Immune response to COVID‐19 vaccination is attenuated by poor disease control and antimyeloma therapy with vaccine driven divergent T‐cell response

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Summary

Myeloma patients frequently respond poorly to bacterial and viral vaccination. A few studies have reported poor humoral immune responses in myeloma patients to COVID‐19 vaccination. Using a prospective study of myeloma patients in the UK Rudy study cohort, we assessed humoral and interferon gamma release assay (IGRA) cellular immune responses to COVID‐19 vaccination post second COVID‐19 vaccine administration. We report data from 214 adults with myeloma ( n = 204) or smouldering myeloma ( n = 10) who provided blood samples at least three weeks after second vaccine dose. Positive Anti‐spike antibody levels (> 50 iu/ml) were detected in 189/203 (92.7%), positive IGRA responses were seen in 97/158 (61.4%) myeloma patients. Only 10/158 (6.3%) patients were identified to have both a negative IGRA and negative anti‐spike protein antibody response. In all, 95/158 (60.1%) patients produced positive results for both anti‐spike protein serology and IGRA. After adjusting for disease severity and myeloma therapy, poor humoral immune response was predicted by male gender. Predictors of poor IGRA included anti‐CD38/anti‐BCMA (B‐cell maturation antigen) therapy and Pfizer‐BioNTech vaccination. Further work is required to understand the clinical significance of divergent cellular response to vaccination.

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Sex differences in immune responses that underlie COVID-19 disease outcomes

Takehiro Takahashi, Mallory Ellingson, Patrick Wong … (2020)

A growing body of evidence indicates sex differences in the clinical outcomes of coronavirus disease 2019 (COVID-19) 1–5 . However, whether immune responses against SARS-CoV-2 differ between sexes, and whether such differences explain male susceptibility to COVID-19, is currently unknown. In this study, we examined sex differences in viral loads, SARS-CoV-2-specific antibody titers, plasma cytokines, as well as blood cell phenotyping in COVID-19 patients. By focusing our analysis on patients with moderate disease who had not received immunomodulatory medications, our results revealed that male patients had higher plasma levels of innate immune cytokines such as IL-8 and IL-18 along with more robust induction of non-classical monocytes. In contrast, female patients mounted significantly more robust T cell activation than male patients during SARS-CoV-2 infection, which was sustained in old age. Importantly, we found that a poor T cell response negatively correlated with patients’ age and was associated with worse disease outcome in male patients, but not in female patients. Conversely, higher innate immune cytokines in female patients associated with worse disease progression, but not in male patients. These findings reveal a possible explanation underlying observed sex biases in COVID-19, and provide important basis for the development of sex-based approach to the treatment and care of men and women with COVID-19.

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Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19

Meagan O’Brien, Eduardo Forleo-Neto, Bret J Musser … (2021)

Background REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19). Whether subcutaneous REGEN-COV prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent Covid-19 in persons at high risk for infection because of household exposure to a person with SARS-CoV-2 infection is unknown. Methods We randomly assigned, in a 1:1 ratio, participants (≥12 years of age) who were enrolled within 96 hours after a household contact received a diagnosis of SARS-CoV-2 infection to receive a total dose of 1200 mg of REGEN-COV or matching placebo administered by means of subcutaneous injection. At the time of randomization, participants were stratified according to the results of the local diagnostic assay for SARS-CoV-2 and according to age. The primary efficacy end point was the development of symptomatic SARS-CoV-2 infection through day 28 in participants who did not have SARS-COV-2 infection (as measured by reverse-transcriptase–quantitative polymerase-chain-reaction assay) or previous immunity (seronegativity). Results Symptomatic SARS-CoV-2 infection developed in 11 of 753 participants in the REGEN-COV group (1.5%) and in 59 of 752 participants in the placebo group (7.8%) (relative risk reduction [1 minus the relative risk], 81.4%; P<0.001). In weeks 2 to 4, a total of 2 of 753 participants in the REGEN-COV group (0.3%) and 27 of 752 participants in the placebo group (3.6%) had symptomatic SARS-CoV-2 infection (relative risk reduction, 92.6%). REGEN-COV also prevented symptomatic and asymptomatic infections overall (relative risk reduction, 66.4%). Among symptomatic infected participants, the median time to resolution of symptoms was 2 weeks shorter with REGEN-COV than with placebo (1.2 weeks and 3.2 weeks, respectively), and the duration of a high viral load (>10 4 copies per milliliter) was shorter (0.4 weeks and 1.3 weeks, respectively). No dose-limiting toxic effects of REGEN-COV were noted. Conclusions Subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. Among the participants who became infected, REGEN-COV reduced the duration of symptomatic disease and the duration of a high viral load. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04452318 .)

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Antibody response to SARS-CoV-2 vaccines in patients with hematologic malignancies

Lee Greenberger, Larry A. Saltzman, Jonathon W. Senefeld … (2021)

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Author and article information

Contributors

Karthik Ramasamy:

ORCID: https://orcid.org/0000-0003-3385-3707

karthik.ramasamy@ndcls.ox.ac.uk

Journal

Journal ID (nlm-ta): Br J Haematol

Journal ID (iso-abbrev): Br J Haematol

Journal ID (doi): 10.1111/(ISSN)1365-2141

Journal ID (publisher-id): BJH

Title: British Journal of Haematology

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Print): 0007-1048

ISSN (Electronic): 1365-2141

Publication date (Electronic): 17 February 2022

Publication date (Print): May 2022

Volume: 197

Issue: 3 ( doiID: 10.1111/bjh.v197.3 )

Pages: 293-301

Affiliations

[ ¹ ] Oxford University Hospitals NHS Trust Radcliffe Department of Medicine Oxford University Oxford UK

[ ² ] Department of Immunology Churchill Hospital, Oxford University Hospitals NHS, Foundation Trust Oxford UK

[ ³ ] The Botnar Research Centre Headington UK

[ ⁴ ] Late Phase Haematology Oxford University Hospital NHS Foundation Trust, Churchill Hospital Oxford UK

[ ⁵ ] Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences University of Oxford Oxford UK

[ ⁶ ] Oxford University Hospitals NHS Trust Oxford UK

[ ⁷ ] Princess Royal University Hospital, King's College Hospital Foundation NHS Trust Kent UK

[ ⁸ ] NIHR Leeds Medtech & In vitro Diagnostics Cooperative Leeds Teaching Hospitals Trust Leeds UK

[ ⁹ ] Department of Haematology University College London Hospitals NHS Trust London UK

[ ¹⁰ ] College of Medical and Dental Sciences Medical School University of Birmingham Birmingham UK

[ ¹¹ ] University of Wolverhampton The Royal Wolverhampton NHS Trust Wolverhampton UK

[ ¹² ] Oxford University Hospitals NHS Trust NHS Foundation Trust Oxford and Bath Royal United Hospitals Bath UK

[ ¹³ ] Myeloma UK Beaverbank Business Park Edinburgh UK

[ ¹⁴ ] MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine University of Oxford Oxford UK

[ ¹⁵ ] Department of Haematology Oxford University Hospitals NHS Trust Oxford UK

Author notes

[*] [* ] Correspondence

Karthik Ramasamy, Oxford University Hospitals NHS Trust and Oxford University.

Email: karthik.ramasamy@ 123456ndcls.ox.ac.uk

Author information

Karthik Ramasamy https://orcid.org/0000-0003-3385-3707

Stella Bowcock https://orcid.org/0000-0002-8195-8960

Gordon Cook https://orcid.org/0000-0003-1717-0412

Article

Publisher ID: BJH18066 Other ID: BJH-2021-02609.R1

DOI: 10.1111/bjh.18066

PMC ID: 9306522

PubMed ID: 35064676

SO-VID: 6f81886b-a1b1-4805-92b5-0db1ae23c1b9

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

History

Date revision received : 13 January 2022

Date received : 10 November 2021

Date accepted : 15 January 2022

Page count

Figures: 3, Tables: 6, Pages: 9, Words: 5382

Funding

Funded by: National Institute for Health Research , doi 10.13039/501100000272;

Funded by: Janssen UK

Funded by: Blood Cancer Vaccine Consortium

Award ID: 21015

Custom metadata

source-schema-version-number 2.0

cover-date May 2022

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.7 mode:remove_FC converted:22.07.2022

ScienceOpen disciplines: Hematology

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ScienceOpen disciplines: Hematology

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Immune response to COVID‐19 vaccination is attenuated by poor disease control and antimyeloma therapy with vaccine driven divergent T‐cell response

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UCL: Covid-19 Research

Most cited references 20

Sex differences in immune responses that underlie COVID-19 disease outcomes

Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19

Antibody response to SARS-CoV-2 vaccines in patients with hematologic malignancies

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