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2.
Front Immunol ; 12: 803742, 2021.
Article in English | MEDLINE | ID: covidwho-1581314

ABSTRACT

Immunocompromised patients are considered high-risk and prioritized for vaccination against COVID-19. We aimed to analyze B-cell subsets in these patients to identify potential predictors of humoral vaccination response. Patients (n=120) suffering from hematologic malignancies or other causes of immunodeficiency and healthy controls (n=79) received a full vaccination series with an mRNA vaccine. B-cell subsets were analyzed prior to vaccination. Two independent anti-SARS-CoV-2 immunoassays targeting the receptor-binding domain (RBD) or trimeric S protein (TSP) were performed three to four weeks after the second vaccination. Seroconversion occurred in 100% of healthy controls, in contrast to 67% (RBD) and 82% (TSP) of immunocompromised patients, while only 32% (RBD) and 22% (TSP) achieved antibody levels comparable to those of healthy controls. The number of circulating CD19+IgD+CD27- naïve B cells was strongly associated with antibody levels (ρ=0.761, P<0.001) and the only independent predictor for achieving antibody levels comparable to healthy controls (OR 1.07 per 10-µL increase, 95%CI 1.02-1.12, P=0.009). Receiver operating characteristic analysis identified a cut-off at ≥61 naïve B cells per µl to discriminate between patients with and without an optimal antibody response. Consequently, measuring of naïve B cells in immunocompromised hematologic patients could be useful in predicting their humoral vaccination response.


Subject(s)
B-Lymphocyte Subsets/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunocompromised Host/immunology , Immunogenicity, Vaccine/immunology , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Female , Humans , Male , Middle Aged , SARS-CoV-2 , Vaccines, Synthetic/immunology , /immunology
3.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-295946

ABSTRACT

ABSTRACT Immunocompromised patients are considered high-risk and prioritized for vaccination against COVID-19. We aimed to analyze B-cell subsets in these patients to identify potential predictors of humoral vaccination response. Patients (n=120) suffering from hematologic malignancies or other causes of immunodeficiency and healthy controls (n=79) received a full vaccination series with an mRNA vaccine. B-cell subsets were analyzed prior to vaccination. Two independent anti-SARS-CoV-2 immunoassays targeting the receptor-binding domain (RBD) or trimeric S protein (TSP) were performed three to four weeks after the second vaccination. Seroconversion occurred in 100% of healthy controls, in contrast to 67% (RBD) and 82% (TSP) of immunocompromised patients, while only 32% (RBD) and 22% (TSP) achieved antibody levels comparable to those of healthy controls. The number of circulating CD19 + IgD + CD27 - naïve B cells was strongly associated with antibody levels (ρ=0.761, P<0.001) and the only independent predictor for achieving antibody levels comparable to healthy controls (OR 1.07 per 10-µl increase, 95%CI 1.02–1.12, P=0.009). Receiver operating characteristic analysis identified a cut-off at ≥61 naïve B cells per µl to discriminate between patients with and without an optimal antibody response. Consequently, measuring naïve B cells in immunocompromised hematologic patients could be useful in predicting their humoral vaccination response.

4.
Crit Care ; 25(1): 335, 2021 09 15.
Article in English | MEDLINE | ID: covidwho-1412565

ABSTRACT

BACKGROUND: Coronavirus disease 19 (COVID-19)-associated pulmonary aspergillosis (CAPA) emerged as important fungal complications in patients with COVID-19-associated severe acute respiratory failure (ARF). Whether mould active antifungal prophylaxis (MAFP) can prevent CAPA remains elusive so far. METHODS: In this observational study, we included all consecutive patients admitted to intensive care units with COVID-19-associated ARF between September 1, 2020, and May 1, 2021. We compared patients with versus without antifungal prophylaxis with respect to CAPA incidence (primary outcome) and mortality (secondary outcome). Propensity score adjustment was performed to account for any imbalances in baseline characteristics. CAPA cases were classified according to European Confederation of Medical Mycology (ECMM)/International Society of Human and Animal Mycoses (ISHAM) consensus criteria. RESULTS: We included 132 patients, of whom 75 (57%) received antifungal prophylaxis (98% posaconazole). Ten CAPA cases were diagnosed, after a median of 6 days following ICU admission. Of those, 9 CAPA cases were recorded in the non-prophylaxis group and one in the prophylaxis group, respectively. However, no difference in 30-day ICU mortality could be observed. Thirty-day CAPA incidence estimates were 1.4% (95% CI 0.2-9.7) in the MAFP group and 17.5% (95% CI 9.6-31.4) in the group without MAFP (p = 0.002). The respective subdistributional hazard ratio (sHR) for CAPA incidence comparing the MAFP versus no MAFP group was of 0.08 (95% CI 0.01-0.63; p = 0.017). CONCLUSION: In ICU patients with COVID-19 ARF, antifungal prophylaxis was associated with significantly reduced CAPA incidence, but this did not translate into improved survival. Randomized controlled trials are warranted to evaluate the efficacy and safety of MAFP with respect to CAPA incidence and clinical outcomes.


Subject(s)
Antifungal Agents/therapeutic use , COVID-19/complications , Pulmonary Aspergillosis/prevention & control , Aged , COVID-19/mortality , Critical Illness , Female , Humans , Intensive Care Units , Male , Middle Aged , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/mortality , Triazoles/therapeutic use
5.
Sci Rep ; 11(1): 17476, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1392881

ABSTRACT

Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker and risk factor for kidney diseases, with a potential prognostic value in critically ill patients. In this monocentric prospective study, we measured plasma suPAR levels immediately after ICU admission in unselected 237 consecutive patients using a turbidimetric assay. Primary objective was the prognostic value for ICU- and 28-day mortality. Secondary objectives were association with sequential organ failure assessment (SOFA) score, coagulation and inflammation markers, AKI-3 and differences in prespecified subgroups. Median suPAR levels were 8.0 ng/mL [25th-75th percentile 4.3-14.4], with lower levels in ICU survivors than non-survivors (6.7 vs. 11.6 ng/mL, p < 0.001). SuPAR levels were higher in COVID-19, kidney disease, moderate-to-severe liver disease, and sepsis. ICU mortality increased by an odds ratio (OR) of 4.7 in patients with the highest compared to lowest quartile suPAR. Kaplan-Meier overall survival estimates at 3 months were 63% and 49%, in patients with suPAR below/above 12 ng/mL (log-rank p = 0.027). Due to an observed interaction between SOFA score and suPAR, we performed a random forest method identifying cutoffs. ICU mortality was 53%, 17% and 2% in patients with a SOFA score > 7, SOFA ≤ 7 & suPAR > 8 ng/mL, and SOFA score ≤ 7 & suPAR ≤ 8 ng/mL, respectively. suPAR was a significant predictor for AKI-3 occurrence (OR per doubling 1.89, 95% CI: 1.20-2.98; p = 0.006). suPAR levels at ICU admission may offer additional value for risk stratification especially in ICU patients with moderate organ dysfunction as reflected by a SOFA score ≤ 7.


Subject(s)
COVID-19/blood , Critical Illness/mortality , Kidney Diseases/blood , Receptors, Urokinase Plasminogen Activator/blood , Renal Insufficiency/mortality , Aged , Female , Humans , Immunoturbidimetry , Intensive Care Units , Male , Middle Aged , Mortality , Odds Ratio , Organ Dysfunction Scores , Prognosis , Prospective Studies , Renal Insufficiency/blood , Survival Analysis
6.
Clin Microbiol Infect ; 28(4): 580-587, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1375916

ABSTRACT

OBJECTIVES: Coronavirus disease 2019 (COVID-19) -associated pulmonary aspergillosis (CAPA) has emerged as a complication in critically ill COVID-19 patients. The objectives of this multinational study were to determine the prevalence of CAPA in patients with COVID-19 in intensive care units (ICU) and to investigate risk factors for CAPA as well as outcome. METHODS: The European Confederation of Medical Mycology (ECMM) conducted a multinational study including 20 centres from nine countries to assess epidemiology, risk factors and outcome of CAPA. CAPA was defined according to the 2020 ECMM/ISHAM consensus definitions. RESULTS: A total of 592 patients were included in this study, including 11 (1.9%) patients with histologically proven CAPA, 80 (13.5%) with probable CAPA, 18 (3%) with possible CAPA and 483 (81.6%) without CAPA. CAPA was diagnosed a median of 8 days (range 0-31 days) after ICU admission predominantly in older patients (adjusted hazard ratio (aHR) 1.04 per year; 95% CI 1.02-1.06) with any form of invasive respiratory support (HR 3.4; 95% CI 1.84-6.25) and receiving tocilizumab (HR 2.45; 95% CI 1.41-4.25). Median prevalence of CAPA per centre was 10.7% (range 1.7%-26.8%). CAPA was associated with significantly lower 90-day ICU survival rate (29% in patients with CAPA versus 57% in patients without CAPA; Mantel-Byar p < 0.001) and remained an independent negative prognostic variable after adjusting for other predictors of survival (HR 2.14; 95% CI 1.59-2.87, p ≤ 0.001). CONCLUSION: Prevalence of CAPA varied between centres. CAPA was significantly more prevalent among older patients, patients receiving invasive ventilation and patients receiving tocilizumab, and was an independent strong predictor of ICU mortality.


Subject(s)
COVID-19 , Invasive Pulmonary Aspergillosis , Pulmonary Aspergillosis , Aged , COVID-19/complications , COVID-19/epidemiology , COVID-19/therapy , Critical Illness , Humans , Intensive Care Units , Invasive Pulmonary Aspergillosis/diagnosis , Invasive Pulmonary Aspergillosis/drug therapy , Invasive Pulmonary Aspergillosis/epidemiology , Mycology , Pulmonary Aspergillosis/complications , Pulmonary Aspergillosis/epidemiology , Risk Factors , SARS-CoV-2
7.
Ann Intensive Care ; 11(1): 73, 2021 May 12.
Article in English | MEDLINE | ID: covidwho-1225785

ABSTRACT

BACKGROUND: This study aimed to quantify the potential survival benefit of convalescent plasma therapy (CVP) in critically ill patients with acute respiratory failure related to coronavirus disease-2019 (COVID-19). METHODS: This is a single-center prospective observational cohort study in COVID-19 patients with acute respiratory failure. Immediately after intensive care unit (ICU) admission patients were allocated to CVP treatment following pre-specified criteria to rapidly identify those patients potentially susceptible for this treatment. A propensity score adjustment [inverse probability of treatment weighted (IPTW) analysis] was implemented to account rigorously for imbalances in prognostic variables between the treatment groups. RESULTS: We included 120 patients of whom 48 received CVP. Thirty percent were female with a median age of 66 years [25th-75th percentile 54-75]. Eighty-eight percent of patients presented with severe acute respiratory failure as displayed by a median paO2/FiO2 ratio (Horowitz Index) of 92 [77-150]. All patients required any kind of ventilatory support with more than half of them (52%) receiving invasive ventilation. Thirty-day ICU overall survival (OS) was 69% in the CVP group and 54% in the non-CVP group (log-rank p = 0.049), respectively. After weighing the time-to-event data for the IPTW, the favorable association between CVP and OS became even stronger (log-rank p = 0.035). Moreover, an exploratory analysis showed an overall survival benefit of CVP therapy for patients with non-invasive ventilation (Hazard ratio 0.12 95% CI 0.03-0.57, p = 0.007) CONCLUSION: Administration of CVP in patients with acute respiratory failure related to COVID-19 is associated with improved ICU survival rates.

8.
J Fungi (Basel) ; 7(2)2021 Jan 27.
Article in English | MEDLINE | ID: covidwho-1050620

ABSTRACT

Viral infections can cause acute respiratory distress syndrome (ARDS), consequently leading to susceptibility for secondary pulmonary infections. Over the past few weeks, a number of studies have reported on secondary pulmonary aspergillosis complicating severe COVID-19. We report the case of a 53-year old male patient with secondary acute myeloid leukemia (AML) who suffered from COVID-19 ARDS and was diagnosed postmortem with mucormycosis.

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