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CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer.

ABSTRACT: Cancer patients have increased morbidity and mortality from Coronavirus Disease 2019 (COVID-19), but the underlying immune mechanisms are unknown. In a cohort of 100 cancer patients hospitalized for COVID-19 at the University of Pennsylvania Health System, we found that patients with hematologic cancers had a significantly higher mortality relative to patients with solid cancers after accounting for confounders including ECOG performance status and active cancer status. We performed flow cytometric and serologic analyses of 106 cancer patients and 113 non-cancer controls from two additional cohorts at Penn and Memorial Sloan Kettering Cancer Center. Patients with solid cancers exhibited an immune phenotype similar to non-cancer patients during acute COVID-19 whereas patients with hematologic cancers had significant impairment of B cells and SARS-CoV-2-specific antibody responses. High dimensional analysis of flow cytometric data revealed 5 distinct immune phenotypes. An immune phenotype characterized by CD8 T cell depletion was associated with a high viral load and the highest mortality of 71%, among all cancer patients. In contrast, despite impaired B cell responses, patients with hematologic cancers and preserved CD8 T cells had a lower viral load and mortality. These data highlight the importance of CD8 T cells in acute COVID-19, particularly in the setting of impaired humoral immunity. Further, depletion of B cells with anti-CD20 therapy resulted in almost complete abrogation of SARS-CoV-2-specific IgG and IgM antibodies, but was not associated with increased mortality compared to other hematologic cancers, when adequate CD8 T cells were present. Finally, higher CD8 T cell counts were associated with improved overall survival in patients with hematologic cancers. Thus, CD8 T cells likely compensate for deficient humoral immunity and influence clinical recovery of COVID-19. These observations have important implications for cancer and COVID-19-directed treatments, immunosuppressive therapies, and for understanding the role of B and T cells in acute COVID-19.

SUBMITTER: Huang A

PROVIDER: S-EPMC7872363 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer.

Bange Erin M EM Han Nicholas A NA Wileyto Paul P Kim Justin Y JY Gouma Sigrid S Robinson James J Greenplate Allison R AR Porterfield Florence F Owoyemi Olutosin O Naik Karan K Zheng Cathy C Galantino Michael M Weisman Ariel R AR Ittner Caroline A G CAG Kugler Emily M EM Baxter Amy E AE Oniyide Olutwatosin O Agyekum Roseline S RS Dunn Thomas G TG Jones Tiffanie K TK Giannini Heather M HM Weirick Madison E ME McAllister Christopher M CM Babady N Esther NE Kumar Anita A Widman Adam J AJ DeWolf Susan S Boutemine Sawsan R SR Roberts Charlotte C Budzik Krista R KR Tollett Susan S Wright Carla C Perloff Tara T Sun Lova L Mathew Divij D Giles Josephine R JR Oldridge Derek A DA Wu Jennifer E JE Alanio Cécile C Adamski Sharon S Garfall Alfred L AL Vella Laura L Kerr Samuel J SJ Cohen Justine V JV Oyer Randall A RA Massa Ryan R Maillard Ivan P IP Maxwell Kara N KN Reilly John P JP Maslak Peter G PG Vonderheide Robert H RH Wolchok Jedd D JD Hensley Scott E SE Wherry E John EJ Meyer Nuala N DeMichele Angela M AM Vardhana Santosha A SA Mamtani Ronac R Huang Alexander C AC

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Cancer patients have increased morbidity and mortality from Coronavirus Disease 2019 (COVID-19), but the underlying immune mechanisms are unknown. In a cohort of 100 cancer patients hospitalized for COVID-19 at the University of Pennsylvania Health System, we found that patients with hematologic cancers had a significantly higher mortality relative to patients with solid cancers after accounting for confounders including ECOG performance status and active cancer status. We performed flow cytomet ...[more]

PMID: 33564756

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Project description:BackgroundWhether human T-lymphotropic virus type 1 (HTLV-1) carriers can develop sufficient humoral immunity after coronavirus disease 2019 (COVID-19) vaccination is unknown.MethodsTo investigate humoral immunity after COVID-19 vaccination in HTLV-1 carriers, a multicenter, prospective observational cohort study was conducted at five institutions in southwestern Japan, an endemic area for HTLV-1. HTLV-1 carriers and HTLV-1-negative controls were enrolled for this study from January to December 2022. During this period, the third dose of the COVID-19 vaccine was actively administered. HTLV-1 carriers were enrolled during outpatient visits, while HTLV-1-negative controls included health care workers and patients treated by participating institutions for diabetes, hypertension, or dyslipidemia. The main outcome was the effect of HTLV-1 infection on the plasma anti-COVID-19 spike IgG (IgG-S) titers after the third dose, assessed by multivariate linear regression with other clinical factors.ResultsWe analyzed 181 cases (90 HTLV-1 carriers, 91 HTLV-1-negative controls) after receiving the third dose. HTLV-1 carriers were older (median age 67.0 vs. 45.0 years, p < 0.001) and more frequently had diabetes, hypertension, or dyslipidemia than did HTLV-1-negative controls (60.0% vs. 27.5%, p < 0.001). After the third dose, the IgG-S titers decreased over time in both carriers and controls. Multivariate linear regression in the entire cohort showed that time since the third dose, age, and HTLV-1 infection negatively influenced IgG-S titers. After adjusting for confounders such as age, or presence of diabetes, hypertension, or dyslipidemia between carriers and controls using the overlap weighting propensity score method, and performing weighted regression analysis in the entire cohort, both time since the third dose and HTLV-1 infection negatively influenced IgG-S titers.ConclusionsThe humoral immunity after the third vaccination dose is impaired in HTLV-1 carriers; thus, customized vaccination schedules may be necessary for them.

Project description:Simple Summary Taking into consideration the high risk of patients with cancer for severe COVID-19 infection, prioritization has been given to primary prevention with both primary and booster vaccination. However, robust evidence for vaccination efficacy remains limited, due to the lack of available clinical trials including patients with active cancer. The rates of both humoral and cellular immune response remain rather vague, and they are mainly based on data deriving from retrospective studies of limited internal and external validity. We aimed to gather and analyze the current available literature on the efficacy of COVID-19 vaccination among patients with different types of malignancies receiving different treatments. Our results highlight that patients with cancer present suboptimal immune responses after COVID-19 vaccination, which is more prominent among patients with hematological malignancies. Abstract The exclusion of patients with cancer in clinical trials evaluating COVID-19 vaccine efficacy and safety, in combination with the high rate of severe infections, highlights the need for optimizing vaccination strategies. The aim of this study was to perform a systematic review and meta-analysis of the published available data from prospective and retrospective cohort studies that included patients with either solid or hematological malignancies according to the PRISMA Guidelines. A literature search was performed in the following databases: Medline (Pubmed), Scopus, Clinicaltrials.gov, EMBASE, CENTRAL and Google Scholar. Overall, 70 studies were included for the first and second vaccine dose and 60 studies for the third dose. The Effect Size (ES) of the seroconversion rate after the first dose was 0.41 (95%CI: 0.33–0.50) for hematological malignancies and 0.56 (95%CI: 0.47–0.64) for solid tumors. The seroconversion rates after the second dose were 0.62 (95%CI: 0.57–0.67) for hematological malignancies and 0.88 (95%CI: 0.82–0.93) for solid tumors. After the third dose, the ES for seroconversion was estimated at 0.63 (95%CI: 0.54–0.72) for hematological cancer and 0.88 (95%CI: 0.75–0.97) for solid tumors. A subgroup analysis was performed to evaluate potential factors affecting immune response. Production of anti-SARS-CoV-2 antibodies was found to be more affected in patients with hematological malignancies, which was attributed to the type of malignancy and treatment with monoclonal antibodies according to the subgroup analyses. Overall, this study highlights that patients with cancer present suboptimal humoral responses after COVID-19 vaccination. Several factors including timing of vaccination in relevance with active therapy, type of therapy, and type of cancer should be considered throughout the immunization process.

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CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer.

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CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer.

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