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2.
JAMA Netw Open ; 5(2): e220130, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1700096

ABSTRACT

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality. Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality. Design, Setting, and Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis. Exposures: SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated. Main Outcomes and Measures: The primary end point was all-cause mortality within the primary hospitalization. Results: Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19-related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86). Conclusions and Relevance: The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed.


Subject(s)
COVID-19/complications , Hematologic Neoplasms/mortality , Lung Neoplasms/mortality , SARS-CoV-2 , Aged , Aged, 80 and over , Cohort Studies , Drug Therapy , Female , Hematologic Neoplasms/complications , Hematologic Neoplasms/therapy , Humans , Immunotherapy , Lung Neoplasms/complications , Lung Neoplasms/therapy , Male , Middle Aged , Prospective Studies , Registries , United Kingdom
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312773

ABSTRACT

We document here that intensive care COVID19 patients suffer a profound decline in hemoglobin levels but show an increase of circulating nucleated red cells, suggesting that SARS-CoV-2 infection either directly or indirectly induces stress erythropoiesis. However, the impact of SARS-CoV-2 on erythropoiesis has not been well investigated. We show that ACE2 expression peaks during erythropoiesis and renders erythroid progenitors vulnerable to infection by SARS-CoV-2. In particular, we characterize two erythroid progenitor populations as primary targets for the virus. Early erythroid progenitors, defined as CD34-CD117+CD71+CD235a-, show the highest levels of ACE2 and constitute the primary target cell to be infected during erythropoiesis. In addition, SARS-CoV-2 can also bind and infect mid-late erythroid precursors, defined as CD34-CD117-CD71+CD235a+. Our findings constitute the first report of SARS-CoV-2 infectivity in erythroid progenitor cells and can contribute to understanding both the clinical symptoms of severe COVID19 patients and how the virus can spread through the circulation to produce local inflammation in tissues, including the bone marrow.Funding: This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001045), the UK Medical Research Council (FC001045) and the Wellcome Trust (FC001045) to DB.Conflict of Interest: The authors declare no competing interests.Ethical Approval: Peripheral blood was isolated from consenting unscreened healthy adult volunteers following approved protocols by the ethics board of the Francis Crick Institute and the regulations of the Human Tissue act 2004. Peripheral blood mononuclear cells (PBMCs) were isolated by centrifugation over a Histopaque-1119 gradient (Sigma-Aldrich 11191).

4.
Marchesi, Francesco, Salmanton-Garcia, Jon, Emarah, Ziad, Piukovics, Klára, Nucci, Marcio, Lopez-Garcia, Alberto, Racil, Zdenek, Farina, Francesca, Popova, Marina, Zompi, Sofia, Audisio, Ernesta, Ledoux, Marie-Pierre, Verga, Luisa, Weinbergerova, Barbora, Szotkowski, Tomas, Silva, Maria, Fracchiolla, Nicola Stefano, De Jonge, Nick, Collins, Graham, Marchetti, Monia, Magliano, Gabriele, GarcÍA-Vidal, Carolina, Biernat, Monika, Doesum, Jaap van, Machado, Marina, Demirkan, Fatih, Khabori, Murtadha Al, Zak, Pavel, Visek, Benjamin, Stoma, Igor, MÉNdez, Gustavo-Adolfo, Maertens, Johan, Khanna, Nina, Espigado, Ildefonso, Dragonetti, Giulia, Fianchi, Luana, Principe, Maria Ilaria Del, Cabirta, Alba, Ormazabal-VÉLez, Irati, Jaksic, Ozren, Buquicchio, Caterina, Bonuomo, Valentina, Batinić, Josip, Omrani, Ali, Lamure, Sylvain, Finizio, Olimpia, FernÁNdez, Noemí, Falces-Romero, Iker, Blennow, Ola, Bergantim, Rui, Ali, Natasha, Win, Sein, Praet, Jens V. A. N.; Tisi, Maria Chiara, Shirinova, Ayten, SchÖNlein, Martin, Prattes, Juergen, Piedimonte, Monica, Petzer, Verena, NavrÁTil, Milan, Kulasekararaj, Austin, Jindra, Pavel, Jiří, Glenthøj, Andreas, Fazzi, Rita, de Ramón, Cristina, Cattaneo, Chiara, Calbacho, Maria, Bahr, Nathan, El-Ashwl, Shaimaa Saber, Córdoba, Raúl, Hanakova, Michaela, Zambrotta, Giovanni, Sciumè, Mariarita, Booth, Stephen, Nunes-Rodrigues, Raquel, Sacchi, Maria Vittoria, GarcÍA-PoutÓN, Nicole, MartÍN-GonzÁLez, Juan-Alberto, Khostelidi, Sofya, GrÄFe, Stefanie, Rahimli, Laman, busca, alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Cornely, Oliver, pagano, Livio.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328805

ABSTRACT

Patients with acute myeloid leukemia (AML) are at high risk of mortality from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients with COVID-19 diagnosis between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the prior 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died. Death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%). Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with an improved survival when AML treatment could be delayed. Patients with COVID-19 diagnosis between January and August 2020 had a significantly lower survival. COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment.

7.
Blood ; 138(19):3696-3696, 2021.
Article in English | EuropePMC | ID: covidwho-1602604

ABSTRACT

Myelodysplastic syndromes (MDS) represent a spectrum of clonal bone marrow neoplasms from low risk disease through to those transforming into acute myeloid leukaemia. The COVID-19 pandemic has presented a great risk to those with hematological malignancies who are at higher risk of severe disease and death than the general population. Previous studies looking at the immune response to influenza vaccination in those with MDS had shown promising results, with immune responses not differing from those of healthy family members. Whilst some data exist to reassure the MDS community that majority of patients show seroconversion following Covid-19 vaccination, little data exists on their neutralizing capacity or post vaccination T-cell responses in this cohort. In addition, the majority of patients in these studies received BNT162b2 and there is little published data on vaccine response to the ChAdOx1 nCoV-19 vaccine. We have investigated the humoral and T-cell response of 39 patients with MDS two to four weeks following Covid-19 booster vaccination with BNT162b2 or ChAdOx1 nCoV-19 through the SOAP study (Sars-cov-2 fOr cAncer Patients, IRAS project ID:282337). Plasma and PBMCs from MDS cases and healthy controls have been collected, and are being assessed for both humoral and cellular responses to SARS_CoV_2, the alpha (B.1.1.7) and delta (B.1.617.2) variants. Humoral responses will be assessed using ELISA (peptide binding) and functional viral neutralization assays. Cellular responses will be assessed using IFNy ELISPOT and flow cytometry (CD25 and CD69 expression) after 24h peptide stimulation. All data at time point 1 (2 - 4 weeks following booster vaccination) have been collected and will subsequently be collected at 6 months and 12 months post-vaccination. We also report on the safety data for these vaccines within this patient population. Of this cohort 64% were male with a median age of 65 years (range 21-84). 54% received vaccination with ChAdOx1 nCoV-19 and 44% received BNT162b2 (2% unrecorded). The vaccines were well tolerated with no serious adverse events to date. The mean interval between doses was 70.7 days (range 50 - 90 days). 71% of the cohort were receiving no disease modifying therapy at the time of vaccination, half of whom were receiving supportive therapy and the other half no intervention for their MDS. Of those receiving disease modifying therapy;5 were receiving azacitidine, (1 in conjunction with low-dose cytarabine) and 3 ciclosporin. We will report the largest study of the humoral and T-cell mediated response to the Covid-19 vaccine in MDS patients to date. This will include cellular response to the delta variant and immunogenicity of both the BNT162b2 and ChAdOx1 nCoV-19 vaccines. Given the vulnerability of these patients to severe disease, investigating the immune response to the vaccines begins to build an evidence base for advising MDS patients on their ongoing risk of infection during the pandemic and going forward. The SOAP study will reassess the immune response at 6 and 12 months post-vaccination to continue to investigate post-vaccine immunity in this cohort. Disclosures Kulasekararaj:  F. Hoffmann-La Roche Ltd.: Consultancy, Honoraria, Speakers Bureau;Apellis: Consultancy;Akari: Consultancy, Honoraria, Speakers Bureau;Biocryst: Consultancy, Honoraria, Speakers Bureau;Achilleon: Consultancy, Honoraria, Speakers Bureau;Alexion: Consultancy, Honoraria, Speakers Bureau;Ra Pharma: Consultancy, Honoraria, Speakers Bureau;Amgen: Consultancy, Honoraria, Speakers Bureau;Novartis: Consultancy, Honoraria, Speakers Bureau;Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau;Alexion, AstraZeneca Rare Disease Inc.: Consultancy, Honoraria, Other: Travel support. Patten:  JANSSEN: Honoraria;NOVARTIS: Honoraria;GILEAD SCIENCES: Honoraria, Research Funding;ROCHE: Research Funding;ASTRA ZENECA: Honoraria;ABBVIE: Honoraria.

8.
Frontiers in immunology ; 12, 2021.
Article in English | EuropePMC | ID: covidwho-1564105

ABSTRACT

The complex pathophysiologic interplay between SARS-CoV-2 infection and complement activation is the subject of active investigation. It is clinically mirrored by the occurrence of exacerbations of complement mediated diseases during COVID-19 infection. These include complement-mediated hemolytic anemias such as paroxysmal nocturnal hemoglobinuria (PNH), autoimmune hemolytic anemia (AIHA), particularly cold agglutinin disease (CAD), and hemolytic uremic syndrome (HUS). All these conditions may benefit from complement inhibitors that are also under study for COVID-19 disease. Hemolytic exacerbations in these conditions may occur upon several triggers including infections and vaccines and may require transfusions, treatment with complement inhibitors and/or immunosuppressors (i.e., steroids and rituximab for AIHA), and result in thrombotic complications. In this manuscript we describe four patients (2 with PNH and 2 with CAD) who experienced hemolytic flares after either COVID-19 infection or SARS-Cov2 vaccine and provide a review of the most recent literature. We report that most episodes occurred within the first 10 days after COVID-19 infection/vaccination and suggest laboratory monitoring (Hb and LDH levels) in that period. Moreover, in our experience and in the literature, hemolytic exacerbations occurring during COVID-19 infection were more severe, required greater therapeutic intervention, and carried more complications including fatalities, as compared to those developing after SARS-CoV-2 vaccine, suggesting the importance of vaccinating this patient population. Patient education remains pivotal to promptly recognize signs/symptoms of hemolytic flares and to refer to medical attention. Treatment choice should be based on the severity of the hemolytic exacerbation as well as of that of COVID-19 infection. Therapies include transfusions, complement inhibitor initiation/additional dose in the case of PNH, steroids/rituximab in patients with CAD and warm type AIHA, plasma exchange, hemodialysis and complement inhibitor in the case of atypical HUS. Finally, anti-thrombotic prophylaxis should be always considered in these settings, provided safe platelet counts.

9.
Br J Haematol ; 196(4): 892-901, 2022 02.
Article in English | MEDLINE | ID: covidwho-1511287

ABSTRACT

Patients with haematological malignancies have a high risk of severe infection and death from SARS-CoV-2. In this prospective observational study, we investigated the impact of cancer type, disease activity, and treatment in 877 unvaccinated UK patients with SARS-CoV-2 infection and active haematological cancer. The primary end-point was all-cause mortality. In a multivariate analysis adjusted for age, sex and comorbidities, the highest mortality was in patients with acute leukaemia [odds ratio (OR) = 1·73, 95% confidence interval (CI) 1·1-2·72, P = 0·017] and myeloma (OR 1·3, 95% CI 0·96-1·76, P = 0·08). Having uncontrolled cancer (newly diagnosed awaiting treatment as well as relapsed or progressive disease) was associated with increased mortality risk (OR = 2·45, 95% CI 1·09-5·5, P = 0·03), as was receiving second or beyond line of treatment (OR = 1·7, 95% CI 1·08-2·67, P = 0·023). We found no association between recent cytotoxic chemotherapy or anti-CD19/anti-CD20 treatment and increased risk of death within the limitations of the cohort size. Therefore, disease control is an important factor predicting mortality in the context of SARS-CoV-2 infection alongside the possible risks of therapies such as cytotoxic treatment or anti-CD19/anti-CD20 treatments.


Subject(s)
Antigens, CD20/immunology , Antineoplastic Agents, Immunological/therapeutic use , COVID-19/complications , Hematologic Neoplasms/complications , Hematologic Neoplasms/drug therapy , Adult , Antineoplastic Agents, Immunological/adverse effects , COVID-19/etiology , COVID-19/immunology , Female , Hematologic Neoplasms/immunology , Humans , Leukemia/complications , Leukemia/drug therapy , Leukemia/immunology , Male , Multiple Myeloma/complications , Multiple Myeloma/drug therapy , Multiple Myeloma/immunology , Prospective Studies , Risk Factors
11.
J Hematol Oncol ; 14(1): 168, 2021 10 14.
Article in English | MEDLINE | ID: covidwho-1468074

ABSTRACT

BACKGROUND: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. METHODS: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. RESULTS: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March-May 2020) and the second wave (October-December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. CONCLUSIONS: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.


Subject(s)
COVID-19/complications , Hematologic Neoplasms/complications , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , Europe/epidemiology , Female , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/therapy , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Registries , Risk Factors , SARS-CoV-2/isolation & purification , Young Adult
12.
Br J Cancer ; 125(7): 939-947, 2021 09.
Article in English | MEDLINE | ID: covidwho-1360191

ABSTRACT

BACKGROUND: Using an updated dataset with more patients and extended follow-up, we further established cancer patient characteristics associated with COVID-19 death. METHODS: Data on all cancer patients with a positive reverse transcription-polymerase chain reaction swab for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at Guy's Cancer Centre and King's College Hospital between 29 February and 31 July 2020 was used. Cox proportional hazards regression was performed to identify which factors were associated with COVID-19 mortality. RESULTS: Three hundred and six SARS-CoV-2-positive cancer patients were included. Seventy-one had mild/moderate and 29% had severe COVID-19. Seventy-two patients died of COVID-19 (24%), of whom 35 died <7 days. Male sex [hazard ratio (HR): 1.97 (95% confidence interval (CI): 1.15-3.38)], Asian ethnicity [3.42 (1. 59-7.35)], haematological cancer [2.03 (1.16-3.56)] and a cancer diagnosis for >2-5 years [2.81 (1.41-5.59)] or ≥5 years were associated with an increased mortality. Age >60 years and raised C-reactive protein (CRP) were also associated with COVID-19 death. Haematological cancer, a longer-established cancer diagnosis, dyspnoea at diagnosis and raised CRP were indicative of early COVID-19-related death in cancer patients (<7 days from diagnosis). CONCLUSIONS: Findings further substantiate evidence for increased risk of COVID-19 mortality for male and Asian cancer patients, and those with haematological malignancies or a cancer diagnosis >2 years. These factors should be accounted for when making clinical decisions for cancer patients.


Subject(s)
COVID-19/epidemiology , Hematologic Neoplasms/epidemiology , Neoplasms/epidemiology , SARS-CoV-2/pathogenicity , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/pathology , COVID-19/virology , Female , Hematologic Neoplasms/complications , Hematologic Neoplasms/pathology , Hematologic Neoplasms/virology , Hospitals , Humans , London/epidemiology , Male , Middle Aged , Neoplasms/complications , Neoplasms/pathology , Neoplasms/virology , Risk Factors
14.
Stem Cell Reports ; 16(3): 428-436, 2021 03 09.
Article in English | MEDLINE | ID: covidwho-1082066

ABSTRACT

We document here that intensive care COVID-19 patients suffer a profound decline in hemoglobin levels but show an increase of circulating nucleated red cells, suggesting that SARS-CoV-2 infection either directly or indirectly induces stress erythropoiesis. We show that ACE2 expression peaks during erythropoiesis and renders erythroid progenitors vulnerable to infection by SARS-CoV-2. Early erythroid progenitors, defined as CD34-CD117+CD71+CD235a-, show the highest levels of ACE2 and constitute the primary target cell to be infected during erythropoiesis. SARS-CoV-2 causes the expansion of colony formation by erythroid progenitors and can be detected in these cells after 2 weeks of the initial infection. Our findings constitute the first report of SARS-CoV-2 infectivity in erythroid progenitor cells and can contribute to understanding both the clinical symptoms of severe COVID-19 patients and how the virus can spread through the circulation to produce local inflammation in tissues, including the bone marrow.


Subject(s)
COVID-19/virology , Erythroid Precursor Cells/virology , Erythropoiesis/physiology , SARS-CoV-2/pathogenicity , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/metabolism , Cell Line , Chlorocebus aethiops , Erythroid Precursor Cells/metabolism , Humans , Inflammation/metabolism , Inflammation/virology , Vero Cells
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