SCREENING OF US VETERANS AT HIGH RISK FOR OUTCOMES FOLLOWING COVID-19 BY FRAILTY STATUS

Frailty increases risk of adverse outcomes in the presence of stressors such as COVID-19 infection. We examined the association between different levels of frailty and outcomes following COVID-19 infection. This is a retrospective cohort study of US Veterans aged ≥50 years, active Veterans Health Administration (VHA) care users, and tested positive for COVID-19 between 02/15/2020 and 09/30/2021. VHA frailty index (VA-FI) was calculated from one year prior to the COVID-19 testing and divided into three groups: robust (≤0.1), prefrail (0.1-0.2), and frail (>0.2). The risk of hospitalization, ICU admission, ventilator use, and in-hospital mortality were calculated using logistic regression adjusted by age, sex, body-mass-index, and race. The performance of VA-FI in predicting outcomes was compared to age or Charlson comorbidity index (CCI) using area under the curve (AUC). Of 204,426 COVID-19 positive Veterans, 32,965 were hospitalized (age: 71.4±10.4 years, BMI: 29.5±7.1 kg/m2). We observed higher odds of hospitalization (frail, adjusted odds ratio (aOR)=8.64;prefrail, aOR=2.57), ICU admission (frail, aOR=1.58;prefrail, aOR=1.32), ventilator use (frail, aOR=1.97;prefrail, aOR=1.57), and mortality (frail aOR=2.15;prefrail, aOR=1.55) in frail and prefrail compared to robust Veterans. We observed that VA-FI had higher AUC in predicting hospitalization (AUC 0.75) independent of age (0.59) and CCI (0.63). Veterans with COVID-19 who were frail and prefrail had a higher risk of hospitalization, ICU admission, ventilator use, mortality compared to robust. VA-FI may be a useful tool at the time of COVID-19 diagnosis to triage patients at risk for adverse outcomes.

Urinary Transcriptomics Identified Inflammatory Signals Associated With COVID-19-Related AKI

Background: SARS-CoV-2, associated with COVID-19, can include dysfunction in many organs including the kidney. Early in the pandemic, a high incidence of acute kidney injury (AKI), with an associated increase in mortality, was observed, particularly in those with severe respiratory failure. Given the effect on the kidney and limited availability of biopsied tissue, we designed a non-invasive protocol to isolate and sequence renal cells from the urine of patients with COVID-19 to identify the cellular and molecular mechanisms of COVID-19-related AKI, and the impact of immunomodulatory treatment. Method(s): Three groups of hospitalized patients, AKI with and without COVID-19 and COVID-19 without AKI, were recruited at Michigan Medicine (N=48). We documented >90 clinical parameters, including serum creatinine trends, treatment exposure to IL-6 inhibitors, and patient outcomes. Urine samples near peak AKI were collected and immediately processed for single cell RNA sequencing (scRNAseq);profiles were generated on the 10x Genomics platform and clustered using Seurat. Differentially expressed gene profiles were generated in a cell type selective manner. Result(s): Urine scRNAseq profiles from 44,440 cells clustered into 5 major celltypes, based on cell marker assignment. Renal cells comprised 12% of the recovered cells. Comparing renal cells from COVID-19-related AKI group to either of the two other groups identified 129 up-regulated and 89 down-regulated genes in common (q<0.05). The COVID-19-related AKI renal cell profile was consistent with activation of one or more inflammatory cytokines including IFN-gamma, IL-6, and IL-1beta. Conversely, patients exposed to IL-6 inhibitors had a reduced expression of inflammatory marker genes. Conclusion(s): This study demonstrates the successful isolation and generation of cell type transcriptional profiles of renal cells in the urine of patients with COVID-19, with or without AKI, and non-COVID-19 AKI. Expression profiles in renal cells were consistent with intra-renal inflammatory activation in COVID-19-related AKI. Association of profiles with renal function and patient outcomes may identify predictive markers of COVID-19-related AKI and potential targets for therapeutic modulation.

Protected Biometric Identification with Multiple Finger Vein

The access control or gaining permission to do a particular activity without claiming your identity is an identification process which involves one is to all matchings. The proposed multi-instance biometric identification utilizes multiple instances of finger vein to identify a person with secured templates. Common pre-processing and texture-based feature extraction is applied to two finger vein instances followed by feature fusion with dimensional reduction keeping the discriminative features to further simplify the system design making it a real time application. Secured templates are created out of fused finger vein features subjected to Gaussian random projection-based Index-of-Max hashing. The hashed templates are not only secured but also forms compact integer vector requiring low storage space and matching time. Use of multiple instances increases the universality of identification and finger vein makes the system contactless. This contactless property of an authentication system highly recommends its use for any infectious situations like covid-19. © 2022 IEEE.

JAK ANTAGONISTS AND IL-6 INHIBITORS FOR MANAGEMENT OF SARS-COV-2 INFECTION: A SYSTEMIC REVIEW AND NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

SESSION TITLE: Medications and Pulmonary Rehabilitation in COVID-19 Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: JAK-antagonists and IL-6 inhibitors are immunomodulators indicated for inflammatory pathologies. With the COVID pandemic, these drugs have been utilized in management of hospitalized patients with SARS-CoV-2. Selection between the two drug classes has been attributed to availability and physician comfort. No existing comparative randomized trial to date. METHODS: We performed a systematic review and network meta-analysis using PRISMA guidelines. Randomized controlled trials evaluating various IL-6 inhibitors and JAK-antagonists were included. Outcomes were 28-day mortality and progression, defined as advancement to mechanical ventilation or ECMO. Subgroup analysis of concomitant steroid and remdesivir usage was also analyzed. P-scores were used to rank treatment groups in class and drug specific classifications. RESULTS: We identified 33 RCTs with 13,680 patients that met our selection criteria. Our analysis revealed that IL-6 inhibitor versus JAK antagonists, IL-6 was associated with greater odds of mortality (OR = 1.23 (1.13, 1.34), p = 0.01). This finding was also evident in the subgroup receiving concomitant steroids and remdesivir (OR = 1.41 (1.00, 2.00), p = 0.049) but no significant differences observed for the outcome of progression in this group. Baricitinib is associated with a significant 30% reduction in 28-day mortality compared to Tocilizamab CONCLUSIONS: JAK-a vs control and IL-6 inhibitors vs control exhibit mortality reducation but JAKs did so at a greater rate. Similarly, for drug specific comparisons, Baricitinib reduced mortality by the greatest amount. Only IL-6 inhibitors seemed to have a significant effect on preventing progression. Siltuximab and Tocilizumab were both effective against control but Tocilizumab reduced progression the best. As a secondary goal, a sub-group analysis on concomitant steroid and Remdesivir usage demonstrated that for drug specific comparisons, Baricitinib performed better for reducing mortality & Tocilizumab continued to be the most effective in preventing progression. However, with Remdesivir and steroids, there was no significant difference between Baricitinib and Tocilizumab in decreasing mortality. This is contrary to the findings without steroids. CLINICAL IMPLICATIONS: We hope to use this data to help clinical decision making between JAK-a and IL-6 inhibitors which are currently being used interchangeably for the management of COVID-19 in hospitalized patients. Through our study results and analysis, we recommend that Baricitinib be used to decrease mortality rates and disease progression for the treatment of COVID-19 with concomitant therapy corticosteroids and Remdesivir. Moving forward with this data, we aim to help restructure COVID-19 treatment algorithms regarding IL-6 and JAK antagonists. DISCLOSURES: No relevant relationships by Monica Bhagavan No relevant relationships by rukhsaar khanam No relevant relationships by Anant Naik No relevant relationships by Aashka Shah

CORRELATION OF RTPCR AND HRCT CHEST FINDINGS IN COVID PATIENTS IN TERTIARY CARE CENTRE: AN ORIGINAL RESEARCH

Aim: The purpose of the present research was to evaluate the co-relation of RTPCR and HRCT chest findings in COVID-19 patients in tertiary care centre. Methodology: In our study, COVID-19 patients with positive RT-PCR results (RT-PCR (+) group) and patients with clinical suspicion of COVID-19 but negative RT-PCR results (RT-PCR (−) group) were compared in terms of CT findings. In CT images, ground-glass opacity and ground-glass opacity + patchy consolidation were the most common lesion patterns in both groups. Results: No statistically significant differences in the rates and types of lesion patterns were observed between the two groups. In both groups, lesion distributions and distribution patterns were similarly frequent in the bilateral, peripheral, and lower lobe distributions. Among the 39 patients who underwent follow-up CT imaging in the first or second month, a regression in lesion number and density was detected in 18 patients from both groups. Conclusion: Due to the false-negative rate of RT-PCR tests caused by various reasons, clinically suspected COVID19 patients with a contact history should be examined with CT scans, even if RT-PCR tests are negative. If the CT findings are positive, these patients should not be removed from isolation.

Application of Deep Learning in Detection of Covid-19 Face Mask

With the increase in the number of Covid-19 cases throughout the globe wearing face masks has proved to be effective in the prevention of the virus. In this work, we have originated a method that can detect if people are violating the rule of wearing a mask outdoors using a two-stage deep learning system. The first stage of the system detects different faces present in the input image using YOLO (You Only Look Once) model trained for the face detection and returns face ROIs. In the second stage extracted face ROI is passed through face mask detector model trained using MobileNetV2 which in turn classifies it as Mask or No mask. The dataset used for training the mask detector model is Real-World Masked Face Dataset (RMFD) and for Face Detection model is the WIDER dataset. The proposed method gives 98% accuracy for mask detection. The promising results derived from the proposed model demonstrate that the deployment of the model can be done in real-time systems. © 2022, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Covid-19 Prevention Kit Based on an Infrared Touchless Thermometer and Distance Detector

Temperature is estimated by detecting the infrared radiation emitted by all materials above absolute zero (0°Kelvin) in an infrared temperature test. IR energy is converted to an electrical signal that may be displayed as a temperature reading after being made up for the surrounding temperature range by using a focal point to focus the IR energy on a finder. With this set-up, you can estimate something's temperature from a distance, without having to go close to the thing you're trying to measure. Because thermocouples or other test type sensors cannot be used or do not provide precise information for a variety of reasons, the infrared temperature sensor is useful for estimating temperature. One of the most essential things to do to avoid COVID is to practise social distancing. This device may be used to maintain a gap of at least 6 feet between devices by measuring distance using ultra-wideband (UWB) technology. There are two nodes in an ultrasonic sensor: a transmitter and a receiver. When the transmitter fires, an ultrasonic wave is thrown out, and this wave hits everything in its path before returning to the transmitter. Using the time it takes for the wave to return to the sensor after being bounced, the sensor determines the obstacle's distance from that sensor. In most cases, ultrasonic sensors are used to detect obstacles in the way and to determine how far away they are from the sensor. © 2021 IEEE.

COVID-19: persistence, precautions, diagnosis and challenges. (Special Issue: Coronaviruses and COVID-19- Past, Present, and Future.)

After a century, the whole world fighting against the pandemic viral infection: a novel coronavirus, COVID-19. Currently, more than 210 countries are suffering from COVID-19 with the number of affected countries and patients are exponentially increasing day by day. It became a global health issue where more than 2.7 million cases were reported with a death ratio of approximate 7% globally by World Health Organization (WHO) (as of 24 April 2020) which is a 22 times higher numbers in 1.5 month and this figure increasing day by day at an alarming rate. The maximum infected cases reported from the most developed country and the world leader America however, the maximum death cases are from the world's second health service provider country Italy. China, the origin country of COVID-19, has taken serious actions in terms of prevention, control against the spreading of this coronavirus through lockdown, sanitation, medication, and social distancing. The risk of transmissions of coronavirus from humans to humans is more and thus a social distancing is the best way for its persistence and precautions. Thus, the COVID-19 outbreak continues must explore and evolve, certain strict and mandatory precautions to stop this dangerous devil virus. Also, it is a major challenge for all global scientists to find out an effective remedial drug to control this deadly coronavirus before uncontrolled conditions. Thus, considering the depth of the spreading of coronavirus and its impact on global health, it is necessitating to know the dos and don'ts for persistence, precautions, and diagnostic strategies against the challenging COVID-19.

Kinetics of 2-methylfuran acylation with fatty acid anhydrides for biorenewable surfactants

Friedel-Crafts acylation using long-chain fatty acid derivatives and biomass-derived furans is the key reaction to produce "alkyl furan ketones", an important precursor for biorenewable oleo-furan surfactants. In this work, the steady-state acylation kinetics and reaction mechanism were investigated using a model system of 2-methylfuran and n-octanoic anhydride in a fixed-bed tubular reactor using Al-MCM-41, a mesoporous aluminosilicate. An apparent activation energy (15.5 +or- 1.4 kcal mol- 1) was obtained for the formation of the acylated product, 2-octanoyl-5-methylfuran (2O5MF), for a temperature range of 348-408 K. The apparent reaction rate orders were ~0.6 and ~0.5 in the 2-methylfuran and anhydride concentrations, respectively, while near-zero apparent rate orders were measured in the product concentrations, indicating negligible product inhibition. An Eley-Rideal catalytic acylation mechanism was proposed to explain the experimentally observed apparent rate orders.

Understanding the Role of Affect Dimensions in Detecting Emotions from Tweets: A Multi-task Approach

We propose VADEC, a multi-task framework that exploits the correlation between the categorical and dimensional models of emotion representation for better subjectivity analysis. Focusing primarily on the effective detection of emotions from tweets, we jointly train multi-label emotion classification and multi-dimensional emotion regression, thereby utilizing the inter-relatedness between the tasks. Co-training especially helps in improving the performance of the classification task as we outperform the strongest baselines with 3.4%, 11%, and 3.9% gains in Jaccard Accuracy, Macro-F1, and Micro-F1 scores respectively on the AIT dataset [17]. We also achieve state-of-the-art results with 11.3% gains averaged over six different metrics on the SenWave dataset [27]. For the regression task, VADEC, when trained with SenWave, achieves 7.6% and 16.5% gains in Pearson Correlation scores over the current state-of-the-art on the EMOBANK dataset [5] for the Valence (V) and Dominance (D) affect dimensions respectively. We conclude our work with a case study on COVID-19 tweets posted by Indians that further helps in establishing the efficacy of our proposed solution. © 2021 ACM.

Allogeneic Stem Cell Transplantation in a Large Urban Cohort of North-American Adult T-Cell Leukemia/Lymphoma

Introduction: Adult T-cell leukemia lymphoma (ATLL) is a rare hematologic malignancy caused by human T-cell lymphotropic virus (HTLV-1) with dismal cure rates and poor response to conventional chemotherapy. Allogeneic Hematopoietic Stem Cell Transplantation (AlloSCT) is the only therapeutic option which may offer the chance of long-term remission and cures in a subset of patients. We sought to investigate the outcomes of transplantation in one of the largest cohorts in North America. Methods: A retrospective chart review study was conducted using the North-American ATLL and the Hematopoietic Precursor Cell transplantation databases at Montefiore Medical Center from 2011 to 2020. Variables collected include age, sex, ethnicity, ATLL subtype, molecular profile, previous treatments, conditioning regimens, type of transplant, immunosuppressive regimen, progression free survival (PFS) post-transplant and overall survival (OS) post-transplant. Results: Fourteen patients with ATLL who received an AlloSCT from 2011-2020 were identified. Fifty-seven percent (8/14) of patients were male. Seventy-one percent (10/14) of patients were African American and twenty-nine percent (4/14) were Hispanic. Median age was 51 years. Sixty-four percent (9/14) of patients had Stage IV disease at the time of diagnosis. Forty-three percent (6/14) patients had acute and fifty-seven percent (8/14) had lymphomatous ATLL. Almost all patients (92%) were treated initially with EPOCH combination chemotherapy. Twenty-eight percent (4/14) of patients received interferon/zidovudine as bridge-to-transplant. Fifty-seven percent (8/14) of patients achieved complete remission (CR) prior to AlloSCT, 7% (1/14) were in partial remission, and 28% (4/14) were relapsed or refractory. Forty-three percent (6/14) of patients received SCT from a matched-related donor (MRD), 36% (5/14) from a haplo-identical donor and 21% (3/14) from a matched-unrelated donor (MUD). Ninety-three percent (13/14) of patients received a reduced-intensity conditioning (RIC) regimen pre-transplantation. Seven percent (1/14) received a myeloablative conditioning (MAC) regimen. RIC regimens consisted of fludarabine with melphalan +/- anti-thymocyte globulin (ATG) or fludarabine with cyclophosphamide with total-body irradiation in doses less than 500 cGy. Patients receiving haplo-identical SCT also received post-transplant cyclophosphamide (PTCy) for prevention of graft vs host disease (GVHD). The MAC regimen used included busulfan with cyclophosphamide at myeloablative doses. Twenty-eight percent (4/14) of patients relapsed post-alloSCT with a median relapse-free survival of 6 months (range 4-18 months). The median OS of the whole cohort was 27 months (8-82 months). Graft-versus-host disease (GVHD) developed in 28% (4/14) percent of patients. The most common manifestation was skin GVHD. Fifty-percent (7/14) of the patients are surviving to-date. Transplant-related mortality (TRM) at day 100 was 21% (3/14) of patients. Causes of death were complex and included several diagnoses in certain patients. The most frequent diagnoses associated with death were infection (28%), graft failure (14%), GVHD (14%), veno-occlusive disease of the liver (VOD) (7%), disease progression (14%) and unknown due to patient lost to follow-up (14%). The main infectious events included fungal (2), bacterial (1), and COVID-19 (1) infection. Forty-three percent (6/14) of patients remain in complete remission to date. Conclusions: Allogeneic Stem Cell Transplantation offers long-term survival with a TRM of 21% in a disease with an inherently dismal prognosis. AlloSCT using several graft sources, is thus, a safe and well tolerated treatment modality and offers long term remissions. Disclosures: Steidl: Pieris Pharmaceuticals: Consultancy;Aileron Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Bayer Healthcare: Research Funding;Stelexis Therapeutics: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advi ory committees. Verma: BMS: Consultancy, Research Funding;acceleron: Consultancy, Honoraria;Janssen: Research Funding;Medpacto: Research Funding;stelexis: Current equity holder in private company. Janakiram: ADC Therapeutics, FATE therapeutics, TAKEDA pharmaceuticals: Research Funding.

Dynamics of Leukocyte Subpopulations Reconstitution Predict Infection Propensity in a Multiethnic Real World Cohort Treated with Anti-CD19 CAR-T Cell Therapy (Axicabtagene-Ciloleucel)

Background: Adoptive immunotherapy using CD19-targeted Chimeric Antigen Receptor T-cells (CAR-T) has revolutionized the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). We have demonstrated the efficacy of FDA-approved axicabtagene ciloleucel (Yescarta) in a multiethnic New York City underserved population with 80% complete response (CR) rate in the first ten patients treated at our institution (Abbasi et al., 2020). There is limited data on the propensity of infections and lymphohematopoietic reconstitution after Day 30 (D30) following CAR-T cell therapy. In this study, we evaluated the prevalence and nature of infectious complications in an expanded cohort of DLBCL patients treated with CD19 CAR-T therapy and its association with the dynamics of leukocyte subpopulation reconstitution post-CAR-T cell therapy. Methods: We conducted a retrospective study of patients who received CAR-T therapy at our institution between 2018-2020. Variables collected include patient demographics, absolute neutrophil (ANC), lymphocyte (ALC) and monocyte counts (AMC) at Day 30, hematologic reconstitution (ANC≥ 1500/µL) at Day 90 (D90), presence or absence of infections after D30 by clinical and/or microbiological parameters. Associations between presence of infection and D30 ANC, ALC, AMC, ANC/ALC ratio, AMC/ALC ratio were assessed using Kruskal-Wallis test. Association between infection and hematologic reconstitution at D90 was done using Chi-square test. Kaplan-Meier curves with log-rank test were used to evaluate overall survival (OS) and progression-free survival (PFS). Results: Nineteen patients were evaluated in our study, consisting of 42% (8) Hispanic, 32% (6) Caucasian, 21% (4) African-American, and 5% (1) Asian subjects. Based on clinical and microbiologic data, 47% (9) developed an infection after D30 (infection group) while 53% (10) of subjects remained infection-free after D30 (non-infection group). The most common infection type observed was viral (11 patients) followed by bacterial (8 patients) and fungal (3 patients) (Table 1). Of 25 total infectious events, 44% (11) were grade 1 or 2 and 48% (12) were grade 3 with 10 being viral in etiology. Two deaths occurred due to an infectious process. Three patients tested SARS-CoV-2 positive and were hospitalized with COVID-19 pneumonia. Median OS and PFS has not been reached in either group. To determine the kinetics of lymphohematopoietic reconstitution and its association with infection risk, we evaluated the relationship between cytopenias and rates of infection after D30. Notably, compared to non-infection group, infection group had a higher median ALC (1000/µL vs 600/µL p=0.04), a lower median ANC/ALC ratio (1.4 vs 4.5 p<0.01) and a lower median AMC/ALC at D30 (0.36 vs 1.33, p=0.01) (Table 2). In addition, patients in the infection group had a lower rate of hematologic reconstitution (ANC >1500/µL) at D90. We observed that only 22% (2) of patients had recovered ANC > 1500/µLin the infection group as opposed to 80% (8) in the non-infection group at D90 (p= 0.038). Rates of cytokine release syndrome (CRS) were comparable between the two groups (55.6% vs 70% p=0.52). Surprisingly, rates of immune-effector cell associated neurotoxicity syndrome (ICANS) was lower (55.6%) in the infection group compared to (90%) non-infection group (p=0.09). Fourteen of 19 patients had follow-up over one year, of which 8 (57%) remained in complete remission (CR). Conclusions: We demonstrate an infection rate of 47% (9) beyond D30 in patients undergoing CD19 CAR-T. Increased ALC, lower ANC/ALC and AMC/ALC ratios at D30 may be predictive of infectious complications. Median OS has not been reached in our cohort. Given the potential clinical impact, our observations should be corroborated using larger datasets. [Formula presented] Disclosures: Steidl: Pieris Pharmaceuticals: Consultancy;Bayer Healthcare: Research Funding;Stelexis Therapeutics: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees;Ai eron Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Janakiram: ADC Therapeutics, FATE therapeutics, TAKEDA pharmaceuticals: Research Funding. Verma: BMS: Consultancy, Research Funding;acceleron: Consultancy, Honoraria;Janssen: Research Funding;stelexis: Current equity holder in private company;Medpacto: Research Funding.

Patient priorities care as framework for what matters

Background: To optimize care for older adults, the John A. Hartford Foundation and the Institute for Healthcare Improvement created the Age-Friendly Health System Initiative based on the 4Ms (What Matters, Medications, Mentation, and Mobility). “What Matters” focuses on identifying and aligning care for each older adult with their unique health outcome goals and care preferences. Matters most is the keystone M, yet is the most challenging to implement. Patient Priorities Care (PPC), an evidence-based approach that aligns healthcare decisions with the priorities (outcome goals and care preferences) of complex older adults, provides a framework for translating the concept of “What Matters” into clinical decision-making. Methods: PPC was adapted for the DeBakey VA Medical Center geriatric clinic in January 2018 following training of 3 geriatricians, 1 PA, and 6 geriatric fellows by co-developers of PPC. Over two years, 24 geriatrics fellows and 9 geriatrics PA residents were trained in the PPC approach. When the clinic transitioned to age-friendly care for all non-urgent clinic visits in February 2020, PPC became the approach for eliciting and acting on “What Matters” for every Veteran. We modified the clinic note template to include documentation of goals and care preferences, anchored to what matters, with relevant alignment of healthcare as the first step in the plan. Results: Findings from a focus group of providers, patients, and caregivers identified the PPC framework as acceptable and reasonable for addressing “What Matters”. The clinic incorporated the 4Ms into 39 of 114 non-urgent visits (34%) over the first 2 months (February and March 2020) of age-friendly care. Only 11% of visits in April and May 2020 incorporated 4Ms following Covid-related changes in clinic workflows. With resumption of traditional clinic workflows, 28 of 44 (64%) non-urgent, in-person visits in December 2020 included 4Ms documentation. Conclusion: Despite initial Covid-19 related disruptions, PPC is a clinically feasible and acceptable framework for identifying what matters and performing relevant alignment of care as part of an age-friendly care transformation.

Age, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohort

The COVID-19 pandemic has affected all individuals across the globe in some way. Despite large numbers of reported seroprevalence studies, there remains a limited understanding of how the magnitude and epitope utilization of the humoral immune response to SARS-CoV-2 viral anti-gens varies within populations following natural infection. Here, we designed a quantitative, multi-epitope protein microarray comprising various nucleocapsid protein structural motifs, including two structural domains and three intrinsically disordered regions. Quantitative data from the microarray provided complete differentiation between cases and pre-pandemic controls (100% sensitivity and specificity) in a case-control cohort (n = 100). We then assessed the influence of disease severity, age, and ethnicity on the strength and breadth of the humoral response in a multi-ethnic cohort (n = 138). As expected, patients with severe disease showed significantly higher antibody titers and interestingly also had significantly broader epitope coverage. A significant increase in antibody titer and epitope coverage was observed with increasing age, in both mild and severe disease, which is promising for vaccine efficacy in older individuals. Additionally, we observed significant differences in the breadth and strength of the humoral immune response in relation to ethnicity, which may reflect differences in genetic and lifestyle factors. Furthermore, our data enabled localization of the immuno-dominant epitope to the C-terminal structural domain of the viral nucleocapsid protein in two independent cohorts. Overall, we have designed, validated, and tested an advanced serological assay that enables accurate quantitation of the humoral response post natural infection and that has revealed unexpected differences in the magnitude and epitope utilization within a population.

SARS-CoV-2 receptor networks in diabetic kidney disease, BK virus nephropathy, and COVID-19 associated AKI

Background: COVID-19 shows increased disease burden in patients with diabetic kidney disease (DKD). SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for host cell entry, so ACE2 levels may influence SARS-CoV-2 susceptibility. We investigated how pre-existing conditions and drug treatments alter receptor expression in kidney cells (Figure 1). Methods: Single cell RNA profiling of 7 healthy living donor kidneys, 44 DKD, 3 BK virus nephropathy (BKVN) and a urine COVID19 patient with acute kidney injury (COV-AKI) revealed ACE2 expression primarily in proximal tubular epithelial cells (PTEC). Results: ACE2 mRNA expression levels were higher in proximal tubule epithelial cells (PTEC) in DKD versus LD, but unaltered by exposures to renin angiotensin aldosterone system inhibitors. Bayesian integrative analysis of public -omics datasets identified molecular network modules induced in ACE2 positive versus negative PTEC in DKD and BKVN (hb.flatironinstitute.org/COVID-kidney), that were linked to viral entry, immune activation, endomembrane reorganization, and RNA processing. Similar programs were seen in COV-AKI ACE2-positive PTEC, and overlapped with programs in SARS-CoV-2 infected cells. Conclusions: A consistent ACE2-coregulated expression program in PTEC may interact with SARS-CoV-2 infection processes. These networks can seed further research into developing therapeutic strategies and assessing risk in patients with COVID-19. (Figure Presented).