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1.
J Immunother Cancer ; 10(7)2022 07.
Article in English | MEDLINE | ID: covidwho-1950234

ABSTRACT

Anti-SARS-CoV-2 antibodies are crucial for protection from future COVID-19 infections, limiting disease severity, and control of viral transmission. While patients with the most common type of hematologic malignancy, B cell lymphoma, often develop insufficient antibody responses to messenger RNA (mRNA) vaccines, vaccine-induced T cells would have the potential to 'rescue' protective immunity in patients with B cell lymphoma. Here we report the case of a patient with B cell lymphoma with profound B cell depletion after initial chemoimmunotherapy who received a total of six doses of a COVID-19 mRNA vaccine. The patient developed vaccine-induced anti-SARS-CoV-2 antibodies only after the fifth and sixth doses of the vaccine once his B cells had started to recover. Remarkably, even in the context of severe treatment-induced suppression of the humoral immune system, the patient was able to mount virus-specific CD4+ and CD8+ responses that were much stronger than what would be expected in healthy subjects after two to three doses of a COVID-19 mRNA vaccine and which were even able to target the Omicron 'immune escape' variant of the SARS-CoV-2 virus. These findings not only have important implications for anti-COVID-19 vaccination strategies but also for future antitumor vaccines in patients with cancer with profound treatment-induced immunosuppression.


Subject(s)
COVID-19 Vaccines , COVID-19 , Lymphoma, B-Cell , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , RNA, Messenger/genetics , SARS-CoV-2 , T-Lymphocytes , Vaccines, Synthetic , Viral Vaccines , mRNA Vaccines/adverse effects
2.
Nat Genet ; 54(8): 1103-1116, 2022 08.
Article in English | MEDLINE | ID: covidwho-1931425

ABSTRACT

The chr12q24.13 locus encoding OAS1-OAS3 antiviral proteins has been associated with coronavirus disease 2019 (COVID-19) susceptibility. Here, we report genetic, functional and clinical insights into this locus in relation to COVID-19 severity. In our analysis of patients of European (n = 2,249) and African (n = 835) ancestries with hospitalized versus nonhospitalized COVID-19, the risk of hospitalized disease was associated with a common OAS1 haplotype, which was also associated with reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in a clinical trial with pegIFN-λ1. Bioinformatic analyses and in vitro studies reveal the functional contribution of two associated OAS1 exonic variants comprising the risk haplotype. Derived human-specific alleles rs10774671-A and rs1131454 -A decrease OAS1 protein abundance through allele-specific regulation of splicing and nonsense-mediated decay (NMD). We conclude that decreased OAS1 expression due to a common haplotype contributes to COVID-19 severity. Our results provide insight into molecular mechanisms through which early treatment with interferons could accelerate SARS-CoV-2 clearance and mitigate against severe COVID-19.


Subject(s)
COVID-19 , 2',5'-Oligoadenylate Synthetase/genetics , 2',5'-Oligoadenylate Synthetase/metabolism , Alleles , COVID-19/genetics , Hospitalization , Humans , SARS-CoV-2/genetics
3.
Blood Rev ; 51: 100888, 2022 01.
Article in English | MEDLINE | ID: covidwho-1385128

ABSTRACT

Hairy cell leukemia (HCL) is an indolent B-cell malignancy, usually driven by the BRAF V600E mutation. For 30 years, untreated and relapsed HCL was successfully treated with purine analogs, but minimal residual disease (MRD) remained in most patients, eventually causing relapse. Repeated purine analogs achieve decreasing efficacy and increasing toxicity, particularly to normal T-cells. MRD-free complete remissions (CRs) are more common using rituximab with purine analogs in both 1st-line and relapsed settings. BRAF inhibitors and Ibrutinib can achieve remission, but due to persistence of MRD, must be used chronically to prevent relapse. BRAF inhibition combined with Rituximab can achieve high MRD-free CR rates. Anti-CD22 recombinant immunotoxin moxetumomab pasudotox is FDA-approved in the relapsed setting and is unique in achieving high MRD-free CR rates as a single-agent. Avoiding chemotherapy and rituximab may be important in ensuring both recovery from COVID-19 and successful COVID-19 vaccination, an area of continued investigation.


Subject(s)
COVID-19 , Leukemia, Hairy Cell/diagnosis , Leukemia, Hairy Cell/therapy , Pandemics , Antineoplastic Agents/therapeutic use , COVID-19/epidemiology , Humans , Leukemia, Hairy Cell/epidemiology , Neoplasm, Residual/diagnosis , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Purines/therapeutic use , Recurrence , Rituximab/therapeutic use
4.
Leukemia ; 35(7): 1864-1872, 2021 07.
Article in English | MEDLINE | ID: covidwho-1216445

ABSTRACT

Standard treatment options in classic HCL (cHCL) result in high response rates and near normal life expectancy. However, the disease itself and the recommended standard treatment are associated with profound and prolonged immunosuppression, increasing susceptibility to infections and the risk for a severe course of COVID-19. The Hairy Cell Leukemia Foundation (HCLF) has recently convened experts and discussed different clinical strategies for the management of these patients. The new recommendations adapt the 2017 consensus for the diagnosis and management with cHCL to the current COVID-19 pandemic. They underline the option of active surveillance in patients with low but stable blood counts, consider the use of targeted and non-immunosuppressive agents as first-line treatment for cHCL, and give recommendations on preventive measures against COVID-19.


Subject(s)
COVID-19/complications , Leukemia, Hairy Cell/therapy , COVID-19/epidemiology , COVID-19/pathology , COVID-19/virology , Consensus , Humans , Leukemia, Hairy Cell/complications , Pandemics , Practice Guidelines as Topic , SARS-CoV-2/isolation & purification , Severity of Illness Index
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