Samstag, 03.10.2020

14:00 - 15:30

Poster DGfN 2020

Covid-19 2 (P154 - P163; LA31 - LA34)

 
Chronische Niereninsuffizienz und SARS-CoV-2 Analyse der Lean European Open Survey on SARS-CoV-2 infected patient (LEOSS)
P154 

L. Eberwein, L. Pilgram, L. Tometten, F. Köhler, M. Stecher, K. Wille, S. Rieg, H. Klinker, M. Wettstein, S. Dolff; Leverkusen, Frankfurt a. M., Potsdam, Köln, Minden, Freiburg, Würzburg, Passau, Essen

Hintergrund: Infektionen mit SARS-CoV-2 zeichnen sich durch eine hohe Variabilität hinsichtlich der klinischen Verläufe aus bis hin zu schwer verlaufenden oder letalen SARS-CoV-2 Infektionen. Ziel der Studie ist die Charakterisierung SARS-CoV-2 infizierter Patient*innen mit CKD und die Identifizierung möglicher Einflussfaktoren auf den Krankheitsverlauf.
Methode: Registerdaten der internationalen, multizentrischen (Lean European Open Survey on SARS-CoV-2 Infected Patients) LEOSS Kohorte wurden analysiert. Die Häufigkeitsverteilungen wurden in absoluten und relativen Werten angegeben und mittels Chi-Quadrat-, Fisher- und Mann-Whitney-U-Test untersucht. Zusammenhänge zwischen Merkmalen von Patient*innen mit einer CKD und fatalem Verlauf wurden mittels logistischer Regression analysiert.
Ergebnisse: Es wurden 2.027 Patient*innen (Männer 1.202/2.027, 59,3%) ausgewertet. Eine CKD bestand bei 15% (n=304) der Patient*innen. Im Vergleich zur Referenzgruppe ohne CKD hatten Patient*innen mit einer CKD signifikant häufiger eine art. Hypertonie (79,9 %), chronische Herzinsuffizienz (31,4%), Vorhofflimmern (31,1%), kardio- und cerebrovaskuläre Erkrankungen (51,2%), Diabetes mellitus (38,7%), Demenz (20,3%), COPD (13,0%) und onkologische Begleiterkrankungen (21,5%). Die COVID-19 assoziierte Mortalität war mit 29% (89/304) in der CKD-Kohorte im Vergleich der Kontrollpopulation doppelt so hoch. Innerhalb der CKD-Kohorte war höheres Alter und männliches Geschlecht im univariaten Modell mit einem höheren Risiko für einen tödlichen Verlauf assoziiert. Eine Körpertemperatur ≥ 38°C (OR 0,04 (95% KI: 1,04 – 3,29), SO2 < 90% (OR 0,29 (95% KI: 1,50 – 5,28)), Atemfrequenz > 21/Minute (OR 2,22 (95% KI: 1,06 – 4,66)) sowie stark erhöhtes Troponin T (2-5x Normwert: OR 11,63 (95% KI: 1,96 – 68,87)), Thrombozytenzahlen < 120.000/µL (OR 2,44 (95% KI: 1,16 – 5,12)), PCT > 0,5 ng/ml (OR 3,64 (95% KI: 1,61 – 8,25)) und Interleukin-6 ≥ 50 pg/ml (OR 4,28 (KI: 1,08 – 16,91)) zum Zeitpunkt der ersten positiven SARS-CoV-2 Testung waren mit letalem Verlauf assoziiert.
Zusammenfassung: COVID-19 Patient*innen haben häufig zum Diagnosezeitpunkt eine CKD. Männliche und ältere CKD Patient*innen haben ein höheres Risiko für einen letalen Verlauf. Vitalparameter sowie die Laborparameter Troponin T, Thrombozytenzahlen, PCT und Interleukin-6 zum Zeitpunkt der ersten positiven Testung sind dabei wichtige Parameter zur Identifikation potentieller Risikopatient*innen.

 
Pre-existing SARS-CoV-2 reactive T cells in renal transplant patients
P155 

M. Anft, A. Blazquez-Navarro, U. Stervbo, O. Witzke, R. Wirth, M. Choi, C. Hugo, P. Reinke, P. Schenker, R. Viebahn, T. H. Westhoff, N. Babel; Herne, Essen, Berlin, Dresden, Bochum

Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused unprecedented public health and economical challenges worldwide. Cellular immunity is known to be crucial for the virus clearance. Recent data demonstrate pre-existing SARS-CoV-2-reactive T cells in samples of healthy blood donors collected before SARS-CoV-2 pandemics. The presence of these potentially protective T cells in SARS-CoV-2 naive population can be explained by cross-reactivity to the endemic common cold coronavirus. Whether such cells are also detectable in immunosuppressed patients is not known so far.
Method: We analysed the presence of SARS-CoV2-cross-reactive T cell immunity in samples of 10 renal transplant patients (RTX) collected in 2019 before the onset of SARS-CoV-2 pandemics. Samples of 10 non-immunosuppressed/immune competent SARS-CoV-2 naive patients matched to transplant patients were analysed as controls. T-cell reactivity against Spike-, Nucleocapsid-, and Membrane- SARS-CoV-2 proteins were analysed by multi-parameter flow cytometry.
Results: 50% of analysed RTX showed CD4+ T-cells reactive against at least one SARS-CoV-2 protein. CD8+ T cells reactive against at least one SARS-CoV2 protein were demonstrated in 30% of RTX. Notably, the detected cells were of diffentiated memory phenotype producing several Th1 cytokines including IFNg, TNFa, IL-2, as well as Granzyme B. The frequencies and cytokine expression pattern of SARS-CoV-2 reactive T-cells did not differ between transplant and non-transplant cohorts.
Conclusion: Despite immunosuppressive treatment and underlined renal disease, transplant patients were able to generate cellular immunity cross-reactive to SARS-CoV-2. The magnitude and functionality of the pre-existing immunity was non-inferior compared to the immune competent cohort. Although several pro-inflammatory cytokines were produced by the detected T cells, further studies are required to prove their antiviral protection.

 
Clinical characterization of COVID-19 in hemodialysis patients
P156 

M. Seidel, H. Appel, T. Pfab, A. Uhle, M. Frahnert, M. Barenbrock, E. Büssemaker, J. H. Hörstrup, A. Doevelaar, F. Bauer, F. Seibert, B. Rohn, N. Babel, T. H. Westhoff; Herne, Hamm, Potsdam, Bochum, Berlin

Objective: Hemodialysis patients may constitute a high-risk population for SARS-CoV-2 infections regarding both exposition and adverse outcome due to their comorbidities. Since the beginning of the pandemic isolated single-center experiences on the clinical course of COVID-19 have been published with different findings. We present multi-center data on the clinical course of COVID-19 in hemodialysis patients.
Method: Clinical data were obtained from five dialysis outpatient centers in Germany. Data included symptoms and the severity of the clinical course stratified as "mild", "severe", "critical", or "fatal". The disease was considered as "mild", if it was successfully managed in an outpatient setting, "severe", if it necessitated hospitalization on a peripheral ward, "critical" in case of necessity of intensive care medicine, and "fatal" in case of death.
Results: 56 hemodialysis patients tested positive for SARS-CoV-2 in RT-PCR. Most frequent symptoms were fever (n=31, 55%) and cough (n=26, 46%). Diarrhea and anosmia/dyseugesia were less frequent (<20% each). 13 (23%) showed a mild course, 43 (77%) showed a severe course with hospitalization, 16 (29%) suffered from a critical course necessitating intensive care medicine, and 15 (27%) died. Logistic regression analysis using the individual underlying diseases as independent variables identified cardiorenal syndrome as an outstanding risk factor for death (p=0.001). Among 6 subjects with cardiorenal syndrome, 5 (83%) died. In line with this finding, subjects without hypertension tended to have a higher mortality (p 0.07).
Conclusion: In this multi-center cohort of hemodialysis patients with COVID-19, severe courses and mortality were substantially higher than in the general population. Among these patients, subjects with cardiorenal syndrome are at highest risk for adverse outcome of COVID-19.

 
Allograft infiltration and meningoencephalitis by SARS-CoV-2 in a pancreas-kidney transplant recipient
P157 

A. Doevelaar, F. Seibert, F. Bauer, U. Stervbo, M. Anft, B. Rohn, G. Winnekendonk, U. Dittmer, P. Schenker, K. Amann, P. Zgoura, R. Viebahn, N. Babel, T. H. Westhoff; Herne, Essen, Bochum, Erlangen

Objective: COVID-19 primarily affects epithelia of the upper and lower respiratory tract. Thus, impairment of kidney function has been primarily attributed to secondary effects like cytokine release or fluid balance disturbances so far.
Method: We provide evidence that SARS-CoV-2 can directly infiltrate a kidney allograft.
Results: A 69-year old male pancreas-kidney transplant recipient presented to our hospital with COVID-19 pneumonia and impaired pancreas and kidney allograft function. Kidney biopsy was performed showing tubular damage and an interstitial mononuclear cell infiltrate. RT-PCR from the biopsy specimen was positive for SARS-CoV-2, while being negative in a peripheral blood sample. Subsequently, he suffered from two convulsive seizures. Magnetic resonance tomography suggested meningoencephalitis, which was confirmed by SARS-CoV-2 RNA transcripts in the cerebrospinal fluid.
Conclusion: The present case demonstrates that SARS-CoV-2 can infiltrate diverse organs. The patient suffered from COVID-19 pneumonia, meningoencephalitis and nephritis. SARS-CoV-2 binds to its target cells through angiotensin-converting enzyme 2, which is expressed in a broad variety of tissues including the lung, brain and kidney. SARS-CoV-2 thereby shares features with other human coronaviruses including SARS-CoV that were identified as pathogens beyond the respiratory tract as well. The present case should provide awareness that extrapulmonary symptoms in COVID-19 may be attributable to viral infiltration of diverse organs.

 
Management und Verlauf von COVID-19 Erkrankungen bei Dialysepatienten: Erfahrungen eines großen Zentrums in Baden-Württemberg
P158 

B. Hohenstein, O. Hergesell, A. Gell, E. Weißbrot, T. Weinreich, F. Gehlen, H. Reichel; Villingen-Schwenningen

Hintergrund: Dialysepatienten (HD-PAT) haben erhebliche Komorbiditäten mit hohem Risiko für einen komplizierten COVID-19 Verlauf. In Baden-Württemberg, einem von COVID-19 stark betroffenen Bundesland, versorgen wir an 11 Standorten eine große Zahl Nierenkranker. Ab 23.02. führten wir sukzessiv stringente, lageadaptierte Maßnahmen zur COVID-19 Prävention bei Patienten (PAT) und Mitarbeitern (MA) ein. Wir berichten über unsere Erfahrungen im ambulanten Dialysesektor und an der Schnittstelle ambulante/stationärer Bereich im Umgang mit COVID-19 Verdachts- und Erkrankungsfällen (VF, EF).
Methode: Es erfolgte die systematische Erfassung und Nachverfolgung sämtlicher COVID-19 VF/ EF bei PAT u. MA. Bei AU wurde jeder MA gezielt auf das COVID-19 Risiko überprüft ggf. diagnostiziert. Die Risikoanalyse bei PAT mit daraus abgeleiteten Maßnahmen erfolgte anhand definierter Kriterien und Statuszuweisung (COVID-19+, Status 1-4). Ziel war es mögliche Übertragungen innerhalb der PAT konsequent zu unterbinden. Die Analyse umfasst den Zeitraum vom 31.01.-31.05.2020.
Ergebnisse: Im Zeitraum traten mehr als 50 VF und 20 EF bei PAT auf, erster VF 8.3., erster EF 11.3.. Das Management wurde durch systematische Testung und Prävention (z.T. materialabhängig) von PAT u. MA ständig optimiert. Medianes Alter der EF 71J  [43-80J].  3 PAT (m: 70J, 77J, w 62J) starben nach 14,6 d [5-25d]. Die mittlere Zeit bis zur Negativität betrug 22,9 d. Initiale Symptome waren erhöhte Temperatur an HD, red. Befinden, Zeichen des Atemwegsinfektes u. GI-Symptome. 3 PAT blieben asymptomatisch. 2 PAT unter IS nach HTx/LTx blieben mehr als 40 d pos.. 2 PAT wurden nach NTx COVID-19 +, dies besteht seit 3 Monaten. 4 HD-PAT wurden komplett ambulant geführt, 6 HD-PAT wurden COVID-19+ aus stationärer Therapie entlassen. Mehr als 100 Abstriche bei MA auf Basis von Indexfällen, auch unter initial eingeschränktem Schutz mit OP-Masken, blieben immer negativ. In der Gruppe der Heimdialysepatienten (PD, HHD, n=60) gab es 2 VF, 1 EF. An einem Standort war ein Taxifahrer wesentlich in die Infektionskette involviert.
Zusammenfassung: Systematischen Maßnahmen begrenzen wirksam Kontamination u. Ausbreitung von COVID-19 in der Risikogruppe der HD-PAT u. bei MA. Morbidität und Mortalität durch COVID-19 erscheinen erhöht. Unsicherheiten hinsichtlich der Kriterien für Infektiosität und Ausheilung stellen im Management an HD und nach Tx eine relevante Herausforderung dar.

 
Clinical course and cellular immunity in COVID-19 patients with different grade of kidney injury
P159 

A. Blazquez-Navarro, L. Mittmann, K. Paniskaki, A. Doevelaar, F. Seibert, B. Hoelzer, M. Anft, M. Konik, T. Brenner, S. Dolff, U. Dittmer, U. Stervbo, O. Witzke, T. H. Westhoff, N. Babel; Herne, Essen

Objective: Chronic kidney disease (CKD) is a known risk factor of SARS-CoV-2 infection and disease progression. It remains elusive, however, whether this increased risk of adverse outcome may be attributable to an attenuated immune response. The present study investigates for the first time the clinical course and the general and SARS-CoV-2 reactive immune response of a COVID-19 in dependence of renal function.
Method: In our bi-centre study, 87 hospitalized patients with different degree of renal insufficiency as detected at the time point of COVID-19 diagnosis were enrolled into the study. Clinical and laboratory follow up as well as cellular immunity data were acquired at days 0, 4, 7, 12, 16, 23, 30. We evaluated the enrolled patients with respect to the COVID-19 progression and outcome, renal function, liver and heart enzymes, coagulation, metabolic regulation, inflammation, as well as immune cell analysis.
Results: 7 patients with GFR <30 ml/min (5 out of 7 on chronic hemodialysis); 23 patients with GFR 30-60 ml/min and 57 patients with GFR > 60 ml/min at COVID-19 diagnosis were enrolled into the study. With respect to the clinical manifestation, we did not find any statistical differences between patients with different GFR. In particular, no differences in lethality rate (9%-17%), duration of hospitalization and severity grade of COVID 19 as well as the most laboratory parameters were observed between different GFR groups. Of interest, no further impairment of renal function was detected in patients during the clinical follow up irrespectively from initial renal function. In contrast, the kidney function even slightly improved in follow up showing median GFR increase of 4.5 [-3.1-13.6] ml/min/1.73m2 without statistical differences between the analyzed groups. Furthermore, the detailed analysis of cellular immunity demonstrated comparable values in absolute and relative T-cell numbers as well as T-cell subset composition in patients with impaired and normal renal function. The frequencies of SARS-CoV-2 reactive T-cells were also comparable between the three analysed GFR groups.
Conclusion: Despite its known negative prognostic value, impairment of renal function was not associated with an inferior outcome of COVID-19 as compared to the patients with normal renal function in the analysed cohort of hospitalized patients. Further larger studies are required to evaluate and understand the role of renal function for the clinical manifestation of COVID-19.

 
Epidemiology of COVID-19 in Hemodialysis Patients: Prevalence in a German Dialysis Center at the Peak of Pandemia
P160 

S. Patyna, B. F. Koch, D. Avaniadi, S. Büttner, H. Rabenau, O. Jung, T. Wolf, M. Vehreschild, S. Ciesek, V. Kempf, D. Hack, H. Geiger, C. Betz; Frankfurt a. M., Wetzlar-Hermannstein

Objective: COVID-19 and chronic dialysis patients make a particular dangerous relationship. Underlying medical conditions and extensive interactions with the health care system predispose this population to Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) infection. We report on the successful application of protective measures and present results from 270 dialysis sessions for 45 chronic dialysis patients in a tertiary care dialysis unit in Germany.
Method: In a prospective study approach, 45 long-term dialysis patients were observed for seven weeks during COVID-19 pandemia in April and May 2020 at Frankfurt University Hospital in Germany. To prevent a nosocomial outbreak, all chronic dialysis patients were tested for SARS-CoV-2 (rRT-PCR) three times during a period of seven weeks, respectively at the outset and after two and four weeks.

P160-1


Moreover, a SARS-CoV-2 antibody test was performed two times in all patients to evaluate inapparent pre-swab infections as well as seroconversion. In cooperation with the general preparations for COVID-19, our dialysis center established and trained strict hygiene standards and preventive measures.

P160-2

Results: Only 3 of 45 long-term hemodialysis patients at Frankfurt University Hospital had a positive test result of SARS-CoV-2 in rRT-PCR. The mean overall patient age was 62 years, without significant difference in age between patients with and without COVID-19 infection (p=0,588). Time since first dialysis differed significantly between positive and negative tested patients with longer dialysis time in the COVID-19 positive group (p<0,001).
One positive tested Patient showed a pathological chest radiography and CT scan of the thorax. In the further course, this patient established an ARDS with the need for mechanical ventilation and finally died at day 8 after the first positive SARS-CoV-2-rRT-PCR test. Hence, we report a mortality rate of 33% of confirmed cases (1 out of 3). Furthermore, we found prolonged SARS-CoV-2 shedding and late IgG seroconversion with implications for virus spreading in vulnerable populations.
Conclusion: By enforcing strict prevention measures, COVID-19 transmission during in-center hemodialysis could be avoided for most of the patients in our dialysis unit. While some SARS-CoV-2-rRT-PCR positive dialysis patients showed no COVID-19 symptoms during screening, they nevertheless developed ARDS. Time to SARS-CoV-2-rRT-PCR negative nasopharyngeal swab and SARS-CoV-2-IgG seroconversion could be markedly delayed, requiring high awareness in order to avoid SARS-CoV-2 spreading in vulnerable populations.

 
Schwere COVID-19 Verläufe bei Nierentransplantierten und Hämodialysepatienten korrelieren mit der Dauer der vorausgegangenen Nierenersatzpflichtigkeit
P161 

G. S. Braun, L. Villa, T. Krüger, C. Werner, U. Kunter, T. Rauen, J. Floege, A. S. Mühlfeld; Aachen, Erkelenz, Geilenkirchen

Hintergrund: Eine terminale Niereninsuffizienz wurde als Risikofaktor für die Schwere des Verlaufes der COVID-19 Erkrankung beschrieben. Unterschiede zwischen den Ersatzverfahren Transplantation (NTX) und Hämodialyse (HD) in diesem Kontext sind jedoch wenig definiert. Ziel war es, diese Interaktionen besser zu charakterisieren.
Methode: Wir etablierten im Rahmen des ersten deutschen Ausbruches im Kreis Heinsberg/Aachen eine Kohorte aus allen identifizierbaren Patienten mit chronischer Nierenersatztherapie, die eine COVID-19 Erkrankung oder SARS-CoV-2-Positivität entwickelten (NTX N=7, HD N=14). Alle Individuen wurden mindestens bis zum Erreichen eines harten Endpunktes (geheilte Entlassung oder Versterben) beobachtet (Median 66 Tage, IQR 40-71).
Ergebnisse: Demographische Struktur, Hospitalisierungsrate und Dauer der CoV-2-RNA-Ausscheidung waren in beiden Gruppen ähnlich. Deutlich unterschiedliche Trends ergaben allerdings folgende Parameter: Mortalität (NTX 43% vs. HD 18%), Entwicklung eines ARDS (NTX 57% vs. HD 27%) sowie eine um 8 bzw. 14 Tage längere Krankheits- bzw. Hospitalisierungsdauer (NTX vs. HD). Univariate Risikofaktoranalysen zeigten eine signifikante Assoziation zwischen der Länge der vorausgegangenen Nierenersatztherapie und der Entwicklung eines ARDS (non-ARDS 4,3 Jahre vs. ARDS 10,6 Jahre, p=0,016). Dieser Effekt der Dauer des vorherigen Nierenersatzes blieb bestehen bei isolierter Betrachtung der NTX Population (p=0,002). Auch die Zeit seit der Transplantation korrelierte mit der Entwicklung eines ARDS (p=0,038).
Zusammenfassung: Zusammenfassend identifizieren unsere Daten insbesondere für nierentransplantierte Patienten die Nierenersatzdauer als potenten neuen Risikofaktor eines schweren Verlaufes von COVID-19.

 
Coronavirus disease 2019 (COVID-19) infection in renal allograft recipients
P162 

C. Speer, U. Merle, F. Kälble, C. Morath, M. Zeier, C. Sommerer; Heidelberg

Objective: Clinical presentation of coronavirus disease 2019 (COVID-19) is various, ranging from asymptomatic infection to a multisystem disorder with a cytokine storm-like clinical syndrome. Immunocompromised renal transplant recipients are supposed to be at particular risk for severe infectious complications as well as for acute renal deterioration associated with COVID-19.
Method: We report about four distinct cases of renal transplant recipients with COVID-19 infection. Patients baseline characteristics, the clinical course, and outcomes are summarized.
Results: A 56-year-old women with deceased donor renal transplantation 29 months ago, developed fever and cough as first symptoms of COVID-19. Except arterial hypertension (HT), she had no other comorbidities. The chest X-ray revealed mild bipulmonal ground-glass opacity (GGO). A 70-year-old man with deceased donor renal transplantation 15 months ago developed dyspnea without cough or fever and was admitted with a positive SARS-CoV-2 RNA swab 3 days after symptom onset. As comorbidities he had coronary heart disease and HT. The chest X-ray revealed moderate bilateral patchy consolidation. A 64-years-old man was admitted 129 months after deceased donor renal transplantation with COVID-19, only 2 days after the onset of his first symptoms as cough and dyspnea. The chest X-ray revealed severe bipulmonal GGO. He had several comorbidities such as atrial fibrillation, factor V Leiden mutation and a treated acute rejection episode 7 days ago. A 54-year-old male deceased donor renal transplant recipient was admitted 33 months after transplantation with cough and fever only one day after the onset of his symptoms. The X-ray revealed only discreet bipulmonal GGO.
Prophylactic antibiotic, antimycotic and immunoregulatory therapy was given. The clinical course of the patients was various with one severe case (case 3) and one with only mild symptoms (case 4). All patients were discharged in well condition.
Detailed description of the clinical course of the disease will be provided.
Conclusion: COVID-19 infection shows a highly various clinical course even in immunocompromised renal allograft recipients ranging from mild symptoms to severe respiratory insufficiency and renal failure.

 
Extracorporeal treatment strategies for severe COVID-19 disease in an intensive care setting
P163 

N. Heyne, M. Guthoff, F. Artunc, P. Rosenberger, H. Häberle; Tübingen

Objective: Infection with SARS-CoV-2 is associated with a highly variable clinical phenotype, ranging from oligosymptomatic carriers to patients developing severe COVID-19 disease requiring intensive care treatment. Associated risk factors and pathophysiologic aspects are increasingly delineated. In all approaches, timing of intervention and patient selection is key. We report our center experience and strategy for extracorporeal treatment of severe COVID-19 disease in an intensive care unit (ICU) setting.
Method: Center experience of extracorporeal therapy for organ support and blood purification is presented, including the use of high cut-off (HCO) membranes in severe cytokine release syndrome.
Results: Within the first outbreak of COVID-19, 251 patients were treated in-house at our University Hospital, whereof 78 required ICU treatment. All ICU patients were on mechanical ventilation. Organ support by extracorporeal membrane oxygenation was required in 20% of ICU patients; 2 patients were on extracorporeal life support. Renal replacement therapy was performed in 35% of patients and delivered as CVVHD or SLEDD. Extracorporeal liver support by plasmapheresis and selective adsorption was required in three patients in the late phase of the disease. As cytokine activation has been shown to play a pivotal role at specific stages of the disease, we used HCO membranes for cytokine removal, an option broader than pharmacologic blockade of single cytokines. This treatment was well tolerated and may provide a promising adjunct in severe cytokine release syndrome.
Conclusion: In summary, we contribute our experience with extracorporeal organ support and blood purification in severe COVID-19 disease. Joining expertise in an interdisciplinary approach is mandatory to generate targeted extracorporeal treatment strategies for these patients.

 
SARS-CoV-2 Infektion in primären humanen proximalen und distalen Tubulusepithelzellen
LA31 

B. F. Koch, A. Kohli, L. Sauerhering, S. K. Fehling, H. Geiger, S. Becker, T. Strecker, C. Münch, P. Baer; Frankfurt a. M., Marburg

Hintergrund: Ein signifikanter Anteil von COVID-19 Patienten weist Anomalien der Nierenfunktion bis hin zu Nephritiden oder akutem Nierenversagen (ANV) auf. Retrospektive Studien berichten von einer hohen ANV-Inzidenz bei kritischen Krankheitsverläufen (bis zu 78%). Die Pathogenitätsdeterminanten des Nierenversagens bei COVID-19 auf molekularer und zellulärer Ebene sind weitestgehend unbekannt, ein hypothetischer Mechanismus könnte die Infektion von renalen Zellen durch das verursachende Virus darstellen. Ziel der aktuellen Studie war es, die SARS-CoV-2-Replikation in primären Tubulusepithelzellen in vitro zu untersuchen und anhand von Translatomics- und Proteomics-Analysen zu charakterisieren.
Methode: Humane proximale und distale Tubulusepithelzellen (PTC und DTC) wurden mittels einer immunomagnetischen Methode aufgereinigt und kultiviert. PTC und DTC wurden unter BSL-4-Bedingungen mit SARS-CoV-2 (Isolat BavPat1/2020) mit einer MOI von 0,01 infiziert. Anschließend wurden Analysen des Translatoms und des Proteoms nach 24h und 48h post Infektion durchgeführt und mit nicht-infizierten Kontrollzellen verglichen. Peptide aus den Zell-Lysaten wurden auf einem Orbitrap Fusion Lumos Massenspektrometer gemessen.
Ergebnisse: SARS-CoV-2 repliziert auf PTC und DTC (Abb. 1A). Morphologisch konnte ein zytopathologischer Effekt (CPE) nur bei PTC nachgewiesen werden, massenspektrometrisch zeigt sich aber eine Translation von Virusproteinen sowohl bei PTC als auch bei DTC (Abb. 1B/C).

LA31-1

Messungen des Translatoms zeigen, dass Translationsprozesse bei PTCs sowohl nach 24 als auch nach 48 Stunden signifikant rückläufig sind, DTC zeigen hingegen einen geringeren translationalen shut off (Abb. 2).

LA31-2

Eine robuste Aktivierung der Immunantwort konnte sowohl in PTC als auch in DTC beobachtet werden. Bereits im hierarchischen Clustering anhand von KEGG Signalwegen (Abb. 2) zeigen SARS-CoV-2-infizierte PTC und DTC zu den untersuchten Zeitpunkten deutliche Unterschiede in v.a. der Aktivität des TCA-Zyklus, verschiedenen Schritten der Translation von Wirts- und Virusproteinen, dem Interferon- und TP53-Signalweg sowie der Synthese von membrangebundenen Phosphatidylinositolen und der RAC1-induzierten Zellmigration.
Zusammenfassung: Sowohl PTC als auch DTC sind permissiv für eine SARS-CoV-2 Infektion, die in einer Virusreplikation resultiert. Die Analyse der Daten zeigt eine starke, jedoch unterschiedliche Immunantwort mit folgender stagnierender Replikation sowie einen virus-induzierten shut off der tubulären Proteintranslation als potentielle Ursache des ANV.

 
Covid-19 Nephropathy: A Path to Predict Disease Severity and for Prevention
LA32 

O. Gross, O. Mörer, T. Rauen, J. Böckhaus, E. Hoxha, A. Jörres, M. Kamm, A. B. El-Fanish, W. Windisch, M. Dreher, J. Floege, S. Kluge, C. Schmidt-Lauber, J.-E. Turner, M. Addo, S. Scheithauer, T. Friede, G. S. Braun, T. B. Huber, S. Blaschke; Göttingen, Aachen, Hamburg, Köln, Erlangen

Objective: Identifying preventive strategies in Covid-19 patients bares the potential to improve resource-allocation and reduce mortality. Previously, we described the renal tropism of SARS-CoV-2, and here we validate an algorithm interrogating urinalysis for the early prediction of the risk of an adverse outcome in Covid-19.

Method: This multi-center cohort study included 223 hospitalized Covid-19 patients from tertiary care centers. Risk for an unfavourable Covid-19 course was categorized using a traffic light color coding system: “green”/low-risk (normal urinalysis), “yellow”/intermediate-risk (abnormal urinalysis with serum-albumin ≥2 g/dl and AT-III activity ≥70%, or “red”/high risk (abnormal urinalysis with hypalbuminemia or low AT-III). Primary endpoint was time to ICU or death. Secondary outcome measures comprised in-hospital mortality and the need for organ support.

Results: On hospital admission, abnormal urinalysis predicted the risk for ICU or death (N=65/102, 63.7%; hazard ratio (HR) 2.6, 95% confidence interval (CI) 1.4 to 4.9, P=0.0020, vs. “green”, N=12/43, 27.9%), which remained virtually unchanged after adjusting for age, sex and co-morbidities (HR 2.9, 95% CI 1.5 to 5.6, P=0.0016), with a 100% risk for the category “red”. During hospital stay, nephropathy was associated with mortality (N=47/165, 28.5%, vs. “green” N=7/58, 12·1%; P=0.012), need for mechanical ventilation (57.6% vs. 15.5%; P<0.0001), extra-corporeal membrane oxygenation (18.9% vs. 1.7%; P=0.0014), and renal replacement therapy (39.6% vs. 12.1%; P<0.0001). On hospital admission, our algorithm allowed to put intermediate-risk patients (N=84/145, 57.9%) in the focus for preventive measures against thromboembolic complications, pulmonary interstitial edema due to severe fluid overload and limited response to some medications by impaired plasma protein binding.

Conclusion: Our data indicate for the first time that at an early clinical stage, Covid-19 nephropathy may predict the risk for disease aggravation, possibly allowing preventive measures and therapeutic stratification. The real-world practicability of our algorithm is evident as it starts with a widely available inexpensive urine dipstick. (Applied for funding by the German Ministry of Education and Research; ClinicalTrials.gov number NCT04347824)

 
Urin-Proteom-Test (COVID31) differenziert den Schweregrad der Erkrankung bei COVID-19
LA33 

R. Wendt, S. Kalbitz, C. Lübbert, H. Mischak, J. Metzger, J. Beige; Leipzig, Hannover

Hintergrund: Eine der vielen Herausforderungen bei COVID-19 ist die frühe Vorhersage von kritischen und tödlichen Krankheitsverläufen, die bei 6-10 % aller Patienten mit einer SARS-CoV-2-Infektion auftreten. Die frühe Identifizierung dieser Patienten würde möglicherweise enormen Einfluss auf das Management dieser Patienten haben.
Methode: Wir haben Urin-Proteom-Analysen bei 15 stationären COVID-19 Patienten zur Entwicklung eines nicht-invasiven diagnostischen Test zur Vorhersage des klinischen Verlaufs bei COVID-19 zu etablieren. Die Urinproteomik wurde mittels Kapillarelektrophorese-Massenspektrometrie durchgeführt. Der generierte Klassifikationsscore wurde zusätzlich mit 45 alters-, geschlechts- und komorbiditätsangepassten Patienten verglichen.
Ergebnisse: Wir konnten 31 natürlich vorkommende Peptide im Urin von 15 COVID-19 Patienten identifizieren. Bei der Anwendung der Support-Vektor-Maschinen-basierten Integration dieser Peptidmarker in einen hochdimensionalen Klassifikator (COVID31) ermöglichte dieser die Unterscheidung von mittelschwerem und schwerem von einem kritischen und tödlichen Krankheitsverläufen mit einer diagnostischen Genauigkeit von 87 % . Das Modell ergab eine korrekte Vorhersage von 8 von 9 mittelschweren und schweren COVID-19 Verläufen sowie 5 von 6 kritischen und tödlichen Verläufen

LA33-1
LA33-2

Zusammenfassung: Die Ergebnisse dieser Proof-of-Concept-Studie zeigen, dass es möglich ist, die Krankheitsverläufe von COVID-19 mit hoher diagnostischer Genauigkeit mittels einer Proteomanalyse im Urin zu klassifizieren. Die Proteomanalyse im Urin unterschied zwischen moderaten/schweren und kritischen/tödlichen Krankheitsverläufen bei COVID-19-Patienten mit einer diagnostischen Genauigkeit von 87%. Diese Vorhersage könnte sowohl das Management als auch therapeutische Maßnahmen beeinflussen und möglicherweise die Prognose von COVID-19-Patienten verbessern.

 
Survey among patients with chronic kidney disease during the COVID19 pandemic
LA34 

L. Bettac, M. Kächele, R. J. van Erp, U. Ludwig, B. Schröppel, L. S. Schulte-Kemna; Ulm

Objective: The COVID19 pandemic is a major challenge for patients and healthcare providers. Patients with renal disease are medically complex with a high burden of prescription medications. We assessed how the COVID19 pandemic affects access to medical care and treatment of patients with renal disease. To address this we conducted a postal letter-based 37-item survey among patients followed in our renal clinic.
Method: 710 surveys were mailed from July 6th – 17th 2020. This interim analysis is based on surveys returned by August 14th 2020. Responses were collected anonymously. Differences between groups were compared using Students t-test for continuous variables. Chi-square test was used for nominal variables.
Results: Of the 710 patients contacted, 288 (41%) responded. Mean age was 61 years (SD 15.8). 72% considered themselves at high risk developing complications after COVID19 infection. This concern was not dependent on the respondents’ age: of those less than 60 years of age, 67% considered themselves at risk, as did 77% of those 65 years and older (p=0.06). When asked to self-evaluate their knowledge about the corona virus, 62% confidently estimated it as good or very good. Availability and understandability of information regarding COVID19 was rated as poor by 8%, and good or excellent by 62%, with no difference between age groups.
Of note, 20% of patients underwent testing for COVID19, one tested positive. Of those tested, more than 81% reported good access to testing facilities.
Out of fear of infection, 30% postponed scheduled doctor’s visits, 16% cancelled appointments without rescheduling, less than 1% omitted some of their prescribed medications. 7% did not seek out a medical professional even when developing urgent complaints, which might have otherwise prompted a doctor’s visit.
44% of the respondents had their appointments cancelled or postponed by the healthcare provider, 13% reported difficulties and delays to refill their prescriptions.
When asked about the ability to cope with social distancing, 18% of the elderly indicated great distress, compared to 28% of the younger patients (p=0.06).
Conclusion: A high percentage of patients with renal disease were negatively impacted by the COVID19 pandemic. Access to healthcare was directly affected, evident by delays and cancellation of appointments – by both patients themselves, and care providers. In a population of medically complex patients, this should raise concern, and warrant the establishment of more solid care structures in times of an ongoing pandemic.

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