Assessment of Corneal Graft Rejection Rates Following Partial Endothelial Keratoplasty in COVID-19 Vaccinated Patients (preprint)

Objectives: The study aims to investigate the incidence of graft rejection following Covid-19 vaccination among patients who had undergone partial endothelial keratoplasty, a form of corneal transplantation.  Methods: The study involved 208 patients who had received two doses of Covid-19 vaccine after undergoing partial endothelial keratoplasty. Patients were identified through electronic medical records and evaluated using a questionnaire designed to assess symptoms of graft rejection.  Results: None of the 208 patients complained of symptoms of acute graft rejection, nor presented with symptoms or signs of graft rejection in the given time frame. None of the patients were diagnosed with graft rejection elsewhere.  Conclusions: The study did not identify any cases of partial endothelial keratoplasty corneal graft rejection after the first or second dose of the Covid-19 vaccine. The absence of blood and lymphatic vessels in the central cornea gives it lymphangiogenic privilege and low rate of graft rejection. Any systemic immune dysregulation may compromise corneal ocular immune privilege and increase the patient’s susceptibility to rejection. Although all reported cases of corneal graft rejection following Covid-19 vaccination were associated with symptoms, the study has limitations as it relied solely on a telephonic survey.

Contribution of the Elevated Thrombosis Risk of Males to the Excess Male Mortality Observed in COVID-19: An Observational Study (preprint)

Background: The mortality rate of COVID-19 is elevated in males compared to females. Objective: Determine the extent that the elevated thrombotic risk in males relative to females contributes to excess COVID-19 mortality in males. Design: Observational study. Setting: Data sourced from electronic medical records from over 200 US hospital systems. Participants: 60,877 patients hospitalized with COVID-19. Exposure: Exposure variable: biological sex; key variable of interest: thrombosis. Main outcome measures: Primary outcome was COVID-19 mortality. We measured: 1) mortality rate of males relative to females, 2) rate of thrombotic diagnoses occurring during hospitalization for COVID-19 in both sexes, and 3) mortality rate when evidence of thrombosis was present. Results: : The COVID-19 mortality rate of males was 29.9% higher than that of females. Males had a 35.8% higher rate of receiving a thrombotic diagnosis compared to females. The mortality rate of all patients with a thrombotic diagnosis was 40.0%— over twice that of COVID-19 patients without a thrombotic diagnosis (adjusted OR 2.50 [2.37 to 2.64], p-value < .001). When defining thrombosis as either a documented thrombotic diagnosis or a D-dimer level ≥ 3.0 μg/mL, 16.4% of the excess mortality in male patients could be explained by increased thrombotic risk. Conclusions: and Relevance: Our findings suggest the higher COVID-19 mortality rate in males may be significantly accounted for by the elevated risk for thrombosis among males. Understanding the mechanisms that underlie increased male thrombotic risk may allow for the advancement of effective anticoagulation strategies that reduce COVID-19 mortality in males.

A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2 (preprint)

As vaccines against SARS-CoV-2 are now being rolled out, a better understanding of immunity to the virus; whether through infection, or passive or active immunisation, and the durability of this protection is required. This will benefit from the ability to measure SARS-CoV-2 immunity, ideally with rapid turnaround and without the need for laboratory-based testing. Current rapid point-of-care (POC) tests measure antibodies (Ab) against the SARS-CoV-2 virus, however, these tests provide no information on whether the antibodies can neutralise virus infectivity and are potentially protective, especially against newly emerging variants of the virus. Neutralising Antibodies (NAb) are emerging as a strong correlate of protection, but most current NAb assays require many hours or days, samples of venous blood, and access to laboratory facilities, which is especially problematic in resource-limited settings. We have developed a lateral flow POC test that can measure levels of RBD-ACE2 neutralising antibodies from whole blood, with a result that can be determined by eye (semi-quantitative) or on a small instrument (quantitative), and results show high correlation with microneutralisation assays. This assay also provides a measure of total anti-RBD antibody, thereby providing evidence of exposure to SARS-CoV-2 or immunisation, regardless of whether NAb are present in the sample. By testing samples from immunised macaques, we demonstrate that this test is equally applicable for use with animal samples, and we show that this assay is readily adaptable to test for immunity to newly emerging SARS-CoV-2 variants. Lastly, using a cohort of vaccinated humans, we demonstrate that our whole-blood test correlates closely with microneutralisation assay data (R 2 =0.75, p<0.0001), and that fingerprick whole blood samples are sufficient for this test. Accordingly, the COVID-19 NAb-test™ device described here can provide a rapid readout of immunity to SARS-CoV-2 at the point of care.

Rationing Scarce Healthcare Capacity: A Study Of The Ventilator Allocation Guidelines During The Covid-19 Pandemic (preprint)

In the United States, even though national guidelines for allocating scarce healthcare resources are lacking, 26 states have specific ventilator allocation guidelines to be invoked in case of a shortage. While several states developed their guidelines in response to the recent Covid-19 pandemic, NYS developed these guidelines in 2015 as "pandemic influenza is a foreseeable threat, one that we cannot ignore." The primary objective of this study is to assess the existing procedures and priority rules in place for allocating/rationing scarce ventilator capacity and propose alternative (and improved) priority schemes. We first build machine learning models using inpatient records of COVID-19 patients admitted to New York-Presbyterian/Columbia University Irving Medical Center and an affiliated community health center to predict survival probabilities as well as ventilator length-of-use. Then, we use the resulting point estimators and their uncertainties as inputs for a multi-class priority queueing model with abandonments to assess three priority schemes: (i) SOFA-P, which most closely mimics the existing practice by prioritizing patients with sufficiently low Sequential Organ Failure Assessment (SOFA) scores, (ii) ISP, which assigns priority based on patient-level survival predictions, and (iii) ISP-LU, which takes into account survival predictions and resource use duration. Our findings highlight that our proposed priority scheme, ISP-LU, achieves a demonstrable improvement over the other two alternatives. Specifically, the expected number of survivals increases and death risk while waiting for ventilator use decreases. We also show that ISP-LU is a robust priority scheme whose implementation yields a Pareto-improvement over both ISP and SOFA-P in terms of maximizing saved lives after mechanical ventilation while limiting racial disparity in access to the priority queue.