Study of the SARS-CoV-2-specific immune T-cell responses in COVID-19-positive cancer patients

Mansi, Laura; Spehner, Laurie; Daguindau, Étienne; Bouiller, Kévin; Almotlak, Hamadi; Stein, Ulrich; Bouard, Adeline; Kim, Stéfano; Klajer, Elodie; Jary, Marine; Meynard, Guillaume; Vienot, Angélique; Nardin, Charlée; Bazán, Fernando; Lepiller, Quentin; Westeel, Virginie; Adotévi, Olivier; Borg, Christophe; Kroemer, Marie

doi:10.1016/j.ejca.2021.03.033

Cited by 30 publications

(39 citation statements)

References 20 publications

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“…While these findings suggested a lack of a protective T-cell response, the patients presented with mild illnesses despite relatively high viral loads. 12 And although we had one death in our patient cohort post-bone marrow transplant, allogeneic, autologous and CAR-T therapy patients have overall favorable outcomes following SARS-CoV-2 infection. 13 Similar to findings from adult studies, we did not see a relationship between clinical presentation and persistent positive SARS-CoV-2 status.…”

Section: Discussionmentioning

confidence: 77%

SARS-CoV-2 Persistence in Immunocompromised Children

Dolan¹,

Levy²,

Moss³

et al. 2021

Preprint

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Introduction/Objectives: We evaluated the length of time immunocompromised children (ICC) remain positive for SARS-CoV-2, identified factors associated with viral persistence and determined cycle threshold (CT) values of children with viral persistence as a surrogate of viral load. Methods: We conducted a retrospective cohort study of ICC at a pediatric hospital from March 2020-2021. Immunocompromised status was defined as primary, secondary or acquired due to medical comorbidities/immunosuppressive treatment. The primary outcome was time to first-of-two consecutive negative SARS-CoV-2 Polymerase chain reaction (PCR) tests at least 24 hours apart. Testing of sequential clinical specimens from the same subject was conducted using the Centers for Disease Control (CDC) 2019-nCoV Real-Time RT-PCR Diagnostic Panel assay. Descriptive statistics, Kaplan-Meier curve median event times and log-rank-sum tests were used to compare outcomes between groups. Results: Ninety-one children met inclusion criteria. Median age was 15.5 years (IQR 8-18 yrs), 64% were male, 58% were white, and 43% were Hispanic/Latinx. Most (67%) were tested in outpatient settings and 58% were asymptomatic. The median time to two negative tests was 42 days (IQR 25.0,55.0), with no differences in median time by illness presentation or level of immunosuppression. Seven children had >1 sample available for repeat testing, and 5/7 (71%) children had initial CT values of <30, (moderate to high viral load); 4 children had CT values of <30 3-4 weeks later, suggesting persistent moderate to high viral loads. Conclusions: Most ICC with SARS-CoV-2 infection had mild disease, with prolonged viral persistence >6 weeks and moderate to high viral load.

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Section: Discussionmentioning

confidence: 77%

SARS-CoV-2 Persistence in Immunocompromised Children

Dolan¹,

Levy²,

Moss³

et al. 2021

Preprint

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“…In contrast, several of the seronegative patients showed an emerging cellular response after dose 3, suggesting a positive effect of a second booster dose despite the absence of humoral response. Given the importance of a T-cell response in critically ill COVID-19 patients (14)(15), this is another expected benefit of the dose 3 vaccine dose, especially for patients treated with anti-CD20 Mab based therapy who are at high risk for death or ongoing SARS-CoV-2 shedding (16)(17).…”

Section: Discussionmentioning

confidence: 99%

Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients treated for lymphoid malignancies

Ré

Seitz-Polski

Carlès

et al. 2021

Preprint

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Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients treated for lymphoid malignancies. BACKGROUND: Immunocompromised patients such as patients with hematological malignancies have impaired immune response to two doses of BNT162b2 (Pfizer / BioNtech) vaccine against SARS-CoV-2. Evaluation of a repeated immune stimulation with a third vaccine dose is needed. METHODS: a vaccine monitoring observatory was conducted in outpatients who were treated for lymphoid malignancies (LM) to monitor both immune and cellular response measured the day of administration of the dose 3 of the mRNA vaccine BNT162b2 and again three to four weeks. Elecsys Anti-SARS-CoV-2 immunoassay was used to asses to the level of SARS-CoV-2 anti-Spike (S) antibodies (Abs) titer and SARS-CoV-2-specific T-cell responses were assessed by a whole blood Interferon-Gamma Release Immuno Assay (IGRA) (QuantiFERON Human IFN-gamma SARS-CoV-2, Qiagen). RESULTS: Among the 43 assessable patients (suffering from chronic lymphocytic leukemia (CLL) (n=15), indolent and aggressive B cell non-Hodgkin lymphoma (NHL) (n=14), and multiple myeloma (MM) (n=16)), 18 (41,8%) had no anti-S Abs before the dose 3 of BNT162b2 vaccine (n=9 CLL, n=8 NHL, n=1 MM), and they all 18 remained negative after the dose 3. Amongst the 25 patients with positive anti-S titers before dose 3, all patients remained positive and 23 patients increased their anti-S titer after dose 3. Patients with CLL and/or with previous anti-CD20 therapy treated within 12 months of administration of dose 3 had no significant increase of the humoral response. Among 22 available patients, dose 3 of BNT162b2 vaccine significantly increased the median IFN-gamma secretion. On eight (36.4%) patients who were double-negative for both immune and cellular response, five (22.7%) patients remained double-negative after dose 3. CONCLUSIONS Dose 3 of BNT162b2 vaccine stimulated humoral immune response among patients with LM, in particular patients with MM (who had higher anti-S baseline titer after dose 2) and those with no anti-CD20 treatment history within a year. T-cell response was increased among patients in particular with no active chemotherapy regimen. Our data support the use of an early third vaccine dose among immunocompromised patients followed for LM though some of them will still have vaccine failure.

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“…In contrast, several of the seronegative patients showed an emerging cellular response after dose 3, suggesting a positive effect of a second booster dose despite the absence of humoral response. Given the importance of a T-cell response in critically ill COVID-19 patients (14)(15), this is another expected bene t of the dose 3 vaccine dose, especially for patients treated with anti-CD20 Mab based therapy who are at high risk for death or ongoing SARS-CoV-2 shedding (16-17).…”

Section: Discussionmentioning

confidence: 99%

Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients with lymphoid malignancies

Ré

Seitz-Polski

Carlès

et al. 2021

Preprint

View full text Add to dashboard Cite

BACKGROUND: Immunocompromised patients such as patients with hematological malignancies have impaired immune response to two doses of BNT162b2 (Pfizer / BioNtech) vaccine against SARS-CoV-2. Evaluation of a repeated immune stimulation with a third vaccine dose is needed.METHODS: a vaccine monitoring observatory was conducted in outpatients who were treated for lymphoid malignancies (LM) to monitor both immune and cellular response measured the day of administration of the dose 3 of the mRNA vaccine BNT162b2 and again three to four weeks. Elecsys ® Anti-SARS-CoV-2 immunoassay was used to asses to the level of SARS-CoV-2 anti-Spike (S) antibodies (Abs) titer and SARS-CoV-2-specific T-cell responses were assessed by a whole blood Interferon-Gamma Release Immuno Assay (IGRA) (QuantiFERON Human IFN-gamma SARS-CoV-2, Qiagen®).RESULTS: Among the 43 assessable patients (suffering from chronic lymphocytic leukemia (CLL) (n=15), indolent and aggressive B cell non-Hodgkin lymphoma (NHL) (n=14), and multiple myeloma (MM) (n=16)), 18 (41,8%) had no anti-S Abs before the dose 3 of BNT162b2 vaccine (n=9 CLL, n=8 NHL, n=1 MM), and they all 18 remained negative after the dose 3. Amongst the 25 patients with positive anti-S titers before dose 3, all patients remained positive and 23 patients increased their anti-S titer after dose 3. Patients with CLL and/or with previous anti-CD20 therapy treated within 12 months of administration of dose 3 had no significant increase of the humoral response. Among 22 available patients, dose 3 of BNT162b2 vaccine significantly increased the median IFN-gamma secretion. On eight (36.4%) patients who were double-negative for both immune and cellular response, five (22.7%) patients remained double-negative after dose 3.CONCLUSIONSDose 3 of BNT162b2 vaccine stimulated humoral immune response among patients with LM, in particular patients with MM (who had higher anti-S baseline titer after dose 2) and those with no anti-CD20 treatment history within a year. T-cell response was increased among patients in particular with no active chemotherapy regimen. Our data support the use of an early third vaccine dose among immunocompromised patients followed for LM though some of them will still have vaccine failure.

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Study of the SARS-CoV-2-specific immune T-cell responses in COVID-19-positive cancer patients

Cited by 30 publications

References 20 publications

SARS-CoV-2 Persistence in Immunocompromised Children

SARS-CoV-2 Persistence in Immunocompromised Children

Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients treated for lymphoid malignancies

Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients with lymphoid malignancies

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