatory cytokines and an increase in the anti‐inflammatory cytokines during COVID‐19 infections. Vitamin D deficiency was found in 82.2% of hospitalized COVID‐19 cases and 47.2% of population‐based controls (p < 0.0001). The available evidence warrants an evaluation of vitamin D supplementation in susceptible populations with respiratory diseases, such as TB, and particularly in those who are deficient in vitamin D. This may mitigate against serious complications of COVID‐19 infections or reduce the impact of ARDS in those who have been infected.

Coronavirus Disease 2019 Vaccination during Pregnancy

Several vaccines have been developed to combat the coronavirus disease 2019 (COVID-19), including messenger Ribonucleic acid (mRNA, Pfizer-BioNtech, and Moderna) and viral vector (AstraZeneca and Janssen) types. Unfortunately, reports of COVID-19 exposure during pregnancy are scarce, as pregnancy and breastfeeding were among the exclusion criteria in the efficacy and safety studies of major COVID-19 vaccines. The U.S. Centers for Disease Control and Prevention recently included pregnancy as a risk factor for severe COVID-19 infection, although the absolute risk is low. Previous experience in pregnant women with mRNA vaccines is lacking despite such vaccines not using live viruses, being unable to cause disease, not interacting with an individual's DNA, and being unable to cause genetic mutations. In addition, previous studies in animals have not revealed any safety issues with such vaccine types for female reproduction or fetal development. Vaccine-induced antibody titers were equivalent in pregnant and lactating women versus non-pregnant women. Given the data on increased mortality and morbidity associated with COVID-19 during pregnancy, it may be unethical to withhold vaccinations based on a theoretical risk and a lack of clinical research in this population. Additionally, a careful review of the vaccination recommendations for pregnant women by the academic community and government through additional efficacy and safety studies tailored to the situation in Korea is needed.

Interferon-α2b induced anemia in severe coronavirus disease 2019 patients: a single centered, retrospective study

Background The current outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread throughout the world. During treatment, we found that the majority of patients had a decrease in hemoglobin (Hb). Interferon-α2b (IFN-α2b) was the primary suspected drug that was related to Hb reduction. Thus, the study aimed to investigate whether IFN-α2b could induce Hb reduction in severe patients with COVID-19 and its potential mechanism. Material and methods A total of 50 patients who were admitted to the First Affiliated Hospital of Harbin Medical University with severe COVID-19 infection were enrolled from February 12th to 24th, 2020. The demographics, baseline characteristics, clinical data, and therapeutic regimen were collected retrospectively. The patients were divided into two groups according to the declined use of IFN-α2b on day 14. The Hb levels on admission, day 7, day14, and day 21 were collected and analyzed. The primary endpoint was the level of Hb on day 21. Results A total of 31 patients in the IFN-stop group and 19 patients in the non-IFN-stop group were reviewed. The age, gender, comorbidities, clinical symptoms, nutritional status, disease severity, complications, and other factors of the patients were compared, no difference was found between the IFN-stop group and the non-IFN-stop group. The Hb levels of all patients significantly decreased on day 7 compared with that on admission (p < .0001). In the IFN-stop group, the Hb level was increased in 7 days after IFN-α2b was stopped (p = .0008), whereas no difference was found between day 14 and day 21 in the non-IFN-stop group (p = .3152). Conclusions IFN-α2b was associated with Hb reduction in the treatment of severe patients of COVID-19. Clinicians should be aware of the high incidence of Hb reduction for patients treated by IFN-α2b.

Eosinophilic Esophagitis Patients Are Not at Increased Risk of Severe COVID-19: A Report From a Global Registry

BackgroundThe impact of coronavirus disease 2019 (COVID-19) on eosinophilic esophagitis (EoE) and eosinophilic gastrointestinal diseases (EGIDs) is unknown.ObjectiveWe aimed to characterize patients with EoE and EGIDs who had COVID-19, assess severity of COVID-19 in the EoE/EGID population, and evaluate for COVID-19-induced EoE/EGID flares.MethodsWe established an online global registry collecting physician entered, deidentified data related to patient demographics, EoE/EGID disease features, comorbidities, and treatments, COVID-19 source of exposure, symptoms, illness severity, hospitalizations, and deaths.ResultsNinety-four cases were reported between March 2020 and April 2021 (median age, 21 years; range, 1.5-53 years; 73% male). Most had atopy (73%), and 80% had isolated EoE. Before COVID-19, the EoE/EGID activity was reported as clinical remission in 51 (54%) and moderate in 20 (21%). EoE/EGID treatments at the time of COVID-19 included proton pump inhibitors 49 (52%), swallowed/topical steroids 48 (51%), and dietary elimination 34 (36%). COVID-19 symptoms included cough (56%), fever (49%), anosmia (21%), and ageusia (22%). Most patients with COVID-19 had a mild course (70%), with 15% asymptomatic, 12% moderate, and 2% severe. Three patients were hospitalized, and no intensive care unit admissions or deaths were reported. Mean time from first symptoms to resolution in symptomatic patients was 10 days (range, 1-90 days). A single EGID flare was reported during COVID-19.ConclusionsIn a global EoE/EGID registry, relatively few COVID-19 cases have been reported. COVID-19 severity was comparable to the general population. Based on this registry, it does not appear that patients with EoE are at increased risk for severe COVID-19 infection or that COVID-19 leads to EGID flares.

Posterior ocular structural and vascular alterations in severe COVID-19 patients.

PurposeThis study aimed to evaluate posterior ocular structural and vascular changes in severe coronavirus disease 2019 (COVID-19) patients.MethodsThis was an observational, prospective, and controlled study including 106 eyes of 53 severe COVID-19 patients, compared to after recovery and 106 eyes of 53 age- and gender-matched healthy controls. All subjects were previously healthy adults and were assessed using spectral domain optical coherence tomography (SD-OCT) and ImageJ software. Subfoveal over a 1500-μm span and macular over a 6000-μm span cross-sectional areas of the vascular, stromal, and total choroid were measured.ResultsOf the 53 included patients, 28 (52.8%) were male, and 25 (47.2%) were female, with a mean age of 50.2 ± 7.4 years. In the active period of the disease, compared to after recovery and healthy controls, the outer plexiform layer thickness showed a significant increase (p = 0.004), and mean choroidal thickness was significantly higher (p < 0.0001); however, choroidal vascularity was significantly lower (p < 0.0001). The stromal area to vascular area (S/V) ratio of the choroid was significantly increased (p < 0.0001). All quadrants of the peripapillary retinal nerve fiber layer (RNFL) thicknesses were significantly increased (for all, p < 0.05). The reflectivity of OCT echo of the choroid and peripapillary RNFL was significantly higher (p = 0.023, p < 0.0001, respectively).ConclusionThis study detected significant posterior ocular structural and vascular alterations in patients with severe COVID-19 infections. These findings may be associated with direct host-virus interaction or linked to an autoimmune process, vasculopathy, or viral-mediated inflammation.

SINUS PAUSE SECONDARY TO ACUTE COVID-19 INFECTION

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Sinus pause/arrest most commonly occurs in medication toxicity, cardiac ischemia, infiltrative or fibrotic disease of SA node, structural heart disease, PE, sleep apnea, electrolyte disturbance (hyperkalemia), Lyme disease. We present to you a case of sinus pause/arrest in a patient with COVID-19 infection. CASE PRESENTATION: Patient is a 59 year male who presented to hospital with complaints of chest pain and dyspnea. Past medical history was significant for recent COVID-19 infection one week ago. Vital signs and physical examination on presentation were normal. Initial workup including CBC, INR, PTT, CMP, troponin and EKG were normal. Chest x-ray was remarkable for reticular nodular infiltrate in the right perihilar lung field. Patient was started on IV antibiotic for suspected pneumonia. On day 1, patient started experiencing skipped heartbeats. Cardiac telemetry demonstrated multiple sinus pauses with greatest pause duration of about 5 seconds. EKG showed normal sinus rhythm without any significant ST/T wave changes, Recent transthoracic echocardiogram was normal. Upon literature review, it was noted that there were cases of severe COVID-19 infection affecting the electrical system of the heart, resulting in sinus pauses. Hence, after ruling out some of the common differential diagnosis for sinus pauses including medications, ischemia, inflammatory, infiltrative or fibrotic disease of the SA node, structural heart disease, PE, OSA (obstructive sleep apnea), electrolyte disturbance (especially hyperkalemia), Lyme disease, patient's sinus pauses were attributed to underlying COVID-19 infection. Patient was discharged with 30 days cardiac event monitor which showed sinus rhythm with no significant pauses. DISCUSSION: SA nodal dysfunction typically results from either abnormality in impulse generation by the P cells or abnormalities in conduction across perinodal transitional (T cells). Hypoxemia, cytokine storm, direct viral infiltration, myocardial inflammation are thought to be responsible for sinus pause in COVID-19 disease, although exact mechanism is not known. Patients are symptomatic when longer episodes of sinus arrest occur resulting in dizziness, syncope, and death. Asymptomatic patients with SA nodal pauses or arrest often do not require treatment. Symptomatic patients are treated with a permanent pacemaker placement. CONCLUSIONS: Moderate to severe COVID-19 infection could be an uncommon cause of sinus pauses. However, before attributing COVID-19 as a cause of sinus pauses, common differential diagnosis for sinus pauses including medications toxicity (digoxin, antiarrhythmics-procainamide, quinidine), cardiac ischemia, infiltrative or fibrotic disease of SA node, structural heart disease, PE, sleep apnea, electrolyte disturbance and Lyme disease should be ruled out. REFERENCE #1: Peigh, Graham, et al. 'Novel Coronavirus 19 (COVID-19) Associated Sinus Node Dysfunction: A Case Series'. European Heart Journal - Case Reports, vol. 4, no. FI1, Oct. 2020, pp. 1–6. Silverchair, doi:10.1093/ehjcr/ytaa132. REFERENCE #2: Clerkin KJ, Fried JA, Raikhelkar J, Sayer G, Griffin JM, Masoumi A, Jain SS, Burkhoff D, Kumaraiah D, Rabbani L, Schwartz A, Uriel N. Coronavirus disease 2019 (COVID-19) and cardiovascular disease. Circulation 2020;doi: 10.1161/CIRCULATIONAHA.120.046941 REFERENCE #3: Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol 2020;17:259–260. DISCLOSURES: No relevant relationships by Luna Khanal, source=Web Response No relevant relationships by Adarsha Ojha, source=Web Response

S1669 A Rare Presentation of Acute Pancreatitis in Mild Coronavirus Disease 2019 Infection

Introduction: Viral-induced pancreatitis has previously been well-defined, however there is limited data regarding the association between Coronavirus Disease 2019 (COVID-19) and pancreatitis. A handful of cases have been described, but most commonly are in conjunction with severe COVID-19 infections as well as pancreatic enzyme elevation. It has been demonstrated that patients with acute pancreatitis and coexistent COVID-19 infections have a significantly higher morbidity and mortality than those without acute pancreatitis. We describe a unique case of mild COVID-19 infection resulting in acute pancreatitis in the absence of lipase elevation. Case Description/Methods: A 39-year-old patient with no significant past medical history, including no history of chronic pancreatitis or alcohol use disorder, presented with epigastric pain, loss of taste and smell, fever and dry cough. Vital signs were within normal limits. Laboratory findings were significant for positive COVID-19 testing. Liver function panel, calcium, triglyceride, and lipase levels were all unremarkable. Computed tomography of the abdomen was consistent with acute pancreatitis without evidence of gallstones and without pancreatic, intra or extrahepatic biliary dilatation. The patient underwent conservative management with bowel rest and intravenous fluids and was discharged without complications. Discussion: This case introduces a rare presentation of acute pancreatitis without lipase elevation in setting of mild COVID-19 infection. It has been unclear whether lipase elevation in COVID-19 is due to direct pancreatic injury or viral-induced systemic inflammatory response causing multiorgan dysfunction. Our case may indicate that there is a direct impact on the pancreas by the SARS-CoV-2 virus, which has been postulated given the presence of ACE-2 receptors in the pancreas. This case also highlights the importance of suspecting pancreatitis in patients with mild COVID-19 infections that present with atypical symptoms such as epigastric pain, even without lipase elevation. Early identification in these cases may help to reduce progression and prevent worse outcomes.Figure 1.: Computed Tomography (CT) of the abdomen demonstrated mild peripancreatic inflammation at the level of the tail, with no clear pancreatic lesion and no loculated fluid collection. There was no calcified gallstone and no pancreatic ductal, intra or extrahepatic biliary dilatation.

S2659 SARS-CoV-2-Associated Cholestatic Liver Injury: A Case Series in Critically Ill Patients

Introduction: Hepatocellular injury has been documented in 14% to 76% of patients suffering from Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is associated with increased rates of intubation and mortality. SARS-CoV-2 enters target cells by binding to angiotensin-converting enzyme 2 present in the lungs, small intestine, cholangiocytes, and hepatocytes. While most patients experience mild acute liver injury, some critically ill patients develop a prolonged cholestatic injury pathologically similar to secondary sclerosing cholangitis. Histologic assessments have demonstrated microvesicular steatosis, diffuse intrahepatic vascular thrombosis, and chronic fibrous endothelial thickening. We present five cases of cholestatic liver injury in critically ill patients, including a novel case of severe hepatic arteriopathy during endoscopic retrograde cholangiopancreatography (ERCP). Case Description/Methods: We identified 5 patients without preexisting liver disease who developed prolonged cholestatic liver injury following severe COVID-19 infection requiring mechanical ventilation, antibiotics, and prolonged hospitalization (Table 1). Four patients developed shock requiring vasopressor support and two required extracorporeal membrane oxygenation. Additionally, Patient 1 underwent ERCP which revealed friable hepatic parenchyma and vascularture that appeared angiographically similar to secondary sclerosing cholangitis. While liver chemistries were normal or mildly elevated at the time of COVID-19 diagnosis, all patients experienced significant cholestasis with predominantly elevated alkaline phosphatase levels ranging from the 900s to 4000s. In patients who survived their initial hospitalization, liver chemistries remained elevated months beyond resolution of their pulmonary and renal injuries, and none had returned to baseline as of this writing. Discussion: We described several cases of prolonged cholestasis in patients with severe COVID-19 infection without preexisting liver disease. While a component of this acute liver injury could be attributed to drugs or ischemia, the timeframe and degree of injury suggest a different etiology, which we postulate may be a combination of secondary sclerosing cholangitis and direct hepatic injury from SARS-CoV-2. Additional research and longitudinal monitoring of these patients is needed to better characterize this type of injury and determine the risk of clinically relevant, long-term liver dysfunction.Table 1-A.: Patient Characteristics (1) COVID-19, Coronavirus Disease 2019 (2) ARDS, Acute Respiratory Distress Syndrome.Table 1-B.: Patient Characteristics (1) COVID-19, Coronavirus Disease 2019 (2) ARDS, Acute Respiratory Distress Syndrome.

Are women with polycystic ovary syndrome more vulnerable to COVID-19 infection?

Severe acute respiratory syndrome-coronavirus-2, the causative virus of Coronavirus disease-2019 (COVID-19), penetrates into the hosts’ tissues via binding of its spike protein to the angiotensin converting enzyme-2 (ACE-2) receptors after activation of the hosts’ protease enzymes. The most prominent effect is observed when the virus binds to the ACE-2 receptors of the alveolar epithelium and endothelium. Testosterone exhibits an immunosuppressive effect, and androgens play a modulatory role on protease enzymes. It is known that various comorbidities, including obesity; pregnancy; diabetes mellitus (type 1 or type 2); hypertension; cancer; chronic kidney, liver, and lung diseases; cerebrovascular disease; heart conditions; human immunodeficiency virus infection; immunologic disease; and immune suppression; affect the severity of COVID-19 infection. Polycystic ovary syndrome (PCOS) affects 5-10% of reproductive aged-women. Hirsutism is observed in 70-80% of the patients, while increased testosterone levels are detected in more than 50% of the women with PCOS. This syndrome is also associated with hyperandrogenism, insulin resistance, increased renin-angiotensin system activity, diabetes, and metabolic syndrome in a remarkable number of cases. PCOS also manifests a chronic pro-inflammatory state. Hyperandrogenism through hyperinsulinemia causes adipocyte hypertrophy and dysfunction that result in increased secretion of pro-inflammatory adipokine, which culminates in the creation of a chronic inflammatory state. In light of the metabolic and hormonal changes observed in women with PCOS, which make them more susceptible to severe COVID-19 infection, health care givers should provide special care and detailed counseling services.

Association between race and risk of ICU mortality in mechanically ventilated COVID-19 patients at a safety net hospital

PurposeTo determine racial differences in intensive care unit (ICU) mortality outcomes among mechanically ventilated patients with severe coronavirus disease 2019 (COVID-19) infection in a safety net hospital. MethodsWe retrospectively analyzed a cohort of patients ≥ 18 years old with confirmed severe acute respiratory syndrome-CoV-2 disease associated respiratory failure who were treated with invasive mechanical ventilation and admitted to the ICU from May 1, 2020 – July 30 -2020 at Grady Memorial Hospital, Atlanta, Georgia – a safety net hospital. We evaluated the association between mortality and demographics, co-morbidities, inpatient laboratory, and radiological parameters. ResultsAmong 181 critically ill mechanically ventilated African American patients treated at a safety net hospital, the mortality rate was 33%. On stratified analysis by race (Table 2), mortality rates were significantly higher in African Americans (39%) and Hispanics (26.3%), compared to Whites (18.9%). On multivariate regression, African Americans were 3 times more likely to die in the ICU compared to Whites (OR 3.1 95% CI 1.6 -5.5). Likewise, the likelihood of mortality was higher in Hispanics compared to Whites (OR 1.3 95% CI 1.0 -3.9). ConclusionsOur study demonstrated a high ICU mortality rate in a cohort of mechanically ventilated patients with severe COVID-19 infection treated at a safety net hospital. African Americans and Hispanics had significantly higher risks of ICU mortality compared to Whites. These study findings further elucidate the disproportionately higher burden of COVID-19 infection in African Americans and Hispanics.

The diagnostic value of neutrophil to lymphocyte ratio in determining the severity of COVID-19

Background: Changes in hematological parameters play a role in the pathogenesis of coronavirus disease 2019 (COVID-19). We aimed to investigate the significance of neutrophil-lymphocyte ratio (NLR) and hematologic parameters in determining the severity of COVID-19. Methods: This retrospective cross-sectional study was conducted on adult patients diagnosed with COVID-19 in two pandemic hospitals between 01, April, and 01, July 2020. Using the COVID-19 diagnostic criteria of the world health organization (WHO), the patients were divided into two groups as severe and non-severe. Demographic and clinical characteristics, white blood cell (WBC), neutrophil, lymphocyte and platelet counts, and NLR of all patients were examined at the first admission. Multivariate analyzes were performed to determine the independent predictive data and ROC analysis to test the diagnostic accuracy of the hematological parameters. Results: Of the 381 patients included in the study, 42 (11%) had severe COVID-19 infection. While the mean NLR was 7.61±7.48 in patients with severe COVID-19, the mean NLR of non-severe patients was 2.97±2.37 (95% CI: 2.294 to 6.984, p&lt;0.001). Long duration of hospital stay, elevated NLR ratio, female gender were predictive variables of severe COVID-19 cases (OR =0.833, 95% CI: 0.744 to 0.934, p=0.002; OR=0.195, 95% CI: 0.057 to 0.6731, p=0.010; OR=0.664, 95% CI: 0.501 to 0.881, p=0.005, respectively). In ROC analysis, NLR ratio had 2.625 optimum cut-off value, 60% specificity (95% CI: 54.7 to 65.4), 86% sensitivity (95% CI: 71.5 to 94.6), positive likelihood ratio (PLR) of 4.2 (95% CI: 2.0 to 8.9) and negative likelihood ratio (NLR) of 0.46 (95% CI: 0.4 to 0.6) for severe COVID-19 cases. Conclusion: The results of this study revealed that there might be a relationship between elevated NLR and severity in COVID-19 cases. IMC J Med Sci 2022; 16(1): 001 *Correspondence: Dr. Umut Gulacti, Adiyaman University Training and Research Hospital, Emergency Medicine, Adiyaman, Turkey. E-mail: umutgulacti@gmail.com

Casirivimab-Imdevimab (REGN-COV2) for Mild to Moderate SARS-CoV-2 Infection in Kidney Transplant Recipients

Casirivimab-Imdevimab (REGN-COV2) for Mild to Moderate SARS-CoV-2 Infection in Kidney Transplant Recipients

Differential plasmacytoid dendritic cell phenotype and type I Interferon response in asymptomatic and severe COVID-19 infection.

SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 (COVID-19) progression. Indeed, critically ill patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, responsible for cell and tissue damage and associated multi-organ failure. Here, the early interaction between SARS-CoV-2 and immune cells was investigated by interrogating an in vitro human peripheral blood mononuclear cell (PBMC)-based experimental model. We found that, even in absence of a productive viral replication, the virus mediates a vigorous TLR7/8-dependent production of both type I and III IFNs and inflammatory cytokines and chemokines, known to contribute to the cytokine storm observed in COVID-19. Interestingly, we observed how virus-induced type I IFN secreted by PBMC enhances anti-viral response in infected lung epithelial cells, thus, inhibiting viral replication. This type I IFN was released by plasmacytoid dendritic cells (pDC) via an ACE-2-indipendent but Neuropilin-1-dependent mechanism. Viral sensing regulates pDC phenotype by inducing cell surface expression of PD-L1 marker, a feature of type I IFN producing cells. Coherently to what observed in vitro, asymptomatic SARS-CoV-2 infected subjects displayed a similar pDC phenotype associated to a very high serum type I IFN level and induction of anti-viral IFN-stimulated genes in PBMC. Conversely, hospitalized patients with severe COVID-19 display very low frequency of circulating pDC with an inflammatory phenotype and high levels of chemokines and pro-inflammatory cytokines in serum. This study further shed light on the early events resulting from the interaction between SARS-CoV-2 and immune cells occurring in vitro and confirmed ex vivo. These observations can improve our understanding on the contribution of pDC/type I IFN axis in the regulation of the anti-viral state in asymptomatic and severe COVID-19 patients.