Sex-related differences in patients with coronavirus disease 2019: results of the Cardio-COVID-Italy multicentre study.

INTRODUCTION: The role of sex compared to comorbidities and other prognostic variables in patients with coronavirus disease (COVID-19) is unclear. METHODS: This is a retrospective observational study on patients with COVID-19 infection, referred to 13 cardiology units. The primary objective was to assess the difference in risk of death between the sexes. The secondary objective was to explore sex-based heterogeneity in the association between demographic, clinical and laboratory variables, and patients' risk of death. RESULTS: Seven hundred and one patients were included: 214 (30.5%) women and 487 (69.5%) men. During a median follow-up of 15 days, deaths occurred in 39 (18.2%) women and 126 (25.9%) men. In a multivariable Cox regression model, men had a nonsignificantly higher risk of death vs. women (P = 0.07).The risk of death was more than double in men with a low lymphocytes count as compared with men with a high lymphocytes count [overall survival hazard ratio (OS-HR) 2.56, 95% confidence interval (CI) 1.72-3.81]. In contrast, lymphocytes count was not related to death in women (P = 0.03).Platelets count was associated with better outcome in men (OS-HR for increase of 50 × 103 units: 0.88 95% CI 0.78-1.00) but not in women. The strength of association between higher PaO2/FiO2 ratio and lower risk of death was larger in women (OS-HR for increase of 50 mmHg/%: 0.72, 95% CI 0.59-0.89) vs. men (OS-HR: 0.88, 95% CI 0.80-0.98; P = 0.05). CONCLUSIONS: Patients' sex is a relevant variable that should be taken into account when evaluating risk of death from COVID-19. There is a sex-based heterogeneity in the association between baseline variables and patients' risk of death.

SARS-CoV-2 vaccine in patients with thymic epithelial tumours with and without active or pre-existing autoimmune disorders: Brief report of a TYME network safety analysis.

BACKGROUND: International guidelines recommend severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine for patients with cancer. A substantial risk of developing vaccine-related autoimmune toxicities could be hypothesised for patients with thymic epithelial tumours (TETs) due to their high risk of autoimmune disorders (ADs). Moreover, a cross-reaction between SARS-CoV-2 spike protein antibodies and various tissue proteins has been shown, and antibodies against nucleoproteins showed overlaps in the autoimmune cross-reaction with antibodies to spike protein. Due to the rarity of TETs, no data addressing this hypothesis are available. METHODS: Patients with TETs who received SARS-CoV-2 vaccine, treated in 4 referral centres of the Italian Collaborative Group for ThYmic MalignanciEs (TYME) network between February 2021 and September 2021, were interviewed through a standardised 15-items questionnaire in order to describe the safety of SARS-CoV-2 vaccine in patients affected by TETs. RESULTS: Data from 245 doses of vaccine administered to 126 patients (41 = thymic carcinoma, 85 = thymoma; 38 with AD, of which 26 with active AD) were collected. Nine patients had a previous COVID-19-positive swab. No cases of AD reactivation or worsening of a pre-existing AD were seen in the study population. A new diagnosis of myasthenia gravis likely unrelated to the vaccine was made in two patients after the vaccination. Sixty-four patients (51%) experienced a total of 103 adverse events, all G1/G2, most commonly fatigue, new or worsening muscle pain and chills. None AE required patients' hospitalisation. CONCLUSIONS: SARS-CoV-2 mRNA vaccines appear to be safe in patients with TET, even in case of active or pre-existing AD.

Patients with locally advanced and metastatic cutaneous squamous cell carcinoma treated with immunotherapy in the era of COVID-19: stop or go? Data from five Italian referral cancer centers.

Since the end of 2019, global healthcare systems have been dealing with the COVID-19 pandemic. In oncology, the biggest questions concern interaction of COVID-19 with pre-existing cancer disease and with systemic anticancer treatments. With regards to immunotherapy, there is uncertainty about its effect in the context of COVID-19 in terms of probability and course of viral infection. Herein, we retrospectively report data of patients with advanced cutaneous squamous cell carcinoma (cSCC) treated with immunotherapy at five Italian referral cancer centers during the pandemic. cSCC is a disease poorly represented in the literature, typically affecting fragile, elderly patients, with multiple comorbidities and often immunosuppressed. Overall, 54 patients were identified, most of them coming from Lombardy and Piedmont, the two regions hit hardest by COVID in Italy. In most cases, our choice was to continue treatment, reserving temporary interruptions only to patients considered particularly at risk for age and comorbidity. A total of 9% of patients developed new-onset symptoms or had chest radiological assessment potentially related to COVID-19. Nasopharyngeal swabs were collected in all suspicious cases and two hospitalized patients were found to be positive. In conclusion, the outbreak of COVID-19 is a major worldwide health concern. Our data indicate that COVID-19 mortality in patients with cancer may be principally driven by advancing age, the presence of other comorbidities, and other cancer-related conditions (i.e. hospitalization). Our data further suggests the safety of continued use of PD-1 blockade during the COVID-19 pandemic (obviously implementing all the safety measures in the hospital environment) also considering the possible negative effects of a prolonged suspension on the course of the tumor evolution. We think it is useful to collect and report case studies coming from reference centers, because they can represent helpful examples for the scientific community of clinical management of patients affected by cancer in this difficult period and guide further research.

Course of Sars-CoV2 Infection in Patients with Cancer Treated with anti-PD-1: A Case Presentation and Review of the Literature.

The outbreak of COVID-19 pandemia is a major health worldwide concern. Patients with cancer might have a worse outcome, because of the immunosuppression determined by the tumor itself and anti-cancer treatments, including chemotherapy and radiotherapy. The impact and course of viral infection in patients receiving immunotherapy remains unknown. We report the case of a patient with metastatic melanoma, long responder to anti PD-1 blockade who got infected with Sars CoV-2, recovering without sequelae. A critical review of literature was performed. Limited data available in literature support the possibility to continue the immunotherapy in patients with cancer under control.

Data of Italian Cancer Centers from two regions with high incidence of SARS CoV-2 infection provide evidence for the successful management of patients with locally advanced and metastatic melanoma treated with immunotherapy in the era of COVID-19.

BACKGROUND: Patients with cancer are presumed to have a higher risk to contract SARS-CoV-2 infection, because of their immunosuppressed status. The impact and course of COVID-19 infection in cancer patients receiving immunotherapy remains unknown. OBJECTIVES: To evaluate the safety of the management of patients with advanced melanoma treated with immunotherapy in 2 Cancer Centers located in areas of Italy with a high incidence of COVID-19 infections. METHODS: We retrospectively analyzed data from January 1 to April 30, 2020 on patients with locally advanced and metastatic melanoma receiving immunotherapy at either Istituto Europeo di Oncologia or Città della Salute e della Scienza University Hospital. RESULTS: One-hundred and sixty-nine patients with stage III and IV melanoma were treated with an immunotherapy regimen at either Istituto Europeo di Oncologia or Città della Salute e della Scienza University Hospital. One-hundred and four patients continued treatment without interruption or delay, while 49 patients had a treatment delay. The main reasons for treatment delay were older age (median age of the group of patients with or without treatment-delay, respectively 60 and 69 years, P value <0.001) and/or presence of comorbidities (percentage of patients with at least one comorbidity respectively 81% and 62%, in patients with or without treatment delay, P value = 0.001). One-hundred and twelve patients had at least 1 thoracic CT scan performed and radiological findings suspicious for COVID-19 were observed in only 7 cases (4%). Fifteen patients (9%) developed symptoms potentially related to COVID-19; nasopharyngeal swabs were collected in 9 patients and only 1 was positive for SARS-CoV-2. CONCLUSIONS: The incidence of symptomatic COVID-19 infection observed in our cohort of patients with advanced malignant melanoma treated with immunotherapy appears meaningfully lower as compared with that reported in the overall population in Italy as well as in patients affected by solid tumors. We conclude that in patients with locally advanced and metastatic melanoma, immunotherapy can be safely continued without delay in the majority of cases, reserving precautionary delay only for the most frail patients.