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
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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.
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SciScore for 10.1101/2022.01.12.22269133: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study, according to the National COVID-19 procedures, was approved by the Italian Regulatory Agency (AIFA) and by the Ethics Committee of IRCCS L.
Consent: A written consent was obtained by the study participant.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Laboratory Procedures: Anti-Spike SARS-CoV-2 antibodies and T-cell response were monitored at 5 time points (Figure 1): the day of first dose administration (T0), the day of second dose administration (T1); between 5 and 7 weeks after T0 for patients receiving Pfizer/BioNTech vaccine and between 6 and 8 weeks after … SciScore for 10.1101/2022.01.12.22269133: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study, according to the National COVID-19 procedures, was approved by the Italian Regulatory Agency (AIFA) and by the Ethics Committee of IRCCS L.
Consent: A written consent was obtained by the study participant.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Laboratory Procedures: Anti-Spike SARS-CoV-2 antibodies and T-cell response were monitored at 5 time points (Figure 1): the day of first dose administration (T0), the day of second dose administration (T1); between 5 and 7 weeks after T0 for patients receiving Pfizer/BioNTech vaccine and between 6 and 8 weeks after T0 for patients receiving Moderna vaccine (T2); the day of the booster dose (T pre-3D) and 3 or 4 weeks after (T post-3D). Anti-Spike SARS-CoV-2suggested: NoneFinally, secondary endpoints included evaluation of neutralization activity of vaccine-induced anti-Spike antibodies. anti-Spikesuggested: NoneThe humoral (anti-Nucleoprotein-IgG and the anti-RBD-IgG, neutralizing antibody) and cell mediated immune response was performed as previously described [22] and detailed in the Supplementary materials. anti-Nucleoprotein-IgGsuggested: Noneanti-RBD-IgG, neutralizing antibodysuggested: NoneSoftware and Algorithms Sentences Resources IBM SPSS vers. SPSSsuggested: (SPSS, RRID:SCR_002865)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:A limitation of our study is the lack of measurement of neutralization titers against the emerging Omicron variant. However, in this context it has to be taken into account that in healthy subjects a significant increase in the neutralizing response against this variant has been observed after the third dose[37,38]. In conclusion, we demonstrated a lower prevalence of seroconversion among immunosuppressed patients compared to HCW. The lowest humoral response was reported among patients treated with anti-B-cell therapies. However, T-cell response results showed more encouraging data, suggesting a possible benefit of the vaccination due to cellular immunity, particularly in light of the observation that T-cell epitopes are shared among wild type and Omicron variant[39]. Finally, data on the third dose indicate a potential immunological benefit and highlights HM as the major fragile group.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a protocol registration statement.
Results from scite Reference Check: We found no unreliable references.
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