Patients with COVID-19 Infection and Stroke have Higher than Expected Mortality, Regardless of the Primary Presentation (preprint)

BackgroundCOVID-19 infection is associated with thrombotic events; however, this phenomenon is poorly understood. Few studies have reported the association between COVID-19 and stroke in the hospital setting. MethodsWe retrospectively reviewed and characterized all patients who presented to a single, quaternary medical center between March and December 2020 (N=603). COVID-19 positive patients who developed ischemic or hemorrhagic stroke were included in the analysis (N=66). This cohort was compared with patients who were COVID-19 negative at the time of stroke presentation in the same period (N=537). Statistical significance was evaluated using Pearsons Chi squared test with Yates continuity correction and linear model ANOVA. ResultsSixty-six patients had COVID-19 and Stroke. Of these patients, 22 (33.4%) patients initially presented with stroke and 44 (66.7%) initially presented with COVID-19. Patients who presented with COVID-19 and had a stroke during their hospitalization (COVID-first) had worse outcomes than patients presenting to the hospital with stroke whose COVID test became positive later in the hospitalization (stroke-first). Patients who presented with COVID-19 and had a stroke during their hospitalization had an increased rate of acute renal failure (48.9% vs 19.0%, p=0.021) and need for ventilation (60.0% vs 28.6%, p=0.017). Further, in the COVID-first cohort, the use of heparin prior to the stroke event was not associated with mortality or type of stroke (ischemic or hemorrhagic). ConclusionIn the early pandemic, patients with COVID-19 infection and stroke had a higher mortality rate compared to COVID-19 negative patients with stroke. Among patients with both COVID-19 and stroke, patients presenting with COVID-19 first had worse outcomes than patients presenting with stroke first. The use of heparin prior to the stroke event was not associated with mortality or type of stroke.

Impact of in-hospital COVID-19 quarantine policy changes on quality of acute stroke care: A single center experience (preprint)

Background and purpose The COVID-19 pandemic is known to impact in-hospital processes for acute stroke patients, potentially resulting in delays due to quarantine and screening measures. The purpose of this study was to determine effects of changes in in-hospital quarantine policies on quality of care for acute stroke patients.Methods Hyperacute ischemic stroke patients who were admitted to Korea University Guro Hospital between January 2019 and February 2021 via the emergency department were included in this study. All had neurological symptoms within six hours before arrival. As a mandatory COVID-19 real-time PCR screening test was implemented in March 2020, changes in quality indicators according to the progress of COVID-19 pandemic and changes in in-hospital quarantine policy, including door-to-image time (DIT), door-to-referral time, door-to-needle time (DNT), door-to-puncture time (DPT), and functional outcomes (discharge and 3-month modified Rankin's scale) were determined.Results A total of 268 hyperacute stroke patients were analyzed. The number of hyperacute stroke patients gradually decreased as the pandemic progressed. Time indicators, including door-to-referral time, DIT, and DPT during the pandemic were increased. When pre- and post-COVID-19 screening epochs were compared, DIT, door-to-neurologist referral time, and DPT showed numerical increases. However, after accounting for potential confounders, a significant delay in DIT was found to be associated with the in-hospital COVID-19 quarantine policy.Conclusions Our study showed that enhancing in-hospital COVID-19 quarantine measures might increase the response time for hyperacute stroke care, suggesting an impact on the quality of care.Trial registration: Not applicable.

COVID-19 induced Multisystem Inflammatory Syndrome in Adult and Acute Limb Ischemia. (preprint)

The patient presented with a chief complaint of lower extremity pain was found to be positive SARS-CoV-2 test. Contrast-enhanced computed tomography scans showed endocarditis, vasculitis and lower extremity ischemia. Despite we treated the patient with dexamethasone, the patient died.

How phytocannabinoids affect cardiovascular health? An update on the most common cardiovascular diseases. (preprint)

Cardiovascular diseases (CVDs) remain the cause of millions of deaths in the world annually. Despite the great progress in therapies, which are available for patients with CVDs, some limitations including drug complications still exist. Hence, the endocannabinoid system (ECS) was proposed as a new avenue for CVDs treatment. The cardiovascular action of cannabinoids is complex as they not only affect vasculature and myocardium directly via specific receptors but also exert indirect effects through the central and peripheral nervous system. The growing interest in phytocannabinoid studies has been broadened the knowledge about their molecular targets as well as therapeutical properties, nonetheless, some areas of their actions are not yet fully recognized. The purpose of this review is to summarize and update the cardiovascular actions of the most potent phytocannabinoids and the potential therapeutic role of ECS in CVDs, including ischemic reperfusion injury, arrhythmia, heart failure, hypertension as well as cardiac complications associated with the novel coronavirus SARS-CoV-2 infections.

Clinical, laboratory, and imaging findings of stage 3-5 chronic kidney disease patients suffering from COVID-19 in Bangladesh: a prospective cross-sectional study (preprint)

Background: Chronic kidney disease (CKD) patients were susceptible to morbidity and mortality once they affected by COVID-19. These patients were more likely to develop severe disease, requiring dialysis, admission to intensive care unit. The aim of this study was to evaluate the presentations and outcomes of COVID-19 in stage 3-5 CKD patients not on dialysis. Methods This prospective observational study was conducted in the COVID-19 unit, at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from September 2020 to August 2021. Hospitalized RT-PCR positive COVID-19 patients with pre-existing CKD having eGFR <60 ml/min/1.73 m 2 but not yet on dialysis were enrolled. Clinical and laboratory parameters were recorded. Outcomes were observed till discharge from the hospital and followed up after 3 months of survived patients. Results Out of 109 patients, the mean age was 58.1(SD: 15.4) years where 61.5% were male. Common co-morbid conditions were hypertension (89.0%), diabetes mellitus (58.7%) and ischemic heart disease (24.8%). Fever, cough, shortness of breath and fatigue were common presenting features. Most of the patients had moderate (41.3%) and severe (41.3%) COVID-19. Sixty-six patients (60.6%) developed AKI on CKD. Twenty patients (30.3%) required dialysis. Death occurred in 16 patients (14.7%) and 12 patients (11%) required ICU admission and 6 patients (9.1%) achieved baseline renal function at discharge. We identified risk factors like low haemoglobin, lymphopenia, high CRP, high procalcitonin, high LDH and low SpO 2 in patients who did not survive. Seventy-six patients were followed up at 3rd month where 17 patients were lost. Ten patients (27.0%) achieved baseline renal function who had persistent AKI at discharge and 34 patients (87.1%) remained stable who had stable renal function at discharge. Conclusion The stage 3-5 chronic kidney patients with COVID-19 are vulnerable to severe to critical morbidity and mortality with higher incidence of AKI which demands a special attention to this group of patients.

Microvascular Capillary and Precapillary Cardiovascular Disturbances Strongly Interact to Severely Affect Tissue Perfusion and Mitochondrial Function in ME/CFS Evolving from the Post COVID-19 Syndrome (preprint)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent, debilitating and still enigmatic disease. There is a broad overlap in the symptomatology of ME/CFS and the Post-COVID Syndrome (PCS). A fraction of the PCS patients develops the full clinical picture of ME/CFS. New observations in microvessels and blood from patients suffering from PCS have appeared and include microclots and malformed pathological blood cells. Capillary blood flow is impaired not only by pathological blood components but also by prothrombotic changes in the vascular wall, endothelial dysfunction, and expression of adhesion molecules in the capillaries. These disturbances can finally cause a low capillary flow and even capillary stasis. A low cardiac stroke volume due to hypovolemia and the inability of the capacitance vessels to adequately constrict to deliver the necessary cardiac preload generate an unfavorable low precapillary perfusion pressure. Furthermore, a predominance of vasoconstrictor over vasodilator influences exists, in which sympathetic hyperactivity and endothelial dysfunction play a strong role, causing constriction of resistance vessels and of precapillary sphincters which leads to a fall in capillary pressure behind the sphincters. The interaction of these two precapillary cardiovascular mechanisms causing a low capillary perfusion pressure is hemodynamically highly unfavorable in the presence of a primary capillary stasis already caused by the pathological blood components and their interaction with the capillary wall, to severely impair organ perfusion. The detrimental coincidence of the microcirculatory with the precapillary cardiovascular disturbances may constitute the key disturbance of the Post-COVID-19 syndrome and finally lead to ME/CFS in pre-disposed patients because the interaction causes a particular kind of perfusion disturbance - capillary ischemia-reperfusion - which has a high potential of causing mitochondrial dysfunction by inducing sodium- and calcium-overload in skeletal muscles. The latter in turns worsens the vascular situation by the generation of reactive oxygen species to close a vicious cycle from which the patient can hardly escape.

Ischemic Stroke after Bivalent COVID-19 Vaccination: A Self-Controlled Case Series Study (preprint)

Introduction The potential association between bivalent COVID-19 vaccination and ischemic stroke remains uncertain, despite several studies conducted thus far. The purpose is to evaluate the risk of ischemic stroke following bivalent COVID-19 vaccination. Methods A self-controlled case series study was conducted among members aged 12 years and older who experienced ischemic stroke between September 1, 2022 and March 31, 2023 in a large California health care system. Ischemic strokes were identified using ICD-10 codes in Emergency Department and inpatient settings. Exposures were Pfizer-BioNTech or Moderna bivalent COVID-19 vaccination. Risk intervals were pre-specified as 1-21 days and 1-42 days after bivalent COVID-19 vaccination; all non-risk-interval person-time served as control interval. We conducted overall and subgroup analyses by age, history of SARS-CoV-2 infection, and co-administration of influenza vaccine. When an elevated risk was detected, we performed chart review of ischemic strokes, and re-evaluated the risk. RESULTS With 4933 cases, we found no increased risk within 21-day risk interval across vaccines and by subgroups. However, an elevated risk emerged within 42-day risk interval among individuals <65 years who received co-administration of Pfizer-BioNTech bivalent vaccine and influenza vaccine on the same day; relative incidence (RI) was 2.14 (95% CI, 1.02-4.49). Among those who also had history of SARS-CoV-2 infection, RI was 3.94 (95% CI, 1.10-14.16). After chart review, RIs were 2.35 (95% CI, 0.98-5.65) and 4.33 (95% CI, 0.98-19.11), respectively. Among individuals <65 years who received Moderna bivalent vaccine and had history of SARS-CoV-2 infection, RI was 2.62 (95% CI, 1.13-6.03) before chart review and 2.24 (95% CI, 0.78-6.47) after chart review. CONCLUSIONS The potential association between bivalent COVID-19 vaccination and ischemic stroke in the 1-42-day analysis warrants further investigation among individuals <65 years with influenza vaccine co-administration and prior SARS-CoV-2 infection.

Risk of Ischemic Stroke after COVID-19 Bivalent Booster Vaccination in an Integrated Health System (preprint)

Abstract: Purpose: What is the absolute occurrence of ischemic stroke and transient ischemic attack after a COVID-19 bivalent vaccination? Methods: We conducted a retrospective cohort study of Kaiser Permanente Northwest (KPNW) patients 18 years and older who were vaccinated with either the Pfizer or Moderna formulation of the COVID19 bivalent vaccine between September 1, 2022 and March 1st 2023. Patients were included in the study if they had KP membership at the time of vaccination and through the 21-day follow up period. We replicated the Vaccine Safety Datalink (VSD) rapid cycle analysis methodology and searched for possible cases of ischemic stroke or TIA in the 21 days following vaccination using ICD10CM diagnosis codes in both the primary position and any position. We waited 90 days from the end of the follow up (March 21, 2023) for complete non KP data accrual before analyzing the data to account for the lag in processing outside hospital insurance claims. Two physicians adjudicated possible cases by reviewing the clinical notes in the electronic health record. The analyses were stratified by age 65 years and older to allow for comparisons with VSDs reporting at the Advisory Committee on Immunization Practices (ACIP) meeting of incidence of ischemic stroke or TIA (VSD reported incidence; 24.6 cases of ischemic stroke or TIA per 100,000 patients vaccinated). Results: The incidence of ischemic stroke or TIA was 34.3 per 100,000 (95% CI, 17.7 to 59.9) in patients 65 years or older who received the bivalent Pfizer vaccine, based on a diagnosis code in the primary position of the emergency department or hospital discharge. The incidence increased to 45.7 per 100,000 (95% CI 26.1 to 74.2) when we expanded the search to a diagnosis in any position and did not adjudicate to confirm. However, most of those additional apparent stroke or TIA diagnoses were false-positive diagnoses based on physicians adjudications. Estimating the incidence based on the primary position agreed closely with estimating the incidence based on any position and physician adjudication: 37.1 per 100,000 (95% CI 19.8 to 63.5). Seventy-nine percent of the ischemic stroke cases were admitted to hospitals that are not owned by the integrated delivery system. Conclusion: We identified a 50% increase in the incidence of ischemic stroke per 100,000 patients ages 65 and older vaccinated with the Pfizer bivalent vaccine, compared to the data presented by the VSD. Seventy-nine percent of the ischemic stroke cases were admitted to hospitals that are not owned by the integrated delivery system and a delay in processing outside hospital insurance claims was likely responsible for the discrepancy in case ascertainment of ischemic stroke. Physician adjudication of all cases in this study allowed accurate absolute incidence estimates of stroke per 100,000 vaccine recipients and is helpful in calculation of net benefit for policy recommendations and shared decision-making.

Emerging Links Between COVID-19 and Cardiovascular & Cerebrovascular Thromboembolic Events: A Systematic Review (preprint)

COVID-19, caused by the SARS-CoV-2 virus, initially identified as a respiratory illness, has increasingly been linked to a broader range of organ complications. This systematic review explores the impact of COVID-19 on cardiovascular and cerebrovascular health, focusing on thromboembolic events in post-COVID patients. A comprehensive literature search was conducted in PubMed and Google Scholar databases up to July 2023, utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies meeting eligibility criteria were analyzed for outcomes and associations between COVID-19 and cardiovascular and cerebrovascular events. The review includes 6 studies involving over 12 million patients, demonstrating a strong connection between COVID-19 and elevated risks of cardiovascular and cerebrovascular thromboembolic events. The risk of these events is evident in conditions such as ischemic heart disease, stroke, and cardiac arrhythmias. The burden of these events beyond the acute phase of the disease is concerning, warranting further exploration of long-term implications. Variability in event rates among different cohorts and healthcare settings underscores the need for understanding underlying factors influencing these differences. Potential mechanisms behind these events include endothelial dysfunction, systemic inflammation, and viral invasion. Implications for public health policies, clinical guidelines, and future research directions are discussed. This review serves as a valuable resource for healthcare providers, policymakers, and researchers to enhance patient care, outcomes, and preparedness for future waves of COVID-19 infections. However, there remain unexplored aspects of the COVID-19 and thromboembolic events relationship, urging further investigations into mechanistic insights and potential therapeutic interventions.

Effect Of Molnupiravir On Ichemia/Reperfusion Damage In Rat Liver, An Experimental Study (preprint)

Background Ischemia occurs when blood supply to tissues is limited, resulting in cellular dysfunction and necrosis. Reperfusion, or the process of restoring blood flow, can result in an overabundance of reactive oxygen species (ROS) and toxic byproducts. The I/R (Ischemia / Reperfusion) technique used in liver resection and transplantation has been linked to liver damage. Molnupiravir, a non-hepatotoxic oral medicine, is converted into N-hydroxycytidine (NHC). The purpose of this study is to see how molnupiravir affects I/R-induced damage of liver in rats.Methods We divided the rats into three groups: Sham operation (SG) (n = 6), Liver I/R (LIR) (n = 6), and Molnupiravir + Liver I/R (MIR) (n = 6) groups. The MIR group (n = 6) received 40 mg/kg of molnupiravir. All animals were subjected to laparotomy, hepatic ischemia (1 hour), and reperfusion (6 hours). At the end of the trial, liver tissue samples were tested for IL-1β, tGSH, NF-κB, MDA, and TNF-α levels, as well as histopathological examination. The levels of ALT and AST in the blood were determined. The MIR group's results were in comparison to the SG and LIR groups.Results Biochemical examination revealed that NF-ƘB, MDA, TNF-α, IL-1β, ALT, and AST measurements were higher in the LIR and MIR groups than in the SG group. The SG group had the highest tGSH values. Histopathological examinations revealed that the MIR group had the most damage.Conclusion While molnupiravir, which is included in COVID-19 treatment regimen since it has no projected liver toxicity, does not affect healthy liver tissue, it does exacerbate ischemia/reperfusion injury in stressed liver tissue. Molnupiravir should be used with caution because it has the potential to aggravate liver damage during procedures such as liver transplantation or resection.

Cerebrovascular Disease in COVID-19 (preprint)

Not in the history of transmissible illnesses has there been an infection as strongly associated with acute cerebrovascular disease as the novel human coronavirus, SARS-CoV-2. While the risk of stroke has known associations with other viral infections, such as influenza and human immunodeficiency virus, the risk of ischemic and hemorrhagic stroke related to SARS-CoV-2 is unprecedented. Furthermore, the coronavirus disease 2019 (COVID-19) pandemic has so profoundly impacted psychosocial behaviors and modern medical care that we have witnessed shifts in epidemiology and have adapted our treatment practices to reduce transmission, address delayed diagnoses, and mitigate gaps in health care. In this narrative review, we summarize the history and impact of the COVID-19 pandemic on cerebrovascular disease, and lessons learned regarding the management of patients as we endure this period of human history.

Retrospective review of complications and outcomes in COVID-19-positive patients with comorbidities undergoing limb salvage procedures in a tertiary care wound center.

INTRODUCTION: COVID-19 illness is associated with increased operative risks, ranging from delayed wound healing and coagulopathy to increased risk of mortality. OBJECTIVE: This article describes the authors' recent experience of the implications of COVID-19 on limb salvage procedures. MATERIALS AND METHODS: Patients who underwent LE limb salvage procedures within 30 days of a positive COVID-19 diagnosis were retrospectively reviewed. Patient demographics, comorbidities, surgical factors, postoperative complications, and management were collected. RESULTS: Of 597 patients screened from February 2020 to March 2022, a total of 67 (11.2%) were diagnosed with COVID-19, of which 17 received the diagnosis within 30 days of surgery and were thus included. Average follow-up was 43 ± 3.2 months, at which point 6 (35.3%) were fully healed. The mortality rate at the most recent follow-up visit was 29.4% of patients (n = 5). Two patients required admission to the SICU following index procedure, and 1 necessitated a return to the operating room. CONCLUSION: COVID-19 may negatively affect the wound healing process while increasing the mortality rate amongst patients with multiple or severe comorbidities undergoing limb salvage procedures. Medical providers need to be aware of the complexity of these patients and apply a multi-disciplinary protocol to obtain successful outcomes.

The fatal trajectory of pulmonary COVID-19 is driven by lobular ischemia and fibrotic remodelling.

BACKGROUND: COVID-19 is characterized by a heterogeneous clinical presentation, ranging from mild symptoms to severe courses of disease. 9-20% of hospitalized patients with severe lung disease die from COVID-19 and a substantial number of survivors develop long-COVID. Our objective was to provide comprehensive insights into the pathophysiology of severe COVID-19 and to identify liquid biomarkers for disease severity and therapy response. METHODS: We studied a total of 85 lungs (n = 31 COVID autopsy samples; n = 7 influenza A autopsy samples; n = 18 interstitial lung disease explants; n = 24 healthy controls) using the highest resolution Synchrotron radiation-based hierarchical phase-contrast tomography, scanning electron microscopy of microvascular corrosion casts, immunohistochemistry, matrix-assisted laser desorption ionization mass spectrometry imaging, and analysis of mRNA expression and biological pathways. Plasma samples from all disease groups were used for liquid biomarker determination using ELISA. The anatomic/molecular data were analyzed as a function of patients' hospitalization time. FINDINGS: The observed patchy/mosaic appearance of COVID-19 in conventional lung imaging resulted from microvascular occlusion and secondary lobular ischemia. The length of hospitalization was associated with increased intussusceptive angiogenesis. This was associated with enhanced angiogenic, and fibrotic gene expression demonstrated by molecular profiling and metabolomic analysis. Increased plasma fibrosis markers correlated with their pulmonary tissue transcript levels and predicted disease severity. Plasma analysis confirmed distinct fibrosis biomarkers (TSP2, GDF15, IGFBP7, Pro-C3) that predicted the fatal trajectory in COVID-19. INTERPRETATION: Pulmonary severe COVID-19 is a consequence of secondary lobular microischemia and fibrotic remodelling, resulting in a distinctive form of fibrotic interstitial lung disease that contributes to long-COVID. FUNDING: This project was made possible by a number of funders. The full list can be found within the Declaration of interests / Acknowledgements section at the end of the manuscript.

Altered tissue oxygenation in patients with post COVID-19 syndrome.

BACKGROUND: Post COVID-19 syndrome (PCS) is a complex condition with partly substantial impact on patients' social and professional life and overall life quality. Currently, the underlying cause(s) of PCS are unknown. Since PCS-specific symptoms could be associated with systemic alterations in tissue oxygen supply, we aimed to investigate changes in tissue oxygenation in patients with PCS. METHODS: A case-control study including 30 PCS patients (66.6 % males, 48.6 ± 11.2 years, mean time after (first) acute infection: 324 days), 16 cardiologic patients (CVD) (65.5 % males, 56.7 ± 6.3 years) and 11 young healthy controls (55 % males, 28.5 ± 7.4 years) was conducted. Near infrared spectroscopy (NIRS) was used to assess changes in tissue oxygenation during an arterial occlusion protocol on the non-dominant forearm (brachioradialis, 760/850 nm, 5 Hz). The protocol included 10-min rest, a 2-min baseline measurement followed by a 3-min ischemic period (upper-arm cuff, 50 mmHg above resting systolic blood pressure) and a 3-min reoxygenation period. PCS patients were grouped by presence of arterial hypertension and elevated BMI to assess the impact of risk factors. RESULTS: No differences in mean tissue oxygenation in the pre-occlusion phase existed between groups (p ≥ 0.566). During ischemia, comparisons of linear regressions slopes revealed slower oxygen desaturation for PCS patients (-0.064 %/s) compared to CVD patients (-0.08 %/s) and healthy subjects (-0.145 %/s) (p < 0.001). After cuff release, slowest speed for reoxygenation was detected in PCS patients at 0.84 %/s compared to CVD patients (1.04 %/s) and healthy controls (CG: 2.07 %/s) (p < 0.001). The differences between PCS patients and CVD patients during ischemia remained significant also after correction for risk factors. Analyses of complications during acute infection, persistence of PCS symptoms (time after acute infection), or PCS severity (number of lead symptoms) as confounding factors did not reveal a significant effect. CONCLUSIONS: This study provides evidence that the rate of tissue oxygen consumption is persistently altered in PCS and that PCS patients show an even slower decline in tissue oxygenation during occlusion than CVD patients. Our observations may at least partly explain PCS-specific symptoms such as physical impairment and fatigue.

[Acute limb ischemia - what is new?] / Akute Extremitätenischämie ­ was gibt es Neues?

Acute limb ischemia is a vascular emergency and current guidelines emphasize the need for rapid treatment in a vascular center with an option of open surgical and interventional revascularization. Endovascular revascularization options for acute limb ischemia are increasingly focused on a wide range of mechanical thrombectomy devices based on different operating principles.For patients with acute limb ischemia in the setting of covid-19 infection high mortality rates and low technical success rates of revascularization procedures have been described.

The Impact of the COVID-19 Pandemic on a Dedicated Vascular Emergency Clinic.

BACKGROUND: Vascular Emergency Clinics (VEC) improve patient outcomes in chronic limb-threatening ischemia (CLTI). They provide a "1 stop" open access policy, whereby "suspicion of CLTI" by a healthcare professional or patient leads to a direct review. We assessed the resilience of the outpatient VEC model to the first year of the coronavirus disease (COVID-19) pandemic. METHODS: A retrospective review of a prospectively maintained database of all patients assessed in our VEC for lower limb pathologies between March 2020 and April 2021 was performed. This was cross-referenced to national and loco-regional Governmental COVID-19 data. Individuals with CLTI were further analysed to determine Peripheral Arterial Disease-Quality Improvement Framework compliance. RESULTS: Seven hundred and ninety one patients attended for 1,084 assessments (Male n = 484, 61%; Age 72.5 ± standard deviation 12.2 years; White British n = 645, 81.7%). In total, 322 patients were diagnosed with CLTI (40.7%). A total of 188 individuals (58.6%) underwent a first revascularization strategy (Endovascular n = 128, 39.8%; Hybrid n = 41, 12.7%; Open surgery n = 19, 5.9%; Conservative n = 134, 41.6%). Major lower limb amputation rate was 10.9% (n = 35) and mortality rate was 25.8% (n = 83) at 12 months of follow-up. Median referral to assessment time was 3 days (interquartile range: 1-5). For the nonadmitted patient with CLTI, the median assessment to intervention was 8 days (interquartile range: 6-15) and median referral to intervention time of 11 days (11-18). CONCLUSIONS: The VEC model has demonstrated strong resilience to the COVID-19 pandemic with rapid treatment timelines maintained for patients with CLTI.

A Comparative Analysis of Critical Limb Ischemia in the Intensive Care Unit since the COVID-19 Pandemic.

BACKGROUND: Emerging data and case reports have found coagulation abnormalities and thrombosis as sequelae of infection with SARS-CoV-2 (COVID-19). Case reports have reported thrombotic complications caused by COVID-19-related coagulopathy leading to limb loss. Alarmingly, many of these patients had no underlying vascular disease prior to being infected with COVID-19. Many of these case reports discuss patients developing gangrene in the intensive care unit (ICU). Our study compares the incidence of gangrene in the ICU in COVID-19 patients to baseline inpatient levels prior to the pandemic. METHODS: This retrospective analysis investigates two subsets of patients from a single institution. The first was from 2020 during the COVID-19 pandemic; the second subset was from 2019 before the pandemic. Demographic data and medication history were ascertained for both groups. Primary outcomes measures included extremity gangrene that developed in the ICU, mortality, and major amputation. RESULTS: There were 249 COVID-19 positive patients admitted to the ICU in 2020. In 2019, 1,846 admissions to the ICU took place, of which 249 patients were randomized to chart review. There were 13 cases of gangrene that developed in the ICU, 12 of which took place in 2020. In-hospital mortality was 11.6% in nonCOVID-19 patients in 2019 vs. 41.4% in 2021 (P < 0.001). Only 16.7% of the COVID-19 gangrene patients had previously known arterial disease. Also, patients in the COVID-19 group with gangrene were four times more likely to be smokers (P = 0.004). When the data were stratified to compare between gangrene development and no gangrene development, the combined total gangrene group had longer hospital stays, higher need for blood transfusions, required major amputations, and revascularization. A multivariate logistic regression from the total study similarly demonstrated that COVID-19 infection is associated with an 18.23 times increased risk of gangrene. CONCLUSIONS: COVID-19 has resulted in an incomprehensible societal impact that will linger for years to come. The last 2 years have reinforced that COVID-19 will be a part of our clinical practice indefinitely. This study emphasizes the importance of clinician awareness of COVID-19 induced critical limb ischemia in those without underlying arterial disease and few medical comorbidities. More research efforts toward preventing limb loss and COVID-19 coagulopathy must be performed expeditiously to achieve a better understanding.