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1.
ESMO Open ; 7(1): 100359, 2022 02.
Article in English | MEDLINE | ID: covidwho-1560850

ABSTRACT

BACKGROUND: The durability of immunogenicity of SARS-CoV-2 vaccination in cancer patients remains to be elucidated. We prospectively evaluated the immunogenicity of the vaccine in triggering both the humoral and the cell-mediated immune response in cancer patients treated with anti-programmed cell death protein 1/programmed death-ligand 1 with or without chemotherapy 6 months after BNT162b2 vaccine. PATIENTS AND METHODS: In the previous study, 88 patients were enrolled, whereas the analyses below refer to the 60 patients still on immunotherapy at the time of the follow-up. According to previous SARS-CoV-2 exposure, patients were classified as SARS-CoV-2-naive (without previous SARS-CoV-2 exposure) and SARS-CoV-2-experienced (with previous SARS-CoV-2 infection). Neutralizing antibody (NT Ab) titer against the B.1.1 strain and total anti-spike immunoglobulin G concentration were quantified in serum samples. The enzyme-linked immunosorbent spot assay was used for quantification of anti-spike interferon-γ (IFN-γ)-producing cells/106 peripheral blood mononuclear cells. Fifty patients (83.0%) were on immunotherapy alone, whereas 10 patients (7%) were on chemo-immunotherapy. We analyzed separately patients on immunotherapy and patients on chemo-immunotherapy. RESULTS: The median T-cell response at 6 months was significantly lower than that measured at 3 weeks after vaccination [50 interquartile range (IQR) 20-118.8 versus 175 IQR 67.5-371.3 IFN-γ-producing cells/106 peripheral blood mononuclear cells; P < 0.0001]. The median reduction of immunoglobulin G concentration was 88% in SARS-CoV-2-naive subjects and 2.1% in SARS-CoV-2-experienced subjects. SARS-CoV-2 NT Ab titer was maintained in SARS-CoV-2-experienced subjects, whereas a significant decrease was observed in SARS-CoV-2-naive subjects (from median 1 : 160, IQR 1 : 40-1 : 640 to median 1 : 20, IQR 1 : 10-1 : 40; P < 0.0001). A weak correlation was observed between SARS-CoV-2 NT Ab titer and spike-specific IFN-γ-producing cells at both 6 months and 3 weeks after vaccination (r = 0.467; P = 0.0002 and r = 0.428; P = 0.0006, respectively). CONCLUSIONS: Our work highlights a reduction in the immune response in cancer patients, particularly in SARS-CoV-2-naive subjects. Our data support administering a third dose of COVID-19 vaccine to cancer patients treated with programmed cell death protein 1/programmed death-ligand 1 inhibitors.


Subject(s)
B7-H1 Antigen , COVID-19 , Immune Checkpoint Inhibitors , Neoplasms , Programmed Cell Death 1 Receptor , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , /immunology , COVID-19/immunology , COVID-19/prevention & control , Follow-Up Studies , Humans , Immune Checkpoint Inhibitors/administration & dosage , Immune Checkpoint Inhibitors/immunology , Immunity, Cellular/drug effects , Immunity, Humoral/drug effects , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/immunology , Neoplasms/drug therapy , Neoplasms/immunology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , SARS-CoV-2/immunology
2.
JCI Insight ; 6(24)2021 12 22.
Article in English | MEDLINE | ID: covidwho-1518198

ABSTRACT

A substantial proportion of patients who have recovered from coronavirus disease-2019 (COVID-19) experience COVID-19-related symptoms even months after hospital discharge. We extensively immunologically characterized patients who recovered from COVID-19. In these patients, T cells were exhausted, with increased PD-1+ T cells, as compared with healthy controls. Plasma levels of IL-1ß, IL-1RA, and IL-8, among others, were also increased in patients who recovered from COVID-19. This altered immunophenotype was mirrored by a reduced ex vivo T cell response to both nonspecific and specific stimulation, revealing a dysfunctional status of T cells, including a poor response to SARS-CoV-2 antigens. Altered levels of plasma soluble PD-L1, as well as of PD1 promoter methylation and PD1-targeting miR-15-5p, in CD8+ T cells were also observed, suggesting abnormal function of the PD-1/PD-L1 immune checkpoint axis. Notably, ex vivo blockade of PD-1 nearly normalized the aforementioned immunophenotype and restored T cell function, reverting the observed post-COVID-19 immune abnormalities; indeed, we also noted an increased T cell-mediated response to SARS-CoV-2 peptides. Finally, in a neutralization assay, PD-1 blockade did not alter the ability of T cells to neutralize SARS-CoV-2 spike pseudotyped lentivirus infection. Immune checkpoint blockade ameliorates post-COVID-19 immune abnormalities and stimulates an anti-SARS-CoV-2 immune response.


Subject(s)
COVID-19/complications , Cytokines/immunology , Immune Checkpoint Inhibitors/pharmacology , Programmed Cell Death 1 Receptor/immunology , SARS-CoV-2/immunology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , B7-H1 Antigen/immunology , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Case-Control Studies , Cytokines/drug effects , DNA Methylation , Female , Humans , Immunophenotyping , In Vitro Techniques , Interleukin 1 Receptor Antagonist Protein/drug effects , Interleukin 1 Receptor Antagonist Protein/immunology , Interleukin-1beta/drug effects , Interleukin-1beta/immunology , Interleukin-8/drug effects , Interleukin-8/immunology , Male , MicroRNAs/metabolism , Middle Aged , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Promoter Regions, Genetic
3.
JCI Insight ; 6(18)2021 09 22.
Article in English | MEDLINE | ID: covidwho-1467778

ABSTRACT

The importance of the adaptive T cell response in the control and resolution of viral infection has been well established. However, the nature of T cell-mediated viral control mechanisms in life-threatening stages of COVID-19 has yet to be determined. The aim of the present study was to determine the function and phenotype of T cell populations associated with survival or death of patients with COVID-19 in intensive care as a result of phenotypic and functional profiling by mass cytometry. Increased frequencies of circulating, polyfunctional CD4+CXCR5+HLA-DR+ stem cell memory T cells (Tscms) and decreased proportions of granzyme B-expressing and perforin-expressing effector memory T cells were detected in recovered and deceased patients, respectively. The higher abundance of polyfunctional PD-L1+CXCR3+CD8+ effector T cells (Teffs), CXCR5+HLA-DR+ Tscms, and anti-nucleocapsid (anti-NC) cytokine-producing T cells permitted us to differentiate between recovered and deceased patients. The results from a principal component analysis show an imbalance in the T cell compartment that allowed for the separation of recovered and deceased patients. The paucity of circulating PD-L1+CXCR3+CD8+ Teffs and NC-specific CD8+ T cells accurately forecasts fatal disease outcome. This study provides insight into the nature of the T cell populations involved in the control of COVID-19 and therefore might impact T cell-based vaccine designs for this infectious disease.


Subject(s)
B7-H1 Antigen/immunology , CD4-Positive T-Lymphocytes/immunology , CD8 Antigens/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Immunity, Cellular , Receptors, CXCR3/immunology , Adult , COVID-19/mortality , COVID-19/pathology , Epitopes, T-Lymphocyte/immunology , Female , France/epidemiology , Humans , Immunologic Memory , Lymphocyte Activation , Male , SARS-CoV-2 , Survival Rate/trends
4.
Front Immunol ; 12: 752612, 2021.
Article in English | MEDLINE | ID: covidwho-1456293

ABSTRACT

Background: Lymphopenia and the neutrophil/lymphocyte ratio may have prognostic value in COVID-19 severity. Objective: We investigated neutrophil subsets and functions in blood and bronchoalveolar lavage (BAL) of COVID-19 patients on the basis of patients' clinical characteristics. Methods: We used a multiparametric cytometry profiling based to mature and immature neutrophil markers in 146 critical or severe COVID-19 patients. Results: The Discovery study (38 patients, first pandemic wave) showed that 80% of Intensive Care Unit (ICU) patients develop strong myelemia with CD10-CD64+ immature neutrophils (ImNs). Cellular profiling revealed three distinct neutrophil subsets expressing either the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), the interleukin-3 receptor alpha (CD123), or programmed death-ligand 1 (PD-L1) overrepresented in ICU patients compared to non-ICU patients. The proportion of LOX-1- or CD123-expressing ImNs is positively correlated with clinical severity, cytokine storm (IL-1ß, IL-6, IL-8, TNFα), acute respiratory distress syndrome (ARDS), and thrombosis. BALs of patients with ARDS were highly enriched in LOX-1-expressing ImN subsets and in antimicrobial neutrophil factors. A validation study (118 patients, second pandemic wave) confirmed and strengthened the association of the proportion of ImN subsets with disease severity, invasive ventilation, and death. Only high proportions of LOX-1-expressing ImNs remained strongly associated with a high risk of severe thrombosis independently of the plasma antimicrobial neutrophil factors, suggesting an independent association of ImN markers with their functions. Conclusion: LOX-1-expressing ImNs may help identifying COVID-19 patients at high risk of severity and thrombosis complications.


Subject(s)
COVID-19/complications , Neutrophils/immunology , Scavenger Receptors, Class E/genetics , Thrombosis/etiology , Adult , Aged , B7-H1 Antigen/genetics , B7-H1 Antigen/immunology , Bronchoalveolar Lavage Fluid/immunology , COVID-19/genetics , COVID-19/immunology , COVID-19/virology , Critical Illness , Female , Humans , Interleukin-3 Receptor alpha Subunit/genetics , Interleukin-3 Receptor alpha Subunit/immunology , Interleukin-8/genetics , Interleukin-8/immunology , Male , Middle Aged , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/genetics , Respiratory Distress Syndrome/immunology , SARS-CoV-2/physiology , Scavenger Receptors, Class E/immunology , Thrombosis/genetics , Thrombosis/immunology
5.
JCI Insight ; 6(13)2021 06 18.
Article in English | MEDLINE | ID: covidwho-1346128

ABSTRACT

We explored the potential link between chronic inflammatory arthritis and COVID-19 pathogenic and resolving macrophage pathways and their role in COVID-19 pathogenesis. We found that bronchoalveolar lavage fluid (BALF) macrophage clusters FCN1+ and FCN1+SPP1+ predominant in severe COVID-19 were transcriptionally related to synovial tissue macrophage (STM) clusters CD48hiS100A12+ and CD48+SPP1+ that drive rheumatoid arthritis (RA) synovitis. BALF macrophage cluster FABP4+ predominant in healthy lung was transcriptionally related to STM cluster TREM2+ that governs resolution of synovitis in RA remission. Plasma concentrations of SPP1 and S100A12 (key products of macrophage clusters shared with active RA) were high in severe COVID-19 and predicted the need for Intensive Care Unit transfer, and they remained high in the post-COVID-19 stage. High plasma levels of SPP1 were unique to severe COVID-19 when compared with other causes of severe pneumonia, and IHC localized SPP1+ macrophages in the alveoli of COVID-19 lung. Investigation into SPP1 mechanisms of action revealed that it drives proinflammatory activation of CD14+ monocytes and development of PD-L1+ neutrophils, both hallmarks of severe COVID-19. In summary, COVID-19 pneumonitis appears driven by similar pathogenic myeloid cell pathways as those in RA, and their mediators such as SPP1 might be an upstream activator of the aberrant innate response in severe COVID-19 and predictive of disease trajectory including post-COVID-19 pathology.


Subject(s)
Arthritis, Rheumatoid/immunology , COVID-19/immunology , Monocytes/immunology , Neutrophils/immunology , Osteopontin/immunology , Arthritis, Rheumatoid/metabolism , B7-H1 Antigen/immunology , Bronchoalveolar Lavage Fluid/immunology , CD48 Antigen/immunology , COVID-19/chemically induced , COVID-19/metabolism , Fatty Acid-Binding Proteins/immunology , Humans , Lectins/immunology , Lipopolysaccharide Receptors/immunology , Lipopolysaccharide Receptors/metabolism , Lung/diagnostic imaging , Lung/immunology , Lung/metabolism , Lung/pathology , Macrophages/immunology , Macrophages/metabolism , Membrane Glycoproteins/immunology , Monocytes/metabolism , Neutrophils/metabolism , Osteopontin/blood , Receptor Protein-Tyrosine Kinases/metabolism , Receptors, Immunologic/immunology , S100A12 Protein/immunology , S100A12 Protein/metabolism , Synovial Membrane/immunology , Tomography, X-Ray Computed
6.
Cell Commun Signal ; 19(1): 76, 2021 07 13.
Article in English | MEDLINE | ID: covidwho-1318284

ABSTRACT

Hypoxia is a pathological condition common to many diseases, although multiple organ injuries induced by hypoxia are often overlooked. There is increasing evidence to suggest that the hypoxic environment may activate innate immune cells and suppress adaptive immunity, further stimulating inflammation and inhibiting immunosurveillance. We found that dysfunctional immune regulation may aggravate hypoxia-induced tissue damage and contribute to secondary injury. Among the diverse mechanisms of hypoxia-induced immune dysfunction identified to date, the role of programmed death-ligand 1 (PD-L1) has recently attracted much attention. Besides leading to tumour immune evasion, PD-L1 has also been found to participate in the progression of the immune dysfunction which mediates hypoxia-induced multiple organ injury. In this review, we aimed to summarise the role of immune dysfunction in hypoxia-induced multiple organ injury, the effects of hypoxia on the cellular expression of PD-L1, and the effects of upregulated PD-L1 expression on immune regulation. Furthermore, we summarise the latest information pertaining to the involvement, diagnostic value, and therapeutic potential of immunosuppression induced by PD-L1 in various types of hypoxia-related diseases, including cancers, ischemic stroke, acute kidney injury, and obstructive sleep apnoea. Video Abstract.


Subject(s)
Adaptive Immunity/genetics , B7-H1 Antigen/immunology , Inflammation/immunology , Tumor Hypoxia/genetics , Acute Kidney Injury/genetics , Acute Kidney Injury/immunology , Adaptive Immunity/immunology , B7-H1 Antigen/genetics , Humans , Immunity, Innate/genetics , Inflammation/genetics , Ischemic Stroke/genetics , Ischemic Stroke/immunology , Monitoring, Immunologic , Neoplasms/genetics , Neoplasms/immunology , Sleep Apnea, Obstructive/genetics , Sleep Apnea, Obstructive/immunology , Tumor Hypoxia/immunology
7.
Cell Immunol ; 364: 104347, 2021 06.
Article in English | MEDLINE | ID: covidwho-1157177

ABSTRACT

Myeloid-derived suppressor cells (MDSC) are important immune-regulatory cells but their identification remains difficult. Here, we provide a critical view on selected surface markers, transcriptional and translational pathways commonly used to identify MDSC by specific, their developmental origin and new possibilities by transcriptional or proteomic profiling. Discrimination of MDSC from their non-suppressive counterparts is a prerequisite for the development of successful therapies. Understanding the switch mechanisms that direct granulocytic and monocytic development into a pro-inflammatory or anti-inflammatory direction will be crucial for therapeutic strategies. Manipulation of these myeloid checkpoints are exploited by tumors and pathogens, such as M. tuberculosis (Mtb), HIV or SARS-CoV-2, that induce MDSC for immune evasion. Thus, specific markers for MDSC identification may reveal also novel molecular candidates for therapeutic intervention at the level of MDSC.


Subject(s)
Biomarkers/metabolism , Gene Expression Profiling/methods , Myeloid-Derived Suppressor Cells/immunology , Proteomics/methods , Signal Transduction/immunology , Animals , B7-H1 Antigen/genetics , B7-H1 Antigen/immunology , B7-H1 Antigen/metabolism , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , Cells, Cultured , Humans , Mice , Myeloid-Derived Suppressor Cells/metabolism , Neoplasms/genetics , Neoplasms/immunology , Neoplasms/metabolism , Programmed Cell Death 1 Receptor/genetics , Programmed Cell Death 1 Receptor/immunology , Programmed Cell Death 1 Receptor/metabolism , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Signal Transduction/genetics , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism
8.
J Immunother Cancer ; 9(3)2021 03.
Article in English | MEDLINE | ID: covidwho-1133309

ABSTRACT

While vaccines directed against the SARS-CoV-2 spike protein will have varying degrees of effectiveness in preventing SARS-CoV-2 infections, the severity of infection will be determined by multiple host factors including the ability of immune cells to lyse virus-infected cells. This review will discuss the complexity of both adaptive and innate immunomes and how a flow-based assay can detect up to 158 distinct cell subsets in the periphery. This assay has been employed to show the effect of age on differences in specific immune cell subsets, and the differences in the immunome between healthy donors and age-matched cancer patients. Also reviewed are the numerous soluble factors, in addition to cytokines, that may vary in the pathogenesis of SARS-CoV-2 infections and may also be employed to help define the effectiveness of a given vaccine or other antiviral agents. Various steroids have been employed in the management of autoimmune adverse events in cancer patients receiving immunotherapeutics and may be employed in the management of SARS-CoV-2 infections. The influence of steroids on multiple immune cells subsets will also be discussed.


Subject(s)
Adaptive Immunity/immunology , B-Lymphocytes/immunology , COVID-19/immunology , Dendritic Cells/immunology , Immunity, Innate/immunology , Killer Cells, Natural/immunology , Neoplasms/immunology , T-Lymphocytes/immunology , Age Factors , B7-H1 Antigen/immunology , CD40 Ligand/immunology , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Cytokines/immunology , Disease Susceptibility , Glucocorticoids/therapeutic use , Granzymes/immunology , Humans , Immune Checkpoint Inhibitors/therapeutic use , Immunosenescence/immunology , Myeloid-Derived Suppressor Cells/immunology , Neoplasms/drug therapy , Programmed Cell Death 1 Receptor/immunology , Proteome , SARS-CoV-2 , Severity of Illness Index , T-Lymphocyte Subsets/immunology , Tumor Necrosis Factor Receptor Superfamily, Member 7/immunology
9.
J Immunother Cancer ; 9(2)2021 02.
Article in English | MEDLINE | ID: covidwho-1081352

ABSTRACT

By the beginning of the global pandemic, SARS-CoV-2 infection has dramatically impacted on oncology daily practice. In the current oncological landscape, where immunotherapy has revolutionized the treatment of several malignancies, distinguishing between COVID-19 and immune-mediated pneumonitis can be hard because of shared clinical, radiological and pathological features. Indeed, their common mechanism of aberrant inflammation could lead to a mutual and amplifying interaction.We describe the case of a 65-year-old patient affected by metastatic squamous head and neck cancer and candidate to an experimental therapy including an anti-PD-L1 agent. COVID-19 ground-glass opacities under resolution were an incidental finding during screening procedures and worsened after starting immunotherapy. The diagnostic work-up was consistent with ICIs-related pneumonia and it is conceivable that lung injury by SARS-CoV-2 has acted as an inflammatory primer for the development of the immune-related adverse event.Patients recovered from COVID-19 starting ICIs could be at greater risk of recall immune-mediated pneumonitis. Nasopharyngeal swab and chest CT scan are recommended before starting immunotherapy. The awareness of the phenomenon could allow an easier interpretation of radiological changes under treatment and a faster diagnostic work-up to resume ICIs. In the presence of clinical benefit, for asymptomatic ICIs-related pneumonia a watchful-waiting approach and immunotherapy prosecution are suggested.


Subject(s)
COVID-19/diagnosis , Lung Neoplasms/diagnosis , Pneumonia/diagnosis , Squamous Cell Carcinoma of Head and Neck/diagnosis , Aged , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , COVID-19/drug therapy , COVID-19/immunology , COVID-19/virology , Diagnosis, Differential , Humans , Immune Checkpoint Inhibitors/administration & dosage , Immune Checkpoint Inhibitors/adverse effects , Immunotherapy/adverse effects , Lung Injury/diagnosis , Lung Injury/diagnostic imaging , Lung Injury/pathology , Lung Injury/virology , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Lung Neoplasms/virology , Male , Nasopharynx/metabolism , Nasopharynx/pathology , Neoplasm Metastasis , Pandemics , Pneumonia/drug therapy , Pneumonia/immunology , Pneumonia/virology , SARS-CoV-2/pathogenicity , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/immunology , Squamous Cell Carcinoma of Head and Neck/virology
10.
Ann Oncol ; 31(10): 1386-1396, 2020 10.
Article in English | MEDLINE | ID: covidwho-987038

ABSTRACT

BACKGROUND: Patients with lung cancers may have disproportionately severe coronavirus disease 2019 (COVID-19) outcomes. Understanding the patient-specific and cancer-specific features that impact the severity of COVID-19 may inform optimal cancer care during this pandemic. PATIENTS AND METHODS: We examined consecutive patients with lung cancer and confirmed diagnosis of COVID-19 (n = 102) at a single center from 12 March 2020 to 6 May 2020. Thresholds of severity were defined a priori as hospitalization, intensive care unit/intubation/do not intubate ([ICU/intubation/DNI] a composite metric of severe disease), or death. Recovery was defined as >14 days from COVID-19 test and >3 days since symptom resolution. Human leukocyte antigen (HLA) alleles were inferred from MSK-IMPACT (n = 46) and compared with controls with lung cancer and no known non-COVID-19 (n = 5166). RESULTS: COVID-19 was severe in patients with lung cancer (62% hospitalized, 25% died). Although severe, COVID-19 accounted for a minority of overall lung cancer deaths during the pandemic (11% overall). Determinants of COVID-19 severity were largely patient-specific features, including smoking status and chronic obstructive pulmonary disease [odds ratio for severe COVID-19 2.9, 95% confidence interval 1.07-9.44 comparing the median (23.5 pack-years) to never-smoker and 3.87, 95% confidence interval 1.35-9.68, respectively]. Cancer-specific features, including prior thoracic surgery/radiation and recent systemic therapies did not impact severity. Human leukocyte antigen supertypes were generally similar in mild or severe cases of COVID-19 compared with non-COVID-19 controls. Most patients recovered from COVID-19, including 25% patients initially requiring intubation. Among hospitalized patients, hydroxychloroquine did not improve COVID-19 outcomes. CONCLUSION: COVID-19 is associated with high burden of severity in patients with lung cancer. Patient-specific features, rather than cancer-specific features or treatments, are the greatest determinants of severity.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Lung Neoplasms/epidemiology , Lung Neoplasms/therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Adult , Aged , Aged, 80 and over , B7-H1 Antigen/immunology , B7-H1 Antigen/therapeutic use , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Female , Follow-Up Studies , Hospitalization/trends , Humans , Hydroxychloroquine/therapeutic use , Lung Neoplasms/immunology , Male , Middle Aged , Pandemics , Pneumonia, Viral/immunology , Retrospective Studies , SARS-CoV-2
11.
J Immunother Cancer ; 8(2)2020 10.
Article in English | MEDLINE | ID: covidwho-873575

ABSTRACT

Immune checkpoint inhibitors (ICI) block negative regulatory molecules, such as CTLA-4, PD-1 and PD-L1, in order to mount an antitumor response. T cells are important for antiviral defense, but it is not known whether patients with cancer treated with ICI are more or less vulnerable to viral infections such as COVID-19. Furthermore, immunosuppressive treatment of immune-related adverse events (irAE) may also impact infection risk. Rheumatic irAEs are often persistent, and can require long-term treatment with immunosuppressive agents. The aim of this study was to determine the incidence of COVID-19 infection and assess changes in ICI and immunosuppressive medication use among patients enrolled in a prospective rheumatic irAE registry during the height of the COVID-19 pandemic. On April 16 2020, following the 'surge' of COVID-19 infections in the New York Tri-State area, we sent a 23-question survey to 88 living patients enrolled in a single institutional registry of patients with rheumatic irAE. Questions addressed current cancer and rheumatic irAE status, ICI and immunosuppressant medication use, history of COVID-19 symptoms and/or diagnosed infection. A follow-up survey was sent out 6 weeks later. Sixty-five (74%) patients completed the survey. Mean age was 63 years, 59% were female, 70% had received anti-PD-(L)1 monotherapy and 80% had had an irAE affecting their joints. Six patients (10%) had definite or probable COVID-19, but all recovered uneventfully, including two still on ICI and on low-to-moderate dose prednisone. Of the 25 on ICI within the last 6 months, seven (28%) had their ICI held due to the pandemic. In patients on immunosuppression for irAE, none had changes made to those medications as a result of the pandemic. The incidence of COVID-19 was no higher in patients still on ICI. Ten percent of rheumatic irAE patients developed COVID-19 during the NY Tri-state 'surge' of March-April 2020. Oncologists held ICI in a quarter of the patients still on them, particularly women, those on anti-PD-(L)1 monotherapy, and those who had had a good cancer response. The incidence of COVID-19 was no higher on patients still on ICI. None of the patients on disease-modifying antirheumatic drugs or biological immunosuppressive medications developed COVID-19.


Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Betacoronavirus/immunology , Coronavirus Infections/immunology , Immunosuppressive Agents/adverse effects , Neoplasms/drug therapy , Pneumonia, Viral/immunology , Rheumatic Diseases/drug therapy , Aged , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , Betacoronavirus/pathogenicity , COVID-19 , COVID-19 Testing , CTLA-4 Antigen/antagonists & inhibitors , CTLA-4 Antigen/immunology , Clinical Decision-Making , Clinical Laboratory Techniques/statistics & numerical data , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Female , Humans , Incidence , Male , Medical Oncology/standards , Medical Oncology/statistics & numerical data , Middle Aged , Neoplasms/immunology , New York City/epidemiology , Pandemics/prevention & control , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Practice Patterns, Physicians'/standards , Practice Patterns, Physicians'/statistics & numerical data , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , Prospective Studies , Registries/statistics & numerical data , Rheumatic Diseases/chemically induced , Rheumatic Diseases/epidemiology , Rheumatic Diseases/immunology , SARS-CoV-2 , Severity of Illness Index , Surveys and Questionnaires/statistics & numerical data
12.
J Immunother Cancer ; 8(2)2020 10.
Article in English | MEDLINE | ID: covidwho-873574

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region. METHODS: This survey (25 questions), promoted by the young section of SCITO (Società Campana di ImmunoTerapia Oncologica) Group, was circulated among Italian young oncologists practicing in regions variously affected by the pandemic: high (group 1), medium (group 2) and low (group 3) prevalence of SARS-CoV-2-positive patients. For Campania region, the physician responders were split into those working in cancer centers (CC), university hospitals (UH) and general hospitals (GH). Percentages of agreement, among High (H) versus Medium (M) and versus Low (L) group for Italy and among CC, UH and GH for Campania region, were compared by using Fisher's exact tests for dichotomous answers and χ2 test for trends relative to the questions with 3 or more options. RESULTS: This is the first Italian study to investigate the COVID-19 impact on cancer immunotherapy, unique in its type and very clear in the results. The COVID-19 pandemic seemed not to affect the standard practice in the prescription and delivery of ICIs in Italy. Telemedicine was widely used. There was high consensus to interrupt immunotherapy in SARS-CoV-2-positive patients and to adopt ICIs with longer schedule interval. The majority of the responders tended not to delay the start of ICIs; there were no changes in supportive treatments, but some of the physicians opted for delaying surgeries (if part of patients' planned treatment approach). The results from responders in Campania did not differ significantly from the national ones. CONCLUSION: Our study highlights the efforts of Italian oncologists to maintain high standards of care for CPs treated with ICIs, regardless the regional prevalence of COVID-19, suggesting the adoption of similar solutions. Research on patients treated with ICIs and experiencing COVID-19 will clarify the safety profile to continue the treatments, thus informing on the most appropriate clinical conducts.


Subject(s)
Antineoplastic Agents, Immunological/administration & dosage , Betacoronavirus/immunology , Coronavirus Infections/epidemiology , Medical Oncology/statistics & numerical data , Neoplasms/drug therapy , Pneumonia, Viral/epidemiology , Adult , Antineoplastic Agents, Immunological/adverse effects , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , Betacoronavirus/pathogenicity , COVID-19 , CTLA-4 Antigen/antagonists & inhibitors , CTLA-4 Antigen/immunology , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Drug Prescriptions/statistics & numerical data , Female , Geography , Humans , Infection Control/standards , Italy/epidemiology , Male , Medical Oncology/standards , Neoplasms/immunology , Oncologists/statistics & numerical data , Pandemics/prevention & control , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Practice Patterns, Physicians'/standards , Practice Patterns, Physicians'/statistics & numerical data , Prevalence , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , SARS-CoV-2 , Surveys and Questionnaires/statistics & numerical data , Time-to-Treatment
13.
Cancer Treat Rev ; 90: 102109, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-842480

ABSTRACT

Treatment with immune-checkpoint inhibitors (ICIs) has shown efficacy against a variety of cancer types. The use of anti PD-1, anti PD-L1, and anti CTLA-4 antibodies is rapidly expanding. The side effects of ICIs are very different from conventional cytocidal anticancer and molecular target drugs, and may extend to the digestive organs, respiratory organs, thyroid gland, pituitary gland, skin, and others. Although the details of these adverse events are becoming increasingly apparent, much is unknown regarding the effects and adverse events related to infections. This review focuses specifically on the impact of ICIs on respiratory infections. The impact of ICIs on pathogens varies depending on the significance of the role of T-cell immunity in the immune response to the specific pathogen, as well as the different modes of infection (i.e., acute or chronic), although the impact of ICIs on the clinical outcome of infections in humans has not yet been well studied. Enhanced clearance of many pathogens has been shown because immune checkpoint inhibition activates T cells. In contrast, reactivation of tuberculosis associated with ICI use has been reported, and therefore caution is warranted. In COVID-19 pneumonia, ICI administration may lead to exacerbation; however, it is also possible that ICI may be used for the treatment of COVID-19. It has also been shown that ICI has potential in the treatment of intractable filamentous fungal infections. Therefore, expanded clinical applications are expected.


Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Respiratory Tract Infections/chemically induced , Animals , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/immunology , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , CTLA-4 Antigen/antagonists & inhibitors , CTLA-4 Antigen/immunology , Humans , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , Randomized Controlled Trials as Topic , Respiratory Tract Infections/immunology
14.
Cell Mol Immunol ; 17(9): 995-997, 2020 09.
Article in English | MEDLINE | ID: covidwho-625131

Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/immunology , Molecular Targeted Therapy/methods , Pneumonia, Viral/immunology , Pneumonia/immunology , Severe Acute Respiratory Syndrome/immunology , Antiviral Agents/therapeutic use , Apyrase/antagonists & inhibitors , Apyrase/genetics , Apyrase/immunology , B-Lymphocytes/immunology , B-Lymphocytes/pathology , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/genetics , B7-H1 Antigen/immunology , Betacoronavirus/immunology , COVID-19 , Case-Control Studies , Coronavirus Infections/drug therapy , Coronavirus Infections/genetics , Coronavirus Infections/virology , Gene Expression/drug effects , Humans , Immunologic Factors/therapeutic use , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , NK Cell Lectin-Like Receptor Subfamily C/antagonists & inhibitors , NK Cell Lectin-Like Receptor Subfamily C/genetics , NK Cell Lectin-Like Receptor Subfamily C/immunology , Pandemics , Pneumonia/drug therapy , Pneumonia/genetics , Pneumonia/virology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/genetics , Pneumonia, Viral/virology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/genetics , Programmed Cell Death 1 Receptor/immunology , SARS-CoV-2 , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/genetics , Severe Acute Respiratory Syndrome/virology , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/pathology
15.
J Immunother Cancer ; 8(1)2020 06.
Article in English | MEDLINE | ID: covidwho-607910

ABSTRACT

Immune-related (IR)-pneumonitis is a rare and potentially fatal toxicity of anti-PD(L)1 immunotherapy. Expert guidelines for the diagnosis and management of IR-pneumonitis include multidisciplinary input from medical oncology, pulmonary medicine, infectious disease, and radiology specialists. Severe acute respiratory syndrome coronavirus 2 is a recently recognized respiratory virus that is responsible for causing the COVID-19 global pandemic. Symptoms and imaging findings from IR-pneumonitis and COVID-19 pneumonia can be similar, and early COVID-19 viral testing may yield false negative results, complicating the diagnosis and management of both entities. Herein, we present a set of multidisciplinary consensus recommendations for the diagnosis and management of IR-pneumonitis in the setting of COVID-19 including: (1) isolation procedures, (2) recommended imaging and interpretation, (3) adaptations to invasive testing, (4) adaptations to the management of IR-pneumonitis, (5) immunosuppression for steroid-refractory IR-pneumonitis, and (6) management of suspected concurrent IR-pneumonitis and COVID-19 infection. There is an emerging need for the adaptation of expert guidelines for IR-pneumonitis in the setting of the global COVID-19 pandemic. We propose a multidisciplinary consensus on this topic, in this position paper.


Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia/therapy , Practice Guidelines as Topic , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , COVID-19 , Consensus , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Humans , Infectious Disease Medicine/standards , Interdisciplinary Communication , Lung/diagnostic imaging , Lung/drug effects , Lung/immunology , Medical Oncology/standards , Neoplasms/drug therapy , Neoplasms/immunology , Pneumonia/chemically induced , Pneumonia/diagnosis , Pneumonia/immunology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Pulmonary Medicine/standards , Radiology/standards , SARS-CoV-2 , United States/epidemiology
16.
Eur J Cancer ; 135: 62-65, 2020 08.
Article in English | MEDLINE | ID: covidwho-605486

ABSTRACT

While confirmed cases of the deadly coronavirus disease 2019 (COVID-19) have exceeded 4.7 million globally, scientists are pushing forward with efforts to develop vaccines and treatments in an attempt to slow the pandemic and lessen the disease's damage. Although no proven effective therapies for treating patients with COVID-19 or for managing their complications currently exist, the rapidly expanding knowledge regarding severe acute respiratory syndrome coronavirus 2 and its interplay with hosts provides a significant number of potential drug targets and the potential to repurpose drugs already tested in other diseases. Herein, we report the biological rationale of immune-activating drugs and a brief summary of literature data on the potential therapeutic value of immune checkpoint inhibitors that have been recently tested beyond cancer treatment for their potential to restore cellular immunocompetence.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/drug therapy , Immunologic Factors/therapeutic use , Neoplasms/drug therapy , Pneumonia, Viral/drug therapy , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Apoptosis/drug effects , Apoptosis/immunology , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , Betacoronavirus/immunology , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/immunology , Coronavirus Infections/virology , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/immunology , Humans , Immunologic Factors/pharmacology , Lymphopenia/blood , Lymphopenia/drug therapy , Lymphopenia/immunology , Lymphopenia/virology , Neoplasms/blood , Neoplasms/immunology , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , Randomized Controlled Trials as Topic , SARS-CoV-2 , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Treatment Outcome
17.
Clin Cancer Res ; 26(16): 4201-4205, 2020 08 15.
Article in English | MEDLINE | ID: covidwho-599654

ABSTRACT

The potential immune intersection between COVID-19 disease and cancer therapy raises important practical clinical questions and highlights multiple scientific gaps to be filled. Among available therapeutic approaches to be considered, immune checkpoint inhibitors (ICI) seem to require major attention as they may act at the crossroads between cancer treatment and COVID-19 disease, due to their profound immunomodulatory activity. On the basis of available literature evidence, we suggest guidance to consider for treating physicians, and propose areas of clinical and preclinical investigation. Comprehensively, although with the necessary caution, ICI therapy seems to remain a suitable therapeutic option for patients with cancer during the COVID-19 pandemic.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Betacoronavirus/immunology , Coronavirus Infections/immunology , Neoplasms/drug therapy , Pneumonia, Viral/immunology , Antineoplastic Agents, Immunological/pharmacology , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , COVID-19 , CTLA-4 Antigen/antagonists & inhibitors , CTLA-4 Antigen/immunology , Clinical Decision-Making , Clinical Trials as Topic , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Humans , Neoplasms/immunology , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Pneumonia, Viral/virology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , SARS-CoV-2 , Treatment Outcome
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