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1.
Cancer Cell ; 39(8): 1081-1090.e2, 2021 08 09.
Article in English | MEDLINE | ID: covidwho-1343145

ABSTRACT

As COVID-19 adversely affects patients with cancer, prophylactic strategies are critically needed. Using a validated antibody assay against SARS-CoV-2 spike protein, we determined a high seroconversion rate (94%) in 200 patients with cancer in New York City that had received full dosing with one of the FDA-approved COVID-19 vaccines. On comparison with solid tumors (98%), a significantly lower rate of seroconversion was observed in patients with hematologic malignancies (85%), particularly recipients following highly immunosuppressive therapies such as anti-CD20 therapies (70%) and stem cell transplantation (73%). Patients receiving immune checkpoint inhibitor therapy (97%) or hormonal therapies (100%) demonstrated high seroconversion post vaccination. Patients with prior COVID-19 infection demonstrated higher anti-spike IgG titers post vaccination. Relatively lower IgG titers were observed following vaccination with the adenoviral than with mRNA-based vaccines. These data demonstrate generally high immunogenicity of COVID-19 vaccination in oncology patients and identify immunosuppressed cohorts that need novel vaccination or passive immunization strategies.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/complications , COVID-19/immunology , Neoplasms/complications , Neoplasms/immunology , SARS-CoV-2/immunology , Seroconversion , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/epidemiology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Female , Host-Pathogen Interactions/immunology , Humans , Immunogenicity, Vaccine , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/therapy , Public Health Surveillance , Risk Factors , Spike Glycoprotein, Coronavirus/blood , Spike Glycoprotein, Coronavirus/immunology , Vaccination
2.
Cancer Immunol Res ; 9(3): 261-264, 2021 03.
Article in English | MEDLINE | ID: covidwho-1033549

ABSTRACT

The immunomodulatory effects of immune-checkpoint blockade (ICB) therapy for cancer may act at the crossroads between the need to increase antiviral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to decrease the inflammatory responses in severe cases of coronavirus disease 2019 (COVID-19). There is evidence from preclinical models that blocking programmed death receptor 1 (PD1) protects against RNA virus infections, which suggests that patients with cancer receiving ICB may have lower rates of viral infection. However, given the heterogeneity of patient characteristics, this would be difficult to demonstrate using population-based registries or in clinical trials. Most studies of the impact of ICB therapy on the course of COVID-19 have centered on studying its potential detrimental impact on the course of the COVID-19 infection, in particular on the development of the most severe inflammatory complications. This is a logical concern as it is becoming clear that complications of COVID-19 such as severe respiratory distress syndrome are related to interferon signaling, which is the pathway that leads to expression of the PD1 ligand PD-L1. Therefore, PD1/PD-L1 ICB could potentially increase inflammatory processes, worsening the disease course for patients. However, review of the current evidence does not support the notion that ICB therapy worsens complications from COVID-19, and we conclude that it supports the continued use of ICB therapy during the COVID-19 pandemic provided that we now collect data on the effects of such therapy on COVID-19 vaccination.


Subject(s)
COVID-19/complications , COVID-19/therapy , Immune Checkpoint Inhibitors/therapeutic use , Neoplasms/therapy , B7-H1 Antigen/metabolism , Biomedical Research/economics , Biomedical Research/legislation & jurisprudence , COVID-19/immunology , COVID-19 Vaccines , Humans , Inflammation , Neoplasms/complications , Neoplasms/immunology , Pandemics , Prognosis , Programmed Cell Death 1 Receptor/metabolism , Signal Transduction
3.
Cancers (Basel) ; 12(8)2020 Aug 10.
Article in English | MEDLINE | ID: covidwho-707483

ABSTRACT

The coronavirus disease 2019 (COVID-19) is currently representing a global health threat especially for fragile individuals, such as cancer patients. It was demonstrated that cancer patients have an increased risk of developing a worse symptomatology upon severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) infection, often leading to hospitalization and intensive care. The consequences of this pandemic for oncology are really heavy, as the entire healthcare system got reorganized. Both oncologists and cancer patients are experiencing rescheduling of treatments and disruptions of appointments with a concurrent surge of fear and stress. In this review all the up-to-date findings, concerning the association between COVID-19 and cancer, are reported. A remaining very debated question regards the use of an innovative class of anti-cancer molecules, the immune checkpoint inhibitors (ICIs), given their modulating effects on the immune system. For that reason, administration of ICIs to cancer patients represents a question mark during this pandemic, as its correlation with COVID-19-associated risks is still under investigation. Based on the mechanisms of action of ICIs and the current evidence, we suggest that ICIs not only can be safely administered to cancer patients, but they might even be beneficial in COVID-19-positive cancer patients, by exerting an immune-stimulating action.

4.
JCO Glob Oncol ; 6: 1248-1257, 2020 08.
Article in English | MEDLINE | ID: covidwho-696845

ABSTRACT

PURPOSE: To understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision making was influenced by the pandemic. METHODS: An online survey was conducted between March 24 and April 29, 2020. RESULTS: A total of 343 oncologists from 28 countries participated. The median age was 43 years (range, 29-68 years), and the majority were male (62%). At the time of the survey, nearly all participants self-reported an outbreak in their country (99.7%). Personal protective equipment was available to all participants, of which surgical mask was the most common (n = 308; 90%). Telemedicine, in the form of phone or video encounters, was common and implemented by 80% (n = 273). Testing patients with cancer for COVID-19 via reverse transcriptase polymerase chain reaction before systemic treatment was not routinely implemented: 58% reported no routine testing, 39% performed testing in selected patients, and 3% performed systematic testing in all patients. The most significant factors influencing an oncologist's decision making regarding choice of systemic therapy included patient age and comorbidities (81% and 92%, respectively). Although hormonal treatments and tyrosine kinase inhibitors were considered to be relatively safe, cytotoxic chemotherapy and immune therapies were perceived as being less safe or unsafe by participants. The vast majority of participants stated that during the pandemic they would use less chemotherapy, immune checkpoint inhibitors, and steroids. Although treatment in neoadjuvant, adjuvant, and first-line metastatic disease was less affected, most of the participants stated that they would be more hesitant to recommend second- or third-line therapies in metastatic disease. CONCLUSION: Decision making by oncologists has been significantly influenced by the ongoing COVID-19 pandemic.


Subject(s)
Betacoronavirus/pathogenicity , Clinical Decision-Making , Coronavirus Infections/prevention & control , Infection Control/statistics & numerical data , Neoplasms/therapy , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Adult , Aged , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Female , Humans , Infection Control/methods , Infection Control/standards , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Infectious Disease Transmission, Professional-to-Patient/prevention & control , Male , Medical Oncology/methods , Medical Oncology/standards , Medical Oncology/statistics & numerical data , Middle Aged , Neoplasms/diagnosis , Oncologists/statistics & numerical data , Personal Protective Equipment/standards , Personal Protective Equipment/statistics & numerical data , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Practice Patterns, Physicians'/standards , Practice Patterns, Physicians'/statistics & numerical data , SARS-CoV-2 , Surveys and Questionnaires/statistics & numerical data , Telemedicine/statistics & numerical data
5.
J Immunother Cancer ; 8(2)2020 07.
Article in English | MEDLINE | ID: covidwho-636110

ABSTRACT

The COVID-19 pandemic has killed over 400 000 people globally. Ecological evidence indicates that countries with national universal BCG vaccination programs for tuberculosis (TB) prevention have a much lower incidence of severe COVID-19 and mortality compared with those that do not have such programs. BCG is a century old vaccine used for TB prevention via infant/childhood vaccination in lowto middle-income countries with high infection prevalence rate and is known to reduce all-cause neonatal mortality. BCG remains the standard immunotherapy treatment for patients with high-risk non-muscle invasive bladder cancer globally for more than 44 years. Several trials are, therefore, investigating BCG as a prophylactic against COVID-19 in healthcare workers and the elderly. In this commentary, we discuss the potential mechanisms that may underlie BCG associated heterologous protection with a focus on tertiary lymphoid structure (TLS) organogenesis. Given the significance of TLSs in mucosal immunity, their association with positive prognosis and response to immune checkpoint blockade with a critical role of Type I interferon (IFN-1) in inducing these, we also discuss potentiating TLS formation as a promising approach to enhance anti-tumor immunity. We propose that lessons learned from BCG immunotherapy success could be applied to not only augment such microbe-based therapeutics but also lead to similar adjunctive IFN-1 activating approaches to improve response to immune checkpoint blockade therapy in cancer.


Subject(s)
BCG Vaccine/therapeutic use , Betacoronavirus , Coronavirus Infections/prevention & control , Interferon Type I/immunology , Neoplasms/therapy , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , COVID-19 , Coronavirus Infections/immunology , Humans , Immunotherapy , Neoplasms/immunology , Pneumonia, Viral/immunology , SARS-CoV-2
6.
Crit Care Explor ; 2(6): e0141, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-605839

ABSTRACT

Taking into consideration the multisystemic clinical and autopsy findings in "severe" coronavirus disease 2019 patients, viral sepsis would be a more accurate term to describe the whole clinical picture. The most significant pathophysiological components of this picture are intense cytokine release, prolonged inflammation, immunosuppression with T cell exhaustion, and the development of organ dysfunctions. Currently, the optimal treatment for severe coronavirus disease 2019 is uncertain. Supportive treatment and immunomodulators have a critical place in the treatment of severe patients until effective antivirals are developed. Interleukin-6 antagonists, one of the immunomodulating agents, appears to be effective in the treatment of cytokine storm, but some patients continue to have severe lymphopenia and immunosuppression. We believe it can be useful as immunomodulator therapy in critical coronavirus disease 2019 patients because of the benefits of immune checkpoint inhibitors in cancer and sepsis patients.

7.
Eur Urol ; 78(2): 276-280, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-598133

ABSTRACT

Preliminary data suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with higher mortality among cancer patients, particularly in those on systemic therapy. It is unclear whether this applies to patients receiving immune checkpoint inhibitors (ICIs). In this case series, 74 patients from a single institution with genitourinary (GU) cancer on ICI were followed up during a 12-wk period. During this period, 11 patients (15%) developed symptoms consistent with coronavirus disease 2019 (COVID-19) and four (5%) tested positive. Two patients had metastatic urothelial cancer (treated with atezolizumab) and two had metastatic renal cancer (treated with ipilimumab and nivolumab). All had additional risk factors associated with COVID-19 mortality and two received steroids within 1 mo of infection. Two patients developed symptoms requiring hospitalisation. All four are alive 32-45 d after their first symptoms and 28-38 d after testing positive. These patients all had multiple risk factors associated with severe COVID-19. These data suggest that the higher risk of COVID-19 death associated with systemic therapy in cancer may not apply to patients on ICIs. Assessment of COVID-19 severity in these patients can be complicated by the underlying cancer and its treatment.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Immunologic Factors/therapeutic use , Kidney Neoplasms/drug therapy , Pneumonia, Viral/complications , Aged , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Female , Follow-Up Studies , Humans , Kidney Neoplasms/complications , Kidney Neoplasms/epidemiology , Male , Middle Aged , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Retrospective Studies , Risk Factors , SARS-CoV-2 , Treatment Outcome
8.
Eur J Clin Invest ; 50(9): e13315, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-597270

ABSTRACT

BACKGROUND: During COVID-19 outbreak, oncological care has been reorganized. Patients with cancer have been reported to experience a more severe COVID-19 syndrome; moreover, there are concerns of a potential interference between immune checkpoint inhibitors (ICIs) and SARS-CoV-2 pathogenesis. MATERIALS AND METHODS: Between 6 and 16 May 2020, a 22-item survey was sent to Italian physicians involved in administering ICIs. It aimed at exploring the perception about SARS-CoV-2-related risks in cancer patients receiving ICIs, and the attitudes towards their management. RESULTS: The 104 respondents had a median age of 35.5 years, 58.7% were females and 71.2% worked in Northern Italy. 47.1% of respondents argued a synergism between ICIs and SARS-CoV-2 pathogenesis leading to worse outcomes, but 97.1% would not deny an ICI only for the risk of infection. During COVID-19 outbreak, to reduce hospital visits, 55.8% and 30.8% opted for the highest labelled dose of each ICI and/or, among different ICIs for the same indication, for the one with the longer interval between cycles, respectively. 53.8% of respondents suggested testing for SARS-CoV-2 every cancer patient candidate to ICIs. 71.2% declared to manage patients with onset of dyspnoea and cough as infected by SARS-CoV-2 until otherwise proven; however, 96.2% did not reduce the use of steroids to manage immune-related toxicities. The administration of ICIs in specific situations for different cancer types has not been drastically conditioned. CONCLUSIONS: These results highlight the uncertainties around the perception of a potential interference between ICIs and COVID-19, supporting the need of focused studies on this topic.


Subject(s)
Coronavirus Infections/epidemiology , Disease Outbreaks/statistics & numerical data , Immunologic Factors/administration & dosage , Neoplasms/drug therapy , Pneumonia, Viral/epidemiology , Adult , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/statistics & numerical data , Coronavirus Infections/diagnosis , Female , Humans , Immunocompromised Host , Italy , Male , Medical Oncology/methods , Middle Aged , Neoplasms/epidemiology , Neoplasms/immunology , Outcome Assessment, Health Care , Pandemics , Pneumonia, Viral/diagnosis , Risk Assessment , Surveys and Questionnaires
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