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Low Vitamin D (VD) levels in COVID-19 patients have been related to increased disease severity and worse outcomes. However, most of these trials designs were not-controlled and retrospective, including patients with demographic differences and biases potentially influencing the reported associations between lower VD levels and severe COVID-19. Aim of this study was to prospectively evaluate VD levels influence on disease severity in a COVID-19 patients cohort matched for age, sex and comorbidities with control subjects. Patients admitted to San Raffaele University Hospital for COVID-19 from March to June 2021 were consecutively enrolled in this study, which was approved by the local IRB, after giving their informed consent. Severe (i. e. those needing high flow oxygen therapy) and non-severe COVID-19 patients matched for age, sex and comorbidities were recruited at admission in Emergency Department (ED). Control subjects from the outpatient Endocrinology Unit of the same Hospital were enrolled in the same period. We excluded patients with comorbidities and therapies influencing VD metabolism. 25OH-VD levels were evaluated at admission in ED and VD deficiency was defined by serum 25OH-VD below 20 ng/mL. A total of 73 COVID-19 patients and 30 control subjects were included in the study. No differences regarding age, sex and comorbidities were found between patients and control groups, but 25OH-VD levels were statistically lower in COVID-19 patients (13.3 vs 23.6 ng/mL, p<0. 001) with a higher prevalence of VD deficiency (75% vs 43%, p=0. 002). After the ED admission, during the hospitalization, a severe disease occurred in a total of 46 COVID-19 patients, and 27 were affected by a non-severe one. No differences regarding age, sex and comorbidities were found between severe vs non-severe groups, but 25OH-VD was significantly lower in the severe one (11.7 vs 16.7 ng/mL, p=0. 007) with a higher prevalence of VD deficiency (85% vs 59%, p=0. 015). We observed lower 25OH-VD levels at admission in patients with non-invasive mechanical ventilation requirement (n.18) and in those admitted in intensive care unit (n.8) during hospitalization, compared to the other patients (p=0. 003 and p=0. 01), although no differences regarding age and comorbidities were found. Moreover, in patients with VD deficiency we found higher levels of inflammatory markers C-reactive protein and ferritin (69 vs 42 mg/L, p=0. 036;723 vs 414 ng/mL, p=0. 028), and lower SaO2/FiO2 and PaO2/FiO2 ratios (433 vs 447, p=0. 005;261 vs 311;p<0. 001) at hospital admission. In conclusion, our prospective data confirm that low VD levels are widely found in hospitalized COVID-19 patients compared to control subjects and predict increased disease severity independently from age, sex and comorbidities of patients affected. We suggest that tackling VD deficiency may be an effective preventive measure to prevent severe COVID-19.Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
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Background: The Omicron (B.1.1.529) SARS-CoV-2 variant is highly transmissible and escapes vaccinal immunity. Evidence is lacking as to the impact of Omicron in oncological patients. Method(s): Capitalizing on OnCovid study data (NCT04393974), we analysed COVID-19 morbidity and case fatality rate at 28 days (CFR28) of unvaccinated patients across 3 phases defined following the evolution of the pandemic in Europe, according to date of COVID-19 diagnosis: "Pre-vaccination" phase (27/02/2020-30/11/2020), "Alpha- Delta variant" phase (01/12/2020-14/12/2021), "Omicron variant" phase (15/12/2021-31/01/2022). Finding(s): By the data lock of 04/02/2022, 3820 patients from 37 institutions across 6 countries were entered. Out of 3473 eligible patients, 2033 (58.6%), 1075 (30.9%) and 365 (10.5%) were diagnosed during the Pre-vaccination, Alpha-Delta and Omicron phases. In total 659 (61.3%) and 42 (11.5%) were unvaccinated in the Alpha-Delta and Omicron. Unvaccinated patients across the Omicron, Alpha-Delta and Pre-vaccination phases experienced similar CFR28 (27.5%, 28%, 29%, respectively). Following propensity score matching, 42 unvaccinated Omicron patients were matched with 122 and 121 patients from the Pre-vaccination and Alpha-Delta phases respectively, based on country of origin, sex, age, comorbidity burden, primary tumour, cancer stage and status, and the receipt of systemic anticancer therapy at COVID-19. Unvaccinated Omicron patients experienced improved COVID-19 outcomes in comparison to patients diagnosed during the Prevaccination phase. Morbidity and mortality were comparable to those of unvaccinated patients diagnosed during the Alpha-Delta phase. Interpretation(s): Despite time-dependent improvements in outcomes reported in the Omicron phase, patients with cancer remain highly vulnerable to SARS-CoV-2 in absence of vaccinal protection. This study provides unequivocal evidence in support of universal vaccination of patients with cancer as a protective measure against morbidity and mortality from COVID-19.
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INTRODUCTION: COVID-19 has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak had an impact on access to cancer diagnosis and treatment of LC pts compared with pre-pandemic time. METHODS: Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared with the same period in 2019. Differences between the 2 years were analyzed using the chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. RESULTS: A slight reduction (-6.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 versus 1637, P = 0.09). Newly diagnosed LC pts in 2020 were more likely to be diagnosed with stage IV disease (P < 0.01) and to be current smokers (someone who has smoked more than 100 cigarettes, including hand-rolled cigarettes, cigars, cigarillos, in their lifetime and has smoked in the last 28 days) (P < 0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop -12% versus -3.2%) compared with the other months included. More LC pts were referred to a low/medium volume hospital in 2020 compared with 2019 (P = 0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (P = 0.94), symptoms onset and cytohistological diagnosis (P = 0.92), symptoms onset and treatment start (P = 0.40), and treatment start and first radiological revaluation (P = 0.36). CONCLUSIONS: Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts.
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COVID-19 , Lung Neoplasms , Communicable Disease Control , Humans , Italy/epidemiology , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Lung Neoplasms/therapy , PandemicsABSTRACT
Background: The long-term impact of COVID-19 in cancer patients (pts) is undefined. Methods: Among 2795 consecutive pts with COVID-19 and cancer registered to OnCovid between 01/2020 and 02/2021, we examined clinical outcomes of pts reassessed post COVID-19 recovery. Results: Among 1557 COVID-19 survivors, 234 (15%) reported sequelae including respiratory symptoms (49.6%), fatigue (41%) and cognitive/psychological dysfunction (4.3%). Persisting COVID-19 sequelae were more likely found in males (p=0.0407) aged ≥65 years (p=0.0489) with ≥2 comorbidities (p=0.0006) and positive smoking history (p=0.0004). Sequelae were associated with history of prior hospitalisation (p<0.0001), complicated disease (p<0.0001) and COVID-19 therapy (p=0.0002). With a median post-COVID-19 follow up of 128 days (95%CI 113-148), multivariable analysis of survival revealed COVID-19 sequelae to be associated with an increased risk of death (HR 1.76, 95%CI 1.16-2.66) after adjusting for sex, age, comorbidities, tumour characteristics, anticancer therapy and COVID-19 severity. Out of 473 patients who were on systemic anticancer therapy (SACT) at COVID-19 diagnosis;62 (13.1%) permanently discontinued therapy and 75 (15.8%) received SACT adjustments, respectively. Discontinuations were due to worsening performance status (45.1%), disease progression (16.1%) and residual organ disfunction (6.3%). SACT adjustments were pursued to avoid hospital attendance (40%), prevent immunosuppression (57.3%) or adverse events (20.3%). Multivariable analyses showed permanent discontinuation to be associated with an increased risk of death (HR 4.2, 95%CI: 1.62-10.7), whereas SACT adjustments did not adversely affect survival. Conclusions: Sequelae post-COVID-19 affect up to 15% of patients with cancer and adversely influence survival and oncological outcomes after recovery. SACT adjustments can be safely pursued to preserve oncological outcomes in patients who remain eligible to treatment.
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Background: The Covid-19 pandemic has radically changed healthcare organizations. Here, we describe the attitude among Italian physicians toward referring patients to early-phase clinical trials during the pandemic. Methods: We analyzed the responses recorded in the first 72 hours from the beginning of the survey. A 20-question web survey was sent to all the associates of the Italian Association of Medical Oncology. Results: Ninety-five physicians completed the survey;87 (96%) were medical oncologists. Table 1 summarizes participants' characteristics. Overall, 37% of the respondents work in an early clinical trial unit. The vast majority of interviewees (74%) already used to refer patients to early clinical trials in the pre- COVID era. Among these, about 30% sent fewer patients during the pandemic particularly due to logistical issues. Interestingly, 25 (26%) never referred patients because of ineffective networking among institutions. It will take more than 12 months to return to pre-pandemic attitude according to half of the physicians. Most of the respondents affirm that one possible tool to facilitate the recovery is: fostering the clinical research network, favouring alliances between referral and satellite centers, and strengthening telemedicine. More than 70% of participants believe that the COVID-19 pandemic will have an impact on the development of new molecules in the coming years both due to a decrease in the number of open studies and to a diversion of funds towards Covid-19 research. Conclusions: In this analysis, we intended to offer an early snapshot of the Covid -19 effects on early phase trials in Italy. One-third of the participants had to decrease the number of referred patients due to the difficulties of a system exposed to unprecedented stress. Furthermore, the challenges of the last year will have repercussions on drug development in the coming years for the majority of interviewees.
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Background: The coronavirus disease 2019 (COVID-19) had an unprecedent impact on the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population, and diagnostic/therapeutic delays might affect the years to come. Aim of the multicenter, real-world, Italian COVID-DELAY study was to evaluate how the 2020 COVID-19 pandemic impacted on LC pts' access to diagnosis and treatment compared to pre-pandemic time. Patients and methods: All consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were reviewed. Monthly access rate and temporal intervals between date of symptom onset, diagnosis and treatment start were analyzed and compared to the same period of 2019. Differences between the two years were analyzed using Fisher's exact test or chi-square test for categorical variables and unpaired Student t test, or the Mann-Whitney U test for continuous variables. Results: Less LC cases (1523 vs 1637, -6.9%) were diagnosed during the 2020 pandemic compared to 2019. LC pts in 2020 were more likely to be diagnosed with stage IV disease (p < 0.01) and to be current smokers (p < 0.01). A major drop of new LC cases was seen during the lockdown period (percentage drop -13.2% vs -5.1%) compared to the other months included. Moreover, a geographic migration was observed with more LC patients referring to low/ medium volume hospital in 2020 compared to 2019 (p = 0.01). Looking at pts management, no differences emerged in terms of interval between symptom onset and radiological diagnosis (p = 0.94), symptom onset and cytohistological diagnosis (p = 0.92), symptoms onset and treatment start (p = 0.40), treatment start and first radiological revaluation (p = 0.36). However, less LC patients were treated in the context of clinical trials during 2020 (5% vs 7%, p = 0.07). Conclusions: Our study pointed out a decrease of new LC cases and a shift towards a higher stage at diagnosis in 2020. Despite this, the efforts put in place by the Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC patients.
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Background: The prospective, multicenter, observational INVIDIa-2 study was designed to investigate the clinical efficacy of influenza vaccination in advanced cancer patients receiving immune checkpoint inhibitors (ICIs) from October 2019 to January 2020. The primary endpoint was the incidence of influenza-like illness (ILI) until April 30, 2020. All ILI episodes, laboratory tests, complications, hospitalizations and pneumonitis were recorded. Therefore, the INVIDIa-2 study prospectively recorded all the COVID-19 ILI events. Methods: Patients were included in this non-prespecified COVID-19 preliminary analysis if potentially exposed to Sars-Cov-2 infection, namely alive on January 31, 2020, when the Italian government declared the National emergency. The incidence of confirmed COVID-19 was assessed among patients with ILI symptoms, describing the hospitalization rate and mortality. Cases with clinicalradiological diagnosis of COVID-19 without laboratory confirmation (COVID-like ILIs), were also reported. The COVID-incidence was exploratively compared basing on influenza vaccination. Results: 1260 patients receiving ICI were enrolled between October 2019 and January 2020;955 patients were analyzed according to the inclusion criterion. Of them, 66 patients had ILI from January 31, to April 30, 2020. 9 were COVID-19 ILIs with laboratory test confirmation. The COVID-19 ILI incidence was 0.9% (9/955 cases), with hospitalization rate of 100% and mortality rate of 67%. Including 5 COVID-like ILIs, the overall COVID-19 incidence was 1.5% (14/955), with hospitalization in 100% of cases and mortality rate of 64%. COVID-19 incidence was 1.2% for patients vaccinated against influenza (6/482 cases) and 1.7%, among unvaccinated patients (8/473 including 3 confirmed COVID-19 and 5 COVID-like), p = 0.52. The difference was not statistically significant, and the clinical trend in favor of vaccinated patients was lost when considering only confirmed COVID-19 (1.2% in vaccinated vs 0.6% in unvaccinated patients, p = 0.33), probably due to the greater presence of male and elderly patients in the vaccinated group (p = 0.009). Conclusions: We obtained the first prospective epidemiological data about symptomatic COVID-19 in advanced cancer patients receiving ICIs. The overall symptomatic COVID-incidence is meaningful, requiring hospitalization in all cases and leading to a high mortality rate, likely due advanced cancer more than to ICI therapy [Mengyuan Dai, Cancer Discov 2020].