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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
3.
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
4.
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
5.
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
6.
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
7.
J Thorac Oncol ; 15(11): 1767-1772, 2020 11.
Article in English | MEDLINE | ID: covidwho-703147

ABSTRACT

A new coronavirus, named severe acute respiratory syndrome-coronavirus-2 by the WHO, has rapidly spread around the world since its first reported case in late December of 2019 from Wuhan, the People's Republic of China. As of mid-April 2020, this virus has affected more than 180 countries and territories, infecting more than 1,650,000 individuals and causing over 100,000 deaths. With approximately 20 million new cases globally per year, cancer affects a substantial portion of the population. Individuals affected by cancer are more susceptible to infections owing to coexisting chronic diseases (cardiovascular, pulmonary, and diabetes), overall poor health status, and systemic immunosuppressive states caused by both cancer and the anticancer treatment. As a consequence, patients with malignancies, especially those with lung cancer who develop coronavirus disease 2019, experience more difficult outcomes. A recent multicenter study carried out by the Hubei Anti-Cancer Association has also documented that patients with lung cancer had an increased risk of death, intensive care unit requirement, risk of presenting severe or critical symptoms, and use of invasive mechanical ventilation. Here, we present two representative cases of patients with lung cancer and coronavirus disease 2019 without respiratory compromise and with atypical and severe skin manifestations-findings that could be influenced by the long-term use of anti-programmed cell death protein 1 antibody.


Subject(s)
B7-H1 Antigen/antagonists & inhibitors , Betacoronavirus , Coronavirus Infections/complications , Lung Neoplasms/drug therapy , Pneumonia, Viral/complications , Skin Diseases/etiology , COVID-19 , Female , Humans , Male , Middle Aged , Pandemics , SARS-CoV-2
8.
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
9.
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
10.
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
13.
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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