production of anti spike antibodies in response to covid vaccine in lymphoma patients CORD-Papers-2022-06-02 (Version 1)

Title: Production of anti-spike antibodies in response to COVID vaccine in lymphoma patients
Abstract: Patients with hematologic malignancies have poor outcomes from COVID infection and are less likely to mount an antibody response after COVID infection. There is limited data on the efficacy of the COVID vaccines in lymphoma patients and to suggest the optimal timing of vaccination to elicit immunity in patients receiving immunochemotherapy. This is a retrospective study of adult lymphoma patients who received the COVID vaccine between 12/1/2020 and 11/30/2021. The primary endpoint was a positive anti-COVID spike protein antibody titer following the primary COVID vaccination series. The primary series was defined as 2 doses of the COVID mRNA vaccines or 1 dose of the COVID adenovirus vaccine. Subgroups were compared using Fisher's exact test and unadjusted and adjusted logistic regression models were used for univariate (UVA) and multivariate (MVA) analyses. A total of 243 patients were included in this study; 72 patients (30%) with indolent lymphomas; 56 patients (23%) with Burkitts diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBL) combined; 55 patients (22%) with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL); and 44 patients (18%) with Hodgkin and T-cell lymphomas (HL/TCL) combined. One-hundred fifty-eight patients (65%) developed anti-COVID spike protein antibodies after completing the primary COVID vaccination series. Thirty-eight of 46 (83%) patients who received an additional primary shot and had resultant levels produced anti-COVID spike protein antibodies. When compared to other lymphoma types patients with CLL/SLL had a numerically lower seroconversion rate of 51% following the primary series whereas patients with HL/TCL appeared to have a robust antibody response with a seropositivity rate of 77% (p=0.04). Lymphoma patients are capable of mounting a humoral response to the COVID mRNA vaccines. Further studies are required to confirm our findings including whether T-cell immunity would be of clinical relevance in this patient population.
Published: 2022-03-24
DOI: 10.1101/2022.03.24.22272883
DOI_URL: http://doi.org/10.1101/2022.03.24.22272883
Author Name: Della Pia A
Author link: https://covid19-data.nist.gov/pid/rest/local/author/della_pia_a
Author Name: Kim G Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/kim_g_y
Author Name: Ip A
Author link: https://covid19-data.nist.gov/pid/rest/local/author/ip_a
Author Name: Ahn J
Author link: https://covid19-data.nist.gov/pid/rest/local/author/ahn_j
Author Name: Liu Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liu_y
Author Name: Koropsak M
Author link: https://covid19-data.nist.gov/pid/rest/local/author/koropsak_m
Author Name: Lukasik B
Author link: https://covid19-data.nist.gov/pid/rest/local/author/lukasik_b
Author Name: Contractor A
Author link: https://covid19-data.nist.gov/pid/rest/local/author/contractor_a
Author Name: Amin K
Author link: https://covid19-data.nist.gov/pid/rest/local/author/amin_k
Author Name: Ayyagari L
Author link: https://covid19-data.nist.gov/pid/rest/local/author/ayyagari_l
Author Name: Zhao C
Author link: https://covid19-data.nist.gov/pid/rest/local/author/zhao_c
Author Name: Gupta A
Author link: https://covid19-data.nist.gov/pid/rest/local/author/gupta_a
Author Name: Batistick M
Author link: https://covid19-data.nist.gov/pid/rest/local/author/batistick_m
Author Name: Leslie L
Author link: https://covid19-data.nist.gov/pid/rest/local/author/leslie_l
Author Name: Goy A
Author link: https://covid19-data.nist.gov/pid/rest/local/author/goy_a
Author Name: Feldman T
Author link: https://covid19-data.nist.gov/pid/rest/local/author/feldman_t
Author Name: Kats S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/kats_s
sha: 1cdf1af45334f2904ac979f6807df4a06dffcdf6
license: medrxiv
source_x: MedRxiv; WHO
source_x_url: https://www.who.int/
url: https://doi.org/10.1101/2022.03.24.22272883 http://medrxiv.org/cgi/content/short/2022.03.24.22272883v1?rss=1
has_full_text: TRUE
Keywords Extracted from Text Content: DLBCL chronic lymphocytic leukemia hematologic malignancies 11/30/2021 anti-COVID anti-COVID spike protein antibodies HL/TCL T-cell Burkitt's lymphoma 42 patients T-cell lymphomas Lymphoma patients PMBL mediastinal B-cell lymphoma adult lymphoma patients small lymphocytic lymphoma adenovirus vaccine COVID Patients HMH lymphomas medRxiv preprint 111 diffuse large B-cell lymphoma UVA patients lymphoma Hodgkin JTCC patient CLL/SLL lymphoma patients anti-CD20 monoclonal antibody DLBCL CLL/SLL anti-CD20 SARS-CoV-2 spike protein Vaccine anticancer chronic lymphocytic leukemia Fig 2 hematologic malignancies B-cell B-cell counts 275 HL/TCL histologies anti-CD20 monoclonal 293 antibody anti-COVID spike protein antibodies HL/TCL PHI indolent lymphomas T-cell Burkitt's convalescent plasma COVID-19 PMBL BTK medRxiv preprint COVID B-cell 76 lymphomas medRxiv https://doi.org/10.1101/2022.03.24.22272883 doi Patients Lymphoma anti-COVID spike antibody [3] cut-173 Pfizer-BioNTech SARS-CoV-2 anti-CD20 monoclonal antibodies CLL/SLL patients patients CLL lymphoma cardiovascular peripheral blood B-cell rituximab patient Bruton's tyrosine kinase 78
Extracted Text Content in Record: First 5000 Characters:Patients with hematologic malignancies have poor outcomes from COVID infection and are less likely to mount an 41 antibody response after COVID infection. There is limited data on the efficacy of the COVID vaccines in lymphoma 42 patients, and to suggest the optimal timing of vaccination to elicit immunity in patients receiving 43 immunochemotherapy. This is a retrospective study of adult lymphoma patients who received the COVID vaccine 44 between 12/1/2020 and 11/30/2021. The primary endpoint was a positive anti-COVID spike protein antibody titer 45 following the primary COVID vaccination series. The primary series was defined as 2 doses of the COVID mRNA 46 vaccines or 1 dose of the COVID adenovirus vaccine. Subgroups were compared using Fisher's exact test, and 47 unadjusted and adjusted logistic regression models were used for univariate (UVA) and multivariate (MVA) 48 analyses. A total of 243 patients were included in this study; 72 patients (30%) with indolent lymphomas; 56 49 patients (23%) with Burkitt's, diffuse large B-cell lymphoma (DLBCL), and primary mediastinal B-cell lymphoma 50 (PMBL) combined; 55 patients (22%) with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL); 51 and 44 patients (18%) with Hodgkin and T-cell lymphomas (HL/TCL) combined. One-hundred fifty-eight patients 52 (65%) developed anti-COVID spike protein antibodies after completing the primary COVID vaccination series. Thirty-eight of 46 (83%) patients who received an additional primary shot and had resultant levels produced anti-54 COVID spike protein antibodies. When compared to other lymphoma types, patients with CLL/SLL had a 55 numerically lower seroconversion rate of 51% following the primary series whereas patients with HL/TCL appeared 56 to have a robust antibody response with a seropositivity rate of 77% (p=0.04). Lymphoma patients are capable of 57 mounting a humoral response to the COVID mRNA vaccines. Further studies are required to confirm our findings, 58 including whether T-cell immunity would be of clinical relevance in this patient population. : medRxiv preprint 111 Demographics, clinical characteristics, treatments, and outcomes were manually extracted by physicians, 112 pharmacists, nurses, and medical students from JTCC and HMH. Data abstracted by the team was entered into an 113 Excel spreadsheet, and quality control was performed by physicians overseeing data collection. Patients with hematologic malignancies have poor outcomes from COVID infection with associated mortality of up 67 to 30-40%. Studies have shown that these patients are less likely to mount an antibody response after COVID 68 infection [1] . The Pfizer-BioNTech and Moderna COVID mRNA vaccines have been shown to be 94% effective in preventing severe disease in the general population [2] . However, it is well known that certain clinically vulnerable 70 populations do not develop protective immunity after completing the COVID vaccine series [3] . Production of antibodies against the SARS-CoV-2 spike protein is the major mechanism of protective immunity 73 induced by COVID vaccination. Patients with lymphoma may be unable to seroconvert following vaccination due to 74 impaired humoral and T-cell immunity secondary to the malignancy itself as well as immunosuppressive treatment 75 [4] . This inability to produce antibodies against the SARS-CoV-2 spike protein is most notable in patients with B-cell 76 lymphomas and chronic lymphocytic leukemia (CLL), with seroconversion rates ranging between 64% to 78% [5] . Treatment with B-cell directed therapies, such as anti-CD20 monoclonal antibodies and Bruton's tyrosine kinase 78 (BTK) inhibitors, further compromises the ability of patients with lymphoma to mount an antibody response 79 following vaccination and persists over time [6] . Vaccine responses in patients with different lymphoma subtypes 80 or receiving B-cell depleting therapies have not been fully elucidated. With the emergence of the omicron variant and availability of an additional primary shot of the COVID vaccine, it 83 has become increasingly important to describe the efficacy of the COVID vaccines in lymphoma patients and to 84 suggest the optimal timing of vaccination to elicit immunity in patients receiving immunochemotherapy. There 85 have been several reports of patients with lymphoma frequently not achieving serologic response to COVID 86 vaccines, especially after recent treatments with B-cell directed therapies [6, 7] . In this study, we evaluated 87 antibody levels against the SARS-CoV-2 spike protein in lymphoma patients following receipt of the primary COVID 88 vaccination series and additional primary shot. We hypothesized that patients with lymphoma are not developing 89 a robust immune response following vaccination. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer
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