A Comparative Outcome Analysis of COVID-19 and Influenza Infection in Patients with Hematological Malignancies
Authors: Ghandili Susanne , Niederwieser Christian , Weisel Katja , Bokemeyer Carsten , Fiedler Walter , Modemann Franziska 
Published: November 2021

Abstract
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 (&lt; 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 &lt;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 &lt; 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, Research 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.