Blood myeloid cells are known to be dysregulated in coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2. It is unknown whether the innate myeloid response differs with disease severity and ...whether markers of innate immunity discriminate high-risk patients. Thus, we performed high-dimensional flow cytometry and single-cell RNA sequencing of COVID-19 patient peripheral blood cells and detected disappearance of non-classical CD14LowCD16High monocytes, accumulation of HLA-DRLow classical monocytes (Human Leukocyte Antigen - DR isotype), and release of massive amounts of calprotectin (S100A8/S100A9) in severe cases. Immature CD10LowCD101−CXCR4+/− neutrophils with an immunosuppressive profile accumulated in the blood and lungs, suggesting emergency myelopoiesis. Finally, we show that calprotectin plasma level and a routine flow cytometry assay detecting decreased frequencies of non-classical monocytes could discriminate patients who develop a severe form of COVID-19, suggesting a predictive value that deserves prospective evaluation.
Display omitted
•Patients with severe COVID-19 accumulate HLA-DRLow monocytes and immature neutrophils in blood/lungs•Calprotectin level positively correlates with neutrophil count and disease severity•Loss of non-classical monocytes could identify high risk of severe COVID-19
An analysis of patients with severe COVID-19 reveals immature neutrophil and non-classical monocyte pools, with levels of the protein calprotectin linked to disease severity.
Background. Anti-cancer treatment and the cancer population have evolved since the last European Organisation for Research and Treatment of Cancer (EORTC) fungemia survey, and there are few recent ...large epidemiological studies. Methods. This was a prospective cohort study including 145 030 admissions of patients with cancer from 13 EORTC centers. Incidence, clinical characteristics, and outcome of fungemia were analyzed. Results. Fungemia occurred in 333 (0.23%; 95% confidence interval CI, .21–.26) patients, ranging from 0.15% in patients with solid tumors to 1.55% in hematopoietic stem cell transplantation recipients. In 297 evaluable patients age ranged from 17 to 88 years (median 56 years), 144 (48%) patients were female, 165 (56%) had solid tumors, and 140 (47%) had hematological malignancies. Fungemia including polymicrobial infection was due to: Candida spp. in 267 (90%), C. albicans in 128 (48%), and other Candida spp. in 145 (54%) patients. Favorable overall response was achieved in 113 (46.5%) patients by week 2. After 4 weeks, the survival rate was 64% (95% CI, 59%–70%) and was not significantly different between Candida spp. Multivariable logistic regression identified baseline septic shock (odds ratio OR 3.04, 95% CI, 1.22–7.58) and tachypnoea as poor prognostic factors (OR 2.95, 95% CI, 1.66–5.24), while antifungal prophylaxis prior to fungemia (OR 0.20, 95% CI, .06–.62) and remission of underlying cancer (OR, 0.18; 95% CI, .06–.50) were protective. Conclusions. Fungemia, mostly due to Candida spp., was rare in cancer patients from EORTC centers but was associated with substantial mortality. Antifungal prophylaxis and remission of cancer predicted better survival.
Over the past 16 years, three coronaviruses (CoVs), severe acute respiratory syndrome CoV (SARS-CoV) in 2002, Middle East respiratory syndrome CoV (MERS-CoV) in 2012 and 2015, and SARS-CoV-2 in 2020, ...have been causing severe and fatal human epidemics. The unpredictability of coronavirus disease-19 (COVID-19) poses a major burden on health care and economic systems across the world. This is caused by the paucity of in-depth knowledge of the risk factors for severe COVID-19, insufficient diagnostic tools for the detection of SARS-CoV-2, as well as the absence of specific and effective drug treatments. While protective humoral and cellular immune responses are usually mounted against these betacoronaviruses, immune responses to SARS-CoV2 sometimes derail towards inflammatory tissue damage, leading to rapid admissions to intensive care units. The lack of knowledge on mechanisms that tilt the balance between these two opposite outcomes poses major threats to many ongoing clinical trials dealing with immunostimulatory or immunoregulatory therapeutics. This review will discuss innate and cognate immune responses underlying protective or deleterious immune reactions against these pathogenic coronaviruses.
Enterocytozoon bieneusi microsporidiosis is an emerging disease in immunocompromised patients. We report 2 cases of this disease in allogeneic hematopoietic stem cell transplant patients successfully ...treated with fumagillin. Thrombocytopenia occurred but without major adverse events. Modifications of immunosuppression could be avoided when E. bieneusi is rapidly identified and fumagillin therapy is started promptly.
We report the occurrence of a high rate of false-positive test results during the surveillance of hematology patients for galactomannan (GM) antigenemia. Among 218 patients surveyed from June 2002 ...through June 2003, 42 (19.3%) had ⩾1 serum sample positive for GM (optical density index, >1.5). Of these patients, 38 had no additional evidence of invasive aspergillosis, and, therefore, their test results were considered to be false-positives. Case-control analysis showed that treatment with piperacillin-tazobactam was the only risk factor significantly associated with receiving false-positive test results. When tested for GM antigen, 3 of 4 piperacillin-tazobactam batches had positive results. Physicians should be aware of the possible interference of treatment with piperacillin-tazobactam when interpreting the results of the GM assay.
Au cours de ces dernières années, le terme d’infection nosocomiale a laissé la place à celui, plus large, d’infection associée aux soins, la plausibilité de l’association entre l’infection et les ...soins prodigués devant dans tous les cas faire l’objet d’une analyse rigoureuse. En expertise, pour qu’une infection associée aux soins soit à la demande du magistrat qualifiée de nosocomiale, il faudra qu’elle ait bien été contractée dans un établissement de santé et soit en lien avec un acte ou l’environnement de soins. Le Code de Santé Publique tout comme la jurisprudence la plus récente, judiciaire et administrative, donnent désormais une définition proche de l’infection nosocomiale. Le principe de la responsabilité sans faute des établissements de santé en matière d’infection nosocomiale a été consacré par la loi du 4 mars 2002, les cas les plus graves (décès ; déficit fonctionnel permanent>25 %) étant indemnisés par l’ONIAM.
These last years in France, the term ‘nosocomial infection’ has been replaced by ‘health-care associated infection’, which has a much broader definition. In all cases, the plausibility of the association between infection and the care provided deserved to be rigorously analyzed. To qualify an infection as nosocomial, the expert witness must at the judge's request determine that infection actually occurred within the health facility and is linked to health care. French Public Health Code as well the most recent jurisprudence give currently a rather close definition of nosocomial infection. The principle of faultness liability in the field of nosocomial infection has been enshrined in the law of March 4th 2002, the most severe situations (death; permanent functional deficit>25 percent) being compensated by ONIAM, the French national office of compensation for nosocomial infection.
Blackwater fever (BWF) is a severe clinical syndrome, characterized by intravascular hemolysis, hemoglobinuria, and acute renal failure that is classically seen in European expatriates chronically ...exposed to Plasmodium falciparum and irregularly taking quinine. BWF virtually disappeared after 1950, when chloroquine superseded quinine. We report 21 cases of BWF seen in France from 1990 through 1999 in European expatriates who lived in sub-Saharan Africa. All patients had macroscopic hemoglobinuria, jaundice, and anemia. Acute renal failure occurred in 15 patients (71%), 7 of whom required dialysis. The presumed triggers of BWF were halofantrine (38%), quinine (24%), mefloquine (24%), and halofantrine or quinine (14%). Glucose-6-phosphate dehydrogenase (G6PD) activity was normal in the 14 patients who underwent this test. Low-level P. falciparum parasitemia was found in 8 patients. All 21 patients survived. Our data and 13 cases reported in the literature suggest a resurgence of classic BWF among Europeans living in Africa and a need to discuss attendant therapeutic implications.
Coronavirus disease 2019 (COVID-19) and its causative virus, SARS-CoV-2, pose considerable challenges for the management of oncology patients. COVID-19 presents as a particularly severe respiratory ...and systemic infection in aging and immunosuppressed individuals, including patients with cancer. Moreover, severe COVID-19 is linked to an inflammatory burst and lymphopenia, which may aggravate cancer prognosis. Here we discuss why those with cancer are at higher risk of severe COVID-19, describe immune responses that confer protective or adverse reactions to this disease and indicate which antineoplastic therapies may either increase COVID-19 vulnerability or have a dual therapeutic effect on cancer and COVID-19.
Invasive fungal infections are responsible for significant morbidity and mortality. Safety and effectiveness of antifungal agents is a particular concern in pediatric populations, where data are ...often limited. Micafungin is an echinocandin with demonstrated antifungal activity against a wide spectrum of Candida spp.; this subanalysis of data from the MYRIADE study describes the use of micafungin and its therapeutic outcomes in pediatric patients, in normal clinical practice.
MYRIADE was an observational, multicenter, national, prospective, longitudinal study conducted from January 2010 to December 2012, in patients treated with micafungin using a prophylactic or curative strategy, across 17 sites oncohematology (n = 8), neonatal intensive care units (ICUs) (n = 5) and pediatric ICUs (n = 4). The treatment regimen, the achievement of the therapeutic objective and the tolerance were reported.
The study population consisted of 110 pediatric patients (31 neonates, 24 children <2 years old and 55 children ≥2 to <16 years old). The therapeutic objective was achieved in 49/64 (76.6%) oncohematology patients, 28/29 (96.6%) neonatal ICU patients and 12/14 (85.7%) pediatric ICU patients. Twenty-four (21.8%) children developed an adverse event (AE); more AEs were observed in oncohematology patients compared with ICU patients 17 (26.1%) vs. 7 (15.6%). Only one serious AE, reported in an oncohematology patient, was considered related to micafungin.
In the first large observational study of micafungin treatment or prophylaxis conducted under real-world conditions in France, micafungin was effective and well tolerated for prophylaxis of invasive fungal infections in pediatric oncohematology patients and for curative purposes in pediatric and neonatal ICU patients.
PDF
