Delays in LEEP associated with the COVID-19 pandemic and impact on resulting pathology

Over the course of the past year, medical providers were forced to make difficult decisions in response to the global COVID-19 pandemic. Many clinics were closed for routine and follow-up visits in order to preserve personal protective equipment and to decrease exposure of patients and staff to the virus. The aim of this study was to assess the effect that the COVID-19 response had on scheduling a loop electrosurgical excision procedure (LEEP) and the potential impact on resulting pathology. A retrospective review of all patients who received a LEEP due to an abnormal cervical cancer screening test at a single inner-city academic institution was performed. Procedures scheduled from March 2020 (start of the COVID-19 pandemic) through July 2020 were included. Baseline patient characteristics (including race), time from colposcopy to LEEP, and pathology results were collected. A total of 37 patients underwent a LEEP in this timeframe. Median age was 33 years (range, 22-63) and 6 patients (16%) were smokers. Median time between colposcopy and LEEP was 80 days (range, 0-303 days), with 25% having a delay of ≥131.5 days. Non-White patients (n=25, median 91 days) experienced numerically higher delays than White patients (n=12, median 34.5 days, p=0.077, Mann-Whitney U test). Expedited treatment (colposcopy and LEEP on same day) occurred in 0/25 non-White patients and in 3/12 White patients (p=0.028, Fisher exact test). On colposcopy, 31/37 patients (84%) had high grade squamous intraepithelial lesion (HSIL);the rest had low grade squamous intraepithelial lesion (LSIL) or lower. On LEEP, 1 patient had squamous cell carcinoma (3%) and 20 patients had HSIL (54%);the rest had LSIL or lower. From colposcopy to LEEP, 14/37 patients (37.8%) had discordant pathologies of which 2 patients (5%) had upgraded pathologies;these two patients underwent LEEP 136 days and 142 days after colposcopy and were upgraded to squamous cell carcinoma and HSIL, respectively. A total of 12 patients (32.4%) had downgraded pathologies. During the COVID-19 pandemic, a large proportion of inner-city patients experienced delays between colposcopy and LEEP, an effect which seemed more pronounced among non-White patients. The patients with upgraded interval pathologies had particularly long delays between the procedures. Additional study is needed to examine the potential negative ramifications of the COVID-19 pandemic on cervical cancer screening and healthcare disparities. [ABSTRACT FROM AUTHOR] Copyright of Gynecologic Oncology is the property of Academic Press Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Genetic mechanisms of critical illness in Covid-19 (preprint)

The subset of patients who develop critical illness in Covid-19 have extensive inflammation affecting the lungs and are strikingly different from other patients: immunosuppressive therapy benefits critically-ill patients, but may harm some non-critical cases. Since susceptibility to life-threatening infections and immune-mediated diseases are both strongly heritable traits, we reasoned that host genetic variation may identify mechanistic targets for therapeutic development in Covid-19. GenOMICC (Genetics Of Mortality In Critical Care, genomicc.org) is a global collaborative study to understand the genetic basis of critical illness. Here we report the results of a genome-wide association study (GWAS) in 2790 critically-ill Covid-19 patients from 208 UK intensive care units (ICUs), representing >95% of all ICU beds. Random controls were drawn from three distinct UK population studies. We identify and replicate several novel genome-wide significant associations including variants chr19p13.3 (rs2109069, P = 3.98 x 10-12), within the gene encoding dipeptidyl peptidase 9 (DPP9), and at chr21q22.1 (rs2236757, P = 4.99 x 10-8) in the interferon receptor IFNAR2. Consistent with our focus on extreme disease in younger patients with less comorbidity, we detect a stronger signal at the known 3p21.31 locus than previous studies (rs73064425, P = 1.2 x 10-27). We identify potential targets for repurposing of existing licensed medications. Using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2, and high expression of TYK2, to life-threatening disease. Transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe Covid-19. We detected genome-wide significant gene-level associations for genes with central roles in viral restriction (OAS1, OAS2, OAS3). These results identify specific loci associated with life-threatening disease, and potential targets for host-directed therapies. Randomised clinical trials will be necessary before any change to clinical practice.

How urgent do intravitreal anti-VEGF injections need to be to justify the risk of transmitting COVID-19? Proof-of-concept calculations to determine the Health Adjusted Life-Year (HALY) trade-off. (preprint)

BackgroundClinical ophthalmological guidelines encourage the assessment of potential benefits and harms when deciding whether to perform elective ophthalmology procedures during the COVID-19 pandemic, in order to minimize the risk of disease transmission. MethodWe performed probability calculations to estimate COVID-19 infection status and likelihood of disease transmission among neovascular age-related macular degeneration patients and health care workers during anti-VEGF procedures, at various community prevalence levels of COVID-19. We then applied the expected burden of COVID-19 illness and death expressed through health-adjusted life-years (HALYs) lost. We compared these results to the expected disease burden of severe visual impairment if sight protecting anti-VEGF injections were not performed. ResultsOur calculations suggest a wide range of contexts where the benefits of treatment to prevent progression to severe visual impairment or blindness are greater than the expected harms to the patient and immediate health care team due to COVID-19. For example, with appropriate protective equipment the benefits of treatment outweigh harms when the chance of progression to severe visual impairment is >0.044% for all scenarios where COVID-19 prevalence was one per thousand, even when the attack rate in the clinical setting is very high (5-43%). ConclusionUnless COVID-19 prevalence is very high, the reduced disease burden from avoiding visual impairment outweighs the expected HALYs lost from COVID-19 transmission. This finding is driven by the fact that HALYs lost when someone suffers severe visual impairment for 5 years are equivalent to nearly 400 moderate cases of infectious disease lasting 2 weeks each.