Alterations in the Covid-19 - Associated Proteome Relative to Length of Hospital Stay

RATIONALE: The proteomic responses of hospitalized patients with SARS Co-V-2 infection may provide insight into risk, time course, and mechanisms associated with this infection. We used a high throughput proteomic platform to examine proteins that were differentially expressed relative to the length of hospital stay (LOS). METHOD:26 patients, hospitalized with SARS CoV-2 infection (mean age 48 yrs, 44% women) had blood samples obtained within 72 hours of admission. Initial plasma samples were analyzed from patients who were hospitalized for < 3 days (n=6), < 7days (n=12) and > 7 days (n=8) of LOS and compared to healthy controls (HC, n=8). Samples were analyzed with the modified aptamer-based array (SomaScan) that measures more than 7,000 human proteins representing different molecular pathways and gene families. Differentially regulated proteins with > 1.5 fold change and a false discovery rate of 5% were analyzed using the Ingenuity Pathway Analysis (IPA). Unique protein categories associated with LOS were assessed. RESULT: Compared to HC, differentially expressed proteins were detected among the 3 groups: 461 at < 3 days, 1,635 proteins at < 7 days and 1,738 proteins in >7 days. 407 proteins were common among all hospitalized COVID 19 individuals independent of LOS and 12, 250 and 361 proteins were uniquely present at < 3 days, < 7 days and > 7 days respectively compared to HC. The table below demonstrates the top highly enriched canonical pathway, molecular function and upstream regulator of differentially expressed proteins. The temporal sequence of these protein networks varied with LOS. Representative examples include early responses;platelet membrane glycoprotein GP6 signaling pathway that involves the FcR gamma-chain and the Src kinases linked to platelet aggregation, signaling involved in T cell receptor-mediated IL-2 production (TEC kinase). Less than 7 days include diacylglycerol associated with T cell activation, carnitine palmitoyltransferase associated with mitochondrial beta-oxidation of long chain fatty acids. CXCR4 a receptor for stromal -cell derived factor 1 and associated with COVID-19 prognosis. Late responses after 7 days include pathways involved in remodeling of epithelial adherens junctions. CONCLUSIONS : A high throughput proteomic approach provides insight into the dynamic regulation of protein pathways associated with the progression of SARS-Co-V2 infection. This may provide additional insight into risk and mechanisms associated with outcomes in COVID. (Table Presented).

A Case of Anti-Ro52 Antibody Myositis-Associated Interstitial Lung Disease

Introduction: Recognition of myositis-associated interstitial lung disease (ILD) has been increasing due to the recent identification of specific antibodies that are linked to a particular phenotype of myositis-ILD such as antisynthetase syndrome. The anti-Ro52 antibody has been found in multiple connective tissue diseases but its association with ILD is unclear. In fact, the literature on the phenotype of patients with an isolated anti-Ro52 antibody is very scarce. Case Presentation: A 57-year-old retired firefighter with history of gastroesophageal reflux presented to the hospital with a 4-week history of cough and progressive dyspnea with no other symptoms. He had presented to an urgent care facility where he tested negative for SARs-CoV-2 and was given antibiotics and inhalers without a clinical response. Patient required 2L/min of oxygen on admission. He had no other signs of autoimmune disease or other organ involvement. Chest CT showed peripheral ground glass opacities with basilar reticulations and bronchiectasis (Figure 1). WBC and CPK were normal and aldolase was mildly elevated. Initial serologies revealed an ANA 1:320 and a weakly positive p-ANCA with negative PR3/MPO antibodies. Patient was started on prednisone 60 mg and discharged five days later on mycophenolate mofetil (MMF) and 2L/min of oxygen. At 2-week follow-up, his extensive autoimmune panel showed a high titer of Anti-Ro52 antibody. An in depth ILD questionnaire revealed a family history of lupus and the remote use of a short course of steroids 20 years ago after a biceps biopsy showed polymyositis. On chart review, 10 years ago the patient had elevated CPK levels of 255 to 404, in the context of a nonspecific flank pain that resolved without intervention. At his 3-month follow-up, the patient still required 40mg of prednisone, reported dyspnea on exertion and required oxygen with ambulation. Rituximab was added to his regimen and his symptoms significantly improved;at 6-month follow-up, his FVC% improved from 53% to 70% and the patient was no longer on oxygen. Prednisone was titrated down to 10mg and he was continued on MMF 3g/day and Rituximab every 6 months. Discussion: We present a patient with Anti-Ro52 antibody myositisassociated ILD who required 3 immunosuppressive agents to control his disease. This case adds to the very scarce literature on ILD secondary to Anti-Ro52 antibody and highlights the importance of an extensive antibody testing for patients with ILD of unclear etiology, for diagnostic and therapeutic purposes. Further studies describing the phenotype of these patients are warranted. (Figure Presented).

Patient satisfaction with telemedicine in a virtual lung transplant clinic

Rationale: During the COVID-19 pandemic telemedicine has emerged as an alternative medical care platform, being used more frequently in an effort to decrease the risk of exposure to both the patients and their health care providers. Close monitoring of lung transplant patients is crucial, as they are at a particularly vulnerable population due to chronic immunosuppression and coexisting comorbidities. Our study evaluates the patient satisfaction and technical feasibility of telemedicine visits after lung transplantation. Methods: A retrospective analysis was performed at the University of Maryland Lung Transplant center during the COVID-19 pandemic. The primary outcome was patient satisfaction with the clinic visit measured by a Telemedicine Satisfaction Questionnaire (23 questions). The telemedicine clinics were conducted between March 2020 and November 2020. The survey was designed after a forum discussion with a representative group of lung transplant patients and was initially sent to all lung transplant patients seen in this timeframe;a second follow-up survey was sent six month later. Results: In March 2020, 148 lung transplant patients received an initial survey via email. Fiftythree patients who completed the survey were included in the study. From the survey responses, 94% of patients considered the care they received via the telemedicine program to be very good to excellent;in subsequent follow-up satisfaction was still high at 89% of patients. In the first and second surveys, 96% and 94% of patients reported a good understanding of the use electronic devices, respectively. The majority of patients (59%) reported decreased travel-associated costs during the first survey, which then increased to 85% of patients during the follow-up survey. Conclusion: High levels of patient satisfaction were seen in lung transplant patients after the implementation of a telemedicine program in the context of the COVID-19 pandemic. Decreased travel-associated costs were reported by the majority of patients, especially in the 6-month follow-up survey. Our study suggests that a telemedicine program may decrease the travel-associated costs while maintaining high levels of satisfaction in a very complex population of lung transplant patients. Studies evaluating the role of telemedicine on clinical outcomes require further investigation.