Neuro-Oncology During the COVID-19 Outbreak: A Hopeful Perspective at the End of the Italian Crisis

Frontiers in Medicine

article

Matteo Simonelli¹  Enrico Franceschi³  Giuseppe Lombardi⁴ 

[1] Department of Biomedical Sciences, Humanitas University;Humanitas Cancer Center, Humanitas Clinical and Research Center — IRCCS;Department of Medical Oncology, Azienda USL/IRCCS Institute of Neurological Sciences;Department of Oncology, Veneto Institute of Oncology IOV-IRCCS

关键词: neuro oncology;    COVID-19;    gliomas;    brain tumors;    SARS–CoV−2;   

DOI  :  10.3389/fmed.2020.594610

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Since December 2019, when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had been identified for the first time in Wuhan, Hubei, China, the outbreak has quickly become a worldwide pandemic with disruptive health, social, and economic impact. As of August 2020, more than 21,600,000 cases and 775,000 confirmed deaths have been reported by the WHO across all continents, with exponential spread initially in Europe, and currently in the East, United States, and Latin America. Italy has been hurt dramatically, being the first European country involved, and the epicenter of the pandemic for a few months (1). The regions of northern Italy (Lombardy, Veneto, Emilia-Romagna, and Piedmont) were particularly affected, requiring immediate and tight emergency measures to contain the infection followed by a national lockdown set since the beginning of March (2). In this complex scenario, the Italian cancer community have faced many arising tough challenges (3). Cancer patients are more susceptible to infections because of their immunosuppressive status and, at least in theory, at major risk of developing severe complications from the coronavirus disease (COVID-19), including adult respiratory distress syndrome (ARDS), intensive care unit admission, and even death. The first reports from China seem to confirm this hypothesis suggesting that patients with cancer are more likely to contract the virus and to develop COVID-19-related complications (4). More recent works indicated with strong evidence that cancer patients are at an increased risk of mortality and severe illness due to SARS-CoV-2 infection, regardless of whether they have active cancer, are on anticancer treatment, or both (5, 6). A recent multicenter European study involving 890 cases with confirmed COVID-19 demonstrated a worsening gradient of mortality from breast cancer to hematological malignancies and identified male gender, older age, and number of comorbidities as negative prognostic variables (7). Patients diagnosed with primary brain tumors (PBTs) are considered one of the most fragile and vulnerable category due to several factors: the older age along with the multiple age-related frailties and comorbidities, the frequent presence of neurological deficits causing loss of autonomy in the activities of daily living and increased risk of thromboembolic events, the often severe lymphopenia both disease and treatment-related (e.g., alkylating agents such as temozolomide and nitrosourea), and finally the chronic use of steroids to control brain edema leading to further immunosuppression and to an increased susceptibility to infection (8). Moreover, preliminary clinical data suggest that the SARS-CoV-2 infection can commonly involve the central nervous system (CNS) especially in those patients with lower lymphocyte counts, causing neurological manifestations both central such as dizziness, headache, acute cerebrovascular disease, depressed level of consciousness, ataxia, and seizures, or peripheral such as hypogeusia, and hyposmia (9). The first reports from autopsies of patients with COVID-19 revealed that the brain tissue was often hyperemic and edematous, with some areas of neuronal degeneration (9). As for other coronaviruses, including SARS-CoV and MERS-CoV, the main pathogenic mechanism may be the direct CNS invasion of SARS-CoV-2. The olfactory nerve has been recently described as the potential neural pathway used by the virus to gain entry into the CNS (10, 11). In addition, the SARS-CoV-2 virus seems to exploit the angiotensinconverting enzyme 2 receptor to entry inside the cells, and these receptors have been detected into the brain over glial cells and neurons (12). Another pathogenic mechanism under current investigation potentially leading to neurological damages in patients with COVID-19 is represented by endothelial ruptures in cerebral capillaries followed by bleeding within the brain parenchyma (12). For all these reasons, it is almost conceivable that PBTs patients, with an already injured brain, could be more exposed in terms of frequency and seriousness to these symptoms. In the context of the COVID-19 pandemic, the need for close and continuous assistance by caregivers, usually family members, could increase exponentially the risk of interfamily infection. Moreover, travel restrictions imposed to mitigate the SARS-CoV-2 spread limit the possibility of patients to move around the country, the attendance for repeat appointments, and continuity in care in the referral centers where they are usually managed and treated. Given the paucity of effective treatments available, the difficult access to clinical trials represents another relevant issue. The opening of new sponsored, multicenter, earlyphase (Phases I–II) clinical studies previously scheduled at our institutions has been postponed, as well as the recruitment into the ongoing ones has been placed on hold, denying our patients a potentially effective therapeutic option. Finally, the drug-to-drug interactions between antiepileptic drugs and antiviral agents or chloroquine derivates, often used as empirical therapy for COVID-19 infection, potentially leading to toxic effects, represent a new concern that we faced. At the time of writing, in northern Italy, pressure on hospitals and intensive care units has sharply declined, while the contagion curve has settled on a plateau with a low number of newly infected cases. As neuro-oncologists working in three Institutions known as national referring hubs for the management of PBTs (Humanitas Cancer Center, Milan; Department of Medical Oncology, Bellaria Hospital, Bologna; and Veneto Institute of Oncology, Padua) and located frontline in the most affected endemic regions of Italy, we have directly experienced the dramatic impact of this pandemic. Moreover, two of the three centers being part of academic, general hospitals with an emergency department admitting SARS-CoV-2 positive subjects on a daily basis were forced to completely revolutionize their organization in just a few days, redefining spaces and reallocating medical resources (13). Several COVID-19 isolated wards have been created, and new intensive care beds have been built up wherever possible. Clinical activities not strictly necessary have been temporarily suspended and physicians working in these sectors redistributed. In our three institutions, oncologists continued to do their job full time giving care to their patients with the best intensity, limiting unnecessary hospital access and implementing COVIDfree paths and all the safety procedures required to protect patients and medical staff. Now, thanks to the strict lockdown measures the biggest storm is moving away behind us and it is the right time to take a first balance, reflecting on the choices made and planning the future, with the concrete possibility of a second wave of infections in the next autumn. In the present paper, we would like to discuss some critical aspects involving management of PBT patients during the pandemic, sharing our personal experience on how we have modified our neuro-oncological daily practice to ensure either the safety and the continuum-of-care of our patients. We also present some preliminary data about the prevalence of the infection among the patient population of our three referral Neuro-Oncology Centers, showing the features and the clinical course of PBTs patients who got infected by SARS-CoV-2.

【 授权许可】

CC BY