COVID-associated acute limb ischemia during the Delta surge and the effect of vaccines.

OBJECTIVE: Hypercoagulability is common in severe acute respiratory syndrome coronavirus 2 and has been associated with arterial thrombosis leading to acute limb ischemia (ALI). Our objective was to determine the outcomes of concurrent coronavirus disease 2019 (COVID-19) infection and ALI, particularly during the Delta variant surge and the impact of vaccination status. METHODS: A retrospective review was performed of patients treated at a single health care system between March 2020 and December 2021 for ALI and recent (<14 days) COVID-19 infection or who developed ALI during hospitalization for the same disease. Patients were grouped by year as well as by pre and post Delta variant emergence in 2021 based on the World Health Organization timeline (January to May vs June to December). Baseline demographics, imaging, interventions, and outcomes were evaluated. A control cohort of all patients with ALI requiring surgical intervention for a 2-year period prior to the pandemic was used for comparison. Primary outcomes were in-hospital mortality and amputation-free survival. Kaplan-Meier survival and Cox proportional hazards analysis were performed. RESULTS: Forty acutely ischemic limbs were identified in 36 patients with COVID-19, the majority during the Delta surge (52.8%) and after the wide availability of vaccines. The rate of COVID-19-associated ALI, although low overall, nearly doubled during the Delta surge (0.37% vs 0.20%; P = .09). Intervention (open or endovascular revascularization vs primary amputation) was performed on 31 limbs in 28 individuals, with the remaining eight treated with systemic anti-coagulation. Postoperative mortality was 48%, and overall mortality was 50%. Major amputation following revascularization was significantly higher with COVID-19 ALI (25% vs 3%; P = .006) compared with the pre-pandemic group. Thirty-day amputation-free survival was significantly lower (log-rank P < .001). COVID-19 infection (adjusted hazard ratio, 6.2; P < .001) and age (hazard ratio, 1.1; P = .006) were associated with 30-day amputation in multivariate analysis. Severity of COVID-19 infection, defined as vasopressor usage, was not associated with post-revascularization amputation. There was a higher incidence of re-thrombosis in the latter half of 2021 with the Delta surge, as reintervention for recurrent ischemia of the same limb was more common than our previous experience (21% vs 0%; P = .55). COVID-19-associated limb ischemia occurred almost exclusively in non-vaccinated patients (92%). CONCLUSIONS: ALI observed with Delta appears more resistant to standard therapy. Unvaccinated status correlated highly with ALI occurrence in the setting of COVID-19 infection. Information of limb loss as a COVID-19 complication among non-vaccinated patients may help to increase compliance.

Multimodality management of sinonasal teratocarcinosarcoma in a 76-year-old Alaska Native female during the COVID-19 pandemic.

Sinonasal teratocarcinosarcoma is a rare, highly aggressive tumor of the anterior skull base composed of malignant epithelial, mesenchymal, and neural tissue. Examination of cases in patients in minority populations is important in order to better understand the behavior of this neoplasm and outcomes of treatment in our nation's diverse population.

COVIDomic: A multi-modal cloud-based platform for identification of risk factors associated with COVID-19 severity.

Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in December 2019 in Wuhan, China. It was quickly established that both the symptoms and the disease severity may vary from one case to another and several strains of SARS-CoV-2 have been identified. To gain a better understanding of the wide variety of SARS-CoV-2 strains and their associated symptoms, thousands of SARS-CoV-2 genomes have been sequenced in dozens of countries. In this article, we introduce COVIDomic, a multi-omics online platform designed to facilitate the analysis and interpretation of the large amount of health data collected from patients with COVID-19. The COVIDomic platform provides a comprehensive set of bioinformatic tools for the multi-modal metatranscriptomic data analysis of COVID-19 patients to determine the origin of the coronavirus strain and the expected severity of the disease. An integrative analytical workflow, which includes microbial pathogens community analysis, COVID-19 genetic epidemiology and patient stratification, allows to analyze the presence of the most common microbial organisms, their antibiotic resistance, the severity of the infection and the set of the most probable geographical locations from which the studied strain could have originated. The online platform integrates a user friendly interface which allows easy visualization of the results. We envision this tool will not only have immediate implications for management of the ongoing COVID-19 pandemic, but will also improve our readiness to respond to other infectious outbreaks.

Sensitive detection and quantification of SARS-CoV-2 in saliva.

Saliva has significant advantages as a test medium for detection of SARS-CoV-2 infection in patients, such as ease of collection, minimal requirement of supplies and trained personnel, and safety. Comprehensive validation in a large cohort of prospectively collected specimens with unknown SARS-CoV-2 status should be performed to evaluate the potential and limitations of saliva-based testing. We developed a saliva-based testing pipeline for detection of SARS-CoV-2 nucleic acids using real-time reverse transcription PCR (RT-PCR) and droplet digital PCR (ddPCR) readouts, and measured samples from 137 outpatients tested at a curbside testing facility and 29 inpatients hospitalized for COVID-19. These measurements were compared to the nasal swab results for each patient performed by a certified microbiology laboratory. We found that our saliva testing positively detects 100% (RT-PCR) and 93.75% (ddPCR) of curbside patients that were identified as SARS-CoV-2 positive by the Emergency Use Authorization (EUA) certified nasal swab testing assay. Quantification of viral loads by ddPCR revealed an extremely wide range, with 1 million-fold difference between individual patients. Our results demonstrate for both community screening and hospital settings that saliva testing reliability is on par with that of the nasal swabs in detecting infected cases, and has potential for higher sensitivity when combined with ddPCR in detecting low-abundance viral loads that evade traditional testing methods.

TMPRSS2, a SARS-CoV-2 internalization protease is downregulated in head and neck cancer patients.

BACKGROUND: SARS-coronavirus-2 enters host cells through binding of the Spike protein to ACE2 receptor and subsequent S priming by the TMPRSS2 protease. We aim to assess differences in both ACE2 and TMPRSS2 expression in normal tissues from oral cavity, pharynx, larynx and lung tissues as well as neoplastic tissues from the same areas. METHODS: The study has been conducted using the TCGA and the Regina Elena Institute databases and validated by experimental model in HNSCC cells. We also included data from one COVID19 patient who went under surgery for HNSCC. RESULTS: TMPRSS2 expression in HNSCC was significantly reduced compared to the normal tissues. It was more evident in women than in men, in TP53 mutated versus wild TP53 tumors, in HPV negative patients compared to HPV positive counterparts. Functionally, we modeled the multivariate effect of TP53, HPV, and other inherent variables on TMPRSS2. All variables had a statistically significant independent effect on TMPRSS2. In particular, in tumor tissues, HPV negative, TP53 mutated status and elevated TP53-dependent Myc-target genes were associated with low TMPRSS2 expression. The further analysis of both TCGA and our institutional HNSCC datasets identified a signature anti-correlated to TMPRSS2. As proof-of-principle we also validated the anti-correlation between microRNAs and TMPRSS2 expression in a SARS-CoV-2 positive HNSCC patient tissues Finally, we did not find TMPRSS2 promoter methylation. CONCLUSIONS: Collectively, these findings suggest that tumoral tissues, herein exemplified by HNSCC and lung cancers might be more resistant to SARS-CoV-2 infection due to reduced expression of TMPRSS2. These observations may help to better assess the frailty of SARS-CoV-2 positive cancer patients.

Discordance of COVID-19 guidelines for patients with cancer: A systematic review.

This review was aimed to systematically evaluate the available literature on the impact of COVID-19 on cancer care and to critically analyze the diagnostic and therapeutic strategies suggested by various healthcare providers, societies, and institutions. Majority guidelines for various types of cancers favored a delay in treatment or a nonsurgical approach wherever feasible. These guidelines are based on a low level of evidence and have significant discordance for the role and timing of surgery, especially in early tumors.

Medically Necessary, Time-Sensitive Procedures: Scoring System to Ethically and Efficiently Manage Resource Scarcity and Provider Risk During the COVID-19 Pandemic.

Hospitals have severely curtailed the performance of nonurgent surgical procedures in anticipation of the need to redeploy healthcare resources to meet the projected massive medical needs of patients with coronavirus disease 2019 (COVID-19). Surgical treatment of non-COVID-19 related disease during this period, however, still remains necessary. The decision to proceed with medically necessary, time-sensitive (MeNTS) procedures in the setting of the COVID-19 pandemic requires incorporation of factors (resource limitations, COVID-19 transmission risk to providers and patients) heretofore not overtly considered by surgeons in the already complicated processes of clinical judgment and shared decision-making. We describe a scoring system that systematically integrates these factors to facilitate decision-making and triage for MeNTS procedures, and appropriately weighs individual patient risks with the ethical necessity of optimizing public health concerns. This approach is applicable across a broad range of hospital settings (academic and community, urban and rural) in the midst of the pandemic and may be able to inform case triage as operating room capacity resumes once the acute phase of the pandemic subsides.

Status and strategies for the management of head and neck cancer during COVID-19 pandemic: Indian scenario.

In India, oral cancer is the most common head and neck cancer (HNC) in men, mainly caused by the consumption of smoked and smokeless tobacco. During the current pandemic, delaying surgery for even 1 or 2 months may lead to more extensive surgery or inoperability, where only supportive care can be provided. Being semi-emergent in nature, treatment for these patients is currently on hold or delayed in most centers across the country. This study was conducted to assess the impact of COVID-19 pandemic and inability of the health system to treat HNC in a timely fashion and how surgeons are coping to this emergent situation. This article highlights the situation in India, a country burdened with one of the highest incidence rates of HNC.

A Surgical Safety Checklist for Performing Tracheotomy in Patients with Coronavirus Disease 19.

Performance of tracheotomy is a potential necessary step in the patient with coronavirus disease 19 (COVID-19) and prolonged mechanical ventilation. Due to viral aerosolization, tracheotomy carries a high risk of transmission of COVID-19 to the health care team performing the procedure. We share our institution's surgical safety checklist for performing tracheotomy in patients with COVID-19, including key modifications intended to mitigate risk to the surgical team.