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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319901

ABSTRACT

Objectives: The aim of our study was to assess the frequency distribution of relevant and incidental vascular events in a retrospective cohort of 42 COVID-19 patients. Methods: All patients were studied by whole-body CT angiography.Twenty-three out of 42 patients were admitted to the intensive care unit (ICU). Results: Relevant vascular events were recorded in the 71.4% of the whole study population. Pulmonary embolism was the most frequent one both in ICU and no-ICU cases (56.5% vs 10.5%, p=0.002). Ischemic infarction of other organs was affecting with an increasing prevalence the gut, the spleen, the liver, the brain and the kidney, with a simultaneous ischemic occurrence in some cases. Multi-focal venous thrombosis was also represented especially in ICU patients (p=0.005). Among incidental findings, splanchnic vessels little-size aneurysms were reported in the 40% of the whole population, with relative frequencies similarly distributed in ICU and no-ICU patients. Conclusions: Vascular involvement is not negligible in COVID-19 and should be carefully investigated as may significantly affect disease behavior and prognosis.

4.
J Transl Med ; 18(1): 405, 2020 10 21.
Article in English | MEDLINE | ID: covidwho-1477432

ABSTRACT

BACKGROUND: Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. METHODS: A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. RESULTS: In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P = 0.52) and 22.4% (97.5% CI: 17.2-28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. CONCLUSIONS: Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adult , Aged , Aged, 80 and over , Betacoronavirus/immunology , COVID-19 , Cohort Studies , Coronavirus Infections/epidemiology , Female , Humans , Italy/epidemiology , Male , Middle Aged , Mortality , Off-Label Use , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Treatment Outcome , Validation Studies as Topic
5.
Biology (Basel) ; 10(8)2021 Aug 01.
Article in English | MEDLINE | ID: covidwho-1376731

ABSTRACT

In December 2019, a novel coronavirus, "SARS-CoV-2", was recognized as the cause of coronavirus disease 2019 (COVID-19). Several studies have explored the changes and the role of inflammatory cells and cytokines in the immunopathogenesis of the disease, but until today, the results have been controversial. Based on these premises, we conducted a retrospective assessment of monocyte intracellular TNF-α expression (iTNF-α) and on the frequencies of lymphocyte sub-populations in twenty-five patients with moderate/severe COVID-19. We found lymphopenia in all COVID-19 infected subjects compared to healthy subjects. On initial observation, in patients with favorable outcomes, we detected a high absolute eosinophil count and a high CD4+/CD8+ T lymphocytes ratio, while in the Exitus Group, we observed high neutrophil and CD8+ T lymphocyte counts. During infection, in patients with favorable outcomes, we observed a rise in the lymphocyte count, in the monocyte and in Treg lymphocyte counts, and in the CD4+ and in CD8+ T lymphocytes count but a reduction in the CD4+/CD8+ T lymphocyte ratio. Instead, in the Exitus Group, we observed a reduction in the Treg lymphocyte counts and a decrease in iTNF-α expression. Our preliminary findings point to a modulation of the different cellular mediators of the immune system, which probably play a key role in the outcomes of COVID-19.

6.
Biology (Basel) ; 10(8)2021 Aug 01.
Article in English | MEDLINE | ID: covidwho-1334990

ABSTRACT

In December 2019, a novel coronavirus, "SARS-CoV-2", was recognized as the cause of coronavirus disease 2019 (COVID-19). Several studies have explored the changes and the role of inflammatory cells and cytokines in the immunopathogenesis of the disease, but until today, the results have been controversial. Based on these premises, we conducted a retrospective assessment of monocyte intracellular TNF-α expression (iTNF-α) and on the frequencies of lymphocyte sub-populations in twenty-five patients with moderate/severe COVID-19. We found lymphopenia in all COVID-19 infected subjects compared to healthy subjects. On initial observation, in patients with favorable outcomes, we detected a high absolute eosinophil count and a high CD4+/CD8+ T lymphocytes ratio, while in the Exitus Group, we observed high neutrophil and CD8+ T lymphocyte counts. During infection, in patients with favorable outcomes, we observed a rise in the lymphocyte count, in the monocyte and in Treg lymphocyte counts, and in the CD4+ and in CD8+ T lymphocytes count but a reduction in the CD4+/CD8+ T lymphocyte ratio. Instead, in the Exitus Group, we observed a reduction in the Treg lymphocyte counts and a decrease in iTNF-α expression. Our preliminary findings point to a modulation of the different cellular mediators of the immune system, which probably play a key role in the outcomes of COVID-19.

7.
Eur Radiol ; 31(10): 7363-7370, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1188091

ABSTRACT

OBJECTIVES: Increasing evidence suggests that SARS-CoV-2 infection may lead to severe and multi-site vascular involvement. Our study aimed at assessing the frequency of vascular and extravascular events' distribution in a retrospective cohort of 42 COVID-19 patients. METHODS: Patients were evaluated by whole-body CT angiography between March 16 and April 30, 2020. Twenty-three out of the 42 patients evaluated were admitted to the intensive care unit (ICU). Vascular and extravascular findings were categorized into "relevant" or "other/incidental," first referring to the need for immediate patient care and management. Student T-test, Mann-Whitney U test, or Fisher exact test was used to compare study groups, where appropriate. RESULTS: Relevant vascular events were recorded in 71.4% of cases (n = 30). Pulmonary embolism was the most frequent in both ICU and non-ICU cases (56.5% vs. 10.5%, p = 0.002). Ischemic infarctions at several sites such as the gut, spleen, liver, brain, and kidney were detected (n = 20), with multi-site involvement in some cases. Systemic venous thrombosis occurred in 30.9% of cases compared to 7.1% of systemic arterial events, the first being significantly higher in ICU patients (p = 0.002). Among incidental findings, small-sized splanchnic arterial aneurysms were reported in 21.4% of the study population, with no significant differences in ICU and non-ICU patients. CONCLUSIONS: Vascular involvement is not negligible in COVID-19 and should be carefully investigated as it may significantly affect disease behavior and prognosis. KEY POINTS: • Relevant vascular events were recorded in 71.4% of the study population, with pulmonary embolism being the most frequent event in ICU and non-ICU cases. • Apart from the lung, other organs such as the gut, spleen, liver, brain, and kidneys were involved with episodes of ischemic infarction. Systemic venous and arterial thrombosis occurred in 30.9% and 7.1% of cases, respectively, with venous events being significantly higher in ICU patients (p = 0.002). • Among incidental findings, small-sized splanchnic arterial aneurysms were reported in 21.4% of the whole population.


Subject(s)
COVID-19 , Pulmonary Embolism , Computed Tomography Angiography , Humans , Pulmonary Embolism/diagnostic imaging , Retrospective Studies , SARS-CoV-2
9.
Ther Adv Med Oncol ; 12: 1758835920968463, 2020.
Article in English | MEDLINE | ID: covidwho-913990

ABSTRACT

BACKGROUND: This prospective, multicentre, observational INVIDIa-2 study is investigating the clinical efficacy of influenza vaccination in advanced-cancer patients receiving immune-checkpoint inhibitors (ICIs), enrolled in 82 Italian centres, from October 2019 to January 2020. The primary endpoint was the incidence of influenza-like illness (ILI) until 30 April 2020. All the ILI episodes, laboratory tests, complications, hospitalizations and pneumonitis were recorded. Therefore, the study prospectively recorded all the COVID-19 ILI events. PATIENTS AND METHODS: Patients were included in this non-prespecified COVID-19 analysis, if alive on 31 January 2020, when the Italian government declared the national emergency. The prevalence of confirmed COVID-19 cases was detected as ILI episode with laboratory confirmation of SARS-CoV-2. Cases with clinical-radiological diagnosis of COVID-19 (COVID-like ILIs), were also reported. RESULTS: Out of 1257 enrolled patients, 955 matched the inclusion criteria for this unplanned analysis. From 31 January to 30 April 2020, 66 patients had ILI: 9 of 955 cases were confirmed COVID-19 ILIs, with prevalence of 0.9% [95% confidence interval (CI): 0.3-2.4], a hospitalization rate of 100% and a mortality rate of 77.8%. Including 5 COVID-like ILIs, the overall COVID-19 prevalence was 1.5% (95% CI: 0.5-3.1), with 100% hospitalization and 64% mortality. The presence of elderly, males and comorbidities was significantly higher among patients vaccinated against influenza versus unvaccinated (p = 0.009, p < 0.0001, p < 0.0001). Overall COVID-19 prevalence was 1.2% for vaccinated (six of 482 cases, all confirmed) and 1.7% for unvaccinated (8 of 473, 3 confirmed COVID-19 and 5 COVID-like), p = 0.52. The difference remained non-significant, considering confirmed COVID-19 only (p = 0.33). CONCLUSION: COVID-19 has a meaningful clinical impact on the cancer-patient population receiving ICIs, with high prevalence, hospitalization and an alarming mortality rate among symptomatic cases. Influenza vaccination does not protect from SARS-CoV-2 infection.

10.
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
11.
Contemp Clin Trials ; 98: 106165, 2020 11.
Article in English | MEDLINE | ID: covidwho-816323

ABSTRACT

BACKGROUND: Pneumonia is the most frequent complication of COVID-19, due to an aberrant host immune response that is associated with an acute respiratory distress syndrome, and, in most critical patients, with a "cytokine storm". IL-6 might play a key role in the cytokine storm and might be a potential target to treat severe and critical COVID-19. Tocilizumab is a recombinant humanized monoclonal antibody, directed against IL-6 receptor. METHODS: This multicentre study project includes a single-arm phase 2 study and a further parallel cohort, enrolling hospitalized patients with COVID-19 pneumonia and oxygen saturation at rest in ambient air ≤93% or requiring respiratory support. Patients receive tocilizumab 8 mg/kg (up to 800 mg) as one intravenous administration. A second administration (same dose) after 12 h is optional. Two-week and one-month lethality rates are the co-primary endpoints. Sample size planned for the phase 2 study is 330 patients. The parallel cohort will include patients who cannot enter the phase 2 study because being intubated from more than 24 h, or having already received tocilizumab, or the phase 2 study has reached sample size. Primary analysis will include patients enrolled in the phase 2 study. Results of the primary analysis will be validated in the prospective cohort of patients consecutively registered after phase 2 closure from March 20 to March 24, who were potentially eligible for the phase 2 study. CONCLUSION: This trial aims to verify the safety and efficacy of tocilizumab in the Italian population with COVID-19 pneumonia and respiratory impairment. EudraCT Number: 2020-001110-38; Clinicaltrials.gov ID NCT04317092.


Subject(s)
Antibodies, Monoclonal, Humanized , COVID-19 , Cytokine Release Syndrome , Pneumonia, Viral , Receptors, Interleukin-6/antagonists & inhibitors , Administration, Intravenous , Adult , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/complications , COVID-19/immunology , COVID-19/physiopathology , COVID-19/therapy , Clinical Trials, Phase II as Topic , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/immunology , Drug Administration Schedule , Drug Monitoring , Female , Humans , Immunologic Factors/administration & dosage , Immunologic Factors/adverse effects , Male , Multicenter Studies as Topic , Pneumonia, Viral/drug therapy , Pneumonia, Viral/etiology , Treatment Outcome
12.
J Immunother Cancer ; 8(2)2020 08.
Article in English | MEDLINE | ID: covidwho-713881

ABSTRACT

BACKGROUND: The inflammatory pathology observed in severe COVID-19 disease caused by the 2019 novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by elevated serum levels of C reactive protein (CRP) and cytokines, including interferon gamma, interleukin 8 (IL-8), and interleukin 6 (IL-6). Initial reports from the outbreak in Italy, China and the USA have provided anecdotal evidence of improved outcomes with the administration of anti-IL-6 agents, and large-scale trials evaluating these therapies are ongoing. STUDY DESCRIPTION: In this retrospective case series, clinical outcomes and correlates of response to treatment with the IL-6 receptor antagonist sarilumab are described for 15 patients with COVID-19 from a single institution in Southern Italy. Among 10 patients whose symptoms improved after sarilumab treatment, rapid decreases in CRP levels corresponded with clinical improvement. Lower levels of IL-6 at baseline as well as lower neutrophil to lymphocyte ratio as compared with patients whose COVID-19 did not improve with treatment were associated with sarilumab-responsive disease. CONCLUSIONS: This observation may reflect a possible clinical benefit regarding early intervention with IL-6-modulatory therapies for COVID-19 and that CRP could be a potential biomarker of response to treatment.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Biomarkers, Pharmacological/blood , Coronavirus Infections/drug therapy , Interleukin-6/blood , Pneumonia, Viral/drug therapy , Aged , Antiviral Agents/therapeutic use , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Female , Humans , Italy , Lymphocyte Count , Male , Middle Aged , Neutrophils , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Receptors, Interleukin-6/antagonists & inhibitors , Retrospective Studies , Treatment Outcome
13.
J Immunother Cancer ; 8(1)2020 05.
Article in English | MEDLINE | ID: covidwho-220167

ABSTRACT

The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around the world. In patients who experience severe disease, acute respiratory distress is often accompanied by a pathological immune reaction, sometimes referred to as 'cytokine storm'. One hallmark feature of the profound inflammatory state seen in patients with COVID-19 who succumb to pneumonia and hypoxia is marked elevation of serum cytokines, especially interferon gamma, tumor necrosis factor alpha, interleukin 17 (IL-17), interleukin 8 (IL-8) and interleukin 6 (IL-6). Initial experience from the outbreaks in Italy, China and the USA has anecdotally demonstrated improved outcomes for critically ill patients with COVID-19 with the administration of cytokine-modulatory therapies, especially anti-IL-6 agents. Although ongoing trials are investigating anti-IL-6 therapies, access to these therapies is a concern, especially as the numbers of cases worldwide continue to climb. An immunology-informed approach may help identify alternative agents to modulate the pathological inflammation seen in patients with COVID-19. Drawing on extensive experience administering these and other immune-modulating therapies, the Society for Immunotherapy of Cancer offers this perspective on potential alternatives to anti-IL-6 that may also warrant consideration for management of the systemic inflammatory response and pulmonary compromise that can be seen in patients with severe COVID-19.


Subject(s)
Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Immunotherapy , Interleukin-6/antagonists & inhibitors , Interleukin-6/immunology , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/drug therapy , Societies, Medical , Adoptive Transfer , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Granulocyte-Macrophage Colony-Stimulating Factor/antagonists & inhibitors , Humans , Inflammation/complications , Inflammation/drug therapy , Inflammation/immunology , Inflammation/pathology , Interferon-gamma/antagonists & inhibitors , Interleukin-1/antagonists & inhibitors , Interleukin-17/antagonists & inhibitors , Interleukin-23/antagonists & inhibitors , Interleukin-6/genetics , Interleukin-6/metabolism , Janus Kinases/antagonists & inhibitors , Neoplasms/immunology , Neoplasms/therapy , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/pathology , STAT Transcription Factors/antagonists & inhibitors , Severe Acute Respiratory Syndrome/pathology , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/antagonists & inhibitors
14.
Eur J Cancer ; 132: 17-23, 2020 06.
Article in English | MEDLINE | ID: covidwho-99154

ABSTRACT

The novel severe acute respiratory syndrome coronavirus-2 pandemic is a global health problem, which started to affect China by the end of 2019. In Europe, Italy has faced this novel disease entity (named novel coronavirus disease [COVID-19]) first and severely. COVID-19 represents a significant hurdle for public health services and a potential harm for patients with cancer. The Collegio Italiano dei Primari Oncologi Medici (CIPOMO) is an Italian association of head physicians in oncology departments, which promotes working and research activities in oncology on a national basis. In the midst of the epidemic in Italy, the CIPOMO promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of oncologists and the implementation of containment measures of COVID-19 diffusion. Overall, 122 head physicians participated in this survey, with a homogeneous distribution on the national territory. Results show that the following measures for oncologic patients have been promptly implemented through the whole country: use of protective devices, triage of patients accessing the hospital, delay of non-urgent visits and use of telemedicine. Results of this survey suggest that Italian oncology departments have promptly set a proactive approach to the actual emergency. Oncologists need to preserve the continuum of care of patients, as the benefit of ensuring a well-delivered anti-cancer treatment plan outweighs the risk of COVID-19 infection. International cooperation is an important starting point, as heavily affected nations can serve as an example to find out ways to safely preserve health activity during the pandemic.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Medical Oncology/organization & administration , Neoplasms , Pneumonia, Viral/epidemiology , Adult , Aged , Aged, 80 and over , COVID-19 , Humans , Italy/epidemiology , Pandemics , SARS-CoV-2 , Surveys and Questionnaires
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