Humoral and T-cell immune response after three doses of mRNA SARS-CoV-2 vaccines in fragile patients: the Italian VAX4FRAIL study

Abstract

Background: Patients with solid or hematological tumors, neurological and immune-inflammatory disorders represent potentially fragile subjects with increased risk to experience severe COVID-19 and inadequate response to SARS-CoV2 vaccination. Methods: We designed a prospective Italian multicentric study to assess humoral and T-cell response to SARS-CoV2 vaccination in patients (n=378) with solid tumors (ST), hematological malignancies (HM), neurological (ND) and immuno-rheumatological diseases (ID). The immunogenicity of primary vaccination schedule and of the booster dose were analyzed. Results: Overall, patient seroconversion rate after two doses was 62.1%. A significant lower rate was observed in HM (52.4%) and ID (51.9%) patients compared to ST (95.6%) and ND (70.7%); a lower median level of antibodies was detected in HM and ID versus the others (p<0.0001). A similar rate of patients with a positive SARS-CoV2 T-cell response was observed in all disease groups, with a higher level observed in the ND group. The booster dose improved humoral responses in all disease groups, although with a lower response in HM patients, while the T-cell response increased similarly in all groups. In the multivariable logistic model, the independent predictors for seroconversion were disease subgroups, type of therapies and age. Notably, the ongoing treatment known to affect the immune system was associated with the worst humoral response to vaccination (p<0.0001), but had no effects on the T-cell responses. Conclusions: Immunosuppressive treatment more than disease type per se is a risk factor for low humoral response after vaccination. The booster dose can improve both humoral and T-cell response.

COVID-19 vaccine immunogenicity in 16 patients with autoimmune systemic diseases. Lack of both humoral and cellular response to booster dose and ongoing disease modifying therapies

“…Furthermore, by analyzing the T-cell response we found that half of the ASD patients did not develop a cellular immunity while only one HC showed an INF-γ level under the positivity cut-off. Although the presence of different diagnoses and the variability of DMT make very difficult a comparison with the few previously published results [ 14 , 18 , 25 , 26 ], the percentage of T-cell response we found is comparable to that reported by Firinu and colleagues that stratified ASD patients based on different treatments [ 18 ]. They found 50% of no response in subjects undergoing MTX (with or without anti-TNF), MMF, and/or low doses of CSs while 21% of those on anti-CD20 had no T-cell response [ 18 ].…”

“…On the other hands, previous observations in multiple sclerosis patients on anti-CD20 therapy [ 31 ] suggested that an impaired humoral response after the booster dose of COVID-19 vaccine could be compensated by an effective T-cell response; however, studies focusing on well-defined ASD are still very limited and partly conflicting [ 18 , 25 , 26 ] as briefly reported in Table 2 .…”

“… 2022 [ 24 ], Spain I cohort (ongoing immune-suppressors):100 II cohort (no immune-suppressors): 47 RA, SLE, SS, pSS I cohort: MTX, AZA, MMF, LFM and/or bDMARDs (Belimumab, ABA, RTX) II cohort: Non-steroidal anti-inflammatory drugs and/or infliximab, tocilizumab, anakinra I cohort Seroconversion: 55% II cohort Seroconversion: 80% Th1 response 52% CD8 response 77% Th1 response 75% CD8 response 53% Marty P·K. 2022 [ 21 ], USA 17 AAV 11 B-cell depleted 8 B-cell recovered 0% 100% 90.9% 88.9% After the booster dose of COVID-19 vaccine Corradini P. et al 2022 [ 26 ], Italy 37 AAV, SSc, mixed connective tissue disease, SLE, pSS, DM, polymyositis, and RA MTX, MMF, AZA, cyclosporine, RTX, CSs 90% 89.2% Firinu D. et al 2022 [ 18 ], Italy 31 RA, SLE, Connective Tissue Disease; MS RTX; OCRE; ADA; ETN; MTX; MMF; csDMARDs 55% among the RTX group, 100% in IMID (immune-mediated inflammatory diseases, naïve to RTX) 21 (68%) 79% among the RTX group, 50% in IMID Azzolini E. et al 2022 [ 25 ], Italy 30 PA/SpA/AS, RA, SLE, DM, pSS, SSc MTX, MMF 96.6% 80% Ag1 83.3% Ag2 Jyssum I. et al …”

“…The majority of the available studies assessed the T cell response among ASD patients after the first 1–2 doses of COVID-19 vaccination [ [15] , [16] , [17] , 19 , [22] , [23] , [24] ] but results concerning both humoral and cellular post booster immunogenicity are still very limited [ 14 , 18 , 25 , 26 ].…”

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).…”