Acute cardiac compromission in patients with MIS-C

Background and Aim: Multisystem inflammatory syndrome in chil-dren (MIS-C) is a late manifestation of SARS-CoV-2 infection. Cardiac involvement is common and presents as ventricular dys-function, shock, and coronary anomalies. The aim of the study is evaluate the influence of cardiac disfunction on clinical presen-tations and outcomes in a single center. Method(s): A retrospective study on patients diagnosed with MIS-C and referred to Buzzi Children's Hospital in Milan from November 2020 to February 2021. Patients were treated with intravenous immunoglobulins, corticosteroids and anti-throm-botic prophylaxis, in respect to our approved multidisciplinary protocol. According to the admission cardiac left ventricular ejec-tion fraction (LVEF), the patients were divided into group A (LVEF lt;45%) and group B (LVEF >=45%). Result(s): We collected 32 consecutive patients. Group A included 10 patients (9M/1F, aged 13 years [IQR 5-15]), and group B included 22 patients (15M/7M, aged 9 years [IQR 7-13]). At the presentation, significant differences were observed among shock (group A 6/10 vs group B 2/22, plt;0.01), gastrointestinal involvement (9/10 vs 11/22, p = 0.04) and duration of fever (5.3 vs 6.9 days, p = 0.02). All patients in group A required inten-sive care hospitalization (10/10 vs 12/22, p = 0.01). Interestingly, despite good cardiac function, two patients in group B presented with shock, probably due to vasoplegic/distributive cardiocircula-tory impairment secondary to the inflammatory state. Among biochemistry parameters, leukocytes, neutrophils, and CRP were significantly worse in group A (p = 0.001, p = 0.001 and p = 0.008, respectively). Pathological level of troponin T and NTproBNP were detected in all patients in group A and also in 33% and 77% of group B;with statistically significant higher median values in group A (Troponin T 72 [40-243] ng/L vs 22 [8-49] ng/L, p = 0.01;NTproBNP 14825 [11340-17810] ng/L vs 5921 [1114-11243] ng/L, p = 0.01). In group A, mitral regurgitation was more frequent (plt;0.01) and one patient had transient left main coronary dilation (Boston z-score +2.39). At the discharge, cardiac function normalized in all patients. Total length of hospital stay and cardiac recovery time were not statistically different between groups. Conclusion(s): If correctly diagnosed and early treated, all the MIS-C patients completely recovered, regardless of the initial cardiac involvement.

Auto-immune toxicity of SARS-CoV2 vaccine in patients with thymic epithelial tumours: A prospective analysis from the tyme network

Background: There are many assumptions that raise fears of auto-immune toxicity of SARS-COV-2 vaccine in patients affected by Thymic epithelial tumours (TETs). TETs are associated with paraneoplastic autoimmune disorders and vaccine autoimmune cross reactivity is associated with many syndromes such as Guillain-Barre, multiple sclerosis, demyelinating neuropathies. Moreover, a crossreaction between SARS-Cov-2 anti protein spike antibodies and several tissue proteins has been reported. Material and methods: We are prospectively collecting data on safety and new onset or recurrence of autoimmune disorders in patients with TETs who received SARSCOV- 2 vaccine and are treated in referral centres of the TYME network. Patients with both Thymoma [T] and Thymic carcinoma [TC], with and without pre-existing autoimmune disorders, treated with chemotherapy, immunotherapy, TKI or just in follow up are included in the analysis. Association between epidemiological-clinical factors and risk of general Adverse Events (AEs), immune-related AEs and worsening of autoimmune disorders will be assessed. Results: Preliminary data from the first 20 patients (14 TC and 4 T) suggest that the administration of SARSCOV- 2 vaccines is well tolerated, with no safety signals nor reactivation or new onset of autoimmune diseases observed. Prospective data collection of all TETs patients treated in referral centres of the TYME network is ongoing and will be presented at the time of AIOM congress. Conclusions: Preliminary data suggest that the administration of SARS-COV-2 vaccines is safe and well tolerated in patients affected by TETs. A comprehensive characterization of general and immune-related safety profile of SARSCOV- 2 vaccines in such rare oncological population, enriched for potential risk factors for AEs, is ongoing.

Seroconversion rate after vaccination against COVID-19 in patients with cancer-a systematic review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has affected >210 million people worldwide. An optimal therapeutic approach for COVID-19 remains uncertain, to date. Since the history of cancer was linked to higher mortality rates due to COVID-19, the establishment of a safe and effective vaccine coverage is crucial in these patients. However, patients with cancer (PsC) were mostly excluded from vaccine candidates' clinical trials. This systematic review aims to investigate the current available evidence about the immunogenicity of COVID-19 vaccines in PsC. PATIENTS AND METHODS: All prospective studies that evaluated the safety and efficacy of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were included, with immunogenicity after the first and the second dose as the primary endpoint, when available. RESULTS: Vaccination against COVID-19 for PsC seems overall safe and immunogenic after well-conducted vaccination schedules. Yet the seroconversion rate remains lower, lagged or both compared to the general population. Patients with hematologic malignancies, especially those receiving B-cell-depleting agents in the past 12 months, are the most at risk of poor seroconversion. CONCLUSION: A tailored approach to vaccination may be proposed to PsC, especially on the basis of the type of malignancy and of the specific oncologic treatments received.

COVID-19 related risk in patients enrolled in early-phase clinical trials

Background: Early phase clinical trials often represent a therapeutical opportunity for cancer patients (pts). However, high logistic commitment is demanded for participation. Here we explore the COVID-19 related risk during the pandemic for pts enrolled in clinical trials compared to pts receiving standard treatments. Methods: We retrospectively assessed the incidence of COVID-19 in pts treated in our Department from March 2020 to April 2021. Pts were divided into two groups;those enrolled in phase I/II clinical trials (A) and those being treated with standard therapies (B). Logistical (telemedicine and drug home-delivery), as well as clinical, characteristics of susceptibility to COVID-19 and number of events (SARS-CoV2 infections) were collected. The number of teleconsultations and COVID-19 events among the two groups were compared through Fisher’s exact test. Results: 115 pts were evaluated: 36 pts (31%) in A and 79 pts (69%) in B. Pts in A were younger, with a median age of 55 years (range 39-77) compared to 62 years (range 31-83) in B. Performance status (PS, ECOG) was similarly distributed: 0 (A 78%, B 83%), 1-2 (A 22%, B 17%). The median of previous treatment was 1 in A (range 0-9) and 2 (range 0-14) in B. The majority of the pts had at least one comorbidity in both groups (A: 72% and B: 83%). None of the pts had pulmonary comorbidity in A and 6% in B. Obesity was similarly distributed (A 11%, B 14%). The mean of monthly scheduled accesses was 1,5 in both groups. However, teleconsultation and delivery of oral cancer treatments at home were given, at least on one occasion, to only 6% of pts in A compared to 43% in B (p<0.01). A total of 15 COVID-19 cases were observed (13%): 8 (22%) in A and 7 (8%) in B. No statistically significant difference was observed (p = 0.068). Conclusions: Pts enrolled in early phase clinical trials had a significantly lower chance to perform teleconsultations compared to pts receiving standard therapy. Even if a trend was observed, they did not have a higher risk of contracting COVID-19. Future pts should then be encouraged to participate, if indicated. Considering the small numbers of pts in our cohorts, the foreseen trend toward a higher infection risk and the subsequent implications should be further explored in larger populations. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: G Curigliano: Financial Interests, Funding: Roche;Financial Interests, Funding: Novartis;Financial Interests, Funding: Lilly;Financial Interests, Funding: Pfizer;Financial Interests, Funding: Seattle Genetics. All other authors have declared no conflicts of interest.

Therapeutic cancer vaccines revamping: technology advancements and pitfalls.

Cancer vaccines (CVs) represent a long-sought therapeutic and prophylactic immunotherapy strategy to obtain antigen (Ag)-specific T-cell responses and potentially achieve long-term clinical benefit. However, historically, most CV clinical trials have resulted in disappointing outcomes, despite promising signs of immunogenicity across most formulations. In the past decade, technological advances regarding vaccine delivery platforms, tools for immunogenomic profiling, and Ag/epitope selection have occurred. Consequently, the ability of CVs to induce tumor-specific and, in some cases, remarkable clinical responses have been observed in early-phase clinical trials. It is notable that the record-breaking speed of vaccine development in response to the coronavirus disease-2019 pandemic mainly relied on manufacturing infrastructures and technological platforms already developed for CVs. In turn, research, clinical data, and infrastructures put in place for the severe acute respiratory syndrome coronavirus 2 pandemic can further speed CV development processes. This review outlines the main technological advancements as well as major issues to tackle in the development of CVs. Possible applications for unmet clinical needs will be described, putting into perspective the future of cancer vaccinology.

Non-thyroidal illness syndrome and SARS-CoV-2-associated multisystem inflammatory syndrome in children.

PURPOSE: COVID-19 disease may result in a severe multisystem inflammatory syndrome in children (MIS-C), which in turn may alter thyroid function (TF). We assessed TF in MIS-C, evaluating its impact on disease severity. METHODS: We retrospectively considered children admitted with MIS-C to a single pediatric hospital in Milan (November 2019-January 2021). Non-thyroidal illness syndrome (NTIS) was defined as any abnormality in TF tests (FT3, FT4, TSH) in the presence of critical illness and absence of a pre-existing hormonal abnormality. We devised a disease severity score by combining severity scores for each organ involved. Glucose and lipid profiles were also considered. A principal component analysis (PCA) was performed, to characterize the mutual association patterns between TF and disease severity. RESULTS: Of 26 (19 M/7F) patients, median age 10.7 (IQR 5.8-13.3) years, 23 (88.4%) presented with NTIS. A low FT3 level was noted in 15/23 (65.3%), while the other subjects had varying combinations of hormone abnormalities (8/23, 34.7%). Mutually correlated variables related to organ damage and inflammation were represented in the first dimension (PC1) of the PCA. FT3, FT4 and total cholesterol were positively correlated and characterized the second axis (PC2). The third axis (PC3) was characterized by the association of triglycerides, TyG index and HDL cholesterol. TF appeared to be related to lipemic and peripheral insulin resistance profiles. A possible association between catabolic components and severity score was also noted. CONCLUSIONS: A low FT3 level is common among MIS-C. TF may be useful to define the impact of MIS-C on children's health and help delineate long term follow-up management and prognosis.