Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters

IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20

Clinical meanings of rapid serological assay in patients tested for SARS-Co2 RT-PCR

Background RT-PCR test for identifiction of viral nucleic acid is the current standard diagnostic method for the diagnosis of COVID-19 disease but technical reasons limit the utilization of this assay on large scale screenings. Method We verified in a consecutive series of 191 symptomatic patients the clinical information that new rapid serological colorimetric test qualitatively analyzing IgM/IgG expression can provide with respect to standard assay and with respect to clinical outcome of patients. Results Rapid serological test showed a sensitivity of 30% and a specificity of 89% with respect to the standard assay but, interestingly, these performances improve after 8 days of symptoms appearance. After 10 days of symptoms the predictive value of rapid serological test is higher than that of standard assay. When the behaviour of the two immunoglobulins was evaluated with respect to time length of symptoms appearance, no significant difference in immunoglobulins behaviour was shown. Conclusions The rapid serological test analyzed in the present study is candidate to provide information on immunoreaction of the subject to COVID-19 exposure

Rapid serological and SARS-CoV-2 RT-PCR assays: comparison performed simultaneously in symptomatic COVID-19 patients

RT-PCR testing for the identification of viral nucleic acid is the current standard diagnostic method for the diagnosis of SARS-CoV-2 infection but technical reasons limit its utilization for large-scale screening. Serological IgM/IgG testing has been proposed as a useful tool to detect SARS-CoV-2 exposure

Thyroglobulin determination in fine needle aspiration biopsy washout of suspicious lymph nodes in thyroid carcinoma follow up

Background: Differentiated thyroid carcinomas (DTCs) account for about 1% of all human malignancies. Cervical lymph nodes metastases and recurrences in the thyroid bed frequently occur. Furthermore, about 10-15% of patients develop distant metastases. Therefore, patients must undergo life-long follow-up. Objective: The aim of this study was to evaluate the usefulness of Thyroglobulin measurement in FNAB washout (FNAB-Tg) in the detection of local metastasis in patients affected by or evaluated for thyroid cancer. Materials and Methods: In a 3-year period, a total of 83 consecutive patients coming to our attention at the Ear-Nose-Throat (ENT) Outpatients Service of the National Cancer Research Center "Istituto Tumori Giovanni Paolo II" of Bari, Italy, because of the finding of one or more cervical lymph node(s), were enrolled in the study. After collection of the cytological specimen, the needle used for performing FNAB was then washed in 1 ml of normal saline. 89 FNAB washouts were collected from the same number of lymph nodes and subsequently investigated for Thyroglobulin levels using a sequential chemiluminescent-immunometric assay. Results: Comparing the cytological or, when performed, histological diagnoses with the results of FNAB-Tg, we found that in 24 cases of lymph node metastases from PTC (19 lymph nodes from patients at the first diagnoses and 5 lymph nodes from PTC patients in follow up) the mean level of Thyroglobulin was 1840.11 ng/ml; range: <0,2 to 11440 ng/ml. In the group of PTC patients (27 lymph nodes) with lymph nodes negative for metastatic involvement at cytology (i.e. no lymph node recurrence at follow-up), as well as in the cases of subjects without PTC and submitted to FNAB because of the appearance of lymph node(s) classified as reactive at cytology (37 lymph nodes), FNAB-Tg was lower than or equal to 0.2 ng/ml. As expected, the Thyroglobulin level was not detectable (< 0.2 ng/ml) also in a lymph node FNAB from a case of anaplastic thyroid carcinoma. Conclusion: In our study, FNAB-Tg was not detectable in all node negative patients showing, when considering together all the lymph node metastases, a 96% sensitivity and 100% specificity

Development of Approaches and Metrics to Measure the Impact and Improve the Clinical Outcomes of Patients With Frailty in the Era of COVID-19. The COMETA Italian Protocol

The outbreak of the coronavirus 2 disease 2019 (COVID-19) puts an enormous burden on healthcare systems worldwide. This may worsen outcomes in patients with severe chronic diseases such as cancer, autoimmune diseases, and immune deficiencies. In this critical situation, only a few available data exist, which do not allow us to provide practical guides for the treatment of oncological or immunocompromised patients. Therefore, a further step forward is needed, addressing the specific needs and demands of frail patients in the pandemic era. Here we aim to present a protocol of a study approved by an ethical committee named "CO.M.E.TA". CO.M.E.TA protocol is a network project involving six Italian institutions and its goals are: i) to measure and compare the impact of the pandemic on the access of cancer and immunocompromised patients to therapies in three Italian regions; ii) to assess how reorganizational measures put in place in these different institutions have impacted specific metrics of performance; iii) to establish a COVID-19 Biobank of biological samples from SARS-CoV-2 infected patients to be used to study immunological alterations in patients with immune frailty

Proteomic Profile and <i>In Silico</i> Analysis in Metastatic Melanoma with and without BRAF Mutation

<div><p>Introduction</p><p>Selective inhibitors of BRAF, vemurafenib and dabrafenib are the standard of care for metastatic melanoma patients with BRAF V600, while chemotherapy continued to be widely used in BRAF wild type patients.</p><p>Materials and Methods</p><p>In order to discover novel candidate biomarkers predictive to treatment, serum of 39 metastatic melanoma vemurafenib (n = 19) or chemotherapy (n = 20) treated patients at baseline, at disease control and at progression, were analyzed using SELDI-TOF technology. In silico analysis was used to identify more significant peaks.</p><p>Results</p><p>In patients with different BRAF status, we found 5 peptides significantly deregulated, with the down-regulation of the m/z 9176 peak strongly associated with BRAF mutation. At baseline as predictive biomarkers we identified 2 peptides - m/z 6411, 4075 – as significantly up-regulated in responders to chemotherapy and 4 peaks - m/z 5900, 12544, 49124 and 11724 - significantly up-regulated in longer vs shorter responders to vemurafenib. After response, 3 peptides (m/z 4658, 18639, and 9307) resulted significantly down regulated while 3 peptides m/z 9292, 7765 and 9176 appeared up-regulated respectively in chemotherapy and vemurafenib responder patients. In vemurafenib treated patients, 16 peaks appeared deregulated at progression compared to baseline time. In silico analysis identified proteins involved in invasiveness (SLAIN1) and resistance (ABCC12) as well as in the pathway of detoxification (NQO1) and apoptosis (RBM10, TOX3, MTEFD1, TSPO2). Proteins associated with the modulation of neuronal plasticity (RIN1) and regulatory activity factors of gene transcription (KLF17, ZBTB44) were also highlighted.</p><p>Conclusion</p><p>Our exploratory study highlighted some factors that deserve to be further investigated in order to provide a framework for improving melanoma treatment management through the development of biomarkers which could act as the strongest surrogates of the key biological events in stage IV melanoma.</p></div

The 4 discriminating m/z peaks among BRAF V600E/K mutated and BRAFwt MM patients. m/z: mass-to-charge ratio; P was generated by peak comparison between BRAF mutated and wild type patients.

<p>The 4 discriminating m/z peaks among BRAF V600E/K mutated and BRAFwt MM patients. m/z: mass-to-charge ratio; P was generated by peak comparison between BRAF mutated and wild type patients.</p

Mascot search result for BRAF wild-type patients.

<p>Mascot search result for BRAF wild-type patients.</p

BMI and pausal status in 300 subjects affected by breast cancer and 300 control cases.

<p>Mantel – Haenszel χ² p<0.05.</p