Humoral and T-Cell Immune Response After 3 Doses of Messenger RNA Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines in Fragile Patients: The Italian VAX4FRAIL Study

Abstract

Background Patients with solid or hematological tumors or neurological and immune-inflammatory disorders are potentially fragile subjects at increased risk of experiencing severe coronavirus disease 2019 and an inadequate response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Methods We designed a prospective Italian multicenter study to assess humoral and T-cell responses to SARS-CoV-2 vaccination in patients (n = 378) with solid tumors (ST), hematological malignancies (HM), neurological disorders (ND), and immunorheumatological diseases (ID). A group of healthy controls was also included. We analyzed the immunogenicity of the primary vaccination schedule and booster dose. Results The overall seroconversion rate in patients after 2 doses was 62.1%. Significantly lower rates were observed in HM (52.4%) and ID (51.9%) than in ST (95.6%) and ND (70.7%); a lower median antibody level was detected in HM and ID versus ST and ND (P < .0001). Similar rates of patients with a positive SARS-CoV-2 T-cell response were found in all disease groups, with a higher level observed in ND. The booster dose improved the humoral response in all disease groups, although to a lesser extent in HM patients, whereas the T-cell response increased similarly in all groups. In the multivariable logistic model, independent predictors of seroconversion were disease subgroup, treatment type, and age. Ongoing treatment known to affect the immune system was associated with the worst humoral response to vaccination (P < .0001) but had no effect on T-cell responses. Conclusions Immunosuppressive treatment more than disease type per se is a risk factor for a low humoral response after vaccination. The booster dose can improve both humoral and T-cell responses.

The third dose of mRNA SARS-CoV-2 vaccines enhances the spike-specific antibody and memory B cell response in myelofibrosis patients

“…Patient #583, affected also by chronic lymphocytic leukemia, is in treatment with ibrutinib; patient #552 received a B-celldepleting treatment with anti CD20 monoclonal antibodies for a non-Hodgkin lymphoma some years ago, without IgG recovery before the vaccination, and patient #497, affected by fibromyalgia, is in chronic therapy with methylprednisolone, that induces lymphopenia and hypogammaglobulinemia. As such, in line with other recent reports, the lower response to mRNA vaccines in hematologic patients seems to be influenced by B-cell depleting therapies, hypogammaglobulinemia (42) and immunosuppressive treatment (43), regardless of therapy with ruxolitinib.…”

Immunogenicity and risks associated with impaired immune responses following SARS-CoV-2 vaccination and booster in hematologic malignancy patients: an updated meta-analysis

“…There were 12 studies [16,21,29,30,59,67,89,92,96,101,110,140] including 1479 patients with solid cancers and 20 studies [20,23,25,28,39,42,43,45,46,49,54,56,59,73,78,92,93,141,144,175] including 1121 healthy controls for comparison. The pooled seroconversion rates of solid cancer patients and healthy controls were 89.2% (95% CI, 87.2-90.9%, I 2 = 83%) and 98.7% (95% CI, 97.7-99.3%, I 2 = 0%), respectively.…”

Safety of third dose of COVID-19 vaccination in frail patients: Results from the prospective Italian VAX4FRAIL study

“…In addition, increased side effects were reported after the second than after the first dose, consisting mainly of systemic symptoms such as fatigue and headache. Therefore, the booster toxicity profile observed in VAX4FRAIL could simply reflect the capability of the third dose of eventually eliciting a specific immune response also in the fragile patient population, as we recently reported ( 14 ). All the reported toxicities we observed are still clinically manageable and have a negligible effect on the cancer care path as already reported ( 6 , 15 ).…”