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1.
Cell Death Differ ; 28(12): 3297-3315, 2021 12.
Article in English | MEDLINE | ID: covidwho-1298835

ABSTRACT

Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus-host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme B+FasL+, EomeshighTCF-1high, PD-1+CD8+ Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity, and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long-term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.

2.
Eur J Cancer ; 153: 123-132, 2021 08.
Article in English | MEDLINE | ID: covidwho-1275290

ABSTRACT

BACKGROUND: Changes in the management of patients with cancer and delays in treatment delivery during the COVID-19 pandemic may impact the use of hospital resources and cancer mortality. PATIENTS AND METHODS: Patient flows, patient pathways and use of hospital resources during the pandemic were simulated using a discrete event simulation model and patient-level data from a large French comprehensive cancer centre's discharge database, considering two scenarios of delays: massive return of patients from November 2020 (early-return) or March 2021 (late-return). Expected additional cancer deaths at 5 years and mortality rate were estimated using individual hazard ratios based on literature. RESULTS: The number of patients requiring hospital care during the simulation period was 13,000. In both scenarios, 6-8% of patients were estimated to present a delay of >2 months. The overall additional cancer deaths at 5 years were estimated at 88 in early-return and 145 in late-return scenario, with increased additional deaths estimated for sarcomas, gynaecological, liver, head and neck, breast cancer and acute leukaemia. This represents a relative additional cancer mortality rate at 5 years of 4.4 and 6.8% for patients expected in year 2020, 0.5 and 1.3% in 2021 and 0.5 and 0.5% in 2022 for each scenario, respectively. CONCLUSIONS: Pandemic-related diagnostic and treatment delays in patients with cancer are expected to impact patient survival. In the perspective of recurrent pandemics or alternative events requiring an intensive use of limited hospital resources, patients should be informed not to postpone care, and medical resources for patients with cancer should be sanctuarised.


Subject(s)
COVID-19/epidemiology , Neoplasms/mortality , Neoplasms/therapy , COVID-19/mortality , COVID-19/virology , Computer Simulation , Delivery of Health Care/organization & administration , Hospital Administration , Hospitals , Humans , Neoplasms/pathology , Pandemics , Proportional Hazards Models , SARS-CoV-2/isolation & purification
5.
JCO Glob Oncol ; 7: 455-463, 2021 04.
Article in English | MEDLINE | ID: covidwho-1171991

ABSTRACT

The speed and spread of the COVID-19 pandemic has been affecting the entire world for the past several months. OncoAlert is a social media network made up of more than 140 oncology stakeholders: oncologists (medical, radiation, and surgical), oncology nurses, and patient advocates who share the mission of fighting cancer by means of education and dissemination of information. As a response to the COVID-19 pandemic, OncoAlert hosted The Round Table Discussions. We have documented this effort along with further discussion about the COVID-19 pandemic and the consequences on patients living with cancer to disseminate this information to our colleagues worldwide.


Subject(s)
COVID-19/prevention & control , Information Dissemination/methods , Medical Oncology/methods , Neoplasms/therapy , Social Media , Telemedicine/methods , COVID-19/epidemiology , COVID-19/virology , Communicable Disease Control/methods , Epidemics , Global Health/statistics & numerical data , Health Personnel/statistics & numerical data , Humans , Neoplasms/diagnosis , Oncologists/statistics & numerical data , Oncology Nursing/statistics & numerical data , Practice Guidelines as Topic , Public Health/methods , Public Health/statistics & numerical data , SARS-CoV-2/physiology
6.
Int J Radiat Oncol Biol Phys ; 110(4): 947-956, 2021 07 15.
Article in English | MEDLINE | ID: covidwho-1144733

ABSTRACT

PURPOSE: Patients with cancer are presumed to be more vulnerable to COVID-19. We evaluated a screening strategy combining chest computed tomography (CT) and reverse-transcription polymerase chain reaction (RT-PCR) for patients treated with radiation therapy at our cancer center located in a COVID-19 French hotspot during the first wave of the pandemic. METHODS AND MATERIALS: Chest CT images were proposed during radiation therapy CT simulation. Images were reviewed by an expert radiologist according to the COVID-19 Reporting and Data System classification. Nasal swabs with RT-PCR assay were initially proposed in cases of suspicious imaging or clinical context and were eventually integrated into the systematic screening. A dedicated radiation therapy workflow was proposed for COVID-19 patients to limit the risk of contamination. RESULTS: From March 18, 2020 to May 1, 2020, 480 patients were screened by chest CT, and 313 patients had both chest CT and RT-PCR (65%). The cumulative incidence of COVID-19 was 5.4% (95% confidence interval [CI], 3.6-7.8; 26 of 480 patients). Diagnosis of COVID-19 was made before radiation therapy for 22 patients (84.6%) and during RT for 4 patients (15.3%). Chest CT directly aided the diagnosis of 7 cases in which the initial RT-PCR was negative or not feasible, out of a total of 480 patients (1.5%) and 517 chest CT acquisitions. Four patients with COVID-19 at the time of the chest CT screening had a false negative CT. Sensitivity and specificity of chest CT screening in patients with both RT-PCR and chest CT testing were estimated at 0.82 (95% CI, 0.60-0.95) and 0.98 (95% CI, 0.96-0.99), respectively. Adaptation of the radiation therapy treatment was made for all patients, with 7 postponed treatments (median: 5 days; interquartile range, 1.5-14.8). CONCLUSIONS: The benefit of systematic use of chest CT screening during CT simulation for patients undergoing radiation therapy during the COVID-19 pandemic seemed limited.


Subject(s)
COVID-19 Nucleic Acid Testing , COVID-19/diagnosis , Multidetector Computed Tomography , Neoplasms/radiotherapy , Adolescent , Adult , Aged , COVID-19/complications , COVID-19/diagnostic imaging , COVID-19/epidemiology , Cancer Care Facilities , Child , Confidence Intervals , Female , France/epidemiology , Humans , Incidence , Male , Middle Aged , Neoplasms/complications , Radiography, Thoracic/methods , Retrospective Studies , Sensitivity and Specificity , Tomography, Spiral Computed , Young Adult
7.
Cell Death Dis ; 12(3): 258, 2021 03 11.
Article in English | MEDLINE | ID: covidwho-1132059

ABSTRACT

The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiologically confirmed pneumonitis, hospitalization and oxygen therapy), and critical disease (in intensive care). This analysis revealed major disease- and stage-associated shifts in the metabolome, meaning that at least 77 metabolites including amino acids, lipids, polyamines and sugars, as well as their derivatives, were altered in critical COVID-19 patient's plasma as compared to mild COVID-19 patients. Among a uniformly moderate cohort of patients who received tocilizumab, only 10 metabolites were different among individuals with a favorable evolution as compared to those who required transfer into the intensive care unit. The elevation of one single metabolite, anthranilic acid, had a poor prognostic value, correlating with the maintenance of high interleukin-10 and -18 levels. Given that products of the kynurenine pathway including anthranilic acid have immunosuppressive properties, we speculate on the therapeutic utility to inhibit the rate-limiting enzymes of this pathway including indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.


Subject(s)
COVID-19/blood , Metabolome , SARS-CoV-2/metabolism , Antibodies, Monoclonal, Humanized/administration & dosage , Biomarkers/blood , COVID-19/diagnosis , COVID-19/drug therapy , Female , Humans , Male , Metabolomics , Prognosis
8.
Nat Commun ; 12(1): 634, 2021 01 27.
Article in English | MEDLINE | ID: covidwho-1049964

ABSTRACT

The SARS-COV-2 pandemic has put pressure on intensive care units, so that identifying predictors of disease severity is a priority. We collect 58 clinical and biological variables, and chest CT scan data, from 1003 coronavirus-infected patients from two French hospitals. We train a deep learning model based on CT scans to predict severity. We then construct the multimodal AI-severity score that includes 5 clinical and biological variables (age, sex, oxygenation, urea, platelet) in addition to the deep learning model. We show that neural network analysis of CT-scans brings unique prognosis information, although it is correlated with other markers of severity (oxygenation, LDH, and CRP) explaining the measurable but limited 0.03 increase of AUC obtained when adding CT-scan information to clinical variables. Here, we show that when comparing AI-severity with 11 existing severity scores, we find significantly improved prognosis performance; AI-severity can therefore rapidly become a reference scoring approach.


Subject(s)
COVID-19/diagnosis , COVID-19/physiopathology , Deep Learning , Neural Networks, Computer , Tomography, X-Ray Computed/methods , Artificial Intelligence , COVID-19/classification , Humans , Models, Biological , Multivariate Analysis , Prognosis , Radiologists , Severity of Illness Index
9.
Cancer Cell ; 38(5): 602-604, 2020 11 09.
Article in English | MEDLINE | ID: covidwho-970849

ABSTRACT

To understand the real impact of COVID-19 on cancer patients, an entirely new data collection effort was initiated within the Thoracic Cancers International COVID-19 Collaboration (TERAVOLT). TERAVOLT reported high mortality related to COVID-19 infection in thoracic cancer patients and identified several negative prognostic factors. In this commentary, we discuss the importance and limits of patient registries to support decision-making in thoracic cancer during the SARS-CoV-2 pandemic.


Subject(s)
Betacoronavirus/isolation & purification , Clinical Decision-Making , Coronavirus Infections/complications , Global Burden of Disease/standards , Pneumonia, Viral/complications , Practice Guidelines as Topic/standards , Thoracic Neoplasms/therapy , COVID-19 , Coronavirus Infections/virology , Humans , International Cooperation , Pandemics , Pneumonia, Viral/virology , Registries , SARS-CoV-2 , Thoracic Neoplasms/epidemiology , Thoracic Neoplasms/virology
12.
13.
Nature Cancer ; 2020.
Article in English | ELSEVIER | ID: covidwho-798872

ABSTRACT

Patients with cancer are presumed to be at increased risk of severe COVID-19 outcomes due to underlying malignancy and treatment-induced immunosuppression. Of the first 178 patients managed for COVID-19 at the Gustave Roussy Cancer Centre, 125 (70.2%) were hospitalized, 47 (26.4%) developed clinical worsening and 31 (17.4%) died. An age of over 70 years, smoking status, metastatic disease, cytotoxic chemotherapy and an Eastern Cooperative Oncology Group score of ≥2 at the last visit were the strongest determinants of increased risk of death. In multivariable analysis, the Eastern Cooperative Oncology Group score remained the only predictor of death. In contrast, immunotherapy, hormone therapy and targeted therapy did not increase clinical worsening or death risk. Biomarker studies found that C-reactive protein and lactate dehydrogenase levels were significantly associated with an increased risk of clinical worsening, while C-reactive protein and D-dimer levels were associated with an increased risk of death. COVID-19 management impacted the oncological treatment strategy, inducing a median 20 d delay in 41% of patients and adaptation of the therapeutic strategy in 30% of patients.

14.
Cell ; 182(6): 1401-1418.e18, 2020 09 17.
Article in English | MEDLINE | ID: covidwho-694669

ABSTRACT

Blood myeloid cells are known to be dysregulated in coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2. It is unknown whether the innate myeloid response differs with disease severity and whether markers of innate immunity discriminate high-risk patients. Thus, we performed high-dimensional flow cytometry and single-cell RNA sequencing of COVID-19 patient peripheral blood cells and detected disappearance of non-classical CD14LowCD16High monocytes, accumulation of HLA-DRLow classical monocytes (Human Leukocyte Antigen - DR isotype), and release of massive amounts of calprotectin (S100A8/S100A9) in severe cases. Immature CD10LowCD101-CXCR4+/- neutrophils with an immunosuppressive profile accumulated in the blood and lungs, suggesting emergency myelopoiesis. Finally, we show that calprotectin plasma level and a routine flow cytometry assay detecting decreased frequencies of non-classical monocytes could discriminate patients who develop a severe form of COVID-19, suggesting a predictive value that deserves prospective evaluation.


Subject(s)
Coronavirus Infections , Coronavirus , Pandemics , Pneumonia, Viral , Betacoronavirus , COVID-19 , Flow Cytometry , Humans , Leukocyte L1 Antigen Complex , Monocytes , Myeloid Cells , Prospective Studies , SARS-CoV-2
15.
Support Care Cancer ; 28(10): 5037-5044, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-688728

ABSTRACT

A novel coronavirus, SARS-CoV-2, was first reported as a respiratory illness in December 2019 in Wuhan, China. Since then, the World Health Organization (WHO) Emergency Committee declared a global health. COVID-19 has now spread worldwide and is responsible of more than 472,216 persons, out of 9,100,090 officially diagnosed worldwide since 23 of June. In the context of cancer patients, COVID-19 has a severe impact, regarding pulmonary infection but also cancer treatments in this fragile and immunocompromised population, and ICU admission for cancer patients in the context of COVID-19 requires ethical and clinical consideration. In our cancer center, intensivists, oncologists, pharmacists, and hospital administrators had to prepare for a substantial increase in critical care bed capacity (from 10 ICU beds, 6 medical intensive care beds, and 12 surgical intensive care beds, bed capacity was increased to 28 medical intensive care beds with ventilating capacity) and to adapt infrastructure (i.e., ICU beds), supplies (i.e., drugs, ventilators, protective materials), and staff (i.e., nurses and medical staff). Overall, thirty-three COVID-19 patients were admitted in our ICU, 17 cancer-free and 16 with cancer, and 23 required mechanical ventilation, resulting in 4 deaths (of them two patients with cancer). We report here management of a dedicated intensive care unit of a cancer center during the COVID-19 infection pandemic, considering resource allocation and redistribution of healthcare workers.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Intensive Care Units , Neoplasms/therapy , Pneumonia, Viral/complications , Adult , Aged , Aged, 80 and over , COVID-19 , Female , Hospitalization , Humans , Male , Middle Aged , Neoplasms/complications , Neoplasms/epidemiology , Pandemics , SARS-CoV-2 , Young Adult
16.
Cancer Cell ; 37(6): 742-745, 2020 06 08.
Article in English | MEDLINE | ID: covidwho-628515

ABSTRACT

Prior publications on small subsets of cancer patients infected with SARS CoV-2 have shown an increased risk of mortality compared to the general population. Furthermore, patients with thoracic malignancies are thought to be at particularly high risk given their older age, smoking habits, and pre-existing cardio-pulmonary comorbidities. For this reason, physicians around the world have formed TERAVOLT, a global consortium dedicated to understanding the impact of COVID-19 on patients with thoracic malignancies.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/therapy , Medical Oncology/organization & administration , Pneumonia, Viral/therapy , Registries , Thoracic Neoplasms/therapy , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Global Burden of Disease , Humans , International Cooperation , Intersectoral Collaboration , Medical Oncology/standards , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Practice Guidelines as Topic , SARS-CoV-2 , Thoracic Neoplasms/complications , Thoracic Neoplasms/mortality
17.
Lancet Oncol ; 21(7): 914-922, 2020 07.
Article in English | MEDLINE | ID: covidwho-597772

ABSTRACT

BACKGROUND: Early reports on patients with cancer and COVID-19 have suggested a high mortality rate compared with the general population. Patients with thoracic malignancies are thought to be particularly susceptible to COVID-19 given their older age, smoking habits, and pre-existing cardiopulmonary comorbidities, in addition to cancer treatments. We aimed to study the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with thoracic malignancies. METHODS: The Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry is a multicentre observational study composed of a cross-sectional component and a longitudinal cohort component. Eligibility criteria were the presence of any thoracic cancer (non-small-cell lung cancer [NSCLC], small-cell lung cancer, mesothelioma, thymic epithelial tumours, and other pulmonary neuroendocrine neoplasms) and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms. Patients of any age, sex, histology, or stage were considered eligible, including those in active treatment and clinical follow-up. Clinical data were extracted from medical records of consecutive patients from Jan 1, 2020, and will be collected until the end of pandemic declared by WHO. Data on demographics, oncological history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes were collected. Associations between demographic or clinical characteristics and outcomes were measured with odds ratios (ORs) with 95% CIs using univariable and multivariable logistic regression, with sex, age, smoking status, hypertension, and chronic obstructive pulmonary disease included in multivariable analysis. This is a preliminary analysis of the first 200 patients. The registry continues to accept new sites and patient data. FINDINGS: Between March 26 and April 12, 2020, 200 patients with COVID-19 and thoracic cancers from eight countries were identified and included in the TERAVOLT registry; median age was 68·0 years (61·8-75·0) and the majority had an Eastern Cooperative Oncology Group performance status of 0-1 (142 [72%] of 196 patients), were current or former smokers (159 [81%] of 196), had non-small-cell lung cancer (151 [76%] of 200), and were on therapy at the time of COVID-19 diagnosis (147 [74%] of 199), with 112 (57%) of 197 on first-line treatment. 152 (76%) patients were hospitalised and 66 (33%) died. 13 (10%) of 134 patients who met criteria for ICU admission were admitted to ICU; the remaining 121 were hospitalised, but were not admitted to ICU. Univariable analyses revealed that being older than 65 years (OR 1·88, 95% 1·00-3·62), being a current or former smoker (4·24, 1·70-12·95), receiving treatment with chemotherapy alone (2·54, 1·09-6·11), and the presence of any comorbidities (2·65, 1·09-7·46) were associated with increased risk of death. However, in multivariable analysis, only smoking history (OR 3·18, 95% CI 1·11-9·06) was associated with increased risk of death. INTERPRETATION: With an ongoing global pandemic of COVID-19, our data suggest high mortality and low admission to intensive care in patients with thoracic cancer. Whether mortality could be reduced with treatment in intensive care remains to be determined. With improved cancer therapeutic options, access to intensive care should be discussed in a multidisciplinary setting based on cancer specific mortality and patients' preference. FUNDING: None.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Registries/statistics & numerical data , Thoracic Neoplasms/epidemiology , Aged , Betacoronavirus , COVID-19 , Cause of Death , Coronavirus Infections/mortality , Coronavirus Infections/pathology , Cross-Sectional Studies , Female , Hospitalization/statistics & numerical data , Humans , Longitudinal Studies , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/pathology , Risk Factors , SARS-CoV-2 , Thoracic Neoplasms/mortality , Thoracic Neoplasms/pathology , Thoracic Neoplasms/therapy
18.
Nat Med ; 26(5): 665-671, 2020 05.
Article in English | MEDLINE | ID: covidwho-153534

ABSTRACT

The current COVID-19 pandemic challenges oncologists to profoundly re-organize oncological care in order to dramatically reduce hospital visits and admissions and therapy-induced immune-related complications without compromising cancer outcomes. Since COVID-19 is a novel disease, guidance by scientific evidence is often unavailable, and impactful decisions are inevitably made on the basis of expert opinions. Here we report how the seven comprehensive cancer centers of Cancer Core Europe have organized their healthcare systems at an unprecedented scale and pace to make their operations 'pandemic proof'. We identify and discuss many commonalities, but also important local differences, and pinpoint critical research priorities to enable evidence-based remodeling of cancer care during the COVID-19 pandemic. Also, we discuss how the current situation offers a unique window of opportunity for assessing the effects of de-escalating anticancer regimens, which may fast-forward the development of more-refined and less-toxic treatments. By sharing our joint experiences, we offer a roadmap for proceeding and aim to mobilize the global research community to generate the data that are critically needed to offer the best possible care to patients.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Neoplasms , Pneumonia, Viral/epidemiology , Ambulatory Care/statistics & numerical data , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/prevention & control , Delivery of Health Care , Humans , Neoplasms/complications , Neoplasms/therapy , Pandemics/prevention & control , Pneumonia, Viral/complications , Pneumonia, Viral/prevention & control , SARS-CoV-2
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