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1.
J Clin Med ; 12(21)2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37959236

ABSTRACT

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-infection is associated with an extremely variable disease course. When interstitial pneumonia (IP) occurs, it can lead to acute respiratory distress syndrome and death. Serum Krebs von den Lungen-6 (KL-6) is an established marker of IP, but its role as a marker of SARS-CoV-2 pneumonia is debated. This bicentric study included 157 patients with SARS-CoV-2 pneumonia. The WHO Ordinal Scale for Clinical Improvement (0-10 points) was used to classify the clinical course. Serum samples were collected at admission, and on days 3 and 7 of hospitalization. KL-6 was measured by using automated chemiluminescence immunoassay. A total of 68 patients developed a severe SARS-CoV-2 pneumonia, 135 of them required oxygen, and 15 died during hospitalization. The patients requiring non-invasive ventilation, invasive ventilation, or extracorporeal membrane oxygenation had significantly higher serum KL-6 levels at admission. The serum KL-6 levels were tendentially higher in patients who died than in those who survived. Logistic regression identified serum KL-6 at a cut-off of 335 U/mL at admission as a significant predictor of severe SARS-CoV-2 pneumonia outcome. Serum KL-6 seems to be a candidate biomarker for the clinical routine to stratify patients with SARS-CoV-2 pneumonia for the risk of a severe disease outcome or death.

2.
Front Immunol ; 14: 1236374, 2023.
Article in English | MEDLINE | ID: mdl-37946732

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused millions of COVID-19 cases and deaths worldwide. Severity of pulmonary pathologies and poor prognosis were reported to be associated with the activation non-virus-specific bystander T cells. In addition, high concentrations of the macrophage migration inhibitory factor (MIF) were found in serum of COVID-19 patients. We hypothesized that these two pathogenic factors might be related and analyzed the expression of receptors for MIF on T cells in COVID-19. T cells from PBMCs of hospitalized patients with mild and severe COVID-19 were characterized. A significantly higher proportion of CD4+ and CD8+ T cells from COVID-19 patients expressed CD74 on the cell surface compared to healthy controls. To induce intracellular signaling upon MIF binding, CD74 forms complexes with CD44, CXCR2, or CXCR4. The vast majority of CD74+ T cells expressed CD44, whereas expression of CXCR2 and CXCR4 was low in controls but increased upon SARS-CoV-2 infection. Hence, T cells in COVID-19 patients express receptors that render them responsive to MIF. A detailed analysis of CD74+ T cell populations revealed that most of them had a central memory phenotype early in infection, while cells with an effector and effector memory phenotype arose later during infection. Furthermore, CD74+ T cells produced more cytotoxic molecules and proliferation markers. Our data provide new insights into the MIF receptor and co-receptor repertoire of bystander T cells in COVID-19 and uncovers a novel and potentially druggable aspect of the immunological footprint of SARS-CoV-2.


Subject(s)
COVID-19 , Humans , Cell Differentiation , Receptors, Immunologic , SARS-CoV-2
3.
Front Immunol ; 14: 1277033, 2023.
Article in English | MEDLINE | ID: mdl-37869001

ABSTRACT

Introduction: Early sepsis is a life-threatening immune dysregulation believed to feature a "cytokine storm" due to activation of pattern recognition receptors by pathogen and danger associated molecular patterns. However, treatments with single toll-like receptor (TLR) blockers have shown no clinical benefit. We speculated that sepsis patients at the time of diagnosis are heterogeneous in relation to their cytokine production and its potential inhibition by a triple cocktail of TLR blockers. Accordingly, we analyzed inflammatory cytokine production in whole blood assays from early sepsis patients and determined the effects of triple TLR-blockade. Methods: Whole blood of 51 intensive care patients sampled within 24h of meeting Sepsis-3 criteria was incubated for 6h without or with specific TLR2, 4, and 7/8 stimuli or suspensions of heat-killed S. aureus or E. coli bacteria as pan-TLR challenges, and also with a combination of monoclonal antibodies against TLR2 and 4 and chloroquine (endosomal TLR inhibition), subsequent to dose optimization. Concentrations of tumor necrosis factor (TNF), Interleukin(IL)-6, IL-8, IL-10, IL-1α and IL-1ß were measured (multiplex ELISA) before and after incubation. Samples from 11 sex and age-matched healthy volunteers served as controls and for dose-finding studies. Results: Only a fraction of sepsis patient samples revealed ongoing cytokine production ex vivo despite sampling within 24 h of first meeting Sepsis-3 criteria. In dose finding studies, inhibition of TLR2, 4 and endosomal TLRs reliably suppressed cytokine production to specific TLR agonists and added bacteria. However, inflammatory cytokine production ex vivo was only suppressed in the high cytokine producing samples but not in the majority. The suppressive response to TLR-blockade correlated both with intraassay inflammatory cytokine production (r=0.29-0.68; p<0.0001-0.04) and cytokine baseline concentrations (r=0.55; p<0.0001). Discussion: Upon meeting Sepsis-3 criteria for less than 24 h, a mere quarter of patient samples exhibits a strong inflammatory phenotype, as characterized by increased baseline inflammatory cytokine concentrations and a stark TLR-dependent increase upon further ex vivo incubation. Thus, early sepsis patient cohorts as defined by Sepsis-3 criteria are very heterogeneous in regard to inflammation. Accordingly, proper ex vivo assays may be useful in septic individuals before embarking on immunomodulatory treatments.


Subject(s)
Sepsis , Toll-Like Receptor 2 , Humans , Toll-Like Receptor 2/genetics , Escherichia coli , Staphylococcus aureus , Toll-Like Receptors , Cytokines , Sepsis/drug therapy
4.
Bioengineering (Basel) ; 10(10)2023 Oct 06.
Article in English | MEDLINE | ID: mdl-37892897

ABSTRACT

Hyperspectral imaging (HSI) is a non-invasive technology that provides information on biochemical tissue properties, including skin oxygenation and perfusion quality. Microcirculatory alterations are associated with organ dysfunction in septic COVID-19 patients. This prospective observational study investigated associations between skin HSI and organ dysfunction severity in critically ill COVID-19 patients. During the first seven days in the ICU, palmar HSI measurements were carried out with the TIVITA® tissue system. We report data from 52 critically ill COVID-19 patients, of whom 40 required extracorporeal membrane oxygenation (ECMO). HSI parameters for superficial tissue oxygenation (StO2) and oxygenation and perfusion quality (NPI) were persistently decreased. Hemoglobin tissue content (THI) increased, and tissue water content (TWI) was persistently elevated. Regression analysis showed strong indications for an association of NPI and weaker indications for associations of StO2, THI, and TWI with sequential organ failure assessment (SOFA) scoring. StO2 and NPI demonstrated negative associations with vasopressor support and lactate levels as well as positive associations with arterial oxygen saturation. These results suggest that skin HSI provides clinically relevant information, opening new perspectives for microcirculatory monitoring in critical care.

5.
Eur J Radiol ; 165: 110892, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37269571

ABSTRACT

PURPOSE: The purpose of this study was to assess the efficacy of transarterial embolization in COVID-19 patients with an arterial bleeding and to investigate differences between various patient groups concerning survival. METHOD: We retrospectively reviewed COVID-19 patients undergoing transarterial embolization due to an arterial bleeding in a multicenter study from April 2020 to July 2022 and analyzed the technical success of embolization and survival rate. 30-day survival between various patient groups was analyzed. The Chi- square test and Fisher's exact test were used for testing association between the categorical variables. RESULTS: 53 COVID-19 patients (age: 57.3 ± 14.3 years, 37 male) received 66 angiographies due to an arterial bleeding. The initial embolization was technically successful in 98.1% (52/53). In 20.8% (11/53) of patients, additional embolization was necessary due to a new arterial bleeding. A majority of 58.5% (31/53) had a severe course of COVID-19 infection necessitating ECMO-therapy and 86.8% (46/53) of patients received anticoagulation. 30-day survival rate in patients with ECMO-therapy was significantly lower than without ECMO-therapy (45.2% vs. 86.4%, p = 0.004). Patients with anticoagulation did not have a lower 30-day survival rate than without anticoagulation (58.7% vs. 85.7%, p = 0.23). COVID-19 patients with ECMO-therapy developed more frequently a re-bleeding after embolization than non-ECMO-patients (32.3% vs. 4.5%, p = 0.02). CONCLUSIONS: Transarterial embolization is a feasible, safe, and effective procedure in COVID-19 patients with arterial bleeding. ECMO-patients have a lower 30-day survival rate than non-ECMO-patients and have an increased risk for re-bleeding. Treatment with anticoagulation could not be identified as a risk factor for higher mortality.


Subject(s)
COVID-19 , Embolization, Therapeutic , Adult , Aged , Humans , Male , Middle Aged , Anticoagulants/therapeutic use , COVID-19/complications , COVID-19/therapy , Embolization, Therapeutic/methods , Hemorrhage/diagnostic imaging , Hemorrhage/therapy , Hemorrhage/etiology , Retrospective Studies , Treatment Outcome , Female
6.
Anesth Analg ; 136(5): 827-828, 2023 05 01.
Article in English | MEDLINE | ID: mdl-37058716
7.
BMC Anesthesiol ; 22(1): 384, 2022 Dec 12.
Article in English | MEDLINE | ID: mdl-36503427

ABSTRACT

BACKGROUND: The aim of this survey was to describe, on a patient basis, the current practice of sedation, pharmacologic and non-pharmacologic measures to promote sleep and facilitation of communication in critically ill patients oro-tracheally intubated or tracheostomized. METHODS: Cross-sectional online-survey evaluating sedation, sleep management and communication in oro-tracheally intubated (IP) or tracheostomized (TP) patients in intensive care units on a single point. RESULTS: Eighty-one intensive care units including 447 patients (IP: n = 320, TP: n = 127) participated. A score of ≤ -2 on the Richmond Agitation Sedation Scale (RASS) was prevalent in 58.2% (IP 70.7% vs. TP 26.8%). RASS -1/0 was present in 32.2% (IP 25.9% vs. TP 55.1%) of subjects. Propofol and alpha-2-agonist were the predominant sedatives used while benzodiazepines were applied in only 12.1% of patients. For sleep management, ear plugs and sleeping masks were rarely used (< 7%). In half of the participating intensive care units a technique for phonation was used in the tracheostomized patients. CONCLUSIONS: The overall rate of moderate and deep sedation appears high, particularly in oro-tracheally intubated patients. There is no uniform sleep management and ear plugs and sleeping masks are only rarely applied. The application of phonation techniques in tracheostomized patients during assisted breathing is low. More efforts should be directed towards improved guideline implementation. The enhancement of sleep promotion and communication techniques in non-verbal critically ill patients may be a focus of future guideline development.


Subject(s)
Conscious Sedation , Hypnotics and Sedatives , Humans , Conscious Sedation/methods , Cross-Sectional Studies , Critical Illness/therapy , Sleep , Communication
8.
Diagnostics (Basel) ; 12(12)2022 Dec 05.
Article in English | MEDLINE | ID: mdl-36553055

ABSTRACT

Superinfections with Aspergillus spp. in patients with Coronavirus disease 2019 (CAPA: COVID-19-associated pulmonary aspergillosis) are increasing. Dexamethasone has shown beneficial effects in critically ill COVID-19 patients. Whether dexamethasone increases the risk of CAPA has not been studied exclusively. Moreover, this retrospective study aimed to identify risk factors for a worse outcome in critically ill COVID-19 patients. Data from 231 critically ill COVID-19 patients with or without dexamethasone treatment from March 2020 and March 2021 were retrospectively analysed. Only 4/169 (6.5%) in the DEXA-group and 13/62 (7.7%) in the Non-DEXA group were diagnosed with probable CAPA (p = 0.749). Accordingly, dexamethasone was not identified as a risk factor for CAPA. Moreover, CAPA was not identified as an independent risk factor for death in multivariable analysis (p = 0.361). In contrast, elevated disease severity (as assessed by Sequential Organ Failure Assessment [SOFA]-score) and the need for organ support (kidney replacement therapy and extracorporeal membrane oxygenation [ECMO]) were significantly associated with a worse outcome. Therefore, COVID-19 treatment with dexamethasone did not increase the risk for CAPA. Moreover, adequately treated CAPA did not represent an independent risk factor for mortality. Accordingly, CAPA might reflect patients' severe disease state instead of directly influencing outcome.

9.
Med Teach ; : 1-6, 2022 Oct 18.
Article in English | MEDLINE | ID: mdl-36257290

ABSTRACT

BACKGROUND: Extended focused assessment with sonography for trauma (eFAST) is now an essential part of the primary survey of an emergency patient. The discrepancy between an increasing number of medical students and growing clinical commitments of lecturers is a major challenge in student teaching that needs to be resolved. The practice of using peers in the clinical education of medical students is a well-established tradition and commonly practiced but lacks definition in its implementation. Therefore, we aimed to investigate whether the level of experience of the tutor affects the effectiveness of learning among students using eFAST during a clinical scenario. METHODS: A prospective randomized single-blinded controlled trial, where 168 medical students in the eighth semester were randomized into control and intervention groups. The control group received the 4-h standard ultrasound (US) tutorial from various resident doctors. All residents were at least stage-1-certified in ultrasound. The intervention group received the tutorial from trained peer teachers (TPTs). These TPTs were medical students who were qualified to teach the procedure. All students received an initial tutorial on basic ultrasound principles and a final lecture on recognizing pathological images. Students completed basic questionnaires requesting pre-existing US experience, theoretical and clinical application questions based on eFAST one day later and at the end of the semester. Students also completed a 6-min OSCE (Objective-Structured-Clinical-Exam) station involving clinical emergency scenarios. RESULTS: Eighty-five percent of participants had no previous eFAST experience. Early and later evaluation of the participants show no significant differences between both groups regarding the theoretical and the clinical application examinations, except the early phase OSCE results, which was not repeated in the late-stage results. CONCLUSIONS: Peer-teaching can be utilized to teach practical skills such as eFAST without a loss of clinical application skills. This relieves the burden of removing doctors from patient care situations and maintains teaching standards.

10.
PLoS One ; 17(8): e0273247, 2022.
Article in English | MEDLINE | ID: mdl-35981050

ABSTRACT

RATIONALE: The immune profile of sepsis patients is incompletely understood and hyperinflammation and hypoinflammation may occur concurrently or sequentially. Immune checkpoint inhibition (ICI) may counter hypoinflammation but effects are uncertain. We tested the reactivity of septic whole blood to bacteria, Toll-like receptor (TLR) ligands and to ICI. METHODS: Whole blood assays of 61 patients' samples within 24h of meeting sepsis-3 criteria and 12 age and sex-matched healthy volunteers. Measurements included pattern/danger-associated molecular pattern (P/DAMP), cytokine concentrations at baseline and in response to TLR 2, 4, and 7/8 ligands, heat-inactivated Staphylococcus aureus or Escherichia coli, E.coli lipopolysaccharide (LPS), concentration of soluble and cellular immune checkpoint molecules, and cytokine concentrations in response to ICI directed against programmed-death receptor 1 (PD1), PD1-ligand 1, or cytotoxic T-lymphocyte antigen 4, both in the absence and presence of LPS. MAIN RESULTS: In sepsis, concentrations of P/DAMPs and inflammatory cytokines were increased and the latter increased further upon incubation ex vivo. However, cytokine responses to TLR 2, 4, and 7/8 ligands, heat-inactivated S. aureus or E. coli, and E. coli LPS were all depressed. Depression of the response to LPS was associated with increased in-hospital mortality. Despite increased PD-1 expression on monocytes and T-cells, and monocyte CTLA-4 expression, however, addition of corresponding checkpoint inhibitors to assays failed to increase inflammatory cytokine concentrations in the absence and presence of LPS. CONCLUSION: Patients first meeting Sepsis-3 criteria reveal 1) depressed responses to multiple TLR-ligands, bacteria, and bacterial LPS, despite concomitant inflammation, but 2) no response to immune checkpoint inhibition.


Subject(s)
Sepsis , Toll-Like Receptor 2 , Cytokines/metabolism , Escherichia coli/metabolism , Humans , Immune Checkpoint Inhibitors , Ligands , Lipopolysaccharides , Monocytes/metabolism , Sepsis/metabolism , Staphylococcus aureus/metabolism , Toll-Like Receptor 2/metabolism , Toll-Like Receptors/metabolism
11.
Thorac Cardiovasc Surg Rep ; 11(1): e23-e26, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35251890

ABSTRACT

Background The majority of patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection present mild symptoms. However, some patients develop severe acute respiratory distress syndrome (ARDS) and subsequent irreversible lung damage despite extracorporeal membrane oxygenation, leaving lung transplantation the ultimate therapeutically option. Case Description Here, we report a case of lung transplantation in a 31-year-old male recipient suffering from post-coronavirus disease 2019 respiratory failure with irreversible ARDS after prolonged extracorporeal membrane oxygenation therapy. Conclusion Patient selection criteria are elucidated. One relevant mechanism for susceptibility to SARS-CoV-2 in the respiratory system, the acid sphingomyelinase/ceramide system might be altered during infection with SARS-CoV-2.

12.
J Fungi (Basel) ; 8(3)2022 Mar 17.
Article in English | MEDLINE | ID: mdl-35330309

ABSTRACT

Due to Coronavirus disease (COVID-19) a new group of patients at risk emerged with COVID-19-associated mucormycosis (CAM). Systematic studies, evaluating the prevalence of CAM are missing. To assess CAM prevalence in a tertiary care hospital in Germany, we applied direct microscopy, fungal culture and quantitative realtime in-house PCR targeting Mucorales-specific fragments of 18S and 28S rRNA on respiratory specimens of 100 critically ill COVID-19 patients. Overall, one Mucorales-PCR positive bronchoalevolar lavage was found whereas direct microscopy and fungal culture were negative in all cases. We conclude that a routine screening for CAM in Germany is not indicated.

13.
Mycoses ; 65(4): 458-465, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35138651

ABSTRACT

BACKGROUND: COVID-19-associated invasive pulmonary aspergillosis (CAPA) is associated with increased mortality. Cases of CAPA caused by azole-resistant Aspergillus fumigatus strains have been reported. OBJECTIVES: To analyse the twelve-month CAPA prevalence in a German tertiary care hospital and to characterise clinical A. fumigatus isolates from two German hospitals by antifungal susceptibility testing and microsatellite genotyping. PATIENTS/METHODS: Retrospective observational study in critically ill adults from intensive care units with COVID-19 from 17 February 2020 until 16 February 2021 and collection of A. fumigatus isolates from two German centres. EUCAST broth microdilution for four azole compounds and microsatellite PCR with nine markers were performed for each collected isolate (N = 27) and additional for three non-COVID A. fumigatus isolates. RESULTS: welve-month CAPA prevalence was 7.2% (30/414), and the rate of azole-resistant A. fumigatus isolates from patients with CAPA was 3.7% with detection of one TR34/L98H mutation. The microsatellite analysis revealed no major clustering of the isolates. Sequential isolates mainly showed the same genotype over time. CONCLUSIONS: Our findings demonstrate similar CAPA prevalence to other reports and a low azole-resistance rate. Genotyping of A. fumigatus showed polyclonal distribution except for sequential isolates.


Subject(s)
COVID-19 , Pulmonary Aspergillosis , Adult , Antifungal Agents/pharmacology , Aspergillus fumigatus , Azoles/pharmacology , Drug Resistance, Fungal/genetics , Fungal Proteins/genetics , Humans , Intensive Care Units , Microbial Sensitivity Tests , Pulmonary Aspergillosis/complications , Pulmonary Aspergillosis/epidemiology
14.
Dtsch Med Wochenschr ; 147(3): e13-e22, 2022 01.
Article in German | MEDLINE | ID: mdl-34965591

ABSTRACT

INTRODUCTION: With more than 1400 COVID-19 inpatients, the university hospital of Essen is the main regional caregiver during COVID-19 pandemic. We present outcome data of our inpatients during the first 12 months of pandemic and our derived clinical care concepts. METHODS: Retrospective analysis of all 1396 COVID-19 inpatients presenting between March, 1st of 2020 and February, 28th of 2021 for comorbidities, survival and complications. Group comparison between patients receiving standard care and those requiring intermediate/ intensive care. RESULTS: Mortality rate of all inpatients was 19,8 % (277/ 1396), whereas 10.6 % (93/877) of the patients with standard care and 35.5 % (184/519) of those with intermediate/intensive care died during hospital stay. Age above 60 years, obesity, need for mechanical ventilation, nitric oxide therapy, ECMO and acute renal failure as well as stroke during the clinical course were independent predictors of mortality. CONCLUSIONS: The mortality of both patient groups ranges within the numbers published by other international groups. The vast impact of usual comorbidities could be observed as well as the high rate of complications in serious ill COVID-19 patients. The mean age of both patient groups was lower than expected (60 years standard care versus 63 years intermediate/ intensive care). A maximum of patient and staff protection measures, a fast and efficient testing strategy during primary triage, standardized concepts from emergency department to intensive care units and dynamic adjustment of resources to daily changing needs can ensure a high quality of care even during peak of pandemic.


Subject(s)
COVID-19 , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/epidemiology , COVID-19/mortality , COVID-19/therapy , Comorbidity , Female , Germany , Humans , Male , Middle Aged , Retrospective Studies , Tertiary Care Centers , Young Adult
16.
J Clin Med ; 10(10)2021 May 11.
Article in English | MEDLINE | ID: mdl-34064851

ABSTRACT

Infections with SARS-CoV-2 spread worldwide early in 2020. In previous winters, we had been treating patients with seasonal influenza. While creating a larger impact on the health care systems, comparisons regarding the intensive care unit (ICU) courses of both diseases are lacking. We compared patients with influenza and SARS-CoV-2 infections treated at a tertiary care facility offering treatment for acute respiratory distress syndrome (ARDS) and being a high-volume facility for extracorporeal membrane oxygenation (ECMO). Patients with COVID-19 during the first wave of the pandemic (n = 64) were compared to 64 patients with severe influenza from 2016 to 2020 at our ICU. All patients were treated using a standardized protocol. ECMO was used in cases of severe ARDS. Both groups had similar comorbidities. Time in ICU and mortality were not significantly different, yet mortality with ECMO was high amongst COVID-19 patients with approximately two-thirds not surviving. This is in contrast to a mortality of less than 40% in influenza patients with ECMO. Mortality was higher than estimated by SAPSII score on admission in both groups. Patients with COVID-19 were more likely to be male and non-smokers than those with influenza. The outcomes for patients with severe disease were similar. The study helps to understand similarities and differences between patients treated for severe influenza infections and COVID-19.

17.
A A Pract ; 15(5): e01447, 2021 May 06.
Article in English | MEDLINE | ID: mdl-33955856

ABSTRACT

Aspergillus spp. are widespread environmental pathogens that can induce invasive aspergillosis, especially in immunocompromised patients. An 86-year-old female patient presented with a rare case of invasive cerebral aspergillosis. The aspergilloma invaded the intracranial region originating from the ethmoidal sinus and the orbital apex. In contrast to routine diagnostic procedures, next-generation sequencing (NGS) was able to identify the fungal pathogen in the cerebrospinal fluid as well as in plasma samples, supporting the biopsy-based diagnosis of invasive cerebral aspergillosis. Therefore, NGS-based diagnostics may be of particular importance for difficult-to-diagnose disease states, when conventional diagnostic procedures fail.


Subject(s)
Aspergillosis , Aged, 80 and over , Female , High-Throughput Nucleotide Sequencing , Humans
18.
Front Genet ; 12: 667231, 2021.
Article in English | MEDLINE | ID: mdl-33968142

ABSTRACT

The transmembrane serine protease 2 (TMPRSS2) is the major host protease that enables entry of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) into host cells by spike (S) protein priming. Single nucleotide polymorphisms (SNPs) in the gene TMPRSS2 have been associated with susceptibility to and severity of H1N1 or H1N9 influenza A virus infections. Functional variants may influence SARS-CoV-2 infection risk and severity of Coronavirus disease 2019 (COVID-19) as well. Therefore, we analyzed the role of SNPs in the gene TMPRSS2 in a German case-control study. We performed genotyping of the SNPs rs2070788, rs383510, and rs12329760 in the gene TMPRSS2 in 239 SARS-CoV-2-positive and 253 SARS-CoV-2-negative patients. We analyzed the association of the SNPs with susceptibility to SARS-CoV-2 infection and severity of COVID-19. SARS-CoV-2-positive and SARS-CoV-2-negative patients did not differ regarding their demographics. The CC genotype of TMPRSS2 rs383510 was associated with a 1.73-fold increased SARS-CoV-2 infection risk, but was not correlated to severity of COVID-19. Neither TMPRSS2 rs2070788 nor rs12329760 polymorphisms were related to SARS-CoV-2 infection risk or severity of COVID-19. In a multivariable analysis (MVA), the rs383510 CC genotype remained an independent predictor for a 2-fold increased SARS-CoV-2 infection risk. In summary, our report appears to be the first showing that the intron variant rs383510 in the gene TMPRSS2 is associated with an increased risk to SARS-CoV-2 infection in a German cohort.

19.
Pharmacogenet Genomics ; 31(8): 165-171, 2021 10 01.
Article in English | MEDLINE | ID: mdl-34001841

ABSTRACT

OBJECTIVES: The RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19). Cell entry is mediated by the human angiotensin-converting enzyme II (ACE2). ACE2 and its close homolog angiotensin-converting enzyme I (ACE) are currently discussed candidate genes, in which single-nucleotide polymorphisms (SNPs) could alter binding or entry of SARS-CoV-2 and enhance tissue damage in the lung or other organs. This could increase the susceptibility for SARS-CoV-2 infection and the severity of COVID-19. PATIENTS AND METHODS: We performed genotyping of SNPs in the genes ACE2 and ACE in 297 SARS-CoV-2-positive and 253 SARS-CoV-2-negative tested patients. We analyzed the association of the SNPs with susceptibility for SARS-CoV-2 infection and the severity of COVID-19. RESULTS: SARS-CoV-2-positive and SARS-CoV-2-negative patients did not differ regarding demographics and clinical characteristics. For ACE2 rs2285666, the GG genotype or G-allele was significantly associated with an almost two-fold increased SARS-CoV-2 infection risk and a three-fold increased risk to develop serious disease or COVID-19 fatality. In contrast, the ACE polymorphism was not related to infection risk or severity of disease. In a multivariable analysis, the ACE2 rs2285666 G-allele remained as an independent risk factor for serious disease besides the known risk factors male gender and cardiovascular disease. CONCLUSIONS: In summary, our report appears to be the first showing that a common ACE2 polymorphism impacts the risk for SARS-CoV-2 infection and the course of COVID-19 independently from previously described risk factors.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/genetics , Genetic Predisposition to Disease , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/pathology , Female , Genotype , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Risk Factors , Severity of Illness Index , Young Adult
20.
Emerg Infect Dis ; 27(5): 1535-1537, 2021 05.
Article in English | MEDLINE | ID: mdl-33900187

ABSTRACT

We describe screening results for detection of co-infections with Legionella pneumophila in patients infected with severe acute respiratory syndrome coronavirus 2. In total, 93 patients were tested; 1 was positive (1.1%) for L. pneumophila serogroup 1. Co-infections with L. pneumophila occur in coronavirus disease patients and should not be missed.


Subject(s)
COVID-19 , Coinfection , Legionella pneumophila , Germany/epidemiology , Humans , SARS-CoV-2 , Tertiary Care Centers
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