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Id Subject Object Predicate Lexical cue
T1 0-43 Sentence denotes COVID‐19 associated pulmonary aspergillosis
T2 44-57 Sentence denotes KOEHLER et al
T3 59-67 Sentence denotes Abstract
T4 68-75 Sentence denotes Summary
T5 77-87 Sentence denotes Objectives
T6 88-236 Sentence denotes Patients with acute respiratory distress syndrome (ARDS) due to viral infection are at risk for secondary complications like invasive aspergillosis.
T7 237-364 Sentence denotes Our study evaluates coronavirus disease 19 (COVID‐19) associated invasive aspergillosis at a single centre in Cologne, Germany.
T8 366-373 Sentence denotes Methods
T9 374-561 Sentence denotes A retrospective chart review of all patients with COVID‐19 associated ARDS admitted to the medical or surgical intensive care unit at the University Hospital of Cologne, Cologne, Germany.
T10 563-570 Sentence denotes Results
T11 571-713 Sentence denotes COVID‐19 associated invasive pulmonary aspergillosis was found in five of 19 consecutive critically ill patients with moderate to severe ARDS.
T12 715-725 Sentence denotes Conclusion
T13 726-913 Sentence denotes Clinicians caring for patients with ARDS due to COVID‐19 should consider invasive pulmonary aspergillosis and subject respiratory samples to comprehensive analysis to detect co‐infection.
T14 915-930 Sentence denotes 1 INTRODUCTION
T15 931-1097 Sentence denotes Since December 2019 coronavirus disease 2019 (COVID‐19) emerged from Wuhan City, Hubei province, China and rapidly spread around the globe becoming a pandemic threat.
T16 1098-1207 Sentence denotes 1 Risk factors for invasive pulmonary aspergillosis (IPA) are well defined in immunocompromised populations.
T17 1208-1429 Sentence denotes However, patients with acute respiratory distress syndrome (ARDS) due to viral infection are prone to secondary complications like invasive aspergillosis despite lack of underlying well‐defined immunocompromising disease.
T18 1430-1591 Sentence denotes 2 , 3 , 4 Possible explanations for this could be an immune‐paralysis caused by viral infection‐induced ARDS and hypoxia compromising the innate host defence.
T19 1592-1776 Sentence denotes 5 In light of influenza‐pulmonary associated aspergillosis, we retrospectively analysed our patients with COVID‐19 associated ARDS in the intensive care unit (ICU) at a single centre.
T20 1778-1801 Sentence denotes 2 PATIENTS AND METHODS
T21 1802-2037 Sentence denotes We performed a retrospective chart review of patients with COVID‐19 and ARDS admitted to the medical and surgical ICU at the University Hospital of Cologne, a 1540‐bed teaching hospital between 7 March 2020 and 22 April 2020 (Table 1).
T22 2038-2140 Sentence denotes TABLE 1 Patient characteristics of patients with COVID‐19 associated invasive pulmonary aspergillosis
T23 2141-2216 Sentence denotes Characteristics Patient #1 Patient #2 Patient #3 Patient #4 Patient #5
T24 2217-2257 Sentence denotes Gender Female Male Male Male Female
T25 2258-2285 Sentence denotes Age (y) 62 70 54 73 54
T26 2286-2341 Sentence denotes Medical history Lap. cholecystectomy for cholecystitis
T27 2342-2363 Sentence denotes Arterial hypertension
T28 2364-2399 Sentence denotes Obesity with sleep apnea (BMI 31.5)
T29 2400-2420 Sentence denotes Hypercholesterolemia
T30 2421-2454 Sentence denotes Ex‐smoker (30 PY; 5 y previously)
T31 2455-2539 Sentence denotes Moderate COPD (GOLD 2) Vertebral disc prolapse left L4/5, flavectomy and nucleotomy
T32 2540-2594 Sentence denotes Ex‐smoker (4 months previously) Arterial hypertension
T33 2595-2612 Sentence denotes Diabetes mellitus
T34 2613-2673 Sentence denotes Aneurysm coiling right A. vertebralis Arterial hypertension
T35 2674-2691 Sentence denotes Bullous Emphysema
T36 2692-2698 Sentence denotes Smoker
T37 2699-2719 Sentence denotes Severe COPD (GOLD 3)
T38 2720-2744 Sentence denotes Previous Hepatitis B No
T39 2745-2926 Sentence denotes Underlying immuno‐compromising condition (inhalational steroids for COPD) No (intravenous corticosteroid therapy 0.4 mg/kg/d, total of 13 d) (inhalational steroids for COPD) No
T40 2927-2965 Sentence denotes ICU Ward MICU MICU SICU SICU MICU
T41 2966-2970 Sentence denotes ARDS
T42 2971-3100 Sentence denotes Horowitz‐Index, admission 12 Severe (53 mm Hg) Severe (93 mm Hg) Moderate (128 mm Hg) Severe (83 mm Hg) Moderate (167 mm Hg)
T43 3101-3143 Sentence denotes Prone positioning Yes Yes Yes Yes Yes
T44 3144-3171 Sentence denotes vvECMO Yes No No No No
T45 3172-3216 Sentence denotes Acute renal failure Yes Yes Yes Yes Yes
T46 3217-3254 Sentence denotes Dialysis No SLEDD SLEDD SLEDD No
T47 3255-3267 Sentence denotes Microbiology
T48 3268-3356 Sentence denotes Serum GM (>0.5) Negative Positive (0.7) Negative Negative 2× positive (2.7 and 1.3)
T49 3357-3378 Sentence denotes Fungal culture BALF:
T50 3379-3421 Sentence denotes Aspergillus fumigatus BALF: negative TA:
T51 3422-3448 Sentence denotes Aspergillus fumigatus TA:
T52 3449-3484 Sentence denotes Aspergillus fumigatus TA: negative
T53 3485-3563 Sentence denotes Susceptibility testing Azole susceptible a Not applicable Azole susceptible
T54 3564-3593 Sentence denotes Itraconazole MIC 0.380 (mg/L)
T55 3594-3642 Sentence denotes Voriconazole MIC 0.094 (mg/L) Azole susceptible
T56 3643-3672 Sentence denotes Itraconazole MIC 0.380 (mg/L)
T57 3673-3718 Sentence denotes Voriconazole MIC 0.094 (mg/L) Not applicable
T58 3719-3736 Sentence denotes Fungal PCR BALF:
T59 3737-3765 Sentence denotes Aspergillus fumigatus BALF:
T60 3766-3794 Sentence denotes Aspergillus fumigatus BALF:
T61 3795-3821 Sentence denotes Aspergillus fumigatus TA:
T62 3822-3857 Sentence denotes Aspergillus fumigatus TA: negative
T63 3858-3882 Sentence denotes TA/BALF GM (>0.5) BALF:
T64 3883-3905 Sentence denotes Positive (>2.5) BALF:
T65 3906-3928 Sentence denotes Positive (>2.5) BALF:
T66 3929-3974 Sentence denotes Positive (>2.5) Not available Not available
T67 3975-3992 Sentence denotes Definition of IPA
T68 3993-4203 Sentence denotes EORTC/MSG Criteria 8 Not classifiable (no host criterion) Not classifiable (no host criterion) Not classifiable (no host criterion) Not classifiable (no host criterion) Not classifiable (no host criterion)
T69 4204-4344 Sentence denotes (modified) AspICU algorithm 3 , 7 Putative Modified putative 3 (GM positivity) Putative Putative Modified putative 3 (GM positivity)
T70 4345-4353 Sentence denotes Virology
T71 4354-4404 Sentence denotes PCR TA: positive for hMPV and SARS‐CoV‐2 (E‐gene:
T72 4405-4423 Sentence denotes C t 13.29; S‐gene:
T73 4424-4480 Sentence denotes C t 12.61) TA: positive for hMPV and SARS‐CoV‐2(E‐gene:
T74 4481-4501 Sentence denotes C t 34.29; ORF1 a/b:
T75 4502-4549 Sentence denotes C t 31.47) TA positive for SARS‐CoV‐2 (E‐gene:
T76 4550-4570 Sentence denotes C t 29.74; ORF1 a/b:
T77 4571-4618 Sentence denotes C t 27.86) TA positive for SARS‐CoV‐2 (E‐gene:
T78 4619-4639 Sentence denotes C t 21.47; ORF1 a/b:
T79 4640-4705 Sentence denotes C t 20.12) TA positive for SARS‐CoV‐2 (C t values not available)
T80 4706-5282 Sentence denotes CT imaging studies Combined bilateral ground‐glass opacities with crazy paving and peripheral nodular consolidations (Video S1, Figure 1A) Ground‐glass opacities with occasional nodules (Video S2, Figure 1B) Bilateral ground‐glass opacities, nodular infiltrates with cavities and air crescent sign (Video S3, Figure 1C) Ground‐glass opacities with occasional nodules, known bullous emphysema (Video S4, Figure 1D) Ground‐glass opacities, smaller areas with crazy paving pattern, central and peripheral consolidations, and smaller nodular infiltrates (Video S5, Figure 1E)
T81 5283-5290 Sentence denotes Therapy
T82 5291-5655 Sentence denotes Antifungal treatment Voriconazole iv (6/4 mg/kg BW twice daily) Isavuconazole iv (200 mg thrice daily for 2 d; 200 mg once daily from 3 d) Caspofungin (70/50 mg once daily) followed by voriconazole iv (6/4 mg/kg BW twice daily) Voriconazole iv (6/4 mg/kg BW twice daily) Caspofungin (70/50 mg once daily) followed by voriconazole iv (6/4 mg/kg BW twice daily)
T83 5656-5918 Sentence denotes Antiviral therapy Supportive only Supportive only Hydroxychloroquine, darunavir and cobicistat at external hospital, in house changed to supportive only Supportive only Ribavirin, lopinavir/ritonavir at external hospital, in house changed to supportive only
T84 5919-5958 Sentence denotes Outcome Died Died Alive Died Alive
T85 5959-6713 Sentence denotes Abbreviations: ARDS, acute respiratory distress syndrome; BALF, bronchoalveolar lavage fluid; BW, body weight; COPD, chronic obstructive pulmonary disease; C t, threshold cycle; EORTC/MSG, European Organization for Research and Treatment of Cancer/Mycoses Study Group; GOLD, global initiative for chronic obstructive lung disease; hMPV, human metapneumovirus; IPA, invasive pulmonary aspergillosis; kg, kilogram; lap, laparoscopic; LVB, lumbar vertebral body; mg, milligram; MIC, minimal inhibitory concentration; MICU, medical ICU; ORF, open reading frame; PCR, polymerase chain reaction; PY, pack‐year history; SICU, surgical ICU; SLEDD, slow low‐efficient daily dialysis; TA, tracheal aspirate; vvECMO, veno‐venous extracorporeal membrane oxygenation.
T86 6714-6764 Sentence denotes a Antifungal susceptibility testing by VIPcheck™.
T87 6765-6766 Sentence denotes 6
T88 6767-6914 Sentence denotes John Wiley & Sons, Ltd This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response.
T89 6915-7097 Sentence denotes It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.
T90 7098-7228 Sentence denotes For patient #1 SARS‐CoV‐2 RT‐PCR Kit (altona Diagnostics) and for patients #2, #3 and #4 cobas® SARS‐CoV‐2 Test (Roche) were used.
T91 7229-7278 Sentence denotes For patient #5, kit manufacturer remains unknown.
T92 7279-7411 Sentence denotes Respective C t values are given in Table 1 where available. hMPV‐PCR was performed with NxTAG® Respiratory Pathogen Panel (Luminex).
T93 7412-7504 Sentence denotes Aspergillus 28S rDNA‐Realtime PCR was performed as in‐house PCR test for screening purposes.
T94 7505-7569 Sentence denotes Species identification was performed by artus® Aspergillus diff.
T95 7570-7590 Sentence denotes RG PCR kit (Qiagen).
T96 7591-7758 Sentence denotes For galactomannan testing from serum, bronchoalveolar lavage fluid (BALF) or tracheal aspirate (TA) Platelia Aspergillus antigen ELISA (Bio‐Rad Laboratories) was used.
T97 7759-7863 Sentence denotes Antifungal susceptibility testing was performed using concentration gradient strips on RPMI agar plates.
T98 7864-8026 Sentence denotes In brief, spore suspensions of the fungal isolates were adjusted to 106 CFU/mL and inoculated with MIC test strips for itraconazole and voriconazole (bioMérieux).
T99 8027-8094 Sentence denotes MICs were determined visually after 48 hours of incubation at 35°C.
T100 8095-8192 Sentence denotes VIPcheck™ (Mediaproducts BV) was performed in patient #1 for early detection of azole resistance.
T101 8193-8194 Sentence denotes 6
T102 8195-8456 Sentence denotes COVID‐19 associated IPA was classified according to the (modified) 3 AspICU algorithm 7 with the addition that positive galactomannan (≥1) from BALF or TA, or two consecutively but separately drawn positive serum samples (≥1) were accepted as entry criterion.
T103 8457-8566 Sentence denotes 8 Severe SARS‐CoV2 infection with ARDS was accepted as host criterion (acquired immunodeficiency) (Table 1).
T104 8567-8825 Sentence denotes This study was carried out in accordance with the ethical principles reflected in the Declaration of Helsinki 9 and was approved by the ethic committee of the University Hospital of Cologne (Identifier of the University of Cologne Ethics Committee 20‐1157).
T105 8827-8837 Sentence denotes 3 RESULTS
T106 8838-8882 Sentence denotes A 62‐year‐old woman was admitted to our ICU.
T107 8883-8961 Sentence denotes She was intubated and developed severe ARDS with a Horowitz‐Index of 53 mm Hg.
T108 8962-9156 Sentence denotes At the contrast‐enhanced CT a combination of emphysema, bilateral ground‐glass opacities with crazy paving and some peripheral nodular consolidations were seen (Video S1, patient #1, Figure 1A).
T109 9157-9267 Sentence denotes Despite prone positioning, the patient required rescue veno‐venous extracorporeal membrane oxygenation (ECMO).
T110 9268-9341 Sentence denotes PCR for SARS‐CoV‐2 and human metapneumovirus (hMPV) was positive in BALF.
T111 9342-9496 Sentence denotes The patient developed severe intrapulmonary bleeding from the right main bronchus, which was stanched by cold lavages and instillation of tranexamic acid.
T112 9497-9623 Sentence denotes BALF culture grew Aspergillus fumigatus, was positive for galactomannan, and intravenous voriconazole treatment was commenced.
T113 9624-9720 Sentence denotes FIGURE 1 Chest CT images of patients with COVID‐19 Associated Invasive Pulmonary Aspergillosis.
T114 9721-9735 Sentence denotes A, Patient #1:
T115 9736-9834 Sentence denotes Combined bilateral ground‐glass opacities with crazy paving and peripheral nodular consolidations.
T116 9835-9849 Sentence denotes B, Patient #2:
T117 9850-9920 Sentence denotes Ground‐glass opacities with small nodular infiltrations of up to 1 cm.
T118 9921-9935 Sentence denotes C, Patient #3:
T119 9936-10046 Sentence denotes Bilateral ground‐glass opacities diffuse nodular infiltrates and cystic cavities and partly air crescent sign.
T120 10047-10061 Sentence denotes D, Patient #4:
T121 10062-10173 Sentence denotes Bullous emphysema and ground‐glass opacities, interstitial changes and consolidations with nodular infiltrates.
T122 10174-10188 Sentence denotes E, Patient #5:
T123 10189-10417 Sentence denotes Ground‐glass opacities, smaller areas with crazy paving pattern, central and peripheral consolidations, and smaller nodular infiltrates A 70‐year‐old man was admitted to the ICU because of ARDS with a Horowitz‐Index of 93 mm Hg.
T124 10418-10497 Sentence denotes PCR on BALF was tested positive for hMPV, SARS‐CoV‐2 and Aspergillus fumigatus.
T125 10498-10555 Sentence denotes Two days before, serum galactomannan had turned positive.
T126 10556-10599 Sentence denotes BALF was tested positive for galactomannan.
T127 10600-10724 Sentence denotes Chest CT showed ground‐glass opacities with some small nodular infiltrations of up to 1 cm (Video S2, patient #2 Figure 1B).
T128 10725-10880 Sentence denotes Due to acute renal failure requiring slow low‐efficient daily dialysis (SLEDD) and elevated liver enzymes, intravenous isavuconazole treatment was started.
T129 10881-10954 Sentence denotes A 54‐year‐old man presented with ARDS with a Horowitz‐Index of 128 mm Hg.
T130 10955-11028 Sentence denotes TA revealed SARS‐CoV‐2 PCR positive and Aspergillus fumigatus in culture.
T131 11029-11065 Sentence denotes BALF was positive for galactomannan.
T132 11066-11226 Sentence denotes Chest CT showed bilateral ground‐glass opacities, diffuse nodular infiltrates and cystic cavities and partly air crescent sign (Video S3, patient #3 Figure 1C).
T133 11227-11276 Sentence denotes Intravenous voriconazole treatment was initiated.
T134 11277-11433 Sentence denotes A 73‐year‐old man was transferred to the ICU due to ARDS with PCR on TA tested positive for SARS‐CoV‐2, and Aspergillus fumigatus that also grew in culture.
T135 11434-11580 Sentence denotes Chest CT showed known bullous emphysema with ground‐glass opacities and consolidations with nodular infiltrates (Video S4, patient #4, Figure 1D).
T136 11581-11616 Sentence denotes Intravenous voriconazole was begun.
T137 11617-11722 Sentence denotes A 54‐year‐old woman was transferred to the ICU due to ARDS with PCR on TA tested positive for SARS‐CoV‐2.
T138 11723-11794 Sentence denotes Serum galactomannan returned positive in two consecutive serum samples.
T139 11795-11991 Sentence denotes Chest CT showed bilateral ground‐glass opacities, smaller areas with crazy paving pattern, central and peripheral consolidations, and smaller nodular infiltrates (Video S5, patient #5, Figure 1E).
T140 11992-12028 Sentence denotes Intravenous caspofungin was started.
T141 12029-12057 Sentence denotes No autopsies were performed.
T142 12058-12112 Sentence denotes Detailed patient characteristics are given in Table 1.
T143 12114-12127 Sentence denotes 4 DISCUSSION
T144 12128-12280 Sentence denotes Patients with ARDS triggered by viral infection, in particular influenza, are prone to invasive aspergillosis even in absence of prior immunodeficiency.
T145 12281-12440 Sentence denotes 2 , 3 We report putative IPA in five of 19 COVID‐19 patients with moderate to severe ARDS without underlying immunocompromising disease on two separate ICUs.
T146 12441-12526 Sentence denotes Spontaneous intrapulmonary bleeding and haemoptysis are typical complications of IPA.
T147 12527-12658 Sentence denotes Ground‐glass opacities characterise COVID‐19 as well as IPA, thus comprehensive microbiological evaluation can prevent missing IPA.
T148 12659-12923 Sentence denotes By applying strict interpretation of the host and risk factors for invasive aspergillosis according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group definitions the risk of missed diagnosis increases in the COVID‐19 population.
T149 12924-13096 Sentence denotes 8 However, a most complicated issue in ARDS patients is to differentiate Aspergillus colonisation from invasive disease—especially as radiological imaging is non‐specific.
T150 13097-13243 Sentence denotes To address this issue, a consensus project will seek to provide standard definitions for invasive fungal disease in critically ill adult patients.
T151 13244-13246 Sentence denotes 10
T152 13247-13418 Sentence denotes Our observations suggest increased risk for critically ill COVID‐19 patients to develop co‐infection with Aspergillus, which is likely to increase mortality rates further.
T153 13419-13595 Sentence denotes Therefore, testing for the presence of Aspergillus in lower respiratory secretions and galactomannan in consecutive serum samples in COVID‐19 ICU patients should be considered.
T154 13596-13598 Sentence denotes 11
T155 13599-13706 Sentence denotes Our findings need to be confirmed in clinical trials to elucidate the role of potential IPA after COVID‐19.
T156 13707-13820 Sentence denotes With this report, we aim to call attention to the critical phenomenon of COVID‐19 associated IA in ARDS patients.
T157 13822-13842 Sentence denotes CONFLICT OF INTEREST
T158 13843-14301 Sentence denotes PK has received non‐financial scientific grants from Miltenyi Biotec GmbH, Bergisch Gladbach, Germany, and the Cologne Excellence Cluster on Cellular Stress Responses in Aging‐Associated Diseases, University of Cologne, Cologne, Germany, and received lecture honoraria from Akademie für Infektionsmedizin e.V., Astellas Pharma, Gilead Sciences, GPR Academy Ruesselsheim, MSD Sharp & Dohme GmbH, and University Hospital, LMU Munich outside the submitted work.
T159 14302-15016 Sentence denotes OAC is supported by the German Federal Ministry of Research and Education, is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy—CECAD, EXC 2030—390 661 388 and has received research grants from, is an advisor to, or received lecture honoraria from Actelion, Allecra Therapeutics, Amplyx, Astellas, Basilea, Biosys UK Limited, Cidara, Da Volterra, Entasis, F2G, Gilead, Grupo Biotoscana, Janssen Pharmaceuticals, Matinas, Medicines Company, MedPace, Melinta Therapeutics, Menarini Ricerche, Roche Diagnostics, Merck/MSD, Nabriva Therapeutics, Octapharma, Paratek Pharmaceuticals, Pfizer, PSI, Rempex, Scynexis, Seres Therapeutics, Tetraphase, Vical.
T160 15017-15539 Sentence denotes BWB is European Resuscitation Council (ERC) Board Director Science and Research; Chairman of the German Resuscitation Council (GRC); Member of the Advanced Life Support (ALS) Task Force of the International Liaison Committee on Resuscitation (ILCOR); Member of the executive committee of the German Interdisciplinary Association for Intensive and Emergency Medicine (DIVI); Associated Editor of the European Journal of Anaesthesiology (EJA), Co‐Editor of ‘Resuscitation’; Editor of the Journal ‘Notfall + Rettungsmedizin’.
T161 15540-15612 Sentence denotes He received professional fees for lectures from the following companies:
T162 15613-15751 Sentence denotes Medupdate GmbH, ‘Forum für medizinische Fortbildung (FomF)’, Baxalta Deutschland GmbH, Bayer Vital GmbH, ZOLL Medical Deutschland GmbH, C.
T163 15752-15754 Sentence denotes R.
T164 15755-15798 Sentence denotes Bard GmbH, GS Elektromedizinische Geräte G.
T165 15799-15860 Sentence denotes Stemple GmbH, Novartis Pharma GmbH, Philips GmbH Market DACH.
T166 15861-16004 Sentence denotes FD reports personal fees from Forum für medizinische Fortbildung GmbH, BioMérieux GmBH, M3 Inc, and pm‐result GmbH, outside the submitted work.
T167 16005-16008 Sentence denotes FD:
T168 16009-16051 Sentence denotes Associated Editor of 'BMC Anesthesiology'.
T169 16052-16094 Sentence denotes DAE has no potential conflict of interest.
T170 16095-16242 Sentence denotes FF reports scientific grants from the Medical Faculty of the University of Cologne (Maria Pesch grant and GEROK grant), outside the submitted work.
T171 16243-16748 Sentence denotes MH reports grants from Roche, personal fees from Roche, personal fees from Roche, grants from Abbvie, personal fees from Abbvie, personal fees from Abbvie, during the conduct of the study; grants from Gilead, personal fees from Gilead, personal fees from Gilead, grants from Janssen, personal fees from Janssen, personal fees from Janssen, personal fees from Celgene, personal fees from Celgene, personal fees from Boehringer Ingelheim, personal fees from Boehringer Ingelheim, outside the submitted work.
T172 16749-16894 Sentence denotes NJ reports lecture fees from Gilead, Infectopharm and MSD and travel grants from Gilead, Basilea, Correvio and Pfizer outside the submitted work.
T173 16895-17108 Sentence denotes FK is supported by the German Center for Infection Research (DZIF), the German Research Foundation (CRC 1279 and CRC 1310), the Bill and Melinda Gates Foundation, and the European Research Council (ERC‐StG639961).
T174 17109-17206 Sentence denotes FK received lecture and consulting honoraria from MSD, Roche and ViiV outside the submitted work.
T175 17207-17248 Sentence denotes TP has no potential conflict of interest.
T176 17249-17276 Sentence denotes JR has nothing to disclose.
T177 17277-17402 Sentence denotes MK reports personal fees from Pfizer, Astellas Pharma, Gilead Sciences and MSD Sharp & Dohme GmbH outside the submitted work.
T178 17403-17581 Sentence denotes BB is a consultant to Baxalta, Celgene, MSD, Mundipharma and received Honoraria and Research funding from Astellas, Celgene, J&J, Maquet, Miltenyi, MSD, Takeda, Roche and Sanofi.
T179 17582-17656 Sentence denotes ASV reports travel grants from Gilead Sciences outside the submitted work.
T180 17658-17678 Sentence denotes AUTHOR CONTRIBUTIONS
T181 17679-17695 Sentence denotes Philipp Koehler:
T182 17696-17807 Sentence denotes Conceptualization (lead); Investigation (lead); Writing‐original draft (lead); Writing‐review & editing (lead).
T183 17808-17817 Sentence denotes Oliver A.
T184 17818-17826 Sentence denotes Cornely:
T185 17827-17938 Sentence denotes Conceptualization (lead); Investigation (lead); Writing‐original draft (lead); Writing‐review & editing (lead).
T186 17939-17947 Sentence denotes Bernd W.
T187 17948-17957 Sentence denotes Böttiger:
T188 17958-18061 Sentence denotes Investigation (supporting); Writing‐original draft (supporting); Writing‐review & editing (supporting).
T189 18062-18075 Sentence denotes Fabian Dusse:
T190 18076-18179 Sentence denotes Investigation (supporting); Writing‐original draft (supporting); Writing‐review & editing (supporting).
T191 18180-18189 Sentence denotes Dennis A.
T192 18190-18201 Sentence denotes Eichenauer:
T193 18202-18305 Sentence denotes Investigation (supporting); Writing‐original draft (supporting); Writing‐review & editing (supporting).
T194 18306-18320 Sentence denotes Frieder Fuchs:
T195 18321-18424 Sentence denotes Investigation (supporting); Writing‐original draft (supporting); Writing‐review & editing (supporting).
T196 18425-18440 Sentence denotes Michael Hallek:
T197 18441-18544 Sentence denotes Investigation (supporting); Writing‐original draft (supporting); Writing‐review & editing (supporting).
T198 18545-18556 Sentence denotes Norma Jung:
T199 18557-18660 Sentence denotes Investigation (supporting); Writing‐original draft (supporting); Writing‐review & editing (supporting).
T200 18661-18675 Sentence denotes Florian Klein:
T201 18676-18779 Sentence denotes Investigation (supporting); Writing‐original draft (supporting); Writing‐review & editing (supporting).
T202 18780-18799 Sentence denotes Thorsten Persigehl:
T203 18800-18903 Sentence denotes Investigation (supporting); Writing‐original draft (supporting); Writing‐review & editing (supporting).
T204 18904-18917 Sentence denotes Jan Rybniker:
T205 18918-19021 Sentence denotes Investigation (supporting); Writing‐original draft (supporting); Writing‐review & editing (supporting).
T206 19022-19040 Sentence denotes Matthias Kochanek:
T207 19041-19144 Sentence denotes Investigation (supporting); Writing‐original draft (supporting); Writing‐review & editing (supporting).
T208 19145-19156 Sentence denotes Boris Böll:
T209 19157-19242 Sentence denotes Investigation (lead); Writing‐original draft (lead); Writing‐review & editing (lead).
T210 19243-19275 Sentence denotes Alexander Shimabukuro‐Vornhagen:
T211 19276-19361 Sentence denotes Investigation (lead); Writing‐original draft (lead); Writing‐review & editing (lead).
T212 19363-19379 Sentence denotes ETHICAL APPROVAL
T213 19380-19504 Sentence denotes The authors confirm that the ethical policies of the journal, as noted in the author's guideline page, have been adhered to.
T214 19505-19656 Sentence denotes Our study was approved by the ethic committee of the University Hospital of Cologne (Identifier of the University of Cologne Ethics Committee 20‐1157).
T215 19658-19680 Sentence denotes Supporting information
T216 19681-19689 Sentence denotes Video S1
T217 19690-19726 Sentence denotes Click here for additional data file.
T218 19727-19735 Sentence denotes Video S2
T219 19736-19772 Sentence denotes Click here for additional data file.
T220 19773-19781 Sentence denotes Video S3
T221 19782-19818 Sentence denotes Click here for additional data file.
T222 19819-19827 Sentence denotes Video S4
T223 19828-19864 Sentence denotes Click here for additional data file.
T224 19865-19873 Sentence denotes Video S5
T225 19874-19910 Sentence denotes Click here for additional data file.
T226 19911-19933 Sentence denotes Supplementary Material
T227 19934-19970 Sentence denotes Click here for additional data file.
T228 19972-19986 Sentence denotes ACKNOWLEDGMENT
T229 19987-20047 Sentence denotes The authors thank Susann Blossfeld for technical assistance.