Item3058 – Sars-Cov-2 Binding in Hematopoietic Stem and Progenitor Cells Under Low Oxygen Conditions(Elsevier, 2021) Dausinas, Paige; Hartman, Melissa; Allman, Lauren; O'Leary, Heather; Anatomy, Cell Biology and Physiology, School of MedicineThe SARS-CoV-2 pandemic highlighted a need for in-depth understanding of interaction/identification of receptors and mechanisms/functional consequences of viral binding/entry. SARS-CoV-2 spike protein (SBP) facilitates viral entry via ACE2 and/or NRP1 binding, with DPP4 as a potential co-receptor. These binding partners are expressed on various cell types including hematopoietic stem and progenitor (HSC/HSPC) cells [1-3]. HSC/HSPCs generate blood cells and reside in the low oxygen (lowO2, 1-4%) bone marrow niches that provide critical signals for maintenance, self-renewal, and differentiation. To investigate aspects of SARS-CoV-2 interactions with HSC/HSPC such as endogenous receptor expression, SPB binding and subsequent functional alterations in native low O2, we performed transcriptional and phenotypic/functional analysis. In lowO2, we identified increased surface expression of ACE2, DPP4 and NRP1, and enhanced binding of SBP to HSC/HSPC populations which amplified proliferation of SBP bound in lowO2. ACE2 and DPP4 surface expression were ∼2-fold higher in HSPCs (p=0.017, p=0.001) and HSCs (p=0.010, p=0.03), and NRP1 was ∼1.5-fold (p=0.002) higher in HSPCs in lowO2 compared to air. Interestingly, in lowO2, overall SBP binding was enhanced in HSPC (2.2-fold, p<.001) and HSC (2.6-fold, p=.018). Although not all cells expressing ACE2/DPP4/NRP1 bind SBP (∼50%), all cells exhibiting SBP binding in HSC/HSPC populations are triple positive for ACE2, NRP1, and DPP4. Additionally, we observed greater than a 2-fold increase in proliferation of SBP bound vs unbound cells in replating assays in lowO2 (p<.001). These data impart compelling evidence that SBP binding/functional outcomes are unique in low O2, providing a foundation that may have potential clinical implications for COVID19 treatment and expanding our baseline understanding of SARS-CoV-2 viral binding implications. ItemRevascularization Outcomes of Acute Limb Ischemia in Patients With COVID-19(Elsevier, 2022) Kabeil, Mahmood; Wohlauer, Max; Moore, Ethan; Harroun, Nikolai; Gillette, Riley; Boggs, Shelbi; Motaganahalli, Raghu L.; Judelson, Dejah R.; Sundaram, Varuna; Mouawad, Nicolas J.; Bonaca, Marc P.; Cuff, Robert; Surgery, School of MedicineObjective: Acute limb ischemia (ALI) is one of the most catastrophic thrombotic manifestations of COVID-19 resulting in limb loss if not promptly treated. Our goal is to evaluate revascularization outcomes of ALI in patients with COVID-19 who underwent either open or endovascular treatment. Methods: The Vascular Surgery COVID-19 Collaborative started in March 2020 to assess hematological changes of COVID-19. We performed an interim data analysis on 46 patients with COVID-19 associated ALI submitted to the ALI module of the Vascular Surgery COVID-19 Collaborative REDcap database from 10 institutions in the United States. Results: Among the 46 patients included in the analysis, the mean age was 62.2 (standard deviation [SD]: 9.51) years. The majority of patients were male (73.9%). A total of 67.4% were White, 13% were Hispanic, and 4.3% were Black. In total, 93.5% of patients met Rutherford’s criteria of ALI class 2 or 3. On average, patients developed ALI 12.2 (SD: 13.5) days after a positive COVID test. Revascularization was attempted using open thrombectomy in 50.0%, endovascular lysis or thrombectomy in 23.9%, and bypass in 2.2%, and revascularization was not attempted in 23.9% of the patients (Table). Revascularization was successful in 41.3% with symptom resolution and 15.2% with limb salvage but persistent symptoms; 2.2% had minor amputation, 4.3% ultimately had a major amputation, 4.3% required reoperation, and revascularization was unsuccessful in 10.9% of patients. The average length of hospital stay was 13.2 (SD: 13.3) days, the average intensive care unit (ICU) length of stay was 4.66 (SD: 6.85) days, and the average ventilation days was 12.3 (SD: 10.8) days. Overall, in-hospital mortality was 21.7%, 8.7% had major amputation, 8.7% had stroke, 6.5% required major limb intervention, and 2.2% had sepsis. Successful revascularization rate was 62.5% in the 24 patients who underwent open surgery vs 36.4% in the 11 patients who underwent endovascular repair. The average length of stay in the ICU was shorter in the open group (mean = 3.24 days) than in the endovascular group (mean = 8.60 days). Of the 11 patients who had no revascularization attempt, 36.4% died, 18.2% had a major amputation, 9.1% had a pulmonary embolism, and 9.1% had a stroke. Conclusions: COVID-19-associated ALI carries a high mortality. Patients with COVID-19 who develop ALI can be managed successfully with open surgery or endovascular intervention. In our cohort, open revascularization resulted in reduced ICU stay and reduced ventilation days with improved limb salvage than the endovascular group. Further data are needed to develop management algorithms for ALI in patients with COVID-19. ItemCritical Illness Cholangiopathy in COVID-19 Long-haulers(Elsevier, 2022) Saleem, Nasir; Li, Betty H.; Vuppalanchi, Raj; Gawrieh, Samer; Gromski, Mark A.; Medicine, School of Medicine ItemCovid 19 and Pericarditis: Should We Be Worried about Tamponade?(Elsevier, 2022) Arshad, Samiullah; Gul, Muhammad Hamdan; Guglin, Maya; Medicine, School of MedicineIntroduction: Little is known about cardiac manifestations of COVID-19 infection, yet cases of pericarditis, pericardial effusion and with tamponade due to COVID-19 have been reported. Because of the life-threatening nature of this complication, we wanted to investigate the features of pericardial effusion and the rate of occurrence of tamponade in patients with COVID-19. Methods: This systematic review was conducted by searching for studies in Pubmed/Medline and Google Scholar for the search terms ‘COVID-19’, ‘SARS-COV-2’, ‘Pericarditis’, ‘Pericardial Effusion’ and ‘Cardiac Tamponade’, performed on December 7, 2020. Results: A total of 47 patients with COVID-19 with pericarditis were included in the review from 39 published cases. There were 29 (62%) males and 18 (38%) females and mean age of patients was 53 years. Pulmonary infiltrates were seen in 30 (64%) patients, while 17 (36%) patients did not have pulmonary manifestations. Concomitant myocarditis was present in 16 (34%) patients. 43 (91%) had pericardial effusion- 4 (9%) had small, 10 (21%) had moderate, 3 (6%) had a large pericardial effusion and 26 (55%) patients had cardiac tamponade. 7 (15%) patients with tamponade died. Pericardiocentesis was done in 27 (57%) patients and pericardial window was created in 5 (11%) patients. Off these 13 (27%) patients had an exudative effusion while 1 (2%) patient had a transudative effusion. Conclusion: We found that pericarditis in patients with COVID-19 infection can be present in patients with pulmonary infiltrates and without them, as well as with myocarditis or as an isolated feature of cardiac involvement. The effusion is predominantly exudative. More than half of the patients with pericardial involvement present with tamponade, and mortality in this subset is high. The pattern of patients presenting solely with pericarditis and effusion without pulmonary infiltrates warrants further investigation. ItemOutcomes of single dose COVID-19 vaccines: Eight month follow-up of a large cohort in Saudi Arabia(Elsevier, 2022) Alharbi, Naif Khalaf; Al-Tawfiq, Jaffar A.; Alghnam, Suliman; Alwehaibe, Amal; Alasmari, Abrar; Alsagaby, Suliman A.; Alsubaie, Faisal; Alshomrani, Majid; Farahat, Fayssal M.; Bosaeed, Mohammad; Alharbi, Ahmad; Aldibasi, Omar; Assiri, Abdullah M.; Medicine, School of MedicineBackground: Two vaccines for COVID-19 have been approved and administered in the Kingdom of Saudi Arabia (KSA); Pfizer-BioNtech BNT162b2 and AstraZeneca-Oxford AZD1222 vaccines. The purpose of this study was to describe the real-world data on the outcome of single dose of these COVID-19 vaccines in a large cohort in KSA and to analyse demographics and co-morbidities as risk factors for infection post one-dose vaccination. Methods: In this prospective cohort study, a total of 18,543 subjects received one dose of either of the vaccines at a vaccination centre in KSA, and were followed up for three to eight months. Data were collected from three sources; clinical data from medical records, adverse events (AEs) from a self-reporting system, and COVID-19 infection data from the national databases. The study was conducted during the pandemic restrictions on travel, mobility, and social interactions. Results: The median age of participants was 33 years with an average body mass index of 27.3. The majority were males (60.1%). Results showed that 92.17% of the subjects had no COVID-19 infection post-vaccination as infection post-vaccination was documented for 1452 (7.83%). Diabetes mellitus 03), organ transplantation (p = 0.02), and obesity (p < 0.01) were associated with infection post-vaccination. Unlike vaccine type, being Saudi, male, or obese was associated with the occurrence breakthrough infections more than other parameters. AEs included injection site pain, fatigue, fever, myalgia, headache and was reported by 5.8% of the subjects. Conclusion: Single dose COVID-19 vaccines showed a protection rate of 92.17% up to eight months follow-up in this cohort. This rate in AZD1222 was higher than what have been previously reported in effectiveness studies and clinical trials. Obese, male, and Saudi were at higher risk of contracting the infection post-vaccination, Saudi and male might have more social interaction with the public when mobility and social interactions were limited during the pandemic. Side effects and AEs were within what has been reported in clinical trials. ItemRecognizing and Managing Myocarditis Following Covid-19 Vaccination: Mitigating Risk of Sudden Cardiac Death in Athletes(Elsevier, 2022) Kauth, Mark; Kovacs, Richard J.; Medicine, School of MedicineBackground: Myocarditis is a risk for sudden cardiac death (SCD) in athletes, and its recognition and appropriate management are of paramount importance for safe return to athletic activity. Myocarditis has been reported as a complication of the mRNA COVID-19 vaccines, especially in young males. It is not known whether prior COVID-19 infection increases risk for myocarditis after vaccination. We present a case of a young athletic male previously infected with COVID-19, who developed myocarditis after a second dose of the Pfizer mRNA COVID-19 vaccine. Case: A 19-year-old healthy male presented to the ED. He described anterior squeezing chest pain without association with activity or rest, and lateral chest pain exacerbated by movement. 6-8 months prior, he tested positive for COVID-19 infection via RT-PCR saliva test with symptoms that included rhinorrhea, cough, anosmia, ageusia, and mild chest pain. Symptoms resolved spontaneously. He later received two doses of the Pfizer vaccine, with second dose given 10 days prior to presentation. Vital signs and physical exam were normal. ECG showed 0.5-1mm ST segment elevation in the inferior and lateral leads. Troponin-I was elevated and peaked at 3.61 ng/mL, CBC, comprehensive metabolic panel, TSH, and C-reactive protein were normal. CT angiogram of the chest was normal. Transthoracic echocardiogram demonstrated normal left ventricular systolic function, normal wall motion, and no pericardial effusion. Decision-making: This patient was clinically diagnosed with myocarditis. He was treated with ibuprofen and beta blocker with improvement. Cardiac magnetic resonance imaging with and without gadolinium demonstrated minimal T2 signal elevation, but did reveal late gadolinium enhancement of 25-75% of the inferior and lateral walls. Athletic activity was restricted for 3-6 months and follow-up testing is yet to be completed. Conclusion: Although rare, myocarditis is a recognized complication following COVID-19 mRNA vaccination. Risk may be increased in younger male patients, and those previously infected with COVID-19. It is important to anticipate this complication of vaccination in the competitive athlete population, to mitigate risk of SCD. ItemActive viral shedding in a vaccinated hospitalized patient infected with the delta variant (B.1.617.2) of SARS-CoV-2 and challenges of de-isolation(Elsevier, 2022) Alshukairi, Abeer N.; Al-Omari, Awad; Al-Tawfiq, Jaffar A.; El-Kafrawy, Sherif A.; El-Daly, Mai M.; Hassan, Ahmed M.; Faizo, Arwa A.; Alandijany, Thamir A.; Dada, Ashraf; Saeedi, Mohammed F.; Alhamlan, Fatma S.; Al Hroub, Mohammad K.; Qushmaq, Ismael; Azhar, Esam I.; Medicine, School of MedicineIn the era of SARS-CoV-2 variants and COVID-19 vaccination, the duration of infectious viral shedding and isolation in post vaccine breakthrough infections is challenging and depends on disease severity. The current study described a case of SARS-CoV-2 Delta variant pneumonia requiring hospitalization. The patient received two doses of BNT162b2 COVID-19 vaccines, and he had positive SARS-CoV-2 viral cultures 12 days post symptom onset. The time between the second dose of vaccine and the breakthrough infection was 6 months. While immunosuppression is a known risk factor for prolonged infectious viral shedding, age and time between vaccination and breakthrough infection are important risk factors that warrant further studies. ItemPrevalence, Predictors and Outcomes of Documented DNR and/or DNI Orders in COVID-19 Patients (S522)(Elsevier, 2022) Comer, Amber; Fettig, Lyle; Bartlett, Stephanie; Schmidt, Amanda; Endris, Katelyn; Zepeda, Isabel; Waite, Carly; Slaven, James; Torke, Alexia; Medicine, School of MedicineOutcomes: 1. Understand the prevalence, predictors, and outcomes associated with DNR and DNI orders for hospitalized patients with COVID-19 throughout the pandemic 2. Understand the reasons for differences in code status order utilization for hospitalized patients with COVID-19 throughout the pandemic Original Research Background: The COVID-19 pandemic created complex challenges regarding timing and appropriateness of do not resuscitate (DNR) and do not intubate (DNI) orders. Research Objectives: This study sought to determine the prevalence, predictors, timing, and outcomes associated with having a documented DNR or DNI order for hospitalized patients with COVID-19. Methods: A retrospective multisite chart review of hospitalized patients with COVID-19 was performed to determine characteristics, medical treatments received, and outcomes associated with having a documented DNR or DNI order. Patients were divided into two cohorts (early and late) by timing of hospitalization during the pandemic. Results: Among 1,358 hospitalized patients with COVID-19, 19% (n = 259) had a documented DNR or DNI order. In multivariate analysis, age (older) (p < .01, OR 1.13), race (White) (p = .01, OR 0.55), and hospitalization during the early half of the pandemic (p = .02, OR 1.8) were associated with having a DNR or DNI order. Palliative care consultation occurred more often in the early cohort (p < .01). Medical treatments, including ICU (p = .31) and level of ventilator support (p = .32) did not differ between cohorts. Hospital mortality was similar between the early and late cohorts (p = .27); however, among hospital decedents median hospital day from DNR or DNI order to death differed between cohorts (p < .01) (6 days from order to death in early vs 2 days in the late cohort). Conclusion: More frequent use of DNR orders and orders written farther from death in decedents characterized the early pandemic phase. White patients were more likely to have DNR or DNI orders, consistent with prior research. Implications for Research, Policy, or Practice: Uncertainty in prognosis may have played a role in the frequency and timing of DNR and DNI orders early in the pandemic. Additional factors, such as fear of resource shortage and transmission of COVID-19 to healthcare workers, may have also played a role. ItemQuality of Care and Outcomes for Patients with Acute Ischemic Stroke and Transient Ischemic Attack During the COVID-19 Pandemic(Elsevier, 2022) Myers, Laura J.; Perkins, Anthony J.; Kilkenny, Monique F.; Bravata, Dawn M.; Medicine, School of MedicineBackground and purpose: Hospitalizations for acute ischemic stroke (AIS) and transient ischemic attack (TIA) decreased during the COVID-19 pandemic. We compared the quality of care and outcomes for patients with AIS/TIA before vs. during the COVID-19 pandemic across the United States Department of Veterans Affairs healthcare system. Methods: This retrospective cohort study compared AIS/TIA care quality before (March-September 2019) vs. during (March-September 2020) the pandemic. Electronic health record data were used to identify patient characteristics, quality of care and outcomes. The without-fail rate was a composite measure summarizing whether an individual patient received all of the seven processes for which they were eligible. Mixed effects logistic regression modeling was used to assess differences between the two periods. Results: A decrease in presentations occurred during the pandemic (N = 4360 vs. N = 5636 patients; p = 0.003) and was greater for patients with TIA (-30.4%) than for AIS (-18.7%). The without-fail rate improved during the pandemic (56.2 vs. before 50.1%). The use of high/moderate potency statins increased among AIS patients (OR 1.26 [1.06-1.48]) and remained unchanged among those with TIA (OR 1.04 [0.83,1.29]). Blood pressure measurement within 90-days of discharge was less frequent during the pandemic (57.8 vs. 89.2%, p < 0.001). Hypertension control decreased among patients with AIS (OR 0.73 [0.60-0.90]) and TIA (OR 0.72 [0.54-0.96]). The average systolic and diastolic blood pressure was 1.9/1.4 mmHg higher during the pandemic than before (p < 0.001). Compared to before, during the pandemic fewer AIS patients had a primary care visit (52.5% vs. 79.8%; p = 0.0001) or a neurology visit (27.9 vs. 41.1%; p = 0.085). Both 30- and 90-day unadjusted all-cause mortality rates were higher in 2020 (3.6% and 6.7%) vs. 2019 (2.9, 5.4%; p = 0.041 and p = 0.006); but these differences were not statistically significant after risk adjustment. Conclusions: Overall quality of care for patients with AIS/TIA did not decline during the COVID-19 pandemic. Item153. AYA Subspecialty Patient and Parent Views on COVID-19 Vaccination(Elsevier, 2022) Hardman, Sara; Jacob, Seethal A.; Coven, Scott L.; Rahim, Mahvish Q.; Miller, Meagan E.; Zimet, Gregory D.; Meagher, Carolyn G.; Ott, Mary A.; Pediatrics, School of MedicinePurpose: Adolescents/young adults (AYA) with hematologic and oncologic (heme-onc) conditions are important targets for vaccine outreach because they are at increased risk for complications from COVID-19. AYA patients may also need additional support, as they are transitioning from parent to independent vaccine decision-making. AYA with sickle cell disease (SCD) are of particular concern because a high proportion are African American and experience structural racism in addition to their illness. Our objective was to examine AYA and parent attitudes regarding the COVID-19 vaccine among heme-onc populations. Methods: As part of a larger IRB-approved study, we recruited vaccine decision-makers in pediatric SCD and oncology survivor clinics, including parents of adolescents under 18 years (n=35), AYA patients 18-21 years old (n=21), and parents of AYA patients 18-21 years old (n=14). After informed consent, participants completed a demographic survey and a semi-structured interview regarding their vaccine decision-making process. Example questions included “What do you see as the benefits of the COVID-19 vaccine?” and “What are your concerns about the COVID-19 vaccine?”. Saturation was reached. Interviews were audio recorded, transcribed, and analyzed using thematic analysis. Codes were developed from the literature and early interviews. Examples included “attitudes against vaccine,” “medical mistrust,” “hesitancy,” “vaccine side effects,” and “vaccine interactions with disease process.” Fisher exact statistical tests were performed to analyze quantitative data. Results: In SCD clinic, we recruited 31 index patients (mean age: 15.1±3.5 years; 30 African American and 1 Other or Mixed), yielding 11 AYA and 26 parent interviews. In survivor clinic, we recruited 26 index patients (mean age: 16.0±3.4 years; 20 White, 2 Hispanic or Latinx; 2 Other or Mixed, 1 African American, and 1 Asian), yielding 10 AYA and 23 parent interviews. Out of the total index patients, 8 had already received the vaccine, 13 were planning to receive it, 27 were considering it, and 9 had declined it. There was no clear relationship between patients’ diagnosis (SCD or cancer) and their vaccine decisions nor between the index patient’s age (under or over 18) and their vaccine decisions. A high proportion of participants saw benefits to vaccination, such as lowering personal risk, community benefits of preventing the spread of COVID-19, and a possible return to “normal.” However, many AYA and parent participants also had concerns toward the vaccine, including concerns about short-term side effects and the potential for unknown, long-term effects. Concerns were also voiced about how rapidly the vaccine was developed and misconceptions about the vaccine were common, namely the vaccine causing infertility or increasing one’s susceptibility to contracting COVID-19. Medical mistrust toward either the vaccine or providers was explicitly stated by several participants, the majority of whom were from minoritized groups. Conclusions: COVID-19 vaccines have the potential to protect medically and socially vulnerable AYA, however patient and parent concerns, misconceptions, and mistrust are still prevalent. These data provide insights into the design and implementation of vaccine counseling interviews for AYA subspecialty patients and families.