ABSTRACT
The 2019 Coronavirus disease (COVID-19) vaccine is a major weapon in the fight against the severe acute respiratory syndrome brought about by coronavirus 2 (SARS-CoV-2). The vaccine significantly reduces the risk and severity of infection by SARS-CoV-2. Patients with systemic lupus erythematosus (SLE) need protection from vaccine-preventable diseases including COVID-19. SLE patients have higher rates of severe infections due to immunosuppressive therapies and multiple immunologic defects - both of which are capable of blunting the immune responses after vaccination. In the management of COVID-19, recommendations have been developed to guide adjustments and/or continuation of immunosuppressive therapies for an effective immune response following vaccination with mRNA-based or viral vector-delivered vaccines. Monoclonal antibodies have also become available since December 2021. Here we present three cases of SLE patients who contracted COVID-19 after vaccination. One was managed in ambulatory settings and two required inpatient hospital admission.Copyright © 2022
ABSTRACT
Digital Contact Tracing (CT) protocols based on Bluetooth are best implemented at the system level to save resources and preserve security aspects. Combined with a government-monitored software platform, these CT-protocols can then be used to support controlling pandemics such as COVID-19. However, it is unclear how these protocols have to be parameterized to ensure the most accurate and reliable CT. This paper describes how we derived optimal parameters for a decentralized CT from extensive measurement campaigns that we carried out together with Deutsche Telekom (DT) and SAP under the supervision of the Robert Koch Institut (RKI). We examined the Google/Apple Exposure Notification Framework (ENF), which in combination with the front-end, i.e., the German Corona-Warn-App (CWA), enables digital CT in Germany. With centimeter accurate optical reference systems we show that optimal parameters are application-specific. However, they cause impractical high resource costs. In contrast, optimized general parameters offer an everyday compromise between energy costs, applicability, accuracy, and reliability of the ENF.
ABSTRACT
Background Pharmacologic immunosuppression and incomplete immune reconstitution after allogeneic stem cell transplant (alloSCT) may impair a patient's ability to mount an immune response to vaccines, including currently available COVID-19 vaccines. Since immunocompromised patients are susceptible to severe COVID-19 and likely to respond poorly to vaccination, we sought to characterize SARS-CoV-2 antibody responses after vaccination in alloSCT patients to determine predictors of serologic response, which may inform timing of vaccine administration. Methods This retrospective analysis included adult patients who underwent alloSCT at the University of Pennsylvania between 1/1/2019 and 1/1/2021. Chart review identified patients who had received COVID-19 vaccines and had post-vaccination antibody titers drawn by July 2021 as part of routine care (n=63). Antibodies to SARS-CoV-2 spike protein receptor binding domain were detected using an assay developed at the Hospital of the University of Pennsylvania. Variables analyzed include interval between transplant date and initial vaccination, active GVHD, concurrent immunosuppressive therapy, absolute CD4 count greater than or equal to 200 cells/mm3 peri-vaccination, and total IgG greater than or equal to 400 mg/dL peri-vaccination. Immunosuppressive therapy was defined as tacrolimus, rituximab, ruxolitinib, prednisone 10 mg daily or greater, or extracorporeal photopheresis. Predictors of positive antibody response were assessed using a multivariate, binary logistic regression. Results Median transplant to vaccine interval was 458 days (range 125 to 813) for the 63 vaccinated patients with serologies available. GVHD was present in 23/63 (37%), and 19/63 (30%) were receiving immunosuppressive therapies at the time of vaccination. CD4 count greater than 200 cells/mm3 was observed in 49 patients (78%), and total IgG greater than 400 mg/dL was observed in 51 patients (81%). In total, 50/63 patients (79%) were positive for SARS-CoV-2 IgG antibodies. Positive serologies were observed in 41/49 (84%) with CD4 counts greater than 200 cells/mm3, compared to 9/14 (64%) with CD4 less than 200 cells/mm3. Our model found that peri-vaccination CD4 count greater than 200 cells/mm3 was a significant predictor of positive SARS-CoV-2 IgG serologies in this population (OR 2.14, 97.5% CI = 0.7 to 3.8, p= 0.005). Transplant to vaccine interval, total IgG levels, GVHD status, and immunosuppressive therapies were not significant predictors of serologic response. As of July 2021 no patients had developed COVID-19 after vaccination, regardless of serologic response. Conclusions This retrospective observational study demonstrates that the majority of alloSCT patients vaccinated against COVID-19 within 2 years of transplant, including those with active GVHD and on immunosuppressive therapies, can mount serologic responses. CD4 count greater than 200 cells/mm3 is a significant predictor of positive serologic response, though even among patients with CD4 counts under 200 cells/mm3 over 60% developed SARS-CoV-2 IgG antibodies. Disclosures: Perry: Incyte: Consultancy, Speakers Bureau;Abbvie,: Speakers Bureau;Kadmon: Consultancy. Pratz: University of Pennsylvania: Current Employment;Abbvie: Consultancy, Honoraria, Research Funding;Astellas: Consultancy, Honoraria, Research Funding;Cellgene: Consultancy, Honoraria;Novartis: Consultancy;BMS: Consultancy, Honoraria;Agios: Consultancy;Millenium: Research Funding. Luger: Syros: Honoraria;Agios: Honoraria;Daiichi Sankyo: Honoraria;Jazz Pharmaceuticals: Honoraria;Brystol Myers Squibb: Honoraria;Acceleron: Honoraria;Astellas: Honoraria;Pfizer: Honoraria;Onconova: Research Funding;Celgene: Research Funding;Biosight: Research Funding;Hoffman LaRoche: Research Funding;Kura: Research Funding. Perl: Astellas: Consultancy, Research Funding;Loxo: Consultancy;AbbVie: Consultancy, Research Funding;Syndax: Consultancy;BMS/Celgene: Consultancy;Roche: Consultancy;Fujifilm: Research Funding;Daiichi Sankyo: Consultancy, Research Funding;Forma: Consult ncy;Arog: Research Funding;Genentech: Consultancy;Actinium: Consultancy;Onconova: Consultancy;Sumitomo Dainippon: Consultancy. Porter: ASH: Membership on an entity's Board of Directors or advisory committees;Incyte: Membership on an entity's Board of Directors or advisory committees;DeCart: Membership on an entity's Board of Directors or advisory committees;Genentech: Current equity holder in publicly-traded company, Ended employment in the past 24 months;American Society for Transplantation and Cellular Therapy: Honoraria;Kite/Gilead: Membership on an entity's Board of Directors or advisory committees;Janssen: Membership on an entity's Board of Directors or advisory committees;National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding;Tmunity: Patents & Royalties;Wiley and Sons Publishing: Honoraria. Hexner: Blueprint medicines: Membership on an entity's Board of Directors or advisory committees, Research Funding;PharmaEssentia: Membership on an entity's Board of Directors or advisory committees;Tmunity Therapeutics: Research Funding. Frey: Sana Biotechnology: Consultancy;Kite Pharma: Consultancy;Syndax Pharmaceuticals: Consultancy;Novartis: Research Funding.