Chemotherapy and Anti-CD20 Monoclonal Antibody Impact on SARS-CoV-2 Nucleic Acid Amplification Tests in Hematologic Malignancies: A Retrospective Study

Chemotherapy and Anti-CD20 Monoclonal Antibody Impact on SARS-CoV-2 Nucleic Acid Amplification Tests in Hematologic Malignancies: A Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Chemotherapy and Anti-CD20 Monoclonal Antibody Impact on SARS-CoV-2 Nucleic Acid Amplification Tests in Hematologic Malignancies: A Retrospective Study Keiichiro Kinoshita, Wataru Maruyama, Hirofumi Miyake, Ryuichi Minoda Sada This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7109579/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Oct, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted 10 You are reading this latest preprint version Abstract Background Patients with hematologic malignancies may experience prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to evaluate risk factors for persistent SARS-CoV-2 infection in patients with hematologic malignancies based on nucleic acid amplification test (NAAT) results. Patients with SARS-CoV-2 NAAT positivity lasting ≥ 8 weeks (persistent NAAT-positive group) were compared with those who became NAAT-negative within 8 weeks (non-persistent NAAT-positive group). Methods We examined patients with COVID-19 and hematologic malignancies between April 2021 and January 2023 at Tenri Hospital in Japan, examining hematologic malignancy type, chemotherapy regimens, and laboratory data. Results NAAT results at 8 weeks were available for 43 patients; eight (19%) remained positive for 8 weeks or more, while 35 (81%) became negative in < 8 weeks. Univariate analysis between the two groups showed significant differences in disease severity (p = 0.001), anti-CD20 monoclonal antibodies (mAB) use within the past 6 months (7/8 [88%] vs. 16/35 [46%], respectively; p = 0.05), obinutuzumab use within the past 6 months (3/8 [38%] vs. 2/35 [6%], respectively; p = 0.037), and anti-CD20 mAbs maintenance treatment (3/8 [38%] vs. 1/35 [3%], respectively; p = 0.016). Seven of the eight patients in the persistent NAAT-positive group had malignant lymphomas, and five had follicular lymphoma. Conclusions The use of anti-CD20 mAbs, especially obinutuzumab and maintenance treatment, is associated with long-term SARS-CoV-2 infection in patients with hematologic malignancies. SARS-CoV-2 COVID-19 hematologic malignancy rituximab obinutuzumab Figures Figure 1 Background Study Design This was a retrospective observational study conducted at Tenri Hospital, Japan. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for observational research. The study protocol was approved by the Institutional Review Board of Tenri Hospital (approval no. 1362). Informed consent was obtained through an opt-out process on the hospital’s website; those who opted out were excluded. The study was conducted in accordance with the Declaration of Helsinki and its later amendments. Participants We included patients with hematologic malignancies who contracted COVID-19 between January 2021 and January 2023 at Tenri Hospital in Japan. Hematologic malignancies were defined as diseases listed in the International Consensus Classification [18, 19]. Among these patients, those for whom consecutive NAAT results were available were categorized into two groups: a persistent NAAT-positive group and a non-persistent NAAT-positive group. The persistent NAAT-positive group comprised patients who remained NAAT-positive for 8 weeks or longer, while the non-persistent NAAT-positive group included those who became NAAT-negative within 8 weeks after their initial positive result [13]. Loop-mediated isothermal amplification (Eiken Chemical, Tokyo, Japan; LoopAmp EXIA) was used to test inpatients; reverse-transcription polymerase chain reaction (RT-PCR) (Mizuhomedy, Tosu, Saga, Japan; Smart Gene) was used to test outpatients from January 2021 to March 2022, and nicking enzyme amplification (Abbot Diagnostics Scarborough, Inc., Scarborough, ME, USA; ID NOW) was used for outpatients from April 2022 to March 2023. Data Collection We collected data from electronic medical records, including the following: Demographics and clinical background: Age, sex, height, weight, smoking history, comorbidities, the Charlson Comorbidity Index, SARS-CoV-2 vaccination status, and prophylactic administration of tixagevimab-cilgavimab. Hematologic characteristics: Type of hematologic malignancy (malignant lymphoma, acute myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, multiple myeloma, chronic myeloid leukemia, chronic lymphocytic leukemia, or myeloproliferative disorders). Laboratory data collected included white blood cell count, lymphocyte count, neutrophil count, and serum immunoglobulin G level. Treatment history was assessed based on the following timeframes prior to COVID-19 onset: Chemotherapy (including cytotoxic agents, glucocorticoids, molecular-targeted agents, BCL-ABL inhibitors, and Bruton's tyrosine kinase inhibitors) within 4 weeks [8] Anti-CD20 mAbs (rituximab or obinutuzumab) within 6 months [20, 21] Allogeneic/autologous hematopoietic stem cell transplantation or chimeric antigen receptor T-cell (CAR-T) therapy within a year [8] COVID-19-related variables: Date of onset, severity of infection [22], presence of pneumonia, hospitalization status, and treatment details. Blood test results, including C-reactive protein, ferritin, D-dimer, and KL-6 levels, were extracted at the time of diagnosis. SARS-CoV-2 variants were categorized by epidemic periods: α and δ (April–December 2021), Omicron BA.2 (January–June 2022), and Omicron BA.5 (July 2022–January 2023) variants [22, 23]. Outcomes: Persistence of NAAT positivity for 8 weeks or longer, COVID-19-related death (defined as death from direct infection-related organ damage within 6 months), and all-cause death (including hematologic and non-hematologic causes within 6 months). The determination of death statistics was carried out by Keiichiro Kinoshita and Ryuichi Minoda Sada. Statistical Analysis All results are summarized as medians and interquartile ranges for continuous variables and counts and percentages for categorical variables. Continuous variables were compared using the Mann–Whitney U test, and categorical variables were compared using Fisher’s exact test. Statistical significance was set at p <0.05. Statistical analyses were performed using IBM SPSS Statistics 22 (IBM Corp., Armonk, NY, USA). Methods Study Design This was a retrospective observational study conducted at Tenri Hospital, Japan. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for observational research. The study protocol was approved by the Institutional Review Board of Tenri Hospital (approval no. 1362). Informed consent was obtained through an opt-out process on the hospital’s website; those who opted out were excluded. The study was conducted in accordance with the Declaration of Helsinki and its later amendments. Participants We included patients with hematologic malignancies who contracted COVID-19 between January 2021 and January 2023 at Tenri Hospital in Japan. Hematologic malignancies were defined as diseases listed in the International Consensus Classification [ 18 , 19 ]. Among these patients, those for whom consecutive NAAT results were available were categorized into two groups: a persistent NAAT-positive group and a non-persistent NAAT-positive group. The persistent NAAT-positive group comprised patients who remained NAAT-positive for 8 weeks or longer, while the non-persistent NAAT-positive group included those who became NAAT-negative within 8 weeks after their initial positive result [ 13 ]. Loop-mediated isothermal amplification (Eiken Chemical, Tokyo, Japan; LoopAmp EXIA) was used to test inpatients; reverse-transcription polymerase chain reaction (RT-PCR) (Mizuhomedy, Tosu, Saga, Japan; Smart Gene) was used to test outpatients from January 2021 to March 2022, and nicking enzyme amplification (Abbot Diagnostics Scarborough, Inc., Scarborough, ME, USA; ID NOW) was used for outpatients from April 2022 to March 2023. Data Collection We collected data from electronic medical records, including the following: Demographics and clinical background: Age, sex, height, weight, smoking history, comorbidities, the Charlson Comorbidity Index, SARS-CoV-2 vaccination status, and prophylactic administration of tixagevimab-cilgavimab. Hematologic characteristics: Type of hematologic malignancy (malignant lymphoma, acute myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, multiple myeloma, chronic myeloid leukemia, chronic lymphocytic leukemia, or myeloproliferative disorders). Laboratory data collected included white blood cell count, lymphocyte count, neutrophil count, and serum immunoglobulin G level. Treatment history was assessed based on the following timeframes prior to COVID-19 onset: Chemotherapy (including cytotoxic agents, glucocorticoids, molecular-targeted agents, BCL-ABL inhibitors, and Bruton's tyrosine kinase inhibitors) within 4 weeks [ 8 ] Anti-CD20 mAbs (rituximab or obinutuzumab) within 6 months [ 20 , 21 ] Allogeneic/autologous hematopoietic stem cell transplantation or chimeric antigen receptor T-cell (CAR-T) therapy within a year [ 8 ] COVID-19-related variables: Date of onset, severity of infection [ 22 ], presence of pneumonia, hospitalization status, and treatment details. Blood test results, including C-reactive protein, ferritin, D-dimer, and KL-6 levels, were extracted at the time of diagnosis. SARS-CoV-2 variants were categorized by epidemic periods: α and δ (April–December 2021), Omicron BA.2 (January–June 2022), and Omicron BA.5 (July 2022–January 2023) variants [ 22 , 23 ]. Outcomes: Persistence of NAAT positivity for 8 weeks or longer, COVID-19-related death (defined as death from direct infection-related organ damage within 6 months), and all-cause death (including hematologic and non-hematologic causes within 6 months). The determination of death statistics was carried out by Keiichiro Kinoshita and Ryuichi Minoda Sada. Statistical Analysis All results are summarized as medians and interquartile ranges for continuous variables and counts and percentages for categorical variables. Continuous variables were compared using the Mann–Whitney U test, and categorical variables were compared using Fisher’s exact test. Statistical significance was set at p < 0.05. Statistical analyses were performed using IBM SPSS Statistics 22 (IBM Corp., Armonk, NY, USA). Results Patient Characteristics A total of 109 patients with hematologic malignancies who contracted COVID-19 between April 12, 2021, and January 18, 2023, were included; among these, 76 (69.7%) developed COVID-19 between July 2022 and January 2023, during the prevalence of the Omicron BA.5 variant. In total, 78 patients (71.6%) were asymptomatic or had mild symptoms, 15 (13.8%) had moderate COVID-19, and 16 (14.7%) developed severe disease. Malignant lymphoma was the most common hematologic malignancy, diagnosed in 69 patients (63.3%). Forty-five patients (41.3%) were undergoing chemotherapy, while 33 (30.3%) had received anti-CD20 mAbs within the past 6 months. Outcomes showed eight deaths (7.3%) directly attributed to COVID-19 and 14 all-cause deaths (12.8%) ( Table 1 ). Risk of Persistent SARS-CoV-2 Infection Of the 109 patients, eight were classified as persistent NAAT-positive and 35 as non-persistent NAAT-positive ( Figure 1 ). Table 1 shows the univariate analysis between the two groups. The median duration of NAAT positivity was 77 days in the persistent NAAT-positive group and 26 days in the non-persistent NAAT-positive group (p < 0.001). COVID-19 severity (p = 0.001) was significantly higher in the persistent NAAT-positive group. There were no significant differences in age, COVID-19 treatment, vaccination history, or tixagevimab-cilgavimab use, types of hematologic malignancies, or blood test results. The use of anti-CD20 mAbs within the last 6 months (7/8 [87.5%] vs. 16/35 [45.7%], p = 0.05), obinutuzumab within the last 6 months (3/8 [37.5%] vs. 2/35 [5.7%], p = 0.037), and anti-CD20 mAbs maintenance therapy (3/8 [37.5%] vs. 1/35 [2.9%], p = 0.016) were significantly higher in the persistent NAAT-positive group than in the non-persistent NAAT-positive group, respectively. There were no significant differences in the use of rituximab (4/8 [50.0%] vs. 13/35 [37.1%], p = 0.692), bendamustine (0/8 [0%] vs. 4/35 [11.4%], p = 0.692), or CAR-T (0/8 [0%] vs. 1/35 [2.9%], p = 1) between the two groups. Among the eight patients in the persistent NAAT-positive group, seven had malignant lymphoma, including five with follicular lymphoma; three of these patients were on obinutuzumab. Three of the eight patients died of COVID-19 pneumonia, and all were persistently NAAT-positive and receiving anti-CD20 mAbs ( Table 2, Additional file 1 ). Additional file 2 describes the clinical course of a representative case. Discussion In this study, we evaluated risk factors for persistent SARS-CoV-2 infection (≥ 8 weeks NAAT-positive) in patients with hematologic malignancies and found that COVID-19 severity and anti-CD20 mAb use, particularly obinutuzumab and maintenance therapy, were significantly associated with prolonged infection. While previous case reports and case series have described persistent SARS-CoV-2 infection in patients treated with anti-CD20 mAbs [ 13 , 14 , 24 , 25 ], our study provides additional observational data, particularly with obinutuzumab. Obinutuzumab has been associated with worse COVID-19 severity and higher mortality compared to rituximab [ 26 , 27 ], which is consistent with our findings. Among the 109 patients in this study, at least eight (7.3%) were confirmed to have a persistent infection lasting 8 weeks or more. Of these, seven had malignant lymphoma, including five with follicular lymphoma. These findings highlight the proportion of patients with hematologic malignancies experiencing prolonged SARS-CoV-2 infection and demonstrate that lymphoma accounts for the majority of these cases. In immunocompromised patients, SARS-CoV-2 capable of replication is generally detected for approximately 15–20 days [ 28 ]. Persistent NAAT positivity does not necessarily indicate a continued risk of infection requiring deferral of hematologic malignancy treatment; however, it does suggest that careful clinical decision-making is necessary when considering treatment strategies for hematologic malignancies in these patients. Persistent infections are likely attributable to mechanisms such as decreased humoral immune responses to the virus or vaccine due to selective B-cell depletion [ 20 , 21 , 29 ], as well as immune evasion caused by spike gene mutations during persistent infection [ 13 , 15 , 30 , 31 ]. Obinutuzumab, with its stronger antibody-dependent cellular cytotoxicity compared to rituximab, induces higher levels of cell death, potentially contributing to prolonged infection [ 27 ]. Although there are no prior reports on maintenance therapy, it likely induces sustained and intense B-cell depletion, impairing the ability to clear the virus. Although some case reports suggest that combining anti-CD20 mAbs with bendamustine (which decreases CD4 + T-cell counts) can result in severe and persistent SARS-CoV-2 infections [ 32 ], our study found no cases of bendamustine use within the past 6 months among patients with long-term positive NAAT results. Considering the clinical management of COVID-19 patients receiving anti-CD20 mAb therapy, we repeatedly administered antiviral agents or combined them with mAb treatments in cases of persistent positivity. However, as Supplementary Fig. 1 represents only a single case, further research is needed to establish an optimal treatment strategy for this high-risk population [ 13 ]. Although the global impact of COVID-19 has lessened, patients with hematologic malignancies remain at high risk due to immunosuppression. Our findings suggest that prolonged NAAT positivity should be anticipated in patients receiving anti-CD20 mAb. Even in the endemic phase, recognizing factors associated with delayed viral clearance can help guide infection control and treatment decisions in this vulnerable population. This study has a few limitations. First, as a single-center retrospective study, its generalizability is limited. Second, NAAT was not performed at standardized intervals, which may have introduced variability in the timing of test negativity. Third, we did not perform multivariate analysis due to the small number of events to avoid overfitting. Fourth, patients with very severe COVID-19 were not included, which limits the applicability of our findings to that subgroup. Finally, we excluded individuals who recovered without follow-up NAAT, potentially introducing selection bias. As a result, our study population mainly consisted of patients requiring prolonged follow-up, such as those undergoing chemotherapy or those with severe disease. Further studies with larger and more diverse cohorts are needed to better understand the factors associated with persistent SARS-CoV-2 infection in patients with hematologic malignancies. Conclusion Persistent SARS-CoV-2 infection was associated with severe COVID-19, recent anti-CD20 mAb use (within the past 6 months), obinutuzumab treatment, and maintenance anti-CD20 mAb therapy in patients with hematologic malignancies. Abbreviations NAAT Nucleic acid amplification test SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 mAB Monoclonal antibodies COVID-19 Coronavirus disease 2019 RT-PCR Reverse-transcription polymerase chain reaction CAR-T Chimeric antigen receptor T-cell Declarations Ethics Approval and Consent to Participate The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for observational research. The study protocol was approved by the Institutional Review Board of Tenri Hospital (approval no. 1362). Informed consent was obtained through an opt-out process on the hospital’s website; those who opted out were excluded. The study was conducted in accordance with the Declaration of Helsinki and its later amendments. Consent for Publication Not applicable Availability of Data and Materials The data supporting the conclusions of this study are available from the corresponding author upon reasonable request, contingent upon compliance with institutional policies and ethical considerations. Competing Interests All authors have completed the ICMJE uniform disclosure form. No conflicts of interest were reported. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors’ Contributions KK, WM and RMS designed the study, the main conceptual ideas, and the proof outline. KK collected the data. HM aided in interpreting the results and worked on the manuscript. RMS supervised the project. 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Cancer Med. 2024;13:e6997. Shafat T, Grupel D, Porges T, Levi I, Yagel Y, Nesher L. Treatment with obinutuzumab leads to worse outcomes in haematological patients diagnosed with Omicron variant COVID-19. Br J Haematol. 2022;198:826-9. Rhee C, Kanjilal S, Baker M, Klompas M. Duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity: when is it safe to discontinue isolation? Clin Infect Dis. 2021;72:1467-74. Marchesi F, Pimpinelli F, Giannarelli D, Ronchetti L, Papa E, Falcucci P, et al: Impact of anti-CD20 monoclonal antibodies on serologic response to BNT162b2 vaccine in B-cell Non-Hodgkin's lymphomas. Leukemia. 2022;36:588-90. Scherer EM, Babiker A, Adelman MW, Allman B, Key A, Kleinhenz JM, et al. SARS-CoV-2 evolution and immune escape in immunocompromised patients. N Engl J Med. 2022;386:2436-8. Kemp SA, Collier DA, Datir RP, Ferreira I, Gayed S, Jahun A, et al: SARS-CoV-2 evolution during treatment of chronic infection. Nature. 2021;592:277-82. Franceschini E, Pellegrino M, Todisco V, Dolci G, Bettelli F, Meschiari M, et al. Persistent SARS-CoV-2 infection with multiple clinical relapses in two patients with follicular lymphoma treated with bendamustine and obinutuzumab or rituximab. Infection. 2023;51:1577-81. Tables Table 1. Clinical characteristics of 109 patients with hematologic malignancies and COVID-19: comparison of persistent (≥8 weeks , n = 8) and non-persistent (<8 weeks , n = 35) NAAT- positive groups . Characteristics Patients who contracted COVID-19 during the research period (n = 109) Persistent NAAT - positive group (≥ 8 weeks) (n = 8) Non-persistent NAAT-positive group (<8 weeks) (n = 35) p-value Male sex, n (%) 69 (63.3) 4 (50) 23 (65.7) 0.443 Age, years (median [IQR]) 72 [62–78] 73.5 [66–75] 72 [65–75] 0.679 Smoking history, n (%) 47 (43.1) 3 (37.5) 20 (57.1) 0.687 Chronic respiratory disease, n (%) 16 (14.7) 1 (12.5) 8 (22.9) 1 Charlson Comorbidity Index (median [IQR]) 2 [2–3] 3 [2–3] 2 [2–3] 1 History of vaccine, n (%) 37/45 (82.2) 2/2 (100) 10/13 (76.9) 1 History of tixagevimab-cilgavimab, n (%) 13 (11.9) 1 (12.5) 6 (17.1) 1 Type of Hematological Malignancy Malignant lymphoma, n (%) 69 (63.3) 7 (87.5) 19 (54.3) 0.719 Acute myeloid leukemia, n (%) 7 (6.4) 1 (12.5) 2 (5.7) 1 Acute lymphocytic leukemia, n (%) 3 (2.8) 0 (0) 2 (5.7) 1 Chronic myeloid leukemia, n (%) 2 (1.8) 0 (0) 0 (0) 1 Chronic lymphocytic leukemia, n (%) 5 (4.6) 0 (0) 1 (2.9) 1 Myelodysplastic syndrome, n (%) 9 (8.3) 0 (0) 5 (14.3) 0.565 Multiple myeloma, n (%) 12 (11.0) 0 (0) 5 (14.3) 0.565 Myeloproliferative disorders, n (%) 3 (2.8) 0 (0) 1 (2.9) 1 Disease state On chemotherapy, n (%) 45 (41.3) 7 (87.5) 22 (62.9) 0.238 Anticancer drug Cytotoxic agent, n (%) 30 (27.5) 4 (50.0) 15 (42.9) 1 Bendamustine, n (%) 5 (4.6) 0 (0) 4 (11.4) 1 Anti-CD20 monoclonal antibody, n (%) 33 (30.3) 7 (87.5) 16 (45.7) 0.05* Rituximab, n (%) 25 (22.9) 4 (50.0) 13 (37.1) 0.692 Obinutuzumab, n (%) 7 (6.4) 3 (37.5) 2 (5.7) 0.037* maintenance therapy, n (%) 7 (6.4) 3 (37.5) 1 (2.9) 0.016* BTK inhibitors, n (%) 5 (4.6) 0 (0) 2 (5.7) 1 BCR-ABL inhibitors, n (%) 5 (4.6) 0 (0) 3 (8.6) 1 Glucocorticoid, n (%) 44 (40.4) 4 (50.0) 21 (60.0) 0.701 Allogeneic HSCT, n (%) 7 (6.4) 1 (12.5) 0 (0) 0.186 Autologous HSCT, n (%) 4 (3.7) 0 (0) 1 (2.9) 1 CAR-T, n (%) 1 (0.9) 0 (0) 0 (0) Laboratory data Neutrophil, /uL (median [IQR]) 2,770 [1,890–4,620] 3,005 [1,627–4,780] 2,310 [1,020–4,505] 0.571 Lymphocyte, /uL (median [IQR]) 1,300 [690–1,960] 695 [405–1,637] 890 [345–1,330] 0.939 Immunoglobulin G, mg/dL (median [IQR]) 956 [613–1,176] 559 [559–559] 640 [613–1,019] 0.545 Period 2021/4–2021/12 α/δ variant, n (%) 3 (2.8) 0 (0) 2 (5.7) 0.767 2022/1–2022/6 Omicron BA.2, n (%) 30 (27.5) 3 (37.5) 11 (31.4) 2022/7–2023/1 Omicron BA.5, n (%) 76 (69.7) 5 (62.5) 22 (62.9) Severity of COVID-19 Asymptomatic/mild, n (%) 78 (71.6) 0 (0) 24 (68.6) 0.002* Moderate, n (%) 15 (13.8) 6 (75.0) 7 (20.0) Severe, n (%) 16 (14.7) 2 (25.0) 4 (11.4) Very severe, n (%) 0 (0) 0 (0) 0 (0) Inpatients, n (%) 54 (49.5) 8 (100) 28 (80.0) 0.24 Therapy for COVID-19 Remdesivir, n (%) 35 (32.1) 6 (75.0) 16 (45.7) Molnupiravir, n (%) 51 (46.8) 7 (87.5) 18 (51.4) 0.111 Nirmatrelvir/ritonavir, n (%) 6 (5.5) 2 (25.0) 3 (8.6) 0.228 Sotrovimab, n (%) 11 (10.1) 3 (37.5) 6 (17.1) 0.332 Casirivimab/imdevimab, n (%) 1 (0.9) 0 (0) 1 (2.9) 1 Baricitinib, n (%) 2 (1.8) 1 (12.5) 0 (0) 0.186 Tocilizumab, n (%) 0 (0) 0 (0) 0 (0) 1 Glucocorticoid, n (%) 18 (16.5) 5 (62.5) 5 (14.3) 0.1 Prognosis of COVID-19 Duration of NAAT positivity, days (median [IQR]) 28 [19–47] 77 [61.5–96] 26 [18–34.5] < 0.001* Death due to COVID-19, n (%) 8/109 (7.3) 3 (37.5) 0 (0) 0.005* Death from all causes, n (%) 14/109 (12.8) 3 (37.5) 3 (8.6) 0.067 Among patients who contracted COVID-19 during the study period (n = 109), those with consecutive NAAT results available were classified into a persistent NAAT-positive group (n = 8) and a non-persistent NAAT-positive group (n = 35). Clinical and treatment-related factors were compared between the two groups, and p-values are reported. * p < 0.05, statistically significant. Abbreviations : NAAT, nucleic acid amplification test; IQR, interquartile range; FL, follicular lymphoma; DLBCL, diffuse large B-cell lymphoma; AML, acute myeloid leukemia; ALL, acute lymphocytic leukemia; CML, chronic myeloid leukemia; CLL, chronic lymphocytic leukemia; MDS, myelodysplastic syndrome; MM, multiple myeloma; MPN, myeloproliferative neoplasms; HSCT, hematopoietic stem cell transplantation; CAR-T, chimeric antigen receptor T-cell therapy; BTK, Bruton's tyrosine kinase; BCR-ABL, breakpoint cluster region-Abelson; IgG, immunoglobulin G; REM, remdesivir; MOL, molnupiravir; NMV/r, nirmatrelvir/ritonavir; GCS, glucocorticoid steroids. Table 2. Detailed clinical information of patients in the persistent NAAT-positive group S. No. Age Sex Type of hematological malignancy Chemotherapy in the last 6 months Use of anti-CD20 monoclonal antibody Treatment for COVID-19 Outcome of COVID-19 1. 89 M B-cell lymphoma Pola-R-CHP Yes (Rituximab) MOL Survival 2. 74 M Follicular lymphoma G Yes (Obinutuzumab) MOL, REM Survival 3. 75 M DLBCL Pola-BR, R-GDP, R-DeVIC Yes (Rituximab) SOT, MOL, REM Death 4. 73 F Follicular lymphoma G Yes (Obinutuzumab) REM Death 5. 54 F Follicular lymphoma R-DeVIC Yes (Rituximab) SOT, REM, MOL, NMV/r Survival 6. 77 F Follicular lymphoma R2 Yes (Rituximab) MOL, REM Survival 7. 54 M CML blast crisis allogenic HSCT No SOT, MOL Survival 8. 71 F Follicular lymphoma G Yes (Obinutuzumab) MOL, REM Death Abbreviations : NAAT, nucleic acid amplification test; M, male; F, female; DLBCL, diffuse large B-cell lymphoma; CML, chronic myeloid leukemia; Pola-R-CHP, polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisolone; G, obinutuzumab; Pola-BR, polatuzumab vedotin, bendamustine, and rituximab; R-GDP, rituximab, gemcitabine, dexamethasone, and cisplatin; R-DeVIC, rituximab, dexamethasone, etoposide, ifosfamide, and carboplatin; R2, lenalidomide and rituximab; HSCT, hematopoietic stem cell transplantation; MOL, molnupiravir; REM, remdesivir; SOT, sotrovimab; NMV/r, nirmatrelvir/ritonavir. Additional Declarations No competing interests reported. Supplementary Files SupplementaryInformation.docx Cite Share Download PDF Status: Published Journal Publication published 22 Oct, 2025 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Revision requested 14 Aug, 2025 Reviews received at journal 14 Aug, 2025 Reviews received at journal 12 Aug, 2025 Reviewers agreed at journal 08 Aug, 2025 Reviewers agreed at journal 06 Aug, 2025 Reviewers invited by journal 06 Aug, 2025 Editor invited by journal 17 Jul, 2025 Editor assigned by journal 17 Jul, 2025 Submission checks completed at journal 17 Jul, 2025 First submitted to journal 12 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7109579","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":498163632,"identity":"0d4bb428-0abb-43de-8b2c-77d256f0cf0d","order_by":0,"name":"Keiichiro Kinoshita","email":"","orcid":"","institution":"Tenri Hospital","correspondingAuthor":false,"prefix":"","firstName":"Keiichiro","middleName":"","lastName":"Kinoshita","suffix":""},{"id":498163633,"identity":"ace0fb75-8dd6-4919-b692-bed09dc2af74","order_by":1,"name":"Wataru Maruyama","email":"","orcid":"","institution":"Tenri Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wataru","middleName":"","lastName":"Maruyama","suffix":""},{"id":498163634,"identity":"bc17c022-95aa-490e-a400-c7c44fa5b24e","order_by":2,"name":"Hirofumi Miyake","email":"","orcid":"","institution":"Tenri Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hirofumi","middleName":"","lastName":"Miyake","suffix":""},{"id":498163635,"identity":"e1b3269a-4a3c-46ed-8f39-3e722fcdd75c","order_by":3,"name":"Ryuichi Minoda Sada","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBElEQVRIiWNgGAWjYHACAwaGCgYehgNwHgQw49dyhmQtjG1ACl0LTiDffnjjh4/z7GT4jvc+YPjwx86Yv4HHgOFHDQO7OS4rzqQVS87clswjeea4AePMtmQziQM8Bow9xxiYLRtwuSrHQJp3G1DZjTQGZt4GZhuG+28MGHgbGJgNDuBwWP8b49+8c4Ba7j9jYOb5U28jD7LlLx4tDDdyzKR5G0C2sAG1sB02MwCymfHZYnDjWZnljGMgv6QxHJzZdtzY8ABbwWGZYxI4/SLfn7z5xocaO3u+48cYH3z4U2047wDzxodvamyScYUYCjiAxJBIJhxD6MCOdC2jYBSMglEwTAEAwu5U+jEPiJYAAAAASUVORK5CYII=","orcid":"","institution":"Osaka University","correspondingAuthor":true,"prefix":"","firstName":"Ryuichi","middleName":"Minoda","lastName":"Sada","suffix":""}],"badges":[],"createdAt":"2025-07-12 17:38:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7109579/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7109579/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-025-11844-z","type":"published","date":"2025-10-22T16:16:45+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88891229,"identity":"78a8f2b2-89ab-4af7-89fb-93dddd130e63","added_by":"auto","created_at":"2025-08-12 12:49:25","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":38372,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePatient flow diagram.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 109 patients with hematologic malignancies who contracted COVID-19 between April 12, 2021, and January 18, 2023, were included. Among them, eight patients remained NAAT-positive for SARS-CoV-2 for 8 weeks or longer (persistent NAAT-positive group), while 35 patients tested negative within 8 weeks (non-persistent NAAT-positive group). \u003cstrong\u003eAbbreviations\u003c/strong\u003e: NAAT, nucleic acid amplification test; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2; COVID-19, coronavirus disease 2019.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7109579/v1/0d2ef3c130530ab58b90969b.jpg"},{"id":94490493,"identity":"ef9cc283-fca3-46e6-be0e-9e1f1cc938e5","added_by":"auto","created_at":"2025-10-27 17:11:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1078871,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7109579/v1/60e3c8f8-2366-4680-b81d-cf7ff2295ff3.pdf"},{"id":88895949,"identity":"eab73e32-176c-4571-b31e-bb4e332ed42f","added_by":"auto","created_at":"2025-08-12 13:05:25","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":138925,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryInformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-7109579/v1/79a190d7b36cc487980107cc.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eChemotherapy and Anti-CD20 Monoclonal Antibody Impact on SARS-CoV-2 Nucleic Acid Amplification Tests in Hematologic Malignancies: A Retrospective Study\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003e\u003cstrong\u003eStudy Design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis was a retrospective observational study conducted at Tenri Hospital, Japan. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for observational research. The study protocol was approved by the Institutional Review Board of Tenri Hospital (approval no. 1362). Informed consent was obtained through an opt-out process on the hospital\u0026rsquo;s website; those who opted out were excluded. The study was conducted in accordance with the Declaration of Helsinki and its later amendments.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe included patients with hematologic malignancies who contracted COVID-19 between January 2021 and January 2023 at Tenri Hospital in Japan. Hematologic malignancies were defined as diseases listed in the International Consensus Classification [18, 19]. Among these patients, those for whom consecutive NAAT results were available were categorized into two groups: a persistent NAAT-positive group and a non-persistent NAAT-positive group. The persistent NAAT-positive group comprised patients who remained NAAT-positive for 8 weeks or longer, while the non-persistent NAAT-positive group included those who became NAAT-negative within 8 weeks after their initial positive result [13]. Loop-mediated isothermal amplification (Eiken Chemical, Tokyo, Japan; LoopAmp EXIA) was used to test inpatients; reverse-transcription polymerase chain reaction (RT-PCR) (Mizuhomedy, Tosu, Saga, Japan; Smart Gene) was used to test outpatients from January 2021 to March 2022, and nicking enzyme amplification (Abbot Diagnostics Scarborough, Inc., Scarborough, ME, USA; ID NOW) was used for outpatients from April 2022 to March 2023.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe collected data from electronic medical records, including the following:\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eDemographics and clinical background: Age, sex, height, weight, smoking history, comorbidities, the Charlson Comorbidity Index, SARS-CoV-2 vaccination status, and prophylactic administration of tixagevimab-cilgavimab.\u003c/li\u003e\n \u003cli\u003eHematologic characteristics: Type of hematologic malignancy (malignant lymphoma, acute myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, multiple myeloma, chronic myeloid leukemia, chronic lymphocytic leukemia, or myeloproliferative disorders). Laboratory data collected included white blood cell count, lymphocyte count, neutrophil count, and serum immunoglobulin G level. Treatment history was assessed based on the following timeframes prior to COVID-19 onset:\u0026nbsp;\u003cul\u003e\n \u003cli\u003eChemotherapy (including cytotoxic agents, glucocorticoids, molecular-targeted agents, BCL-ABL inhibitors, and Bruton\u0026apos;s tyrosine kinase inhibitors) within 4 weeks [8]\u003c/li\u003e\n \u003cli\u003eAnti-CD20 mAbs (rituximab or obinutuzumab) within 6 months [20, 21]\u003c/li\u003e\n \u003cli\u003eAllogeneic/autologous hematopoietic stem cell transplantation or chimeric antigen receptor T-cell (CAR-T) therapy within a year [8]\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/li\u003e\n \u003cli\u003eCOVID-19-related variables: Date of onset, severity of infection [22], presence of pneumonia, hospitalization status, and treatment details. Blood test results, including C-reactive protein, ferritin, D-dimer, and KL-6 levels, were extracted at the time of diagnosis. SARS-CoV-2 variants were categorized by epidemic periods: \u0026alpha; and \u0026delta; (April\u0026ndash;December 2021), Omicron BA.2 (January\u0026ndash;June 2022), and Omicron BA.5 (July 2022\u0026ndash;January 2023) variants [22, 23].\u003c/li\u003e\n \u003cli\u003eOutcomes: Persistence of NAAT positivity for 8 weeks or longer, COVID-19-related death (defined as death from direct infection-related organ damage within 6 months), and all-cause death (including hematologic and non-hematologic causes within 6 months). The determination of death statistics was carried out by Keiichiro Kinoshita and Ryuichi Minoda Sada.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll results are summarized as medians and interquartile ranges for continuous variables and counts and percentages for categorical variables. Continuous variables were compared using the Mann\u0026ndash;Whitney U test, and categorical variables were compared using Fisher\u0026rsquo;s exact test. Statistical significance was set at p \u0026lt;0.05. Statistical analyses were performed using IBM SPSS Statistics 22 (IBM Corp., Armonk, NY, USA).\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cb\u003eStudy Design\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis was a retrospective observational study conducted at Tenri Hospital, Japan. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for observational research. The study protocol was approved by the Institutional Review Board of Tenri Hospital (approval no. 1362). Informed consent was obtained through an opt-out process on the hospital’s website; those who opted out were excluded. The study was conducted in accordance with the Declaration of Helsinki and its later amendments.\u003c/p\u003e\u003cp\u003e\u003cb\u003eParticipants\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe included patients with hematologic malignancies who contracted COVID-19 between January 2021 and January 2023 at Tenri Hospital in Japan. Hematologic malignancies were defined as diseases listed in the International Consensus Classification [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Among these patients, those for whom consecutive NAAT results were available were categorized into two groups: a persistent NAAT-positive group and a non-persistent NAAT-positive group. The persistent NAAT-positive group comprised patients who remained NAAT-positive for 8 weeks or longer, while the non-persistent NAAT-positive group included those who became NAAT-negative within 8 weeks after their initial positive result [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Loop-mediated isothermal amplification (Eiken Chemical, Tokyo, Japan; LoopAmp EXIA) was used to test inpatients; reverse-transcription polymerase chain reaction (RT-PCR) (Mizuhomedy, Tosu, Saga, Japan; Smart Gene) was used to test outpatients from January 2021 to March 2022, and nicking enzyme amplification (Abbot Diagnostics Scarborough, Inc., Scarborough, ME, USA; ID NOW) was used for outpatients from April 2022 to March 2023.\u003c/p\u003e\u003cp\u003e\u003cb\u003eData Collection\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe collected data from electronic medical records, including the following:\u003c/p\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eDemographics and clinical background: Age, sex, height, weight, smoking history, comorbidities, the Charlson Comorbidity Index, SARS-CoV-2 vaccination status, and prophylactic administration of tixagevimab-cilgavimab.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eHematologic characteristics: Type of hematologic malignancy (malignant lymphoma, acute myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, multiple myeloma, chronic myeloid leukemia, chronic lymphocytic leukemia, or myeloproliferative disorders). Laboratory data collected included white blood cell count, lymphocyte count, neutrophil count, and serum immunoglobulin G level. Treatment history was assessed based on the following timeframes prior to COVID-19 onset:\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eChemotherapy (including cytotoxic agents, glucocorticoids, molecular-targeted agents, BCL-ABL inhibitors, and Bruton's tyrosine kinase inhibitors) within 4 weeks [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eAnti-CD20 mAbs (rituximab or obinutuzumab) within 6 months [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eAllogeneic/autologous hematopoietic stem cell transplantation or chimeric antigen receptor T-cell (CAR-T) therapy within a year [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eCOVID-19-related variables: Date of onset, severity of infection [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], presence of pneumonia, hospitalization status, and treatment details. Blood test results, including C-reactive protein, ferritin, D-dimer, and KL-6 levels, were extracted at the time of diagnosis. SARS-CoV-2 variants were categorized by epidemic periods: α and δ (April–December 2021), Omicron BA.2 (January–June 2022), and Omicron BA.5 (July 2022–January 2023) variants [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eOutcomes: Persistence of NAAT positivity for 8 weeks or longer, COVID-19-related death (defined as death from direct infection-related organ damage within 6 months), and all-cause death (including hematologic and non-hematologic causes within 6 months). The determination of death statistics was carried out by Keiichiro Kinoshita and Ryuichi Minoda Sada.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eAll results are summarized as medians and interquartile ranges for continuous variables and counts and percentages for categorical variables. Continuous variables were compared using the Mann–Whitney U test, and categorical variables were compared using Fisher’s exact test. Statistical significance was set at p \u0026lt; 0.05. Statistical analyses were performed using IBM SPSS Statistics 22 (IBM Corp., Armonk, NY, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatient Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 109 patients with hematologic malignancies who contracted COVID-19 between April 12, 2021, and January 18, 2023, were included; among these, 76 (69.7%) developed COVID-19 between July 2022 and January 2023, during the prevalence of the Omicron BA.5 variant. In total, 78 patients (71.6%) were asymptomatic or had mild symptoms, 15 (13.8%) had moderate COVID-19, and 16 (14.7%) developed severe disease. Malignant lymphoma was the most common hematologic malignancy, diagnosed in 69 patients (63.3%). Forty-five patients (41.3%) were undergoing chemotherapy, while 33 (30.3%) had received anti-CD20 mAbs within the past 6 months. Outcomes showed eight deaths (7.3%) directly attributed to COVID-19 and 14 all-cause deaths (12.8%) (\u003cstrong\u003eTable 1\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRisk of Persistent SARS-CoV-2 Infection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOf the 109 patients, eight were classified as persistent NAAT-positive and 35 as non-persistent NAAT-positive (\u003cstrong\u003eFigure 1\u003c/strong\u003e). \u003cstrong\u003eTable 1\u003c/strong\u003e shows the univariate analysis between the two groups. The median duration of NAAT positivity was 77 days in the persistent NAAT-positive group and 26 days in the non-persistent NAAT-positive group (p \u0026lt; 0.001). COVID-19 severity (p = 0.001) was significantly higher in the persistent NAAT-positive group. There were no significant differences in age, COVID-19 treatment, vaccination history, or tixagevimab-cilgavimab use, types of hematologic malignancies, or blood test results. The use of anti-CD20 mAbs within the last 6 months (7/8 [87.5%] vs. 16/35 [45.7%], p = 0.05), obinutuzumab within the last 6 months (3/8 [37.5%] vs. 2/35 [5.7%], p = 0.037), and anti-CD20 mAbs maintenance therapy (3/8 [37.5%] vs. 1/35 [2.9%], p = 0.016) were significantly higher in the persistent NAAT-positive group than in the non-persistent NAAT-positive group, respectively. There were no significant differences in the use of rituximab (4/8 [50.0%] vs. 13/35 [37.1%], p = 0.692), bendamustine (0/8 [0%] vs. 4/35 [11.4%], p = 0.692), or CAR-T (0/8 [0%] vs. 1/35 [2.9%], p = 1) between the two groups.\u003c/p\u003e\n\u003cp\u003eAmong the eight patients in the persistent NAAT-positive group, seven had malignant lymphoma, including five with follicular lymphoma; three of these patients were on obinutuzumab. Three of the eight patients died of COVID-19 pneumonia, and all were persistently NAAT-positive and receiving anti-CD20 mAbs (\u003cstrong\u003eTable 2,\u003c/strong\u003e\u003cstrong\u003eAdditional file 1\u003c/strong\u003e). \u003cstrong\u003eAdditional file 2\u003c/strong\u003e describes the clinical course of a representative case.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we evaluated risk factors for persistent SARS-CoV-2 infection (\u0026ge;\u0026thinsp;8 weeks NAAT-positive) in patients with hematologic malignancies and found that COVID-19 severity and anti-CD20 mAb use, particularly obinutuzumab and maintenance therapy, were significantly associated with prolonged infection. While previous case reports and case series have described persistent SARS-CoV-2 infection in patients treated with anti-CD20 mAbs [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], our study provides additional observational data, particularly with obinutuzumab. Obinutuzumab has been associated with worse COVID-19 severity and higher mortality compared to rituximab [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], which is consistent with our findings.\u003c/p\u003e\u003cp\u003eAmong the 109 patients in this study, at least eight (7.3%) were confirmed to have a persistent infection lasting 8 weeks or more. Of these, seven had malignant lymphoma, including five with follicular lymphoma. These findings highlight the proportion of patients with hematologic malignancies experiencing prolonged SARS-CoV-2 infection and demonstrate that lymphoma accounts for the majority of these cases. In immunocompromised patients, SARS-CoV-2 capable of replication is generally detected for approximately 15\u0026ndash;20 days [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Persistent NAAT positivity does not necessarily indicate a continued risk of infection requiring deferral of hematologic malignancy treatment; however, it does suggest that careful clinical decision-making is necessary when considering treatment strategies for hematologic malignancies in these patients.\u003c/p\u003e\u003cp\u003ePersistent infections are likely attributable to mechanisms such as decreased humoral immune responses to the virus or vaccine due to selective B-cell depletion [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], as well as immune evasion caused by spike gene mutations during persistent infection [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Obinutuzumab, with its stronger antibody-dependent cellular cytotoxicity compared to rituximab, induces higher levels of cell death, potentially contributing to prolonged infection [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Although there are no prior reports on maintenance therapy, it likely induces sustained and intense B-cell depletion, impairing the ability to clear the virus. Although some case reports suggest that combining anti-CD20 mAbs with bendamustine (which decreases CD4\u0026thinsp;+\u0026thinsp;T-cell counts) can result in severe and persistent SARS-CoV-2 infections [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], our study found no cases of bendamustine use within the past 6 months among patients with long-term positive NAAT results. Considering the clinical management of COVID-19 patients receiving anti-CD20 mAb therapy, we repeatedly administered antiviral agents or combined them with mAb treatments in cases of persistent positivity. However, as Supplementary Fig.\u0026nbsp;1 represents only a single case, further research is needed to establish an optimal treatment strategy for this high-risk population [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough the global impact of COVID-19 has lessened, patients with hematologic malignancies remain at high risk due to immunosuppression. Our findings suggest that prolonged NAAT positivity should be anticipated in patients receiving anti-CD20 mAb. Even in the endemic phase, recognizing factors associated with delayed viral clearance can help guide infection control and treatment decisions in this vulnerable population.\u003c/p\u003e\u003cp\u003eThis study has a few limitations. First, as a single-center retrospective study, its generalizability is limited. Second, NAAT was not performed at standardized intervals, which may have introduced variability in the timing of test negativity. Third, we did not perform multivariate analysis due to the small number of events to avoid overfitting. Fourth, patients with very severe COVID-19 were not included, which limits the applicability of our findings to that subgroup. Finally, we excluded individuals who recovered without follow-up NAAT, potentially introducing selection bias. As a result, our study population mainly consisted of patients requiring prolonged follow-up, such as those undergoing chemotherapy or those with severe disease. Further studies with larger and more diverse cohorts are needed to better understand the factors associated with persistent SARS-CoV-2 infection in patients with hematologic malignancies.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePersistent SARS-CoV-2 infection was associated with severe COVID-19, recent anti-CD20 mAb use (within the past 6 months), obinutuzumab treatment, and maintenance anti-CD20 mAb therapy in patients with hematologic malignancies.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNAAT\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Nucleic acid amplification test\u003c/p\u003e\n\u003cp\u003eSARS-CoV-2\u0026nbsp;\u0026nbsp;Severe acute respiratory syndrome coronavirus 2\u003c/p\u003e\n\u003cp\u003emAB\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Monoclonal antibodies\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCOVID-19\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Coronavirus disease 2019\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRT-PCR\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Reverse-transcription polymerase chain reaction\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCAR-T \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Chimeric antigen receptor T-cell\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for observational research. The study protocol was approved by the Institutional Review Board of Tenri Hospital (approval no. 1362). Informed consent was obtained through an opt-out process on the hospital’s website; those who opted out were excluded. The study was conducted in accordance with the Declaration of Helsinki and its later amendments.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the conclusions of this study are available from the corresponding author upon reasonable request, contingent upon compliance with institutional policies and ethical considerations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have completed the ICMJE uniform disclosure form. No conflicts of interest were reported.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKK, WM and RMS designed the study, the main conceptual ideas, and the proof outline. KK collected the data. HM aided in interpreting the results and worked on the manuscript. RMS supervised the project. KK wrote the manuscript with support from RMS. All authors discussed the results and commented on the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Editage (www.editage.com) for English language editing. This research was conducted as part of the All-Osaka U Research in “The Nippon Foundation–Osaka University Infectious Disease Response Project.”\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eUnderlying medical conditions associated with higher risk for severe COVID-19: Information for healthcare professionals. [https://archive.cdc.gov/www_cdc_gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html].\u003c/li\u003e\n\u003cli\u003eVijenthira A, Gong IY, Fox TA, Booth S, Cook G, Fattizzo B, et al. Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients. Blood. 2020;136:2881-92.\u003c/li\u003e\n\u003cli\u003eSharafeldin N, Bates B, Song Q, Madhira V, Yan Y, Dong S, et al. Outcomes of COVID-19 in patients with cancer: report from the National COVID Cohort Collaborative (N3C). 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Infection. 2023;51:1577-81.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e \u003cstrong\u003eClinical\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003echaracteristics\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;of 109\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003epatients\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;with\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ehematologic malignancies\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;and COVID-19:\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ecomparison\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;of\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003epersistent\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;(\u0026ge;8\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eweeks\u003c/strong\u003e\u003cstrong\u003e, n = 8) and\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003enon-persistent\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;(\u0026lt;8\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eweeks\u003c/strong\u003e\u003cstrong\u003e, n = 35) NAAT-\u003c/strong\u003e\u003cstrong\u003epositive groups\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients who contracted COVID-19 during the research period (n = 109)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Persistent NAAT\u003c/strong\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003cstrong\u003epositive group\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(\u0026ge;\u003c/strong\u003e\u003cstrong\u003e8 weeks) (n = 8)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Non-persistent NAAT-positive group (\u0026lt;8 weeks) (n = 35)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eMale sex, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e69 (63.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e4 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e23 (65.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.443\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eAge, years (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e72 [62\u0026ndash;78]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e73.5 [66\u0026ndash;75]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e72 [65\u0026ndash;75]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.679\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eSmoking history, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e47 (43.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e3 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e20 (57.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.687\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eChronic respiratory disease, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e16 (14.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e1 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e8 (22.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eCharlson Comorbidity Index (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e2 [2\u0026ndash;3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e3 [2\u0026ndash;3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e2 [2\u0026ndash;3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eHistory of vaccine, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e37/45 (82.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e2/2 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e10/13 (76.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eHistory of tixagevimab-cilgavimab, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e13 (11.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e1 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e6 (17.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eType of Hematological Malignancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eMalignant lymphoma, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e69 (63.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e7 (87.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e19 (54.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.719\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eAcute myeloid leukemia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e7 (6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e1 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e2 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eAcute lymphocytic leukemia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e3 (2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e2 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eChronic myeloid leukemia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e2 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eChronic lymphocytic leukemia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e5 (4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eMyelodysplastic syndrome, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e9 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e5 (14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.565\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eMultiple myeloma, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e12 (11.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e5 (14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.565\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eMyeloproliferative disorders, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e3 (2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eDisease state\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eOn chemotherapy, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e45 (41.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e7 (87.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e22 (62.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.238\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eAnticancer drug\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eCytotoxic agent, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e30 (27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e4 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e15 (42.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eBendamustine, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e5 (4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e4 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eAnti-CD20 monoclonal antibody, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e33 (30.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e7 (87.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e16 (45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.05*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eRituximab, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e25 (22.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e4 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e13 (37.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.692\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eObinutuzumab, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e7 (6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e3 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e2 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.037*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003emaintenance therapy, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e7 (6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e3 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.016*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eBTK inhibitors, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e5 (4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e2 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eBCR-ABL inhibitors, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e5 (4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e3 (8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eGlucocorticoid, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e44 (40.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e4 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e21 (60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.701\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eAllogeneic HSCT, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e7 (6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e1 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.186\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eAutologous HSCT, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e4 (3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eCAR-T, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e1 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eLaboratory data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eNeutrophil, /uL (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e2,770 [1,890\u0026ndash;4,620]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e3,005 [1,627\u0026ndash;4,780]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e2,310 [1,020\u0026ndash;4,505]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.571\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eLymphocyte, /uL (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e1,300 [690\u0026ndash;1,960]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e695 [405\u0026ndash;1,637]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e890 [345\u0026ndash;1,330]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.939\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eImmunoglobulin G, mg/dL (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e956 [613\u0026ndash;1,176]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e559 [559\u0026ndash;559]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e640 [613\u0026ndash;1,019]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.545\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003ePeriod\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e2021/4\u0026ndash;2021/12\u0026nbsp;\u0026alpha;/\u0026delta;\u0026nbsp;variant, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e3 (2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e2 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.767\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e2022/1\u0026ndash;2022/6 Omicron BA.2, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e30 (27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e3 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e11 (31.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003e2022/7\u0026ndash;2023/1 Omicron BA.5, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e76 (69.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e5 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e22 (62.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eSeverity of COVID-19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eAsymptomatic/mild, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e78 (71.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e24 (68.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.002*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eModerate, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e15 (13.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e6 (75.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e7 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eSevere, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e16 (14.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e2 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e4 (11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eVery severe, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eInpatients, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e54 (49.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e8 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e28 (80.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eTherapy for COVID-19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eRemdesivir, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e35 (32.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e6 (75.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e16 (45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eMolnupiravir, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e51 (46.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e7 (87.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e18 (51.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.111\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eNirmatrelvir/ritonavir, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e6 (5.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e2 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e3 (8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.228\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eSotrovimab, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e11 (10.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e3 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e6 (17.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.332\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eCasirivimab/imdevimab, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e1 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eBaricitinib, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e2 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e1 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.186\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eTocilizumab, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eGlucocorticoid, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e18 (16.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e5 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e5 (14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003ePrognosis of COVID-19\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eDuration of NAAT positivity, days (median [IQR])\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e28 [19\u0026ndash;47]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e77 [61.5\u0026ndash;96]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e26 [18\u0026ndash;34.5]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eDeath due to COVID-19, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e8/109 (7.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e3 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.005*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 192px;\"\u003e\n \u003cp\u003eDeath from all causes, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 210px;\"\u003e\n \u003cp\u003e14/109 (12.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e3 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 174px;\"\u003e\n \u003cp\u003e3 (8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 102px;\"\u003e\n \u003cp\u003e0.067\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAmong patients who contracted COVID-19 during the study period (n = 109), those with consecutive NAAT results available were classified into a persistent NAAT-positive group (n = 8) and a non-persistent NAAT-positive group (n = 35). Clinical and treatment-related factors were compared between the two groups, and p-values are reported. * p \u0026lt; 0.05, statistically significant. \u003cstrong\u003eAbbreviations\u003c/strong\u003e: NAAT, nucleic acid amplification test; IQR, interquartile range; FL, follicular lymphoma; DLBCL, diffuse large B-cell lymphoma; AML, acute myeloid leukemia; ALL, acute lymphocytic leukemia; CML, chronic myeloid leukemia; CLL, chronic lymphocytic leukemia; MDS, myelodysplastic syndrome; MM, multiple myeloma; MPN, myeloproliferative neoplasms; HSCT, hematopoietic stem cell transplantation; CAR-T, chimeric antigen receptor T-cell therapy; BTK, Bruton\u0026apos;s tyrosine kinase; BCR-ABL, breakpoint cluster region-Abelson; IgG, immunoglobulin G; REM, remdesivir; MOL, molnupiravir; NMV/r, nirmatrelvir/ritonavir; GCS, glucocorticoid steroids.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Detailed clinical information of patients in the persistent NAAT-positive group\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"882\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eS. No.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of hematological malignancy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChemotherapy in the last 6 months\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUse of anti-CD20 monoclonal antibody\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment for COVID-19\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome of COVID-19\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e1.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eB-cell lymphoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 156px;\"\u003e\n \u003cp\u003ePola-R-CHP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003eYes (Rituximab)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eMOL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eSurvival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e2.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eFollicular lymphoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 156px;\"\u003e\n \u003cp\u003eG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003eYes (Obinutuzumab)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eMOL, REM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eSurvival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e3.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eDLBCL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 156px;\"\u003e\n \u003cp\u003ePola-BR, R-GDP, R-DeVIC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003eYes (Rituximab)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eSOT, MOL, REM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eDeath\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e4.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eFollicular lymphoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 156px;\"\u003e\n \u003cp\u003eG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003eYes (Obinutuzumab)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eREM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eDeath\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e5.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eFollicular lymphoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 156px;\"\u003e\n \u003cp\u003eR-DeVIC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003eYes (Rituximab)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eSOT, REM, MOL, NMV/r\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eSurvival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e6.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eFollicular lymphoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 156px;\"\u003e\n \u003cp\u003eR2 \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003eYes (Rituximab)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eMOL, REM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eSurvival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e7.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eCML blast crisis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 156px;\"\u003e\n \u003cp\u003eallogenic HSCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eSOT, MOL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eSurvival\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e8.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 42px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003eFollicular lymphoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 156px;\"\u003e\n \u003cp\u003eG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e\n \u003cp\u003eYes (Obinutuzumab)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eMOL, REM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eDeath\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: NAAT, nucleic acid amplification test; M, male; F, female; DLBCL, diffuse large B-cell lymphoma; CML, chronic myeloid leukemia; Pola-R-CHP, polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisolone; G, obinutuzumab; Pola-BR, polatuzumab vedotin, bendamustine, and rituximab; R-GDP, rituximab, gemcitabine, dexamethasone, and cisplatin; R-DeVIC, rituximab, dexamethasone, etoposide, ifosfamide, and carboplatin; R2, lenalidomide and rituximab; HSCT, hematopoietic stem cell transplantation; MOL, molnupiravir; REM, remdesivir; SOT, sotrovimab; NMV/r, nirmatrelvir/ritonavir.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"SARS-CoV-2, COVID-19, hematologic malignancy, rituximab, obinutuzumab","lastPublishedDoi":"10.21203/rs.3.rs-7109579/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7109579/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003ePatients with hematologic malignancies may experience prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to evaluate risk factors for persistent SARS-CoV-2 infection in patients with hematologic malignancies based on nucleic acid amplification test (NAAT) results. Patients with SARS-CoV-2 NAAT positivity lasting\u0026thinsp;\u0026ge;\u0026thinsp;8 weeks (persistent NAAT-positive group) were compared with those who became NAAT-negative within 8 weeks (non-persistent NAAT-positive group).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eWe examined patients with COVID-19 and hematologic malignancies between April 2021 and January 2023 at Tenri Hospital in Japan, examining hematologic malignancy type, chemotherapy regimens, and laboratory data.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eNAAT results at 8 weeks were available for 43 patients; eight (19%) remained positive for 8 weeks or more, while 35 (81%) became negative in \u0026lt;\u0026thinsp;8 weeks. Univariate analysis between the two groups showed significant differences in disease severity (p\u0026thinsp;=\u0026thinsp;0.001), anti-CD20 monoclonal antibodies (mAB) use within the past 6 months (7/8 [88%] vs. 16/35 [46%], respectively; p\u0026thinsp;=\u0026thinsp;0.05), obinutuzumab use within the past 6 months (3/8 [38%] vs. 2/35 [6%], respectively; p\u0026thinsp;=\u0026thinsp;0.037), and anti-CD20 mAbs maintenance treatment (3/8 [38%] vs. 1/35 [3%], respectively; p\u0026thinsp;=\u0026thinsp;0.016). Seven of the eight patients in the persistent NAAT-positive group had malignant lymphomas, and five had follicular lymphoma.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThe use of anti-CD20 mAbs, especially obinutuzumab and maintenance treatment, is associated with long-term SARS-CoV-2 infection in patients with hematologic malignancies.\u003c/p\u003e","manuscriptTitle":"Chemotherapy and Anti-CD20 Monoclonal Antibody Impact on SARS-CoV-2 Nucleic Acid Amplification Tests in Hematologic Malignancies: A Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-12 12:49:20","doi":"10.21203/rs.3.rs-7109579/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-14T18:36:44+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-14T05:59:24+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-12T15:58:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"32385720376056492630378353096935255736","date":"2025-08-08T09:57:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"12744485539125437434663178737857867338","date":"2025-08-06T19:21:05+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-06T18:58:01+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-07-17T16:44:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-17T07:09:13+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-17T07:06:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2025-07-12T17:33:07+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5a8eceb7-d716-486b-b430-2714cfb39210","owner":[],"postedDate":"August 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-27T16:26:09+00:00","versionOfRecord":{"articleIdentity":"rs-7109579","link":"https://doi.org/10.1186/s12879-025-11844-z","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2025-10-22 16:16:45","publishedOnDateReadable":"October 22nd, 2025"},"versionCreatedAt":"2025-08-12 12:49:20","video":"","vorDoi":"10.1186/s12879-025-11844-z","vorDoiUrl":"https://doi.org/10.1186/s12879-025-11844-z","workflowStages":[]},"version":"v1","identity":"rs-7109579","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7109579","identity":"rs-7109579","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}