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2.
Blood Adv ; 7(13): 3069-3074, 2023 Jul 11.
Article in English | MEDLINE | ID: covidwho-2271432

ABSTRACT

The use of bispecific antibodies (BsAbs) in the treatment of relapsed/refractory multiple myeloma (MM) is showing early promising overall response rates in heavily pretreated patients. Infectious complications related to the use of BsAbs are not well described. We conducted a pooled analysis that included all single-agent BsAbs used in MM with no prior use of different BsAbs. A total of 1185 patients with MM were treated with a BsAb in the studied period (71.6% of the patients treated with an agent targeting B-cell maturation antigen (BCMA). Pooled median follow-up was short at 6.1 months (7.5 vs 5.2 months for BCMA vs non-BCMA BsAbs, respectively). Adverse events of interest included all grade neutropenia in 38.6%, all grade infections in 50% (n = 542/1083), all grade cytokine release syndrome in 59.6% (n = 706/1185), grade III/IV neutropenia in 34.8% (n = 372/1068), grade III/IV infections in 24.5% (n = 272/1110), grade III/IV pneumonia in 10% (n = 52.4/506), and grade III/IV coronavirus disease 2019 in 11.4% (n = 45.4/395) of the patients. Non-BCMA-targeted BsAbs were associated with lower grade III/IV neutropenia (25.3% vs 39.2%) and lower grade III/IV infections (11.9% vs 30%) when compared with BCMA-targeted BsAbs. Hypogammaglobulinemia was reported in 4 studies, with a prevalence of 75.3% (n = 256/340) of the patients, with IV immunoglobulin used in 48% (n = 123/256) of them. Death was reported in 110 patients, of which 28 (25.5%) were reported to be secondary to infections. Certain precautions should be used when using BsAbs to mitigate the risk and/or identify and treat infections promptly.


Subject(s)
Antibodies, Bispecific , COVID-19 , Multiple Myeloma , Neoplasms, Plasma Cell , Neutropenia , Humans , Multiple Myeloma/drug therapy , Antibodies, Bispecific/adverse effects , Neutropenia/etiology
3.
Front Immunol ; 14: 1087502, 2023.
Article in English | MEDLINE | ID: covidwho-2262940

ABSTRACT

Vaccines against SARS-CoV-2 are the most effective measure against the COVID-19 pandemic. The safety profile of mRNA vaccines in patients with rare diseases has not been assessed systematically in the clinical trials, as these patients were typically excluded. This report describes the occurrence of agranulocytosis within days following the first dose of an mRNA-1273 vaccination against COVID-19 in a previously healthy older adult. The patient was diagnosed with a suspected STAT3 wild-type T-cell large granular lymphocytic leukaemia (T-LGL). Neutropenia was successfully treated with IVIG, glucocorticoids, and G-CSF. In vitro experiments aimed at elucidating the pathways potentially causing the mRNA vaccine-associated neutropenia indicated that the mRNA, but not the adenoviral Ad26.COV2.S vector vaccine, triggered strong IL-6/STAT3 activation in vitro, resulting in excessive T-cell activation and neutrophil degranulation in the patient but not in controls. mRNA-1273 activated TLR-3 suggesting TLR mediated IL-6/STAT3 pathway activation. To complete the primary series of COVID-19 immunization, we used a single dose of Ad26.COV2.S vector vaccine without reoccurrence of neutropenia. The T-LGL clone remained stable during the follow-up of more than 12 months without ongoing therapy. Our data suggest that switching the immunization platform may be a reasonable approach in subjects with rare associated hematologic side effects due to excess STAT3-mediated stimulation following mRNA vaccination. Using in vitro testing before re-administration of a (COVID) vaccine also has relevance for other rare immune events after (mRNA) vaccination.


Subject(s)
COVID-19 , Leukemia, Large Granular Lymphocytic , Neutropenia , Humans , Aged , 2019-nCoV Vaccine mRNA-1273 , Ad26COVS1 , COVID-19 Vaccines , Interleukin-6 , Pandemics , SARS-CoV-2 , Vaccination , Adenoviridae , STAT3 Transcription Factor
4.
Pediatr Infect Dis J ; 42(5): 423-428, 2023 05 01.
Article in English | MEDLINE | ID: covidwho-2262060

ABSTRACT

BACKGROUND: The SARS-CoV-2 variants of concern exhibit distinct features in terms of transmissibility and virulence. This study compared the clinical characteristics of COVID-19 in children during pre-Delta, Delta and Omicron waves. METHODS: Medical records of 1163 children <19 years of age with COVID-19 admitted to a designated hospital in Seoul, South Korea, were analyzed. Clinical and laboratory findings during the pre-Delta (March 1, 2020, to June 30, 2021; 330 children), Delta (July 1, 2021, to December 31, 2021; 527 children) and Omicron (January 1, 2022, to May 10, 2022; 306 children) waves were compared. RESULTS: Children during the Delta wave were older and had a higher proportion of fever ≥5 days and pneumonia than children during the pre-Delta and Omicron waves. The Omicron wave was characterized by younger age and a higher proportion of fever ≥39.0 °C, febrile seizure and croup. More children <2 years of age and adolescents aged 10 to <19 years experienced neutropenia and lymphopenia, respectively, during the Delta wave. Children aged 2 to <10 years had a higher incidence of leukopenia and lymphopenia during the Omicron wave. CONCLUSIONS: Distinct features of COVID-19 were observed in children during the Delta and Omicron surges. Continuous scrutiny of the manifestations of variants of concern is needed for appropriate public health response and management.


Subject(s)
COVID-19 , Lymphopenia , Neutropenia , Adolescent , Humans , Child , Young Adult , Adult , Child, Preschool , COVID-19/epidemiology , SARS-CoV-2 , Fever
5.
Future Microbiol ; 18: 217-234, 2023 02.
Article in English | MEDLINE | ID: covidwho-2261624

ABSTRACT

Mucormycosis is an emerging opportunistic angioinvasive fungal infection. Predisposing factors such as diabetes, neutropenia, long-term corticosteroid therapy, solid organ transplantation and immunosuppression contribute to its occurrence. This disease was not of significant concern prior to the COVID-19 pandemic, but gained prominence due to infections in COVID-19 patients. Mucormycosis needs special attention and coordinated efforts of the scientific community and medical professionals to reduce morbidity and mortality. Here we present an overview of the epidemiology and prevalence of mucormycosis in the pre- and post-COVID-19 eras, the factors that contributed to the abrupt increase in COVID-19-associated mucormycosis (CAM), the actions taken by the regulatory agencies (including Code Mucor and CAM registry), the existing diagnostic tools and CAM management strategies.


The devastating effects of the COVID-19 pandemic have been further enhanced by various secondary illnesses, particularly opportunistic fungal infections such as mucormycosis. Mucormycosis or 'black fungus' primarily affects people with weakened immunity, those with medical conditions such as diabetes or cancer and those who use medications that reduce the body's capacity to resist infections and disease. The infection starts in the sinuses or the lungs after breathing in spores of the black fungus from the air. In just 2 months between 5 May and 12 July 2021, this uncommon but fatal fungal illness was responsible for 41,512 cases and 3554 fatalities in India alone. The government of India declared a mucormycosis epidemic in May 2021. The majority of such cases occurred during active SARS-CoV-2 outbreaks in India in 2021. Black fungus took over while the host defenses were compromised and the globe was preoccupied tackling the COVID-19 pandemic. Steroids prescribed in amounts and time spans that far exceeded WHO recommendations to manage severe COVID-19 cases, potentially weakened patients' immune systems, and raised blood sugar levels making them vulnerable to fungal invasion. Early diagnosis and treatment are the keys to a patient's survival. Simple means such as maintaining hygienic conditions, avoiding contact with an infected person, judiciously using steroid medications and antibiotics and properly managing high blood sugar can help protect an individual from black-fungus infection.


Subject(s)
COVID-19 , Mucormycosis , Neutropenia , Opportunistic Infections , Humans , Mucormycosis/diagnosis , Mucormycosis/drug therapy , Mucormycosis/epidemiology , Pandemics , Immunosuppression Therapy
6.
Lancet ; 400(10349): 369-379, 2022 07 30.
Article in English | MEDLINE | ID: covidwho-2184620

ABSTRACT

BACKGROUND: Upadacitinib, a Janus kinase inhibitor, has been shown to be effective in patients with ankylosing spondylitis. We aimed to assess the efficacy and safety of upadacitinib in non-radiographic axial spondyloarthritis. METHODS: The SELECT-AXIS 2 non-radiographic axial spondyloarthritis study was a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 113 sites across 23 countries (Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, France, Germany, Hungary, Israel, Japan, Mexico, Poland, Russia, Slovakia, South Korea, Spain, Taiwan, Turkey, Ukraine, and the USA). Eligible adults had active non-radiographic axial spondyloarthritis, with objective signs of inflammation based on MRI or elevated C-reactive protein and an inadequate response to non-steroidal anti-inflammatory drugs. Patients were randomly assigned (1:1) to receive oral upadacitinib 15 mg once daily or placebo using interactive response technology. Random treatment assignment was stratified by MRI inflammation in the sacroiliac joints and screening high-sensitivity C-reactive protein status (MRI-positive and C-reactive protein-positive, MRI-positive and C-reactive protein-negative, and MRI-negative and C-reactive protein-positive) and previous exposure to biologic disease-modifying antirheumatic drugs (yes vs no). Treatment assignment was masked from patients, investigators, study site personnel, and the study sponsor. The primary endpoint was the proportion of patients with an Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Analyses were performed on the full analysis set of patients, who underwent random allocation and received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04169373. FINDINGS: Between Nov 26, 2019, and May 20, 2021, 314 patients with active non-radiographic axial spondyloarthritis were enrolled into the study, and 313 received study drug (156 in the upadacitinib group and 157 in the placebo group); 295 (94%) patients (145 in the upadacitinib group and 150 in the placebo group) received treatment for the full 14 weeks. A significantly higher ASAS40 response rate was achieved with upadacitinib compared with placebo at week 14 (70 [45%] of 156 patients vs 35 [23%] of 157 patients; p<0·0001; treatment difference 22%, 95% CI 12-32). The rate of adverse events up to week 14 was similar in the upadacitinib group (75 [48%] of 156 patients) and placebo group (72 [46%] of 157 patients). Serious adverse events and adverse events leading to discontinuation of study drug occurred in four (3%) of 156 patients in the upadacitinib group and two (1%) of 157 patients in the placebo group. Few patients had serious infections or herpes zoster in either treatment group (each event occurred in two [1%] of 156 patients in the upadacitinib group and one [1%] of 157 patients in the placebo group). Five (3%) of 156 patients in the upadacitinib group had neutropenia; no events of neutropenia occurred in the placebo group. No opportunistic infections, malignancies, major adverse cardiovascular events, venous thromboembolic events, or deaths were reported with upadacitinib treatment. INTERPRETATION: Upadacitinib significantly improved the signs and symptoms of non-radiographic axial spondyloarthritis compared with placebo at week 14. These findings support the potential of upadacitinib as a new therapeutic option in patients with active non-radiographic axial spondyloarthritis. FUNDING: AbbVie.


Subject(s)
Axial Spondyloarthritis , Neutropenia , Non-Radiographic Axial Spondyloarthritis , Adult , C-Reactive Protein , Double-Blind Method , Heterocyclic Compounds, 3-Ring , Humans , Inflammation , Treatment Outcome
7.
Indian J Med Res ; 155(5&6): 546-553, 2022.
Article in English | MEDLINE | ID: covidwho-2110448

ABSTRACT

Background & objectives: High mortality has been observed in the cancer population affected with COVID-19 during this pandemic. We undertook this study to determine the characteristics and outcomes of cancer patients with COVID-19 and assessed the factors predicting outcome. Methods: Patients of all age groups with a proven history of malignancy and a recent diagnosis of SARS-CoV-2 infection based on nasal/nasopharyngeal reverse transcriptase (RT)-PCR tests were included. Demographic, clinical and laboratory variables were compared between survivors and non-survivors groups, with respect to observed mortality. Results: Between May 11 and August 10, 2020, 134 patients were included from the three centres and observed mortality was 17.1 per cent. The median age was 53 yr (interquartile range 39-61 yr) and thirty four patients (25%) were asymptomatic. Solid tumours accounted for 69.1 per cent and breast cancer was the most common tumour type (20%). One hundred and five patients (70.5%) had received chemotherapy within the past four weeks and 25 patients (19.3%) had neutropenia at presentation. On multivariate analysis, age [odds ratio (OR) 7.99 (95% confidence interval [CI] 1.18-54.00); P=0.033], haemoglobin [OR 6.28 (95% CI 1.07-37.04); P=0.042] neutrophil-lymphocyte ratio [OR 12.02 (95% CI 2.08-69.51); P=0.005] and baseline serum albumin [OR 18.52 (95% CI 2.80-122.27); P=0.002], were associated with higher mortality. Recent chemotherapy, haematological tumours type and baseline neutropenia did not affect the outcome. Interpretation & conclusions: Higher mortality in moderate and severe infections was associated with baseline organ dysfunction and elderly age. Significant proportion of patients were asymptomatic and might remain undetected.


Subject(s)
COVID-19 , Neoplasms , Neutropenia , Humans , Aged , Middle Aged , Retrospective Studies , SARS-CoV-2 , India/epidemiology , Neoplasms/complications , Neoplasms/epidemiology , Neutropenia/complications
8.
Support Care Cancer ; 30(12): 9921-9928, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2094629

ABSTRACT

INTRODUCTION: Afebrile chemotherapy-induced neutropenia represents a frequent clinical situation where chemotherapy protocol, patient's comorbidities, and disease status determine the risk of infection hence the management plan. Internationally distributed, this questionnaire aims to evaluate the routine practice and the impact of the COVID-19 pandemic on afebrile chemotherapy-induced neutropenia management. MATERIAL AND METHODS: Coordinators from Egypt, Morocco, Azerbaijan, and Russia developed a 12-item questionnaire using Google forms to explore how oncologists deal with afebrile chemotherapy-induced neutropenia. The link to the survey was available internationally through social media and to their local societies over the period from July to September 2021. RESULTS: We received 151 responses from 4 world regions: 58.9, 9.9, 11.3, and 15.2% from the Mena area, Russia, Europe, and Asia. The responses deviated from the guideline-driven practice as G-CSF was the most chosen option for intermediate risk that was statistically different based on the academic background of the treating physician. Half of the responders ignored patients and disease risk factors in the intermediate-risk cases that trend was statistically different based on the geographical distribution. The steroid was a valid option for intermediate and low-risk as per oncologists practicing in Russia. COVID-19 pandemic positively affected the rate of prescription of G-CSF as expected. CONCLUSION: The disparities in the routine practice of oncologists based on their geographical and academic backgrounds highlight the need to analyze the underlying obstacles that hinder guideline-based practice like workload or lack of the proper knowledge.


Subject(s)
Antineoplastic Agents , COVID-19 , Neoplasms , Neutropenia , Oncologists , Humans , Pandemics , Standard of Care , Practice Patterns, Physicians' , Neutropenia/chemically induced , Neutropenia/epidemiology , Neutropenia/drug therapy , Granulocyte Colony-Stimulating Factor/therapeutic use , Antineoplastic Agents/adverse effects , Surveys and Questionnaires , Neoplasms/therapy
9.
Int J Mol Sci ; 23(17)2022 Aug 24.
Article in English | MEDLINE | ID: covidwho-1997651

ABSTRACT

Cytomegalovirus (CMV) syndrome and infectious disease are defined as pathogen detection with appropriate clinical symptoms, but there are not pathognomonic signs of CMV disease. Although the prodrome of acute minor viral infections leukopenia (lymphopenia and neutropenia) is noted with onset of fever, followed by monocytosis, the role of monocytosis in CMV disease has not been described. Furthermore, under influence of corticosteroid therapy, CMV reactivation and monocytosis are described, but without a strict relationship with steroids dose. In the study, the monocyte level was investigated during the CMV infectious process. Regrettably, a non-selected group of 160 patients with high CMV viremia showed high dispersion of monocyte level and comparable with the median value for healthy subjects. Therefore, we investigated monocyte level in CMV-infected patients in relation to the logarithmic phase of the infectious process. Samples from patients with active CMV replication (exponential growth of CMV viremia) were tested. Significant monocytosis (above 1200/µL) during the logarithmic phase of CMV infection (with exponent between 3.23 and 5.77) was observed. Increased count and percentage of monocytes correlated with viral replication in several clinical situations except when there was a rapid recovery without relapse. Furthermore, glucocorticoids equivalent to 10 and 20 mg of dexamethasone during a 2-3-week period caused monocytosis-significant increase (to 1604 and 2214/µL, respectively). Conclusion: In light of the logarithmic increase of viral load, high monocytosis is a hallmark of CMV replication. In the COVID-19 era, presence of high virus level, especially part of virome (CMV) in the molecular technique, is not sufficient for the definition of either proven or probable CMV replication at any site. These preliminary observations merit additional studies to establish whether this clinical response is mediated by monocyte production or by decrease of differentiation to macrophages.


Subject(s)
COVID-19 , Cytomegalovirus Infections , Neutropenia , Cytomegalovirus/physiology , Glucocorticoids/therapeutic use , Humans , Monocytes , Viremia/complications , Viremia/drug therapy
10.
Blood ; 140(4): 349-358, 2022 07 28.
Article in English | MEDLINE | ID: covidwho-1978749

ABSTRACT

CD19-directed chimeric antigen receptor (CAR) T cells have evolved as a new standard-of-care (SOC) treatment in patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL). Here, we report the first German real-world data on SOC CAR T-cell therapies with the aim to explore risk factors associated with outcomes. Patients who received SOC axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) for LBCL and were registered with the German Registry for Stem Cell Transplantation (DRST) were eligible. The main outcomes analyzed were toxicities, response, overall survival (OS), and progression-free survival (PFS). We report 356 patients who received axi-cel (n = 173) or tisa-cel (n = 183) between November 2018 and April 2021 at 21 German centers. Whereas the axi-cel and tisa-cel cohorts were comparable for age, sex, lactate dehydrogenase (LDH), international prognostic index (IPI), and pretreatment, the tisa-cel group comprised significantly more patients with poor performance status, ineligibility for ZUMA-1, and the need for bridging, respectively. With a median follow-up of 11 months, Kaplan-Meier estimates of OS, PFS, and nonrelapse mortality (NRM) 12 months after dosing were 52%, 30%, and 6%, respectively. While NRM was largely driven by infections subsequent to prolonged neutropenia and/or severe neurotoxicity and significantly higher with axi-cel, significant risk factors for PFS on the multivariate analysis included bridging failure, elevated LDH, age, and tisa-cel use. In conclusion, this study suggests that important outcome determinants of CD19-directed CAR T-cell treatment of LBCL in the real-world setting are bridging success, CAR-T product selection, LDH, and the absence of prolonged neutropenia and/or severe neurotoxicity. These findings may have implications for designing risk-adapted CAR T-cell therapy strategies.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Neutropenia , Antigens, CD19 , Germany/epidemiology , Humans , Immunotherapy, Adoptive/adverse effects , Lymphoma, Large B-Cell, Diffuse/pathology , Neutropenia/chemically induced
11.
Cochrane Database Syst Rev ; 7: CD008766, 2022 07 12.
Article in English | MEDLINE | ID: covidwho-1958662

ABSTRACT

BACKGROUND: Ovarian cancer is the seventh most frequent cancer diagnosis worldwide, and the eighth leading cause of cancer mortality. Epithelial ovarian cancer is the most common kind, accounting for 90% of cases. First-line therapy for women with epithelial ovarian cancer consists of a combination of cytoreductive surgery and platinum and taxane-based chemotherapy. However, more than 50% of women with epithelial ovarian cancer will experience a relapse and require further chemotherapy and at some point develop resistance to platinum-based drugs. Currently, guidance on the use of most chemotherapy drugs, including taxanes, is unclear for women whose epithelial ovarian cancer has recurred. Paclitaxel, topotecan, pegylated liposomal doxorubicin hydrochloride, trabectedin and gemcitabine are all licensed for use in the UK at the discretion of clinicians, following discussion with the women as to potential adverse effects. Taxanes can be given in once-weekly regimens (at a lower dose) or three-weekly regimens (at a higher dose), which may have differences in the severity of side effects and effectiveness. As relapsed disease suggests incurable disease, it is all the more important to consider side effects and the impact of treatment schedules, as well as quality of life, and not only the life-prolonging effects of treatment. OBJECTIVES: To assess the efficacy and toxicity of different taxane monotherapy regimens for women with recurrent epithelial ovarian, tubal or primary peritoneal cancer. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase, up to 22 March 2022. Other related databases and trial registries were searched as well as grey literature and no additional studies were identified. A total of 1500 records were identified. SELECTION CRITERIA: We included randomised controlled trials of taxane monotherapy for adult women diagnosed with recurrent epithelial ovarian, tubal or primary peritoneal cancer, previously treated with platinum-based chemotherapy. We included trials comparing two or more taxane monotherapy regimens. Participants could be experiencing their first recurrence of disease or any line of recurrence. DATA COLLECTION AND ANALYSIS: Two review authors screened, independently assessed studies, and extracted data from the included studies. The clinical outcomes we examined were overall survival, response rate, progression-free survival, neurotoxicity, neutropenia, alopecia, and quality of life. We performed statistical analyses using fixed-effect and random-effects models following standard Cochrane methodology. We rated the certainty of evidence according to the GRADE approach. MAIN RESULTS: Our literature search yielded 1500 records of 1466 studies; no additional studies were identified by searching grey literature or handsearching. We uploaded the search results into Covidence. After the exclusion of 92 duplicates, we screened titles and abstracts of 1374 records. Of these, we identified 24 studies for full-text screening. We included four parallel-group randomised controlled trials (RCTs). All trials were multicentred and conducted in a hospital setting. The studies included 981 eligible participants with recurrent epithelial ovarian cancer, tubal or primary peritoneal cancer with a median age ranging between 56 to 62 years of age. All participants had a WHO (World Health Organization) performance status of between 0 to 2. The proportion of participants with serous histology ranged between 56% to 85%. Participants included women who had platinum-sensitive (71%) and platinum-resistant (29%) relapse. Some participants were taxane pre-treated (5.6%), whilst the majority were taxane-naive (94.4%). No studies were classified as having a high risk of bias for any of the domains in the Cochrane risk of bias tool. We found that there may be little or no difference in overall survival (OS) between weekly paclitaxel and three-weekly paclitaxel, but the evidence is very uncertain (risk ratio (RR) of 0.94, 95% confidence interval (CI) 0.66 to 1.33, two studies, 263 participants, very low-certainty evidence). Similarly, there may be little or no difference in response rate (RR of 1.07, 95% CI 0.78 to 1.48, two studies, 263 participants, very low-certainty evidence) and progression-free survival (PFS) (RR of 0.83, 95% CI 0.46 to 1.52, two studies, 263 participants, very low-certainty evidence) between weekly and three-weekly paclitaxel, but the evidence is very uncertain. We found differences in the chemotherapy-associated adverse events between the weekly and three-weekly paclitaxel regimens. The weekly paclitaxel regimen may result in a reduction in neutropenia (RR 0.51, 95% 0.27 to 0.95, two studies, 260 participants, low-certainty evidence) and alopecia (RR 0.58, 95% CI 0.46 to 0.73, one study, 205 participants, low-certainty evidence). There may be little or no difference in neurotoxicity, but the evidence was very low-certainty and we cannot exclude an effect (RR 0.53, 95% CI 0.19 to 1.45, two studies, 260 participants). When examining the effect of paclitaxel dosage in the three-weekly regimen, the 250 mg/m2 paclitaxel regimen probably causes more neurotoxicity compared to the 175 mg/m2 regimen (RR 0.41, 95% CI 0.21 to 0.80, one study, 330 participants, moderate-certainty evidence). Quality-of-life data were not extractable from any of the included studies. AUTHORS' CONCLUSIONS: Fewer people may experience neutropenia when given weekly rather than three-weekly paclitaxel (low-certainty evidence), although it may make little or no difference to the risk of developing neurotoxicity (very low-certainty evidence). This is based on the participants receiving lower doses of drug more often. However, our confidence in this result is low and the true effect may be substantially different from the estimate of the effect. Weekly paclitaxel probably reduces the risk of alopecia, although the rates in both arms were high (46% versus 79%) (low-certainty evidence). A change to weekly from three-weekly chemotherapy could be considered to reduce the likelihood of toxicity, as it may have little or no negative impact on response rate (very low-certainty evidence), PFS (very low-certainty evidence) or OS (very low-certainty evidence). Three-weekly paclitaxel, given at a dose of 175 mg/m2 compared to a higher dose,probably reduces the risk of neurotoxicity.We are moderately confident in this result; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. A change to 175 mg/m2 paclitaxel (from a higher dose), if a three-weekly regimen is used, probably has little or no negative impact on PFS or OS (very low-certainty evidence).


Subject(s)
Neutropenia , Ovarian Neoplasms , Adult , Alopecia/drug therapy , Bridged-Ring Compounds , Carcinoma, Ovarian Epithelial/drug therapy , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Paclitaxel/adverse effects , Taxoids/adverse effects
12.
J Int Med Res ; 50(7): 3000605221109392, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1950741

ABSTRACT

OBJECTIVES: Early detection of coronavirus disease 2019 (COVID-19) is crucial for patients and public health to ensure pandemic control. We aimed to correlate clinical and laboratory data of patients with COVID-19 and their polymerase chain reaction (PCR) results and to assess the accuracy of a deep learning model in diagnosing COVID-19. METHODS: This was a retrospective study using an anonymized dataset of patients with suspected COVID-19. Only patients with a complete dataset were included (n = 440). A deep analytics framework and dual-modal approach for PCR-based classification was used, integrating symptoms and laboratory-based modalities. RESULTS: Participants with loss of smell or taste were two times more likely to have positive PCR results (odds ratio [OR] 1.86). Participants with neutropenia, high serum ferritin, or monocytosis were three, four, and five times more likely to have positive PCR results (OR 2.69, 4.18, 5.42, respectively). The rate of accuracy achieved using the deep learning framework was 78%, with sensitivity of 83.9% and specificity of 71.4%. CONCLUSION: Loss of smell or taste, neutropenia, monocytosis, and high serum ferritin should be routinely assessed with suspected COVID-19 infection. The use of deep learning for diagnosis is a promising tool that can be implemented in the primary care setting.


Subject(s)
COVID-19 , Deep Learning , Neutropenia , Anosmia , COVID-19/diagnosis , Ferritins , Hospitals, University , Humans , Retrospective Studies , SARS-CoV-2
13.
Infection ; 50(5): 1373-1382, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1920272

ABSTRACT

BACKGROUND: We evaluated clinical features and risk factors for mortality in patients with haematological malignancies and COVID-19. METHODS: Retrospective, case-control (1:3) study in hospitalized patients with COVID-19. Cases were patients with haematological malignancies and COVID-19, controls had COVID-19 without haematological malignancies. Patients were matched for sex, age and time of hospitalization. RESULTS: Overall, 66 cases and 198 controls were included in the study. Cases had higher prior corticosteroid use, infection rates, thrombocytopenia and neutropenia and more likely received corticosteroids and antibiotics than controls. Cases had higher respiratory deterioration than controls (78.7% vs 65.5%, p = 0.04). Notably, 29% of cases developed respiratory worsening > 10 days after hospital admission, compared to only 5% in controls. Intensive Care Unit admission and mortality were higher in cases than in controls (27% vs 8%, p = 0.002, and 35% vs 10%, p < 0.001). At multivariable analysis, having haematological malignancy [OR4.76, p < 0.001], chronic corticosteroid therapy [OR3.65, p = 0.004], prior infections [OR57.7, p = 0.006], thrombocytopenia [OR3.03, p < 0.001] and neutropenia [OR31.1, p = 0.001], low albumin levels [OR3.1, p = 0.001] and ≥ 10 days from hospital admission to respiratory worsening [OR3.3, p = 0.002] were independently associated with mortality. In cases, neutropenia [OR3.1, p < 0.001], prior infections [OR7.7, p < 0.001], ≥ 10 days to respiratory worsening [OR4.1, p < 0.001], multiple myeloma [OR1.5, p = 0.044], the variation of the CT lung score during hospitalization [OR2.6, p = 0.006] and active treatment [OR 4.4, p < 0.001] all were associated with a worse outcome. CONCLUSION: An underlying haematological malignancy was associated with a worse clinical outcome in COVID-19 patients. A prolonged clinical monitoring is needed, since respiratory worsening may occur later during hospitalization.


Subject(s)
COVID-19 , Hematologic Neoplasms , Neutropenia , Thrombocytopenia , Adrenal Cortex Hormones/therapeutic use , Albumins , Anti-Bacterial Agents , COVID-19/epidemiology , Case-Control Studies , Hematologic Neoplasms/complications , Humans , Neutropenia/complications , Retrospective Studies , SARS-CoV-2 , Thrombocytopenia/complications
14.
Am J Ther ; 29(5): e544-e552, 2022.
Article in English | MEDLINE | ID: covidwho-1909034

ABSTRACT

BACKGROUND: Clozapine is the only approved antipsychotic for treatment-resistant schizophrenia. Despite its therapeutic benefits, it is still widely underused, mainly because of its potential to cause agranulocytosis and neutropenia. Prescribing clozapine in COVID-19-positive patients became more challenging because of this potential side effect. This article is a review of literature on the risk of neutropenia associated with clozapine treatment in patients with COVID-19. AREAS OF UNCERTAINTY: In clozapine-treated COVID-19-positive patients, neutropenia was reported in some cases; is it a consequence of clozapine treatment or of SARS-Co2 infection? DATA SOURCES: Data were extracted from 2 databases: PubMed/MEDLINE and Google Scholar. We selected all original reports, from March 2020 until May 2022, on neutropenia associated with clozapine treatment in positive COVID-19 patients. Eleven studies were selected for the final analysis. THERAPEUTIC ADVANCES: Before the COVID-19 pandemic, neutropenia in clozapine-treated patients was reported in 3.8% of cases. During the pandemic, neutropenia rates seemed to be higher. As per the cause of neutropenia, studies reported contradictory results. We aim to clarify rates and causes of neutropenia in clozapine-treated COVID-19-positive patients. RESULTS: Three hundred eighty-eight articles were initially selected from the 2 databases. After excluding duplicates, unrelated articles, reviews, and guidelines, 11 studies were analyzed, all centered on clozapine treatment, COVID-19 infection, and associated neutropenia. CONCLUSIONS: Clozapine treatment in COVID-19-positive patients may be associated with a transient reduction of absolute neutrophils count, in some cases reaching neutropenia levels. Neutropenia rates reported in SARS-CoV-2-infected patients are higher than the prepandemic reports; therefore, we assume that the cause might be a result of the immunological interference between clozapine and SARS-CoV-2. Clozapine treatment needs to be continued whenever possible, with dose adjustments in relation to blood test results.


Subject(s)
Antipsychotic Agents , COVID-19 Drug Treatment , Clozapine , Neutropenia , Schizophrenia , Antipsychotic Agents/adverse effects , Clozapine/adverse effects , Humans , Neutropenia/chemically induced , Neutropenia/epidemiology , Pandemics , SARS-CoV-2 , Schizophrenia/drug therapy
15.
PLoS One ; 17(6): e0269368, 2022.
Article in English | MEDLINE | ID: covidwho-1879321

ABSTRACT

INTRODUCTION: We systematically assessed benefits and harms of tocilizumab (TCZ), which is an antibody blocking IL-6 receptors, in hospitalized COVID-19 patients. METHODS: Five electronic databases and two preprint webpages were searched until March 4, 2021. Randomized controlled trials (RCTs) and inverse probability treatment weighting (IPTW) cohorts assessing TCZ effects in hospitalized, COVID-19 adult patients were included. Primary outcomes were all-cause mortality, clinical worsening, clinical improvement, need for mechanical ventilation, and adverse events (AE). Inverse variance random-effects meta-analyses were performed with quality of evidence (QoE) evaluated using GRADE methodology. RESULTS: Nine RCTs (n = 7,021) and nine IPTW cohorts (n = 7,796) were included. TCZ significantly reduced all-cause mortality in RCTs (RR 0.89, 95%CI 0.81-0.98, p = 0.03; moderate QoE) and non-significantly in cohorts (RR 0.67, 95%CI 0.44-1.02, p = 0.08; very low QoE) vs. control (standard of care [SOC] or placebo). TCZ significantly reduced the need for mechanical ventilation (RR 0.80, 95%CI 0.71-0.90, p = 0.001; moderate QoE) and length of stay (MD -1.92 days, 95%CI -3.46 to -0.38, p = 0.01; low QoE) vs. control in RCTs. There was no significant difference in clinical improvement or worsening between treatments. AEs, severe AEs, bleeding and thrombotic events were similar between arms in RCTs, but there was higher neutropenia risk with TCZ (very low QoE). Subgroup analyses by disease severity or risk of bias (RoB) were consistent with main analyses. Quality of evidence was moderate to very low in both RCTs and cohorts. CONCLUSIONS: In comparison to SOC or placebo, TCZ reduced all-cause mortality in all studies and reduced mechanical ventilation and length of stay in RCTs in hospitalized COVID-19 patients. Other clinical outcomes were not significantly impacted. TCZ did not have effect on AEs, except a significant increased neutropenia risk in RCTs. TCZ has a potential role in the treatment of hospitalized COVID-19 patients.


Subject(s)
COVID-19 Drug Treatment , Neutropenia , Adult , Antibodies, Monoclonal, Humanized/adverse effects , Humans , Neutropenia/drug therapy , Randomized Controlled Trials as Topic
16.
Acta Haematol ; 145(3): 297-309, 2022.
Article in English | MEDLINE | ID: covidwho-1874915

ABSTRACT

BACKGROUND: The clinical presentation of coronavirus disease 19 (COVID-19) is the result of intricate interactions between the novel coronavirus and the immune system. In patients with hematologic malignancies (HM), these interactions dramatically change the clinical course and outcomes of COVID-19. SUMMARY: Patients with HM and COVID-19 are at an increased risk for prolonged viral shedding, more protracted and severe presentation, and death, even when compared to other immunocompromised hosts. HM (e.g., multiple myeloma, chronic lymphocytic leukemia) and anticancer treatments (e.g., anti-CD20 agents) that impair humoral immunity markedly increase the risk of severe COVID-19 as well as protracted viral shedding and possibly longer infectivity. Cytokine release syndrome (CRS) is an important player in the pathophysiology of severe and fatal COVID-19. Treatments targeting specific cytokines involved in CRS such as interleukin-6 and Janus kinase have proven beneficial in COVID-19 patients but were not assessed specifically in HM patients. Although neutropenia (as well as neutrophilia) was associated with increased COVID-19 mortality, granulocyte colony-stimulating factors were not beneficial in patients with COVID-19 and may have been associated with worse outcomes. Decreased levels of T lymphocytes and especially decreased CD4+ counts, and depletion of CD8+ lymphocytes, are a hallmark of severe COVID-19, and even more so among patients with HM, underlying the important role of T-helper dysfunction in severe COVID-19. In HM patients with intact cellular immunity, robust T-cell responses may compensate for an impaired humoral immune system. Further prospective studies are needed to evaluate the mechanisms of severe COVID-19 among patients with HM and assess the efficacy of new immunomodulating COVID-19 treatments in this population. KEY MESSAGES: Understanding the immunopathology of COVID-19 has greatly benefited from the previous research in patients with HM. So far, no COVID-19 treatments were properly evaluated in patients with HM. Patients with HM should be included in future RCTs assessing treatments for COVID-19.


Subject(s)
COVID-19 , Hematologic Neoplasms , Multiple Myeloma , Neutropenia , COVID-19/complications , Hematologic Neoplasms/complications , Humans , Immunity , Multiple Myeloma/complications , Neutropenia/complications
17.
Microb Drug Resist ; 28(5): 601-610, 2022 May.
Article in English | MEDLINE | ID: covidwho-1864944

ABSTRACT

This retrospective study aims to describe the etiology and resistance patterns of pathogens causing bacteremia in children with solid tumors in a tertiary pediatric hematology-oncology center in Jerusalem, Israel (2011-2019). Factors associated with multidrug-resistant (MDR) bacteremia and mortality were analyzed. A total of 228 pathogens were isolated in 126 patients; 61.0% were gram-negative rods (GNR) and 38.2% were gram-positive cocci (GPC). The most common pathogens were Klebsiella pneumoniae (19.3%), Escherichia coli (17.5%), and coagulase-negative staphylococci (16.2%). The proportion of MDR-GNR was 18.2%, while the proportion of MDR-GPC was 55.2%. In logistic regression analysis, breakthrough bacteremia on a penicillin-group antibiotic (odds ratio [OR] 5.69, [95% confidence interval 1.42-22.76], p-value = 0.014) was associated and underlying diagnosis of neuroblastoma was inversely associated (OR 0.17, [0.04-0.81], p-value = 0.026) with MDR-GNR bacteremia; while the previous hospitalizations' duration (OR 1.032/day, [1.01-1.06], p-value = 0.007) and oncologic treatment intensity (OR 2.19, [1.08-4.45, p-value = 0.03) were associated with MDR-GPC bacteremia. Shock, prolonged profound neutropenia, and pediatric intensive care unit (PICU) admission were associated with 7-day mortality; and relapsed disease, oncologic treatment intensity, prolonged profound neutropenia, and PICU admission-with 30-day mortality in the univariate analyses. Empirical antibiotic choice should be based on factors associated with MDR infections in this specific population.


Subject(s)
Bacteremia , Gram-Negative Bacterial Infections , Neoplasms , Neutropenia , Anti-Bacterial Agents/pharmacology , Bacteremia/drug therapy , Bacteremia/epidemiology , Child , Drug Resistance, Multiple , Escherichia coli , Gram-Negative Bacteria , Gram-Negative Bacterial Infections/drug therapy , Humans , Neoplasms/complications , Neoplasms/drug therapy , Neoplasms/pathology , Neutropenia/complications , Neutropenia/drug therapy , Retrospective Studies
18.
J Trop Pediatr ; 68(3)2022 04 05.
Article in English | MEDLINE | ID: covidwho-1860907

ABSTRACT

BACKGROUND: Studies on age-related differences in clinical and laboratory features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited. We aimed to evaluate the demographic, clinical, laboratory findings of SARS-CoV-2 infection in children younger than 6 months old and compare them with older children. METHODS: A single-center retrospective study, including 209 confirmed SARS-CoV-2 infection cases, was conducted between 11 March 2020 and 1 September 2021. The case group consisted of 47 patients younger than 6 months old, whereas the control group consisted of 162 patients older than 6 months old. RESULTS: The mean age of the case group was 2.77 ± 1.52 months, and the control group was 101.89 ± 65.77 months. Cough was statistically higher in the control group, and poor feeding was higher in the case group (p = 0.043, 0.010). The underlying disease rate was statistically higher in the control group; however, the hospitalization rate was higher in the case group (p = 0.036, 0.001). The case group had significantly lower median values of the absolute neutrophil count, hemoglobin and higher median values of white blood cell, absolute lymphocyte count and platelet than the control group (p < 0.05). C-reactive protein, fibrinogen values were significantly lower, and procalcitonin, D-dimer, troponin T, N-terminal pro-B-type natriuretic peptide significantly higher in the case group (p < 0.05). Lymphopenia was more common in the control group, whereas neutropenia was more common in the case group (p = 0.001, 0.011). CONCLUSIONS: We showed that most children younger than 6 months old had mild and asymptomatic SARS-CoV-2 infection; however, the hospitalization rate was higher, and neutropenia was more common in older children. Lay summaryStudies on age-related differences in clinical and laboratory features on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pediatric patients are limited. We aimed to evaluate the demographic, clinical and laboratory findings of SARS-CoV-2 infection in children younger than 6 months old and compare them with older children. A single-center retrospective study was conducted, including 209 SARS-CoV-2 infection cases. The case group consisted of 47 patients younger than 6 months old, and the control group consisted of 162 patients older than 6 months old. Most children younger than 6 months old had mild and asymptomatic SARS-CoV-2 infection; however, the hospitalization rate was higher than older children. Neutropenia was more common in patients younger than 6 months than older children with SARS-CoV-2 infection, even if underlying diseases were excluded.


Subject(s)
COVID-19 , Lymphopenia , Neutropenia , Adolescent , COVID-19/diagnosis , Child , Humans , Infant , Neutropenia/epidemiology , Retrospective Studies , SARS-CoV-2
19.
Ital J Pediatr ; 48(1): 43, 2022 Mar 15.
Article in English | MEDLINE | ID: covidwho-1745433

ABSTRACT

BACKGROUND: Investigations on haematological alterations in paediatric COVID-19 have been focused mostly on lymphocytes and clotting profiles. Neutropenia has been occasionally reported and its course and impact on the disease have not been elucidated. The aim of this study was to describe the epidemiology, course, and impact of neutropenia in children with COVID-19 hospitalised in a tertiary care referral paediatric ward. METHODS: A single-centre retrospective study was conducted. Hospitalised children between 1 month and 18 years with confirmed COVID-19 and neutropenia were included and compared to non neutropenic patients. Complete blood picture with differential blood count, serum biochemistry, clotting profiles were performed; clinical data, length of hospitalisation, and prescription of drugs were collected. RESULTS: Twelve out of 95 patients (12.63%) with documented SARS-CoV-2 infection were neutropenic and met the inclusion criteria. The mean age was 161 days (range 38-490 days). The mean duration of symptoms in neutropenic children was 3.82 days, while the mean length of hospitalisation was 7.67 days. These findings were not significantly different in the two study groups. All patients had mild clinical manifestations and were discharged without sequelae. CONCLUSIONS: We provided the first comprehensive study on neutropenia in mild paediatric COVID-19 infection. Our findings show that the main features of this haematological disorder in COVID-19 are analogous to the well-known transient benign neutropenia associated with other common viral infections. In our setting, neutropenia does not emerge as a potential negative prognostic factor in paediatric COVID-19.


Subject(s)
COVID-19 , Neutropenia , Virus Diseases , COVID-19/epidemiology , Child , Humans , Neutropenia/complications , Neutropenia/epidemiology , Retrospective Studies , SARS-CoV-2 , Virus Diseases/diagnosis
20.
Pediatr Blood Cancer ; 69(5): e29647, 2022 05.
Article in English | MEDLINE | ID: covidwho-1729184

ABSTRACT

Because they can experience neutropenia due to bone marrow failure, patients with Shwachman-Diamond syndrome (SDS) carry increased risk for serious infections compared with the general population; however, there has been a paucity of data on the incidence and severity of coronavirus disease 2019 (COVID-19) in patients with SDS. We compiled results from a survey distributed to participants in the SDS Registry in May-June 2021. In this report, we describe the characteristics and outcomes of patients with SDS who had COVID-19. Patients reported a short clinical course without significant complications or cytopenias. Additionally, COVID-19 vaccines were well tolerated with minor side effects.


Subject(s)
Bone Marrow Diseases , COVID-19 , Exocrine Pancreatic Insufficiency , Neutropenia , COVID-19/complications , COVID-19 Vaccines/adverse effects , Humans , Shwachman-Diamond Syndrome , Vaccination
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