COVID-19-associated pulmonary aspergillosis (CAPA) in hematological patients: Could antifungal prophylaxis be necessary? A nationwide study.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a relatively common complication. Multiple studies described this relationship in critical patients, however its incidence and outcome in other risk groups such as immunosuppressed patients remains unknown. In this sense, we aimed to evaluate the rates and outcomes of CAPA in hematological patients and according to the different hematological malignances, comparing to invasive pulmonary aspergillosis (IPA) in non-COVID-19 ones. METHODS: Nationwide, population-based and retrospective observational cohort study including all adult patients with hematological malignancies admitted in Spain since March 1, 2020 to December 31, 2021. The main outcome variable was the diagnosis of IPA during hospitalization in hematological patients with or without COVID-19 at admission. The rate of CAPA compared to IPA in non-COVID-19 patients in each hematological malignancy was also performed, as well as survival curve analysis. FINDINGS: COVID-19 was diagnosed in 3.85 % (4367 out of 113,525) of the hematological adult inpatients. COVID-19 group developed more fungal infections (5.1 % vs. 3 %; p < 0.001). Candida spp. showed higher rate in non-COVID-19 (74.2 % vs. 66.8 %; p = 0.015), meanwhile Aspergillus spp. confirmed its predominance in COVID-19 hematological patients (35.4 % vs. 19.1 %; p < 0.001). IPA was diagnosed in 703 patients and 11.2 % (79 cases) were CAPA. The multivariate logistic regression analysis found that the diagnosis of COVID-19 disease at hospital admission increased more than two-fold IPA development [OR: 2.5, 95CI (1.9-3.1), p < 0.001]. B-cell malignancies - specifically B-cell non-Hodgkin lymphoma, multiple myeloma, chronic lymphocytic leukemia and acute lymphoblastic leukemia - showed between four- and six-fold higher CAPA development and 90-day mortality rates ranging between 50 % and 72 %. However, myeloid malignancies did not show higher CAPA rates compared to IPA in non-COVID-19 patients. CONCLUSION: COVID-19 constitutes an independent risk factor for developing aspergillosis in B-cell hematological malignancies and the use of antifungal prophylaxis during hospitalizations may be warranted.

Fibrinogen Deficiency with Thrombotic Manifestations.

Fibrinogen deficiencies are very rare. Qualitative fibrinogen deficiencies (dysfibrinogenaemia and hypodysfibrinogenemia) are functional disorders that can present with both haemorrhagic symptoms and with thrombotic phenomena as unique and paradoxical manifestation. We present the case of a 77-year-old man being investigated for a partially thrombosed abdominal aortic aneurysm as well as an ischaemic stroke 20 years previously. Basic coagulation tests were normal but extended tests revealed a lengthened thrombin time (TT) combined with a significant drop in fibrinogen concentration measured with the Clauss assay and by nephelometry. After secondary fibrinogen deficiencies were ruled out, a heterozygous variant in the FGG gene was detected by next-generation sequencing, and congenital hypodysfibrinogenemia was diagnosed. Acenocumarol was initiated and no new thrombotic or haemorrhagic events had occurred after a year of follow-up. In almost 25% of cases, thrombotic events may be the only clinical manifestation of functional fibrinogen deficiencies. They are a rare cause of thrombophilia, and are probably underdiagnosed due to normal standard coagulation test results as well as a possible absence of haemorrhagic events. Consequently, a TT test (an initial 'rule out' test) should be requested in order to promptly identify these patients. Moreover, discrepancies in derived and Clauss fibrinogen test results should suggest a functional disorder. Finally, new coagulation techniques based on the functional characterization of clot formation, such as ROTEM or thrombin generation assay, could help characterize these entities and suggest new therapeutic approaches. LEARNING POINTS: Functional fibrinogen deficiencies can present with thrombotic manifestations only, and are a rare and probably underdiagnosed cause of thrombophilia.Thrombin time is a highly sensitive test to rule out other conditions as aPTT and PT results may be within normal ranges, especially in functional deficiencies.Discrepancies between derived and Clauss fibrinogen findings, fibrinogen protein measurements and the use of new techniques (ROTEM or thrombin generation) are important for correct approach.

Full Characterization of Thrombotic Events in All Hospitalized COVID-19 Patients in a Spanish Tertiary Hospital during the First 18 Months of the Pandemic.

The presence of a procoagulant state, COVID-19-related coagulopathy, and an increased rate of thrombotic events (TEs) is widely known about. However, descriptive studies are scarce. Here, we conducted a large retrospective study including 2894 hospitalized COVID-19 patients followed up during the first 18 months of the pandemic to completely characterize any TE. Major TEs showed a 3.45% incidence rate. TEs were associated with increased intubation/90-day mortality risk [OR = 1.71, 95% CI (1.12−2.61), p < 0.013]. Venous thrombotic events (VTEs) were more frequent than arterial thrombotic events (ATEs) (72% vs. 28%), associated with enhanced levels of D-dimer (cross-linked fibrin derivatives formed during thrombolysis), which were related to mortality but more useful for early detection of thrombosis. In this regard, D-dimer plasma levels above 2014 µg/mL at hospital admission identify TEs with 91% accuracy (AUC = 0.91, p < 0.001), rising to almost 95% (AUC = 0.94, p < 0.001) with a cut-off value of 2666 µg/mL in VTEs. Moreover, 41% of TEs occurred in patients receiving LMWH thromboprophylactic treatments in hospital or domiciliary therapies. SARS-CoV-2 infection along with a sedentary lifestyle derived from the confinement in 2020 could be more determinant than a procoagulant state in patients with risk factors for TEs. Furthermore, the normal results obtained from the thrombophilia study after the acute process are linked to this independent procoagulant state and to SARS-CoV-2-derived coagulopathy.

ABO Blood System and COVID-19 Susceptibility: Anti-A and Anti-B Antibodies Are the Key Points.

The implication of the ABO blood group in COVID-19 disease was formulated early, at the beginning of the COVID-19 pandemic more than 2 years ago. It has now been established that the A blood group is associated with more susceptibility and severe symptoms of COVID-19, while the O blood group shows protection against viral infection. In this review, we summarize the underlying pathophysiology of ABO blood groups and COVID-19 to explain the molecular aspects behind the protective mechanism in the O blood group. A or B antigens are not associated with a different risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than that of other antigens. In this case, the cornerstone is natural anti-A and anti-B antibodies from the ABO system. They are capable of interfering with the S protein (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2; host cell receptor), thereby conferring protection to patients with sufficient antibodies (O blood group). Indeed, the titers of natural antibodies and the IgG isotype (specific to the O blood group) may be determinants of susceptibility and severity. Moreover, older adults are associated with a higher risk of bad outcomes due to the lack of antibodies and the upregulation of ACE2 expression during senescence. A better understanding of the role of the molecular mechanism of ABO blood groups in COVID-19 facilitates better prognostic stratification of the disease. Furthermore, it could represent an opportunity for new therapeutic strategies.

Can the Cytokine Profile According to ABO Blood Groups Be Related to Worse Outcome in COVID-19 Patients? Yes, They Can.

Severe status of coronavirus disease 2019 (COVID-19) is extremely associated to cytokine release. Moreover, it has been suggested that blood group is also associated with the prevalence and severity of this disease. However, the relationship between the cytokine profile and blood group remains unclear in COVID-19 patients. In this sense, we prospectively recruited 108 COVID-19 patients between March and April 2020 and divided according to ABO blood group. For the analysis of 45 cytokines, plasma samples were collected in the time of admission to hospital ward or intensive care unit and at the sixth day after hospital admission. The results show that there was a risk of more than two times lower of mechanical ventilation or death in patients with blood group O (log rank: p = 0.042). At first time, all statistically significant cytokine levels, except from hepatocyte growth factor, were higher in O blood group patients meanwhile the second time showed a significant drop, between 20% and 40%. In contrast, A/B/AB group presented a maintenance of cytokine levels during time. Hepatocyte growth factor showed a significant association with intubation or mortality risk in non-O blood group patients (OR: 4.229, 95% CI (2.064-8.665), p < 0.001) and also was the only one bad prognosis biomarker in O blood group patients (OR: 8.852, 95% CI (1.540-50.878), p = 0.015). Therefore, higher cytokine levels in O blood group are associated with a better outcome than A/B/AB group in COVID-19 patients.

Predictive Modeling of Poor Outcome in Severe COVID-19: A Single-Center Observational Study Based on Clinical, Cytokine and Laboratory Profiles.

Pneumonia is the main cause of hospital admission in COVID-19 patients. We aimed to perform an extensive characterization of clinical, laboratory, and cytokine profiles in order to identify poor outcomes in COVID-19 patients. METHODS: A prospective and consecutive study involving 108 COVID-19 patients was conducted between March and April 2020 at Hospital Clínico Universitario de Valladolid (Spain). Plasma samples from each patient were collected after emergency room admission. Forty-five serum cytokines were measured in duplicate, and clinical data were analyzed using SPPS version 25.0. RESULTS: A multivariate predictive model showed high hepatocyte growth factor (HGF) plasma levels as the only cytokine related to intubation or death risk at hospital admission (OR = 7.38, 95%CI-(1.28-42.4), p = 0.025). There were no comorbidities included in the model except for the ABO blood group, in which the O blood group was associated with a 14-fold lower risk of a poor outcome. Other clinical variables were also included in the predictive model. The predictive model was internally validated by the receiver operating characteristic (ROC) curve with an area under the curve (AUC) of 0.94, a sensitivity of 91.7% and a specificity of 95%. The use of a bootstrapping method confirmed these results. CONCLUSIONS: A simple, robust, and quick predictive model, based on the ABO blood group, four common laboratory values, and one specific cytokine (HGF), could be used in order to predict poor outcomes in COVID-19 patients.

Evaluation of Cytokines as Robust Diagnostic Biomarkers for COVID-19 Detection.

Antigen tests or polymerase chain reaction (PCR) amplification are currently COVID-19 diagnostic tools. However, developing complementary diagnosis tools is mandatory. Thus, we performed a plasma cytokine array in COVID-19 patients to identify novel diagnostic biomarkers. A discovery-validation study in two independent prospective cohorts was performed. The discovery cohort included 136 COVID-19 and non-COVID-19 patients recruited consecutively from 24 March to 11 April 2020. Forty-five cytokines' quantification by the MAGPIX system (Luminex Corp., Austin, TX, USA) was performed in plasma samples. The validation cohort included 117 patients recruited consecutively from 15 to 25 April 2020 for validating results by ELISA. COVID-19 patients showed different levels of multiple cytokines compared to non-COVID-19 patients. A single chemokine, IP-10, accurately identified COVID-19 patients who required hospital admission (AUC: 0.962; 95%CI (0.933-0.992); p < 0.001)). The results were validated in an independent cohort by multivariable analysis (OR: 25.573; 95%CI (8.127-80.469); p < 0.001) and AUROC (AUC: 0.900; 95%CI (0.846-0.954); p < 0.001). Moreover, showing IP-10 plasma levels over 173.35 pg/mL identified COVID-19 with higher sensitivity (86.20%) than the first SARS-CoV-2 PCR. Our discover-validation study identified IP-10 as a robust biomarker in clinical practice for COVID-19 diagnosis at hospital. Therefore, IP-10 could be used as a complementary tool in clinical practice, especially in emergency departments.

HGF, IL-1α, and IL-27 Are Robust Biomarkers in Early Severity Stratification of COVID-19 Patients.

Pneumonia is the leading cause of hospital admission and mortality in coronavirus disease 2019 (COVID-19). We aimed to identify the cytokines responsible for lung damage and mortality. We prospectively recruited 108 COVID-19 patients between March and April 2020 and divided them into four groups according to the severity of respiratory symptoms. Twenty-eight healthy volunteers were used for normalization of the results. Multiple cytokines showed statistically significant differences between mild and critical patients. High HGF levels were associated with the critical group (OR = 3.51; p < 0.001; 95%CI = 1.95-6.33). Moreover, high IL-1α (OR = 1.36; p = 0.01; 95%CI = 1.07-1.73) and low IL-27 (OR = 0.58; p < 0.005; 95%CI = 0.39-0.85) greatly increased the risk of ending up in the severe group. This model was especially sensitive in order to predict critical status (AUC = 0.794; specificity = 69.74%; sensitivity = 81.25%). Furthermore, high levels of HGF and IL-1α showed significant results in the survival analysis (p = 0.033 and p = 0.011, respectively). HGF, IL-1α, and IL 27 at hospital admission were strongly associated with severe/critical COVID-19 patients and therefore are excellent predictors of bad prognosis. HGF and IL-1α were also mortality biomarkers.

Linfoma MALT y tumor carcinoide sincrónicos de íleon / Synchronic MALT lymphoma and carcinoid tumor of the ileum

No disponible

Diagnosis of a primary testicular lymphoma by echography and magnetic resonance imaging.

We here describe a primary large B cell non-Hodgkin lymphoma of the right testicle in a 73-year-old male diagnosed with echography and magnetic resonance imaging. Treatment was based upon orchiectomy and chemotherapy, without any recurrence 2 years later. Ultrasonography and magnetic resonance findings with normal serum tumoural markers (AFP and B-HCG) can differentiate these tumors from germinal testicular tumors.