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1.
Acta Biomed ; 93(2): e2022057, 2022 05 11.
Article in English | MEDLINE | ID: covidwho-1848015

ABSTRACT

BACKGROUND AND AIM: Dysregulation of iron metabolism and hyper-inflammation are two key points in the pathogenesis of coronavirus disease 2019 (COVID-19). Since high hepcidin levels and low serum iron can predict COVID-19 severity and mortality, we decided to investigate iron metabolism and inflammatory response in 32 COVID-19 adult patients with a diagnosis of COVID-19 defined by a positive result of RT-PCR nasopharyngeal swab, and admitted to an Italian emergency department for acute respiratory failure at different degree. METHODS: Patients were stratified in 3 groups based on PaO2/FiO2 ratio at admission: 13 (41%) were normoxemic at rest and suffered from exertional dyspnea (group 1); 14 (44%) had a mild respiratory failure (group 2), and 5 (15%) a severe hypoxiemia (group 3). RESULTS: White blood cells were significantly higher in group 3, while lymphocytes and hemoglobin were significantly reduced. Serum iron, transferrin saturation, non-transferrin-bound iron (NTBI) and ferritin were significantly increased in group 2. All the groups showed high hepcidin levels, but in group 3 this parameter was significantly altered. It is noteworthy that in group 1 inflammatory and oxidative indices were both within the normal range. CONCLUSIONS: We are aware that our study has some limitations, the small number of enrolled patients and the short period of data collection, but few works have been performed in the Emergency Room. However, we strongly believe that our results confirm the pivotal role of both iron metabolism dysregulation and hyper-inflammatory response in the pathogenesis of tissue and organ damage in COVID-19 patients.


Subject(s)
COVID-19 , Adult , Emergency Service, Hospital , Hepcidins/metabolism , Homeostasis , Humans , Iron/metabolism , Prospective Studies , SARS-CoV-2
2.
Blood Adv ; 6(1): 327-338, 2022 01 11.
Article in English | MEDLINE | ID: covidwho-1622201

ABSTRACT

Lymphoma represents a heterogeneous hematological malignancy (HM), which is characterized by severe immunosuppression. Patients diagnosed of coronavirus disease 2019 (COVID-19) during the course of HM have been described to have poor outcome, with only few reports specifically addressing lymphoma patients. Here, we investigated the clinical behavior and clinical parameters of a large multicenter cohort of adult patients with different lymphoma subtypes, with the aim of identifying predictors of death. The study included 856 patients, of whom 619 were enrolled prospectively in a 1-year frame and were followed-up for a median of 66 days (range 1-395). Patients were managed as outpatient (not-admitted cohort, n = 388) or required hospitalization (n = 468), and median age was 63 years (range 19-94). Overall, the 30- and 100-days mortality was 13% (95% confidence interval (CI), 11% to 15%) and 23% (95% CI, 20% to 27%), respectively. Antilymphoma treatment, including anti-CD20 containing regimens, did not impact survival. Patients with Hodgkin's lymphoma had the more favorable survival, but this was partly related to significantly younger age. The time interval between lymphoma diagnosis and COVID-19 was inversely related to mortality. Multivariable analysis recognized 4 easy-to-use factors (age, gender, lymphocyte, and platelet count) that were associated with risk of death, both in the admitted and in the not-admitted cohort (HR 3.79 and 8.85 for the intermediate- and high-risk group, respectively). Overall, our study shows that patients should not be deprived of the best available treatment of their underlying disease and indicates which patients are at higher risk of death. This study was registered with ClinicalTrials.gov, NCT04352556.


Subject(s)
COVID-19 , Lymphoma , Adult , Aged , Aged, 80 and over , Cohort Studies , Humans , Lymphoma/diagnosis , Lymphoma/therapy , Middle Aged , Prognosis , SARS-CoV-2 , Young Adult
3.
Eur J Cancer ; 157: 441-449, 2021 11.
Article in English | MEDLINE | ID: covidwho-1573973

ABSTRACT

INTRODUCTION: Patients with cancer are presumed a frail group at high risk of contracting coronavirus disease (COVID-19), and vaccination represents a cornerstone in addressing the COVID-19 pandemic. However, data on COVID-19 vaccination in cancer patients are fragmentary and poor. METHODS: An observational study was conducted to evaluate the seropositivity rate and safety of a two-dose regimen of the BNT162b2 or messenger RNA-1273 vaccine in adult patients with solid cancer undergoing active anticancer treatment or whose treatment had been terminated within 6 months of the start of the study. The control group was composed of healthy volunteers. Serum samples were evaluated for SARS-COV-2 antibodies before vaccinations and 2-6 weeks after the administration of the second vaccine dose. Primary end-point: seropositivity rate. Secondary end-points: safety, factors influencing seroconversion, IgG titers of patients versus healthy volunteers, COVID-19 infection. RESULTS: Between 20th March 2021 and 12th June 2021, 293 consecutive patients with cancer-solid tumours underwent a program of COVID-19 vaccinations; of these, 2 patients refused vaccination, 13 patients did not receive the second dose of the vaccine because of cancer progression, and 21 patients had COVID-19 antibodies at baseline and were excluded. The 257 evaluable patients had a median age of 65 years (range 28-86), 66.15% with metastatic disease. Primary end-point: seropositivity rate in patients was 75.88% versus 100% in the control group. Secondary end-points: no Grade 3-4 side-effects, no COVID-19 infections were reported. Patients median IgG titer was significantly lower than in the control group; male sex and active anticancer therapy influenced negative seroconversion. BNT162b2 or messenger RNA-1273 vaccines were immunogenic in cancer patients, showing good safety profile.


Subject(s)
COVID-19 Vaccines/immunology , Neoplasms/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/immunology , COVID-19/immunology , Female , Humans , Immunogenicity, Vaccine/immunology , Italy , Male , Middle Aged , Neoplasms/virology , Pandemics/prevention & control , Prospective Studies , SARS-CoV-2/immunology , Vaccination/methods
4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292548

ABSTRACT

Dysregulation of iron metabolism and hyper-inflammation are two key points in the pathogenesis of coronavirus disease 2019 (COVID-19). Since high hepcidin levels and low serum iron can predict COVID-19 severity and mortality, we decided to investigate iron metabolism and inflammatory response in 32 COVID-19 adult patients with a diagnosis of COVID-19 defined by a positive result of RT-PCR nasopharyngeal swab, and admitted to an Italian emergency department for acute respiratory failure at different degree. Patients were stratified in 3 groups based on PaO 2 /FiO 2 ratio at admission: 13 (41%) were normoxemic at rest and suffered from exertional dyspnea (group 1);14 (44%) had a mild respiratory failure (group 2), and 5 (15%) a severe hypoxiemia (group 3). White blood cells were significantly higher in group 3, while lymphocytes and hemoglobin were significantly reduced. Serum iron, transferrin saturation, non-transferrin-bound iron (NTBI) and ferritin were significantly increased in group 2. All the groups showed high hepcidin levels, but in group 3 this parameter was significantly altered. It is noteworthy that in group 1 inflammatory and oxidative indices were both within the normal range. We are aware that our study has some limitations, the small number of enrolled patients and the short period of data collection, but few works have been performed in the Emergency Room. However, we strongly believe that our results confirm the pivotal role of both iron metabolism dysregulation and hyper-inflammatory response in the pathogenesis of tissue and organ damage in COVID-19 patients.

5.
Blood ; 136(Supplement 1):32-33, 2020.
Article in English | PMC | ID: covidwho-1338993

ABSTRACT

COVID-19 is a severe infectious complication in patients with underlying medical conditions such as having undergone hematopoietic stem cell transplantation (HCT). This prospective survey reports outcome on 272 COVID-19 patients from 19 countries having undergone allogeneic (n = 175) or autologous (n = 97) HCT reported to the EBMT registry or to the GETH. All patients had the diagnosis of SARS-CoV-2 documented by PCR. Patients were included in this analysis if COVID-19 diagnosis was before April 10, 2020. The overall survival was estimate by using the Kaplan Meier methods, considering the death due to any cause as an event and the time from COVID-19 infection to the latest follow-up as survival time;difference between groups were tested by the log-rank test. Univariate and multivariate risk factor analysis for overall survival were performed with the Cox regression model.The median age was 54.4 years (1.0 - 80.3) for allogeneic and 60.9 years (7.7 - 73.4) for autologous HCT patients. 20 patients were children (<18 years of age;median age 11.3 (1.0 - 16.9)). The median time from HCT to diagnosis of COVID-19 was 13.7 months (0.2 - 254.3) in allogeneic and 25.0 months (-0.9 - 350.3) in autologous recipients. Lower respiratory tract disease (LRTD) developed in 84.8% and 21.5% were admitted to an intensive care unit (ICU). At the time of analysis, 68/238 (28.6%) patients had died (47/155 allogeneic patients;21/83 autologous patients). No follow-up had been received on 34 patients. The median time from infection to death was 19 days (0-102). Five patients were reported to have other primary causes of death than COVID-19. Of the patients reported to be alive, the median follow-up was 44 days. 144 (84.7%) patients (93 allogeneic;51 autologous) had virologic resolution of the COVID-19 infection having at least one negative PCR. 26 patients were alive and known to be still COVID-19 positive (15 allogeneic;11 autologous). For 34 patients the resolution status was unknown. Factors influencing the likelihood of resolution in multivariate analysis were underlying diagnosis (p=.01) and longer time from transplant to diagnosis of COVID-19 (p=.035).Overall survival at 6 weeks from COVID-19 diagnosis was 76.8% and 83.8% in allogeneic and autologous HCT recipients (p =ns), respectively (figure 1). Children (n=20) tended to do better with a 6-week survival of 95.0% although the difference was not significantly different (p =.12). In multivariate analysis of the total population older age (HR 1.26;95% CI 1.05 - 1.51;p = .01) increased the risk and better performance status decreased the risk for fatal outcome (HR 0.79;95% CI 0.69 - 0.90;p = .0003). The same factors had significant impact on overall survival in allogeneic HCT recipients (age HR 1.28;95% CI 1.05 - 1.55;p=.01;performance status HR 0.79;95% CI 0.68 - 0.92);p=.002) while only age impacted survival among autologous HCT patients (data not shown). Other transplant factors such as underlying diagnosis, time from HCT to diagnosis of COVID-19, graft-vs-host disease, or ongoing immunosuppression did not have a significant impact on overall survival.We conclude that HCT patients are at an increased risk compared to the general population to develop LRTD, require admission to ICU, and have increased mortality in COVID-19.Figure 1

6.
Leukemia ; 35(10): 2885-2894, 2021 10.
Article in English | MEDLINE | ID: covidwho-1253922

ABSTRACT

This study reports on 382 COVID-19 patients having undergone allogeneic (n = 236) or autologous (n = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0-80.3) for allogeneic, and 60.6 years (7.7-81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2-292.7) in allogeneic and 24.6 months (-0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age (p = 0.02), need for ICU (p < 0.0001) and moderate/high immunodeficiency index (p = 0.04) increased the risk while better performance status (p = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19.


Subject(s)
COVID-19/complications , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/methods , SARS-CoV-2/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/virology , Child , Child, Preschool , Female , Follow-Up Studies , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/virology , Humans , Infant , Male , Middle Aged , Prognosis , Prospective Studies , Survival Rate , Transplantation, Homologous , Young Adult
7.
Front Oncol ; 10: 582901, 2020.
Article in English | MEDLINE | ID: covidwho-1084178

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects humans through the angiotensin converting enzyme-2 (ACE-2) receptor expressed on many cells, including lymphocytes. In Covid-19 patients IL-6 is overexpressed, and hyperactivated plasmacytoid lymphocytes are detected in peripheral blood film. We hypothesize that, due to the unpredictable interaction between the new virus and the B cell lineage of infected patients, a cascade of out of control events can ensue, capable of determining unexpected pathologic disorders involving such lineage. Here we report two cases of autoimmune hemolytic anemia (AIHA) and two cases of B-cell hematological malignancies developed or reactivated during acute SARS-CoV-2 infection. The temporal relationship of the events may suggest a potential causal relationship between SARS-CoV-2 infection and the hematopoietic disorders. We suggest that special attention should be paid to COVID-19 patients with underlining B cell lineage disorders.

8.
Acta Biomed ; 91(3): e2020013, 2020 09 07.
Article in English | MEDLINE | ID: covidwho-1068225

ABSTRACT

BACKGROUND: The COVID epidemic hit like a tsunami worldwide. At the time of its arrival in Italy, available literary data were meager, and most of them concerned its epidemiology. World Health Organization proposed guidelines in march 2020, a strategy of treatment has been developed, and a significant number of subsequent articles have been published to understand, prevent, and cure COVID patients. METHODS: From the observation of two patients, we performed a careful analysis of scientific literature to unearth the relation between COVID infection, clinical manifestations as pneumonia and thrombosis, and to find out why it frequently affects obese, diabetics, and elderly patients. RESULTS: The analysis shows that hepcidin could represent one of such correlating factors. Hepcidin is most elevated in older age, in non-insulin diabetics patients and in obese people. It is the final target therapy of many medicaments frequently used. Viral disease, and in particular SARS-CoV19, could induce activation of the hepcidin pathway, which in turn is responsible for an increase in the iron load. Excess of iron can lead to cell death by ferroptosis and release into the bloodstream, such as free iron, which in turn has toxic and pro-coagulative effects. CONCLUSIONS: Overexpression of hepcidin and iron overload might play a crucial role in COVID infection, becoming potential targets for treatment. Hepcidin could also be considered as a biomarker to measure the effectiveness of our treatments and the restoration of iron homeostasis the final intent. (www.actabiomedica.it).


Subject(s)
COVID-19 , Diabetes Mellitus , Iron Overload , Aged , Hepcidins , Humans , Italy , Obesity , SARS-CoV-2
9.
Lancet Haematol ; 7(10): e737-e745, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-712017

ABSTRACT

BACKGROUND: Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19. METHODS: This multicentre, retrospective, cohort study included adult patients (aged ≥18 years) with diagnosis of a WHO-defined haematological malignancy admitted to 66 Italian hospitals between Feb 25 and May 18, 2020, with laboratory-confirmed and symptomatic COVID-19. Data cutoff for this analysis was June 22, 2020. The primary outcome was mortality and evaluation of potential predictive parameters of mortality. We calculated standardised mortality ratios between observed death in the study cohort and expected death by applying stratum-specific mortality rates of the Italian population with COVID-19 and an Italian cohort of 31 993 patients with haematological malignancies without COVID-19 (data up to March 1, 2019). Multivariable Cox proportional hazards model was used to identify factors associated with overall survival. This study is registered with ClinicalTrials.gov, NCT04352556, and the prospective part of the study is ongoing. FINDINGS: We enrolled 536 patients with a median follow-up of 20 days (IQR 10-34) at data cutoff, 85 (16%) of whom were managed as outpatients. 440 (98%) of 451 hospitalised patients completed their hospital course (were either discharged alive or died). 198 (37%) of 536 patients died. When compared with the general Italian population with COVID-19, the standardised mortality ratio was 2·04 (95% CI 1·77-2·34) in our whole study cohort and 3·72 (2·86-4·64) in individuals younger than 70 years. When compared with the non-COVID-19 cohort with haematological malignancies, the standardised mortality ratio was 41·3 (38·1-44·9). Older age (hazard ratio 1·03, 95% CI 1·01-1·05); progressive disease status (2·10, 1·41-3·12); diagnosis of acute myeloid leukaemia (3·49, 1·56-7·81), indolent non-Hodgin lymphoma (2·19, 1·07-4·48), aggressive non-Hodgkin lymphoma (2·56, 1·34-4·89), or plasma cell neoplasms (2·48, 1·31-4·69), and severe or critical COVID-19 (4·08, 2·73-6·09) were associated with worse overall survival. INTERPRETATION: This study adds to the evidence that patients with haematological malignancies have worse outcomes than both the general population with COVID-19 and patients with haematological malignancies without COVID-19. The high mortality among patients with haematological malignancies hospitalised with COVID-19 highlights the need for aggressive infection prevention strategies, at least until effective vaccination or treatment strategies are available. FUNDING: Associazione italiana contro le leucemie, linfomi e mieloma-Varese Onlus.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Hematologic Neoplasms/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Adult , Aged , Aged, 80 and over , COVID-19 , Comorbidity , Coronavirus Infections/drug therapy , Female , Follow-Up Studies , Hematologic Neoplasms/therapy , Humans , Inpatients , Italy/epidemiology , Leukemia/epidemiology , Leukemia/therapy , Lymphoma, Non-Hodgkin/epidemiology , Lymphoma, Non-Hodgkin/therapy , Male , Middle Aged , Myeloproliferative Disorders/epidemiology , Myeloproliferative Disorders/therapy , Neoplasms, Plasma Cell/epidemiology , Neoplasms, Plasma Cell/therapy , Retrospective Studies , Risk Factors , SARS-CoV-2 , Young Adult
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