Whole blood‐based measurement of SARS‐CoV‐2‐specific T cells reveals asymptomatic infection and vaccine immunogenicity in healthy subjects and patients with solid‐organ cancers

Scurr, Martin; Zelek, Wioleta M.; Lippiatt, George; Somerville, Michelle; Burnell, Stephanie E.A.; Capitani, Lorenzo; Davies, Kate; Lawton, Helen; Tozer, Thomas N.; Rees, Tracey; Roberts, Kerry; Evans, Mererid; Jackson, Amanda; Young, Charlotte Aimee; Fairclough, Lucy; Tighe, Paddy; Wills, Mark R.; Westwell, Andrew D.; Morgan, B. Paul; Gallimore, Awen; Godkin, Andrew

doi:10.1111/imm.13433

Cited by 23 publications

(21 citation statements)

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“…Higher incidence and/or worse outcomes in the context of in vivo COVID-19 infection in people receiving anti-CD20, [5,6] and fingolimod,[7] have been observed in some large population-based studies performed prior to the widespread availability of booster vaccines. These observations require further study to fully understand the clinical implications of booster vaccination and their underlying mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Whole blood samples were incubated at 37°C for 20-24 hours before harvesting plasma from each sample to quantify IFN-g by ELISA (BioLegend). SARS-CoV-2-specific T-cell responses were identified as positive using previously defined criteria for differentiating naïve controls from prior COVID-19 vaccinated and/or infected individuals (sensitivity 96.0% and specificity 84.4%) [5].…”

Section: Methodsmentioning

confidence: 99%

“…Further explanations could be that the relevant T-cells are trapped in secondary lymphoid organs due to the mode of action of fingolimod, or that circulating fingolimod in whole blood samples blocks in vitro responses. Higher incidence and/or worse outcomes in the context of in vivo COVID-19 infection in people receiving anti-CD20, [5,6] and fingolimod, [7] have been observed in some large population-based studies performed prior to the widespread availability of booster vaccines. These observations require further study to fully understand the clinical implications of booster vaccination and their underlying mechanisms.…”

Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 99%

“…The copyright holder for this preprint this version posted March 13, 2022. ; https://doi.org/10.1101/2022.03.12.22272083 doi: medRxiv preprint 96.0% and specificity 84.4%) [5].…”

Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 99%

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Response to COVID-19 booster vaccinations in seronegative people with MS

Tallantyre

Scurr

Vickaryous

et al. 2022

Preprint

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Importance: Uncertainties remain about the benefit of a 3rd COVID-19 vaccine for people with attenuated response to earlier vaccines. This is of particular relevance for people with multiple sclerosis (pwMS) treated with anti-CD20 therapies and fingolimod, who have substantially reduced antibody responses to initial vaccine course. Objective: To report humoral and T-cell responses following COVID-19 vaccine 3 in pwMS who were seronegative after COVID-19 vaccines 1&2. Design, setting and participants: PwMS taking part in a seroprevalence study without a detectable IgG response following COVID-19 vaccines 1&2 were invited to participate. Participants provided a dried blood spot +/- venous blood sample 2-12 weeks following COVID-19 vaccine 3. Data on demographics, MS treatment, and COVID-19 infection/vaccine dates were derived from the medical notes. Methods: Humoral and T cell responses to SARS-CoV-2 spike protein and nucleocapsid antigen were measured. The relationship between evidence of prior COVID-19 infection and immune response to COVID-19 vaccine 3 was evaluated using Fishers exact test. Results: Of 81 participants, 79 provided a dried blood spot sample, of whom 38 also provided a whole blood sample; 2 provided only whole blood. Anti-SARS-CoV-2-spike IgG seroconversion post-COVID-19 vaccine 3 occurred in 26/79 (33%) participants; 26/40 (65%) had positive T-cell responses. Overall, 31/40 (78%) demonstrated either humoral or cellular immune response post-COVID-19 vaccine 3. There no association between laboratory evidence of prior COVID-19 infection and anti-spike seroconversion following COVID-19 vaccine 3. Conclusions: Approximately one third of pwMS who were seronegative after initial COVID-19 vaccination seroconverted after booster (third) vaccination, supporting the use of boosters in this group. Almost 8 out of 10 had a measurable immune response following 3rd COVID-19 vaccine.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 99%

“…The copyright holder for this preprint this version posted March 13, 2022. ; https://doi.org/10.1101/2022.03.12.22272083 doi: medRxiv preprint 96.0% and specificity 84.4%) [5].…”

Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 99%

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Response to COVID-19 booster vaccinations in seronegative people with MS

Tallantyre

Scurr

Vickaryous

et al. 2022

Preprint

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“…Studies of viral infections such as influenza have reported that physical distancing is effective at limiting disease spread, a scenario certainly influential for the protection of COVID-19 infections. The most effective preventive measure for deadly contagious diseases, including COVID-19, is vaccination, which fundamentally boosts the immune system, especially in susceptible populations [ 145 , 146 ]. Vaccines allow for preemptive development of memory B- and T-cells to neutralize pathogens; however, the efficacy of vaccines depends on age, existing immunity, underlying medical conditions, and/or and immunological disorders.…”

Section: Therapeutic Approaches For the Prevention And Treatment Of C...mentioning

confidence: 99%

Healthy Immunity on Preventive Medicine for Combating COVID-19

2022

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Immunomodulation is influenced by the consumption of nutrients, and healthy immunity is pivotal to defending an individual from a variety of pathogens. The immune system is a network of intricately regulated biological processes that is comprised of many organs, cellular structures, and signaling molecules. A balanced diet, rich in vitamins, minerals, and antioxidants, is key to a strengthened immune system and, thus, crucial to proper functioning of various physiological activities. Conversely, deficiencies of these micronutrients, involving impaired immunity, are linked to numerous health complications, along with a host of pathologies. Coronavirus disease 2019 (COVID-19) is a dangerous infectious disease caused by a β-form of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its genomic variants, which enter host cells upon binding to the angiotensin converting enzyme 2 receptors, and is associated with substantial morbidities and mortalities globally. Patients afflicted with COVID-19 display asymptomatic to severe symptoms, occurrences of which are multifactorial and include diverse immune responses, sex and gender differences, aging, and underlying medical conditions. Geriatric populations, especially men in comparison to women, regardless of their states, are most vulnerable to severe COVID-19-associated infections and complications, with fatal outcomes. Advances in genomic and proteomic technologies help one understand molecular events, including host–pathogen interactions and pathogenesis of COVID-19 and, subsequently, have developed a variety of preventive measures urgently, ranging from mask wearing to vaccination to medication. Despite these approaches, no unique strategy is available today that can effectively prevent and/or treat this hostile disease. As a consequence, the maintenance of a boosted immune system could be considered a high priority of preventive medicine for combating COVID-19. Herein, we discuss the current level of understanding underlining the contribution of healthy immunity and its relevance to COVID-19 molecular pathogenesis, and potential therapeutic strategies, in the management of this devastating disease.

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COVID‐19 Vaccine Response in People with Multiple Sclerosis

Tallantyre

Vickaryous

Anderson

et al. 2021

Annals of Neurology

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127

115

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Objective The purpose of this study was to investigate the effect of disease modifying therapies on immune response to severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) vaccines in people with multiple sclerosis (MS). Methods Four hundred seventy‐three people with MS provided one or more dried blood spot samples. Information about coronavirus disease 2019 (COVID‐19) and vaccine history, medical, and drug history were extracted from questionnaires and medical records. Dried blood spots were eluted and tested for antibodies to SARS‐CoV‐2. Antibody titers were partitioned into tertiles with people on no disease modifying therapy as a reference. We calculated the odds ratio of seroconversion (univariate logistic regression) and compared quantitative vaccine response (Kruskal Wallis) following the SARS‐CoV‐2 vaccine according to disease modifying therapy. We used regression modeling to explore the effect of vaccine timing, treatment duration, age, vaccine type, and lymphocyte count on vaccine response. Results Compared to no disease modifying therapy, the use of anti‐CD20 monoclonal antibodies (odds ratio = 0.03, 95% confidence interval [CI] = 0.01–0.06, p < 0.001) and fingolimod (odds ratio = 0.04; 95% CI = 0.01–0.12) were associated with lower seroconversion following the SARS‐CoV‐2 vaccine. All other drugs did not differ significantly from the untreated cohort. Both time since last anti‐CD20 treatment and total time on treatment were significantly associated with the response to the vaccination. The vaccine type significantly predicted seroconversion, but not in those on anti‐CD20 medications. Preliminary data on cellular T‐cell immunity showed 40% of seronegative subjects had measurable anti‐SARS‐CoV‐2 T cell responses. Interpretation Some disease modifying therapies convey risk of attenuated serological response to SARS‐CoV‐2 vaccination in people with MS. We provide recommendations for the practical management of this patient group. ANN NEUROL 2021

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Whole blood‐based measurement of SARS‐CoV‐2‐specific T cells reveals asymptomatic infection and vaccine immunogenicity in healthy subjects and patients with solid‐organ cancers

Cited by 23 publications

References 35 publications

Response to COVID-19 booster vaccinations in seronegative people with MS

Response to COVID-19 booster vaccinations in seronegative people with MS

Healthy Immunity on Preventive Medicine for Combating COVID-19

COVID‐19 Vaccine Response in People with Multiple Sclerosis

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