The Initial Response of Nuclear Medicine to the COVID-19 Pandemic

Objectives: COVID-19 posed profound challenges to nuclear medicine (NM) practice and education on an international scope. Initial lessons learned may be useful in understanding and optimizing dissemination of critical information during global disasters. To better understand the pandemic's initial manifold impact and responses that were in turn enacted, we systematically reviewed relevant articles published during the 2020 calendar year. Method(s): A librarian experienced in systematic reviews performed a rapid scoping review of the English language literature indexed in PubMed, Embase and Web of Science by crossing NM and COVID terms;445 citations were returned. Duplicate, extraneous, non-English and non-full text articles were excluded leaving 248 articles which were analyzed by origin, topic, design, and imaging details. Result(s): An array of topics, techniques, journals and countries of origin were encountered. 158 articles appeared in primary NMjournals, 26 appeared in generic radiology journals and 65 in non-imaging journals. Most frequent countries represented were USA (55), Italy (33), France (19) and UK (17), reflecting the hard-hit countries early during the pandemic. 118 clinical articles were case reports or small series of which 80 featured FDG-PET/CT. There were 36 observational studies. Among non-clinical topics, articles focused on safetymeasures (102), economics and recovery (23), remote reading (17) and education (8). There were 17 surveys. Society-based guidelines (47) and individual-group best practices (79) were published relating to cardiology (33), lung scintigraphy (12), andmultiple topics (48). Systematic (10) and narrative reviews (61) were less frequent than opinion articles (75). Frequent modalities discussed were FDG PET (156), nuclear cardiology (56) and lung scintigraphy (35). Conclusion(s): The medical literature has memorialized a robust response of information sharing during the initial challenges the COVID-19 pandemic relating to patient care, operations and education. Through scoping review, we have analyzed the nature of information disseminated. Opinions and single group best practices dominated the literature. Clinical reports during the first year were primarily case reports or small series, frequently FDG-PET/ CT. The nature of the literature matured as the year progressed, and sources of information broadened as the epidemic spread.

Digital microscopy for teaching cytomorphology during the COVID-19 pandemic and beyond

Introduction: The COVID-19 pandemic profoundly impacts education in hematology residency programs due to contact restrictions imposed by national and local authorities. Nevertheless, education with face-to-face trainings is essential, particularly in teaching cytomorphology of bone marrow, peripheral blood and body fluids. The development of high resolution digital microscopy (DM) allows digitalization of cytomorphological specimens. In the COVID-19 pandemic we have established several teaching formats using DM. This work was supported by DKH and DGHO. Methods: Throughout 2020, more than 150 slides from peripheral blood films, bone marrow smears, CSF and pleural, pericardiac and peritoneal effusions were scanned and digitalized. We used a high-speed camera combined with manual scanning software. For DM courses (DMC) we used commercially available software (ZoomTM). Evaluation of in-house teaching was performed by a Likert scale survey to assess acceptance, technical problems and motivation. Results: We established several teaching formats, including weekly in-house cytology rounds for residents and the DMC series 'Hematology for beginners', a 90-minutes webinar on certain topics, including myeloma, acute leukemia, anemia and myelodysplastic syndromes that took place four times during the last year. Further DMC are planned in 2021. There was a growing number of participants with a maximum of up to 139 participants. The evaluation showed that DMC were well accepted by in-house residents and participants of different institutions and also by faculty members. Technical performance was feasible with only very few technical problems due to poor bandwidth of internet connection. Conclusion: DMC in cytomorphology are feasible. The limitations of DM include availability of sufficient bandwidth, quality of the blood or bone marrow smears, and inability of participants to physically handle the microscope. Nonetheless, DMC may help to bridge the educational gap for cytomorphology teaching during these unprecedented circumstances in the COVID-19 pandemic. It supports preserving the health and live of our patients, colleagues and trainees by distanced learning and can be performed both for smaller and larger audience. These advantages of DM may prevail after the COVID-19 pandemic, further support daily education and have the potential to shape the future of morphology teaching.

A Comparative Outcome Analysis of COVID-19 and Influenza Infection in Patients with Hematological Malignancies

Introduction: Patients with hematological malignancies and concomitant SARS-CoV-2 infection suffer from a more severe course of their infection than patients without underlying concomitant disease. Similar observations have been made for concomitant influenza infections. The aim of this retrospective study is to compare the clinical courses of COVID-19 and seasonal influenza in patients with hematological malignancies. Methods: In this retrospective, single center analysis all patients with hematological malignancies aged 18 years and older were included with a laboratory confirmed SARS-CoV-2 or influenza A or B infection who were admitted or were already under treatment at the Department of Oncology and Hematology or at the Department of Stem Cell Transplantation at the University Medical Center Hamburg-Eppendorf, Germany, between January 2012 and January 2021. Primary and secondary endpoints of this study are the rate of acute respiratory distress syndrome (ARDS) and virus-associated 30- and 90-day mortalities. The retrospective data collection was performed in accordance with local legal requirements and was reviewed and approved by the Ethics Committee of the Medical Council of Hamburg. Results: A total of 79 patients were included in this study. 29 patients had laboratory confirmed SARS-CoV-2 infection and 50 patients had influenza A or B infection. 69% in the COVID-19 group and 68% in the influenza group were male. Median age in the COVID-19 group were 59 years vs 58.5 years in the influenza group. Distribution of hematological malignancies in the COVID-19 group was as follows: 59% had acute leukemia (AL), 24% malignant lymphoma, 14% multiple myeloma (MM) and 3% myelodysplastic syndrome (MDS). 89% of the patients with concomitant SARS-CoV-2 diagnosis were currently under treatment with chemotherapy, CD20 or CD38 antibody-therapy, underwent allogeneic stem cell transplantation (SCT) or received CAR-T-cells shortly before (< 2 months) or during SARS-CoV-2 positivity. In the influenza group, 60% had AL, 8% lymphoma, 24% MM and 8% MDS or myeloproliferative neoplasm. 84% of these patients were under treatment with chemotherapy, CD33-, CD38- or SLAMF7-directed antibodies or underwent allogeneic SCT shortly before or during infection with seasonal influenza. At the time of infection, 41% of all SARS-CoV-2 positive patients were in refractory or relapsed setting compared to 42% in the influenza group whereas 28% in the COVID-19 and 36% in the influenza cohort were in complete remission. At the time of SARS-CoV-2 detection 38% of patients had grade IV neutropenia (defined as neutrophil count <0.5 x 10 9/L) with a median duration of 3.5 days which is comparable to 33% of patients and a median neutropenia duration of three days in the influenza group. The incidence of ARDS was significantly higher in the COVID-19 group compared to the influenza group (48% vs. 14%, p = 0.001). Furthermore, virus infection related 30-day and 90-day mortality was significantly higher in the COVID-19 group (28% vs. 8%, p = 0.026 and 41% vs. 12%, p = 0.005). In the COVID-19 group, a duration of aplasia ≥ 7 days had no negative impact on 90-day mortality or development of an ARDS (p = 0.599 and 0.982 respectively) whereas in the patients infected with influenza A or B, an aplasia ≥ 7 days had a negative impact on 90-day mortality and development of ARDS (p < 0.001 each). Conclusion: Based on our results, we conclude that comparable to the general population, infections with SARS-CoV-2 result in a significantly higher rate of ARDS and a significantly higher 30- and 90-day mortality compared to influenza A or B infections in patients with underlying hematological malignancies. Disclosures: Weisel: Adaptive: Consultancy, Honoraria;Amgen: Consultancy, Honoraria, Research Funding;BMS: Consultancy, Honoraria;Celgene: Consultancy, Honoraria, Research Funding;Janssen: Consultancy, Honoraria, Research Funding;GSK: Consultancy, Honoraria;Karyopharm: Consultancy, Honoraria;Takeda: Consultancy, Honoraria;Sanofi: Consultancy, Honoraria, Resear h Funding. Bokemeyer: Gilead Sciences: Research Funding;Bayer Schering Pharma: Consultancy;Merck Serono: Consultancy, Other: Travel accomodation;AOK Health insurance: Consultancy;Alexion Pharmaceuticals: Research Funding;Agile Therapeutics: Research Funding;ADC Therapeutics: Research Funding;Abbvie: Research Funding;GSO: Consultancy;Lilly/ImClone: Consultancy;Amgen: Research Funding;Apellis Pharmaceuticals: Research Funding;Astellas: Research Funding;BerGenBio: Research Funding;Blueprint Medicine: Research Funding;Boehringer Ingelheim: Research Funding;Celgene: Research Funding;Daiichi Sankyo: Research Funding;Eisai: Research Funding;Gylcotope GmbH: Research Funding;GlaxoSmithKline: Research Funding;Inside: Research Funding;IO Biotech: Research Funding;Isofol Medical: Research Funding;Janssen-Cilag: Research Funding;Sanofi: Consultancy, Honoraria, Other: Travel accomodation;Merck KGaA: Honoraria;Roche: Honoraria, Research Funding;Merck Sharp Dohme: Consultancy, Honoraria;AstraZeneca: Honoraria, Research Funding;BMS: Honoraria, Other: Travel accomodation, Research Funding;Bayer: Honoraria, Research Funding;Karyopharm Therapeutics: Research Funding;Lilly: Research Funding;Millenium: Research Funding;MSD: Research Funding;Nektar: Research Funding;Rafael Pharmaceuticals: Research Funding;Springworks Therapeutics: Research Funding;Taiho Pharmaceutical: Research Funding;Pfizer: Other. Fiedler: Novartis: Honoraria;Pfizer: Consultancy, Honoraria, Research Funding;Daiichi Sanyko: Consultancy, Other: Meeting attendance, Preparation of information material;Stemline: Consultancy;Servier: Consultancy, Other: Meeting attendance, Preparation of information material;MorphoSys: Consultancy, Honoraria;Jazz: Consultancy, Honoraria, Other: Meeting attendance, Preparation of information material;Celgene: Consultancy, Honoraria;Ariad/Incyte: Honoraria;Amgen: Consultancy, Honoraria, Other: Meeting attendance, Preparation of information material, Patents & Royalties, Research Funding;Abbvie: Consultancy, Honoraria, Other: Meeting attendance, Preparation of information material. Modemann: Teva: Other: Travel accomodation;Novartis: Other: Travel accomodation;Jazz Pharmaceuticals: Other: Travel accomodation;Gilead: Other: Travel accomodation;Incyte: Other: Travel accomodation;Servier: Honoraria, Other: Travel accomodation;Pfizer: Other: Travel accomodation;Amgen: Other: Travel accomodation;Daiichi Sankyo: Research Funding;Abbvie: Honoraria, Other: Travel accomodation.

CD19+ B Lymphocytes Are Predictive for Anti-Sars-Cov-2 Vaccination Response in Multiple Myeloma Patients

Introduction: Up to now,reliable results regarding the efficacy of anti-SARS-CoV-2 vaccines in patients with multiple myeloma (MM), especially under current myeloma-directed therapy, are scarcely available. Here, we report an analysis describing the level of post-vaccination antibody titers after the 1 stand 2 ndanti-SARS-CoV-2 vaccination depending on therapy, remission status, and B- and T-cell numbers in patients with MM and related plasma cell neoplasia. Methods: This observational single-center study included patients aged ≥18 years with diagnoses of MM, monoclonal gammopathies of clinical significance (MGCS), or systemic light-chain amyloidosis (AL) who were eligible for Anti-SARS-CoV-2 vaccination according to the International Myeloma Society recommendations. Patients with prior COVID-19 infections were excluded. Samples were analyzed for the presence of SARS-CoV-2 specific antibodies using the quantitative anti-spike IgG (SARS-CoV-2 spike RBD IgG, cut off ≥ 0.8 BAU/ml) according to manufacturer's recommendations. SARS-CoV-2 spike protein antibody titer (SP-AbT) were evaluated after at least 7 days after the 1 stand 2 ndvaccination, respectively. This study was performed between January 1 - July 15, 2021, at the University Medical Center Hamburg-Eppendorf, Germany, as part of the COVIDOUT trial (NCT04779346). All patients provided written informed consent. Aims of this study were to evaluate a possible correlation between SP-AbT and CD19+ B lymphocyte count, as well as to identify other factors impacting vaccination response. Results: 82 patients who received SARS-CoV-2 vaccines (including 67 patients with mRNA-, 8 with vector-based vaccines and 4 heterologous vaccinations) were included. 74 patients had diagnosis of MM, 4 of MGCS/smoldering MM and 4 of AL. Median age was 68 years (range 35-85) and 49 patients were male. In total, 37 patients (45.1%) received anti-CD38- and 2 (2.4%) anti-SLAMF7-targeting therapies at the time of vaccination, 52 (63.4%) patients received immunomodulatory drug (IMID)-based treatments and 13 patients (15.9%) were under active surveillance. 59% of patients had newly diagnosed and 41% refractory or relapsed disease. In total, 75.6% of all patients were in deep remissions (very good partial remission or better). Assessment of anti-SARS-CoV-2 antibody titers took place in median 23 days (range [r] 8-63 days) after the 1 stand 21 days (r: 6-53) after the 2 ndvaccination. A positive SARS-CoV-2 SP-AbT was detected in 31.9% of assessable patients with an overall median SP-AbT of 0 BAU/ml (r: 0-10328, mean 202.36) after the 1 stvaccination and increased up to 88.9% (median SP-AbT of 216.87 BAU/ml, r: 0-25720, mean 2139.29) after 2 ndvaccination. Of the patients not showing positive SP-AbT after the 1 stvaccination, 80.9% became positive after 2 ndvaccination, while 19.1 % remained negative. Median SP-AbT titer was significantly lower compared to patients who became positive already after 1 stvaccination (51.04 vs. 2191.87 BAU/ml, p<0.0001). Regarding immune status, a CD19+ B cell count of median 33.5/µl (r: 1-696/µl) was seen in the overall patient cohort;in patients with negative SP-AbT, median CD19+ B cell numbers were significantly lower compared to patients with positive titers (median CD19+ B cells: 2.0 vs. 52.5/µl, p=0.005). Overall, CD19+ B lymphocyte numbers correlate significantly with positive SP-AbT results and were identified as predictive factor in multivariate analysis. The previously suggested threshold of 30 CD19+ B cells/µl as being predictive for SP-AbT development could be validated. SP-AbT concentration was significantly lower with older age. Furthermore, median SP-AbT were significantly lower in patients with current anti-CD38 directed therapy (median SP-AbT: 1085.4 vs. 62.05 BAU/ml, p < 0.005). Conclusions: In spite of immunodeficiency and immunosuppressive therapy, most MM patients develop SP-AbT. However, about 11% of MM patients failed to develop SP-AbT after full vaccination, and thus remain on risk for COVID-19. Higher counts of CD19+ B lymphocytes, ith a threshold of 30 CD19+ B lymphocytes/µl, are predictive for SP-AbT formation and may further help to identify patients at higher risk of insufficient vaccination response in whom control of vaccination success and potential third vaccination are particularly important. Disclosures: Bokemeyer: GlaxoSmithKline: Research Funding;Inside: Research Funding;IO Biotech: Research Funding;Eisai: Research Funding;Daiichi Sankyo: Research Funding;Gilead Sciences: Research Funding;Blueprint Medicine: Research Funding;BerGenBio: Research Funding;Janssen-Cilag: Research Funding;Isofol Medical: Research Funding;AOK Health insurance: Consultancy;GSO: Consultancy;Bayer Schering Pharma: Consultancy;Gylcotope GmbH: Research Funding;ADC Therapeutics: Research Funding;Apellis Pharmaceuticals: Research Funding;Amgen: Research Funding;Alexion Pharmaceuticals: Research Funding;Agile Therapeutics: Research Funding;Merck Serono: Consultancy, Other: Travel accomodation;Lilly/ImClone: Consultancy;Merck Sharp Dohme: Consultancy, Honoraria;AstraZeneca: Honoraria, Research Funding;BMS: Honoraria, Other: Travel accomodation, Research Funding;Bayer: Honoraria, Research Funding;Roche: Honoraria, Research Funding;Sanofi: Consultancy, Honoraria, Other: Travel accomodation;Merck KGaA: Honoraria;Abbvie: Research Funding;Boehringer Ingelheim: Research Funding;Celgene: Research Funding;Astellas: Research Funding;Karyopharm Therapeutics: Research Funding;Lilly: Research Funding;Millenium: Research Funding;MSD: Research Funding;Nektar: Research Funding;Rafael Pharmaceuticals: Research Funding;Springworks Therapeutics: Research Funding;Taiho Pharmaceutical: Research Funding;Pfizer: Other. Sinn: Incyte: Honoraria, Research Funding;Pfizer: Honoraria;Servier: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Research Funding;Astra Zenica: Consultancy, Research Funding;MSD: Consultancy, Research Funding;Sanofi: Consultancy;Bayer: Research Funding;BMS: Honoraria, Research Funding. Leypoldt: GSK: Consultancy, Other: Meeting attendance;Sanofi: Consultancy;Abbvie: Other: Meeting attendance. Weisel: Adaptiv Biotec: Consultancy;Abbvie: Consultancy;BMS: Consultancy, Honoraria, Research Funding;Celgene: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Honoraria, Research Funding;GSK: Consultancy, Honoraria;Janssen: Consultancy, Honoraria, Research Funding;Karyopharm: Honoraria;Novartis: Honoraria;Oncopeptides: Consultancy, Honoraria;Pfizer: Honoraria;Roche: Honoraria;Takeda: Honoraria;Sanofi: Consultancy, Honoraria, Research Funding.

A comparative outcome analysis of covid-19 vs influenza infection in patients with acute leukemia

Background: Patients with acute leukemia and concomitant SARSCoV- 2 infection suffer from a more severe course of their infection than patients without underlying disease including a higher admission rate to ICU and a higher death rate. Similar observations have been made for concomitant influenza infections. Aims: The aim of this study is to compare the clinical courses of COVID- 19 and seasonal influenza in patients with acute leukemia (AL). This could help to find evidence for certain therapy modifications in AL patients with COVID-19 based on long lasting experience in patients with AL and influenza. Methods: This is a retrospective single center analysis including all patients with AL and concomitant influenza or SARS-CoV-2 infection who were treated in the department of oncology and hematology of the University Medical Center Hamburg-Eppendorf, Germany, between February 2013 until now. Data of the clinical course were collected from the patient's electronic medical records. Statistical analysis was performed by using IBM SPSS Statistics, version 26. Results: In the Influenza-group (n = 21), 71 % were male, the median age was 58 years (r: 20-81). 17 patients (81%) had acute myeloid leukemia (AML), four patients (19%) had acute lymphoblastic leukemia (ALL). 29% had newly diagnosed AL at influenza infection, 33% were in complete remission and 38% were under treatment due to refractory or relapsed disease. 95% were currently under chemotherapy treatment at diagnosis of influenza, 80% of them were treated with intensive chemotherapy. Median duration of aplasia was six days (r: 0-38), five patients had no aplasia during influenza infection. 18 patients were treated with Oseltamivir. 15 patients had an Influenza A with ten cases of H1N1, six patients had an Influenza B. The distribution in the COVID-19 group (n = 15) was similar: 73% were male, the median age was 59 years (r: 21-76). Nine patients (60%) had AML, six (40%) had ALL or acute lymphoblastic lymphoma. 27% had first diagnosis of AL, 27% were in complete remission, 46% had relapsed or refractory disease. All patients were under chemotherapy during SARS-CoV-2 positivity, 80% were treated with intensive chemotherapy protocols. Duration of aplasia during SARS-CoV-2 positivity was 0-36 days (median: 10 days), four patients had no aplasia. With 67% compared to 38% in the influenza group, we scored significantly more critical and severe courses in the COVID-19 group (p = 0.042, Mann Whitney U test) according to WHO-grading. We observed higher rates of pneumonia (93% vs. 67%) in COVID-19 patients with a rate of 40% of acute respiratory distress syndrome (ARDS) in the COVID-19 group compared to 19% of ARDS in the influenza-group. Rate of death due to COVID-19 after 90 days was 20% compared to influenza-associated deaths of 14%. Regardless of the type of infection (SARS-CoV-2 or influenza), we could show that a long aplasia duration is an adverse prognostic marker for 90-days mortality due to COVID-19 or influenza (p = 0.016, Mann Whitney U test). Summary/Conclusion: Patients with acute leukemia and concomitant SARS-CoV-2 diagnosis present with more severe clinical courses than patients with concomitant influenza, even though the rates of ARDS and critical disease of patients with AL and influenza are high. Therapy regimes with expected long duration aplasia should be possibly avoided in both patient cohorts due to higher mortality in patients with late regeneration of the blood count.