Immune-Guided Therapy of COVID-19

Ferraccioli, Gianfranco; Gremese, Elisa; Goletti, Delia; Petrone, Linda; Cantini, Fabrizio; Ugel, Stefano; Canè, Stefania; Bronte, Vincenzo

doi:10.1158/2326-6066.cir-21-0675

Cited by 22 publications

(18 citation statements)

References 209 publications

(236 reference statements)

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“…Correlates of protection against SARS-CoV-2 infection are not yet established, and, up to now, we evaluated B-and T-cell parameters altogether (49)(50)(51). Therefore, looking at the overall specific B-and T-cell responses, patients may be stratified as full responders (both humoral and cellular), not responders, or partial responders (only humoral or T-cell response).…”

Section: Discussionmentioning

confidence: 99%

Kinetics of the B- and T-Cell Immune Responses After 6 Months From SARS-CoV-2 mRNA Vaccination in Patients With Rheumatoid Arthritis

et al. 2022

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ObjectiveTo assess the kinetics of the humoral and cell-mediated responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in rheumatoid arthritis (RA) patients treated with different immunosuppressive therapies.MethodsFollowing vaccine completed schedule, health care workers (HCWs, n = 49) and RA patients (n = 35) were enrolled at 5 weeks (T1) and 6 months (T6) after the first dose of BNT162b2-mRNA vaccination. Serological response was assessed by quantifying anti-receptor-binding domain (RBD)-specific immunoglobulin G (IgG) and SARS-CoV-2 neutralizing antibodies, while cell-mediated response was assessed by a whole-blood test quantifying the interferon (IFN)-γ response to spike peptides. B-cell phenotype and IFN-γ-specific T-cell responses were evaluated by flow cytometry.ResultsAfter 6 months, anti-RBD antibodies were still detectable in 91.4% of RA patients, although we observed a significant reduction of the titer in patients under Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4)-Ig [median: 16.4 binding antibody units (BAU)/ml, interquartile range (IQR): 11.3–44.3, p < 0.0001] or tumor necrosis factor (TNF)-α inhibitors (median: 26.5 BAU/ml, IQR: 14.9–108.8, p = 0.0034) compared to controls (median: 152.7 BAU/ml, IQR: 89.3–260.3). All peripheral memory B-cell (MBC) subpopulations, in particular, the switched IgG+ MBCs (CD19+CD27+IgD-IgM-IgG+), were significantly reduced in RA subjects under CTLA-4-Ig compared to those in HCWs (p = 0.0012). In RA patients, a significantly reduced anti-RBD IgG titer was observed at T6 vs. T1, mainly in those treated with CTLA-4-Ig (p = 0.002), interleukin (IL)-6 inhibitors (p = 0.015), and disease-modifying antirheumatic drugs (DMARDs) ± corticosteroids (CCSs) (p = 0.015). In contrast, a weak nonsignificant reduction of the T-cell response was reported at T6 vs. T1. T-cell response was found in 65.7% of the RA patients at T6, with lower significant magnitude in patients under CTLA-4-Ig compared to HCWs (p < 0.0001). The SARS-CoV-2 IFN-γ-S-specific T-cell response was mainly detected in the CD4+ T-cell compartment.ConclusionsIn this study, in RA patients after 6 months from COVID-19 vaccination, we show the kinetics, waning, and impairment of the humoral and, to a less extent, of the T-cell response. Similarly, a reduction of the specific response was also observed in the controls. Therefore, based on these results, a booster dose of the vaccine is crucial to increase the specific immune response regardless of the immunosuppressive therapy.

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Section: Discussionmentioning

confidence: 99%

Kinetics of the B- and T-Cell Immune Responses After 6 Months From SARS-CoV-2 mRNA Vaccination in Patients With Rheumatoid Arthritis

et al. 2022

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“…T-cell-mediated immunity is pivotal for viral clearance and the subsequent induction of a B-cell response. Unlike the humoral response, T-cell response is more enduring and detectable even in the absence of seroconversion (Ferraccioli et al, 2022;Grifoni et al, 2020;Sekine et al, 2020), and takes on a greater importance in the context of the emerging variants that escape the antibody response (Geers et al, 2021;Liu et al, 2022;Tarke et al, 2022). Despite many commercial tests are available for the antibody evaluation, reliable tests for detecting the SARS-CoV-2 T-cell response are still needed.…”

Section: Introductionmentioning

confidence: 99%

Accuracy of QuantiFERON SARS-CoV-2 research use only assay and characterization of the CD4+ and CD8+ T cell-SARS-CoV-2 response: comparison with a homemade interferon-γ release assay

Aiello¹,

Coppola²,

Vanini³

et al. 2022

International Journal of Infectious Diseases

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“…COVID-19 still needs more effective therapies [ 8 ]. For instance, human monoclonal antibodies (mAbs) do not work in advanced severe disease and some of them were found to be ineffective against the emerging variants of the virus, in particular for the Omicron variant [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Cysteamine exerts in vitro antiviral activity against the SARS-CoV-2 Delta and Omicron variants

et al. 2022

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The novel SARS-CoV-2 variants of concern (VOC) represent a considerable global alarm because their mutations are known to affect transmissibility and cause immune escape. While preventing severe disease and deaths, the available vaccines do not avoid infection; therefore, COVID-19 disease management still requires effective therapies. We have recently reported that the aminothiol cysteamine, a drug already applied to humans, exerts direct antiviral activity against SARS-CoV-2 and has in vitro immunomodulatory effect. To evaluate whether this compound exerts antiviral effects also against SARS-CoV-2 variants, we performed different infected cell-based assays using Wild type, Delta, or Omicron VOC. We found that cysteamine significantly reduces the cytopathic effect induced by SARS-CoV-2 Wild type strain and Delta variant in Vero E6 cells. On the other hand, cysteamine had no effects on the survival of cells infected with the Omicron variant, due to the lack of cytotoxicity on Vero E6 cells, at least when infected at MOI = 0.001 for 72 h. Moreover, cysteamine significantly reduced the production of Wild type, Delta, and Omicron variants as measured by the virus released in the culture media (Vero E6 and Calu-3 cells) and by transmission electron microscopy analysis (Vero E6 cells). Notably, cysteamine is more effective in inhibiting the Omicron rather than Delta or Wild type viruses, with an 80% inhibition of Omicron production compared to 40% of Wild type and Delta variant. Overall, our findings demonstrate that cysteamine exerts direct antiviral actions against SARS-CoV-2 Delta and Omicron variants, in addition to the Wild type virus. Our data further demonstrate that cysteamine is a good candidate as repurposing drug for the treatment of SARS-CoV-2 infection for the present and, likely, the future VOC and, therefore, it would be important to investigate its clinical relevance in randomized clinical trials.

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Immune-Guided Therapy of COVID-19

Cited by 22 publications

References 209 publications

Kinetics of the B- and T-Cell Immune Responses After 6 Months From SARS-CoV-2 mRNA Vaccination in Patients With Rheumatoid Arthritis

Kinetics of the B- and T-Cell Immune Responses After 6 Months From SARS-CoV-2 mRNA Vaccination in Patients With Rheumatoid Arthritis

Accuracy of QuantiFERON SARS-CoV-2 research use only assay and characterization of the CD4+ and CD8+ T cell-SARS-CoV-2 response: comparison with a homemade interferon-γ release assay

Cysteamine exerts in vitro antiviral activity against the SARS-CoV-2 Delta and Omicron variants

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