COVID-19 Infection of HSCT Recipients Is Associated with High Mortality but No Detectable Cytokine Storm at Presentation

Abstract Introduction The clinical manifestations of COVID-19 infection in recipients of allogeneic hematopoietic stem cell transplantation (HSCT) have been reported in multiple retrospective cohorts of patients, but there have been no prospective studies to date. Previous studies report that HSCT recipients are at higher risk, with cumulative incidence of death between 17-35%. Although an excessive pro-inflammatory viral response has been documented in the general population, its role in the immune incompetent HSCT setting has not been documented. We present a combined prospective and retrospective national study run through the UK IMPACT trial network to characterize the clinical and immunological features of COVID-19 infection in 96 adult and pediatric recipients of HSCT in the United Kingdom. Methods HSCT recipients of any age and transplanted for any indication, with an RT-PCR-proven COVID-19 infection, were eligible for this study. Patients within 72 hours of COVID-19 diagnosis, who had not received cytokine-targeted treatment, were recruited to a prospective cohort. All other patients were eligible for a retrospective cohort. Prospective patients provided blood samples within 72 hours of COVID-19 diagnosis, and again within 72 hours of clinical deterioration (defined as requirement for oxygen administration) if applicable. Follow-up data were collected on patients 30 and 100 days after COVID-19 diagnosis. Results 100 patients were recruited from 16 sites across the UK between May 2020-June 2021, comprising 12 in a prospective cohort and 88 recruited retrospectively. 96 patients were evaluable, as 4 proved ineligible post-registration. Patients were diagnosed with COVID-19 at a median of 11 months after HSCT. Patient/HSCT characteristics are shown Table 1. The most common symptoms associated with the onset of COVID-19 were fever in 8 prospective (73%) and 35 (41%) retrospective patients, followed by cough in 5 (45%) prospective and 35 (41%) retrospective patients and dyspnea in 4 (36%) prospective and 16 (19%) retrospective patients. 8 (73%) prospective and 40 (47%) retrospective patients were actively immunosuppressed at the time of COVID-19 infection. 16% of the patients had moderate/severe disease at baseline. At day 30 (±2 days) after COVID-19 diagnosis, 2 prospective and 8 retrospective patients continued to demonstrate SARS-CoV-2 positivity on respiratory PCR testing. The median time to viral clearance was 40 (IQR 17-78) days for the prospective and 34 (IQR 15-70) days for the retrospective cohort. Prolonged (more than 14 days) neutropenia was reported in 4 (5%) patients in the retrospective cohort, prolonged thrombocytopenia in 2 (18%) prospective and 11 (13%) retrospective patients. 1 retrospective patient developed secondary hemophagocytic lymphohistiocytosis, and graft rejection was reported in 1 (1%) retrospective patient, within 30 days of COVID-19 diagnosis. In the prospective cohort, 3 (27%) patients died, all by day 30, and all due to COVID-19. In the retrospective cohort, 13 (17%) patients died by day 30, rising to 18 (21%) by day 100, 61% of deaths were attributed to COVID-19. Lower baseline platelets (p=0.013, Mann-Whitney U test), lymphocytes (p=0.012), albumin (p=0.028), and higher baseline CRP (p=0.007), were seen in patients who died following COVID-19 diagnosis. Additionally, exploratory univariate logistic regression of the retrospective cohort found mortality at day 100 to be associated with increased age at diagnosis (OR 1.04, 95% CI 1.01-1.08, p=0.04), and no requirement compared with requirement for invasive ventilation (OR 0.02, 95% CI 0.00-0.16, p=0.001). The 11 prospective patients showed normal levels of interleukin (IL)-2, -4, -10, interferon gamma and tumor necrosis factor alpha at COVID-19 presentation. IL-6 was minimally raised (up to 127 pg/ml, nv<50) in 3/11 pts at presentation. Respiratory deterioration was not associated with detectable cytokine storm. Conclusion Our study confirms a significant mortality rate in patients affected by COVID-19 post HSCT and confirms age as well as requirement for invasive ventilation to be independent risk factors associated with death at day 100. Baseline laboratory data at disease presentation can identify patients at higher risk of COVID-19 related death. In the prospective cohort of our study, pathophysiology of the viral disease did not seem related to cytokine storm-mediated inflammation. Figure 1 Figure 1. Disclosures Protheroe: Jazz Pharmaceuticals: Honoraria; Astellas: Honoraria; Kite Gilead: Honoraria. Peggs: Autolus: Consultancy, Current equity holder in publicly-traded company. Craddock: Novartis Pharmaceuticals: Other: Advisory Board ; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding. Nicholson: BMS/Celgene: Consultancy; Kite, a Gilead Company: Other: Conference fees, Speakers Bureau; Novartis: Consultancy, Other: Conference fees; Pfizer: Consultancy. Amrolia: ADC Therapeutics: Other: Named inventor on a patent which is being transferred to ADCT.; Autolus: Patents & Royalties.

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Acute Megakaryocytic Leukemia with or Without Acquired Trisomy 21 in 15 Pediatric Patients

10.21203/rs.3.rs-107199/v1 ◽

2020 ◽

Author(s):

Wenzhi ZHANG ◽

Hui LI ◽

Jingzhen LIU ◽

Jiawei XU ◽

Jinjin HAO ◽

...

Keyword(s):

Trisomy 21 ◽

Poor Prognosis ◽

Clinical Characteristics ◽

Pediatric Patients ◽

Laboratory Data ◽

Clinical Manifestations ◽

The Other ◽

Hematopoietic Stem ◽

Acute Megakaryocytic Leukemia

Abstract The knowledge of clinical characteristics and prognosis of pediatric acute megakaryocytic leukemia (AMKL) with or without acquired +21 was limited. We reported 15 AMKL pediatric patients without Down Syndrome (four cases with acquired +21 and 11 cases without acquired +21) with the clinical manifestations, laboratory data, and prognosis. The clinical features and laboratory data between patients with acquired +21 and patients without acquired +21 are similar. As for prognosis, three of the 11 cases without acquired +21 obtained complete remission (CR) after 1st induction. The median follow-up time of the 11 cases was 9 months. Among four cases with acquired +21, one case gave up treatment during 1st induction, one obtained CR after 1st induction and was still alive after 49 months of follow-up. One case obtained CR after 2nd induction and was still alive for 15 months of follow-up after bone marrow transplantation, the other patient was planning for allogeneic hematopoietic stem cell transplantation (HSCT) without CR. The median follow-up time of the four cases was 12 months. None relapsed in our study. In conclusion, acquired trisomy 21 may not be an indicator for poor prognosis. Cytogenetics analysis can help us for diagnosis stratification, prognostic judgment and individualized treatment of AMKL.

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INTERLEUKIN 6, AN IMPORTANT BIOMARKER OF CYTOKINE STORM IN COVID-19

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v5i4.1894 ◽

2021 ◽

Vol 5 (4) ◽

Author(s):

Alok Verma ◽

Archana Shrivastava ◽

Divyansh Verma

Keyword(s):

Early Detection ◽

Virus Disease ◽

Severe Disease ◽

Clinical Manifestations ◽

Specific Treatment ◽

Rapid Progression ◽

Cytokine Storm ◽

Corona Virus ◽

Current Scenario ◽

Patients Experience

Background: The Corona virus disease, COVID-19 is characterised by varied clinical course. Most patients experience only mild symptoms and get cured while others develop severe disease with increasing hypoxia ending in acute respiratory failure In current scenario, disease progression mainly relies on clinical manifestations and some investigations. It has been suggested that one of the possible mechanism underlying rapid progression is a Cytokine storm . Objective: The study was aimed to early detection of IL-6 that could help in identifying Cytokine storm and direct patients to specific treatment so as to reduce severity of disease. Material and Methods: This is the study done on patients presented with symptoms of corona virus disease. These patients were examined clinically and investigated according. Result: 321 patients were found positive for Corona virus out of which 206 males & 115 females. Fever (84%) and cough (71.4%)are the most common symptoms. 167 patients had increased IL-6 who presented with severe symptoms These patients were followed up strictly and proper treatment given Out of which maximum patients responded well within 15 days and 27 patients required hospitalisation and were managed Conclusion: Early detection of IL-6 along with clinical assessment of the patient condition could help clinician identifying and treating those most at risk of deterioration Therefore early identification of Cytokine storm and managing hyper inflammation could be a key route to reduce severity and mortality in COVID-19 patients. Keywords: COVID-19, IL-6 , Cytokine storm .

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Activated Phosphoinositide 3-Kinase Delta Syndrome 1: Clinical and Immunological Data from an Italian Cohort of Patients

Journal of Clinical Medicine ◽

10.3390/jcm9103335 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3335

Author(s):

Giulio Tessarin ◽

Stefano Rossi ◽

Manuela Baronio ◽

Luisa Gazzurelli ◽

Michael Colpani ◽

...

Keyword(s):

Laboratory Data ◽

Clinical Manifestations ◽

Lymphoproliferative Disease ◽

Clinical Feature ◽

Hematopoietic Stem ◽

Replacement Treatment ◽

Phosphoinositide 3 Kinase ◽

First Time

Activated phosphoinositide 3-kinase delta syndrome 1 (APDS-1) is a recently described inborn error of immunity caused by monoallelic gain-of-function mutations in the PIK3CD gene. We reviewed for the first time medical records and laboratory data of eight Italian APDS-1 patients. Recurrent sinopulmonary infections were the most common clinical feature at onset of disease. Seven patients presented lymphoproliferative disease, at onset or during follow-up, one of which resembled hemophagocytic lymphohistiocytosis (HLH). Genetic analysis of the PIK3CD gene revealed three novel mutations: functional testing confirmed their activating nature. In the remaining patients, the previously reported variants p.E1021K (n = 4) and p.E525A (n = 1) were identified. Six patients were started on immunoglobulin replacement treatment (IgRT). One patient successfully underwent hematopoietic stem cell transplantation (HSCT), with good chimerism and no GVHD at 21 months post-HSCT. APDS-1 is a combined immune deficiency with a wide variety of clinical manifestations and a complex immunological presentation. Besides IgRT, specific therapies targeting the PI3Kδ pathway will most likely become a valid aid for the amelioration of patients’ clinical management and their quality of life.

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The novel coronavirus disease (COVID-19) in children with cancer, hematologic malignancies, and severe immunodeficiencies. Results of monocenter study

Pediatric Hematology/Oncology and Immunopathology ◽

10.24287/1726-1708-2021-20-4-89-99 ◽

2021 ◽

Vol 20 (4) ◽

pp. 89-99

Author(s):

G. G. Solopova ◽

E. V. Tsyganova ◽

A. V. Kondrashova ◽

G. N. Gordeeva ◽

E. V. Rozanceva ◽

...

Keyword(s):

Risk Factors ◽

Clinical Symptoms ◽

Severe Disease ◽

Clinical Manifestations ◽

Specific Treatment ◽

Hematologic Malignancies ◽

Underlying Disease ◽

Hematopoietic Stem ◽

Female Ratio ◽

Factors Associated

Data on clinical manifestations of COVID-19 in immunocompromised patients in Russia is lacking, which prompted us to conduct a study to investigate clinical manifestations, risk factors, and outcomes of SARS-CoV-2 infection in children with oncological and hematological diseases treated at the D. Rogachev NMRCPHOI (Center). In this retrospective-prospective, nonrandomized, non-interventional study we enrolled children under 18 years with cancer, hematologic malignancies, and primary immunodeficiencies (PIDs) who underwent treatment at the Center from April 2020 to October 2021. COVID-19 cases were confirmed by polymerase chain reaction testing and classified as asymptomatic, mild, moderate, severe and critical. The study was approved by the Independent Ethics Committee and the Scientific Council of the Center. The study included 89 patients with a median age of 9.7 years and almost equal gender distribution (the male-to-female ratio was 1.1:1). Most patients (74%) were infected in a family claster. The main underlying diseases were: hemoblastoses (43.8%), solid tumors (33.7%), PIDs (14.6%). The most common clinical symptoms were fever (29%) and respiratory symptoms (47%). In 79% of cases, patients were asymptomatic or had mild symptoms; 21% of patients had moderate and severe disease (16% and 5%, accordingly). Risk factors associated with severe COVID-19 included lymphopenia (p < 0.001) and hematopoietic stem cell transplantation (HSCT) (p = 0.002). Full recovery was documented in 84% of the patients, 16% died, however COVID-attributed mortality was 5.5%. The highest mortality was in patients with moderate/severe COVID-19 (47% vs 7%, p < 0.001), in those with progression/ relapse of the underlying disease (36.3% vs 6%, p = 0.02), in children who had received specific therapy within a year before the SARS-CoV-2 diagnosis (21% vs 0%, p = 0.02), among HSCT recipients (31.6% vs 12.1%, p = 0.02), and patients with concomitant infections (33% vs 9.2%, p < 0.01). Factors associated with poor prognosis were moderate or severe COVID-19, relapse/ progression of the underlying disease, specific treatment (HSCT in particular) within 1 year before the SARS-CoV-2 diagnosis, concomitant infections, and lymphopenia. Data obtained in this study can help physicians with management decisions at this population of patients.

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The role of SARC-F scale in predicting progression risk of COVID-19 in elderly patients: a prospective cohort study in Wuhan

BMC Geriatrics ◽

10.1186/s12877-021-02310-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yao Ma ◽

Min He ◽

Li-Sha Hou ◽

Shen Xu ◽

Zhi-Xin Huang ◽

...

Keyword(s):

Cohort Study ◽

High Risk ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Older Patients ◽

Poor Prognosis ◽

Severe Disease ◽

Laboratory Data ◽

Geriatric Syndrome ◽

Severe Condition

Abstract Background Since the outbreak of COVID-19, it has been documented that old age and underlying illnesses are associated with poor prognosis among COVID-19 patients. However, it is unknown whether sarcopenia, a common geriatric syndrome, is associated with poor prognosis among older COVID-19 patients. The aim of our prospective cohort study is to investigate the association between sarcopenia risk and severe disease among COVID-19 patients aged ≥60 years. Method A prospective cohort study of 114 hospitalized older patients (≥60 years) with confirmed COVID-19 pneumonia between 7 February, 2020 and 6 April, 2020. Epidemiological, socio-demographic, clinical and laboratory data on admission and outcome data were extracted from electronic medical records. All patients were assessed for sarcopenia on admission using the SARC-F scale and the outcome was the development of the severe disease within 60 days. We used the Cox proportional hazards model to identify the association between sarcopenia and progression of disease defined as severe cases in a total of 2908 person-days. Result Of 114 patients (mean age 69.52 ± 7.25 years, 50% woman), 38 (33%) had a high risk of sarcopenia while 76 (67%) did not. We found that 43 (38%) patients progressed to severe cases. COVID-19 patients with higher risk sarcopenia were more likely to develop severe disease than those without (68% versus 22%, p < 0.001). After adjustment for demographic and clinical factors, higher risk sarcopenia was associated with a higher hazard of severe condition [hazard ratio = 2.87 (95% CI, 1.33–6.16)]. Conclusion We found that COVID-19 patients with higher sarcopenia risk were more likely to develop severe condition. A clinician-friendly assessment of sarcopenia could help in early warning of older patients at high-risk with severe COVID-19 pneumonia.

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Cerebral Amyloid Angiopathy in Combination with Paroxysmal Atrial Fibrillation

Russian neurological Journal ◽

10.30629/2658-7947-2020-25-4-31-37 ◽

2020 ◽

Vol 25 (4) ◽

pp. 31-37

Author(s):

A. A. Kornilova ◽

O. V. Lagoda ◽

M. M. Tanashyan

Keyword(s):

Atrial Fibrillation ◽

Cerebral Amyloid Angiopathy ◽

Paroxysmal Atrial Fibrillation ◽

Past History ◽

Laboratory Data ◽

Clinical Manifestations ◽

Cerebral Haemorrhage ◽

Exclusion Criterion ◽

Amyloid Angiopathy ◽

Cerebral Amyloid

The present article addresses the definition of cerebral amyloid angiopathy (CAA) and its symptoms based on the analysis of the medical case; the issues of diagnosis and treatment of this pathology are discussed. The Boston criteria, which became the basis for diagnosis, study of clinical manifestations and progression of CAA and approaches to its therapy, are presented. Methods and modes of neuroimaging, including magnetic resonance imaging (MRI), which verify micro cerebral haemorrhage, are described. At the same time, the role and significance of cardiac arrhythmias in the genesis of ischemic stroke are discussed, and scales for assessing the risk of its occurrence are presented. The observation of the neurological, somatic, neuroimaging, neuropsychological status of a 62-year-old patient confirms quite rare combination of probable CAA, paroxysmal atrial fibrillation and repeated hemorrhagic functional apoplexy (FA). The relevance of the case described, is a complex clinical dilemma based on mutually exclusive recommendations for the pharmacological correction of such conditions. It is emphasized that in many multicenter clinical studies on the effectiveness of antithrombotic medication (antiaggregants, anticoagulants) in the treatment and prevention of ischaemic functional apoplexy , an important exclusion criterion is a hemorrhagic stroke in past history (including the multiple changes in haemostasis indicators). Taking into account the obtained clinical and laboratory data in the dynamics, the tactics of treating the described patient were determined. The results of studies related to the treatment of comorbid pathology that should become the subject of the development of a personalized algorithm for managing patients in each specific case, are discussed.

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Faculty Opinions recommendation of Evaluation of the economic burden of kidney stone disease in the UK: a retrospective cohort study with a mean follow-up of 19 years.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.737186277.793570254 ◽

2020 ◽

Author(s):

Walter Strohmaier

Keyword(s):

Cohort Study ◽

Economic Burden ◽

Retrospective Cohort Study ◽

Kidney Stone ◽

Retrospective Cohort ◽

Stone Disease ◽

Kidney Stone Disease ◽

The Uk

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Multiple Myeloma or Brucellosis: A Case Report

Infectious Disorders - Drug Targets ◽

10.2174/1871526519666190307123047 ◽

2020 ◽

Vol 20 (1) ◽

pp. 102-105 ◽

Cited By ~ 1

Author(s):

Hossein A. Rahdar ◽

Mansoor Kodori ◽

Mohamad R. Salehi ◽

Mahsa Doomanlou ◽

Morteza Karami-Zarandi ◽

...

Keyword(s):

Multiple Myeloma ◽

Brucella Melitensis ◽

Severe Disease ◽

Correct Diagnosis ◽

Clinical Manifestations ◽

Bone Marrow Aspiration ◽

Major Health Problem ◽

Brucella Infection ◽

Wide Range ◽

Parental Treatment

Background: Brucellosis, a major health problem in developing countries, is a multisystem infection with a broad spectrum of clinical manifestations. Hematological complications, ranging from an intravascular coagulopathy to mild homeostasis disorders (such as gammopathy), have been reported in brucella infection. These signs and symptoms may lead to misdiagnosis of brucellosis with other hematological diseases. Case: A 65-year-old male whose occupation was shepherding was referred to our hospital as a known case of multiple myeloma with continuous fever, muscle weakness, and night sweating after taking 2 courses of chemotherapy. The laboratory diagnosis of multiple myeloma had been based on the observation of a high percent of plasma cells in the bone marrow aspiration. At follow- up, the result of patient's fever workup, with 2 sets of blood cultures, was positive for Brucella melitensis. Isolated brucella was confirmed as B. melitensis by 16S rRNA sequencing. Brucellosis serologic test was performed by agglutination test and positive results were obtained. The patient was discharged with the cessation of fever and general improvement after the end of the parental treatment phase of brucella bacteremia. Conclusions: Brucella infection may cause a severe disease, mimicking a primary hematological disease, which could complicate the correct diagnosis. In brucellosis cases, due to the wide range of symptoms, in addition to cultivation and serological methods, molecular methods should also be used to prevent inappropriate diagnosis and additional costs.

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Genetic polymorphism for IFNγ +874T/A in patients with acute toxoplasmosis

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86822012000600020 ◽

2012 ◽

Vol 45 (6) ◽

pp. 757-760 ◽

Cited By ~ 11

Author(s):

Elizabeth de Souza Neves ◽

André Luis Land Curi ◽

Maira Cavalcanti de Albuquerque ◽

Cassius Schnel Palhano-Silva ◽

Laura Berriel da Silva ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

Case Control Study ◽

Severe Disease ◽

Clinical Manifestations ◽

Nucleotide Polymorphism ◽

Gene Encoding ◽

Single Nucleotide ◽

Duration Of Disease ◽

Acute Toxoplasmosis ◽

Control Study

INTRODUCTION: A single nucleotide polymorphism (SNP) in the gene encoding gamma interferon influences its production and is associated with severity of infectious diseases. This study aimed to evaluate the association of IFNγ+874T/A SNP with duration of disease, morbidity, and development of retinochoroiditis in acute toxoplasmosis. METHODS: A case-control study was conducted among 30 patients and 90 controls. RESULTS: Although statistical associations were not confirmed, A-allele was more common among retinochoroiditis cases and prolonged illness, while T-allele was more frequent in severe disease. CONCLUSIONS: Despite few cases, the results could indicate a relation between IFNγ+874T/A single nucleotide polymorphism and clinical manifestations of toxoplasmosis.

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