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Article ; Online: Reply to Author.

Walk, Jona / Janssen, Rob / Dofferhoff, Anton S M

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2021 Volume 73, Issue 7, Page(s) 1325

Language	English
Publishing date	2021-03-18
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciab166
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Article ; Online: COVID-19-associated pulmonary aspergillosis: a prospective single-center dual case series.

Meijer, Eelco F J / Dofferhoff, Anton S M / Hoiting, Oscar / Meis, Jacques F

Mycoses

2021 Volume 64, Issue 4, Page(s) 457–464

Abstract: Background: COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as an invasive fungal disease, often affecting previously immunocompetent, mechanically ventilated, intensive care unit (ICU) patients. Incidence rates of 3.8%-33.3% have been ... ...

Abstract	Background: COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as an invasive fungal disease, often affecting previously immunocompetent, mechanically ventilated, intensive care unit (ICU) patients. Incidence rates of 3.8%-33.3% have been reported depending on the geographic area, with high (47%) mortality. Objectives: Here, we describe a single-centre prospective case series with CAPA cases from both the first (March-May, n = 5/33) and second (mid-September through mid-December, n = 8/33) COVID-19 wave at a 500-bed teaching hospital in the Netherlands. Patients/methods: In the first COVID-19 wave, a total of 265 SARS-CoV-2 PCR-positive patients were admitted to our hospital of whom 33 needed intubation and mechanical ventilation. In the second wave, 508 SARS-CoV-2 PCR-positive patients were admitted of whom 33 needed mechanical ventilation. Data were prospectively collected. Results: We found a significant decrease in COVID-19 patients needing mechanical ventilation in the ICU in the second wave (p < .01). From these patients, however, a higher percentage were diagnosed with CAPA (24.2% vs 15.2%), although not significant (p = .36). All CAPA patients encountered in the second wave received dexamethasone. Mortality between both groups was similarly high (40%-50%). Moreover, we found environmental TR Conclusions: In this series, 19.7% (n = 13/66) of mechanically ventilated SARS-CoV-2 patients were diagnosed with CAPA. In addition, we found a significant reduction in COVID-19 patients needing mechanical ventilation on the ICU in the second wave. Numbers are too small to determine whether there is a true difference in CAPA incidence in mechanically ventilated patients between the two waves, and whether it could be attributed to dexamethasone SARS-CoV-2 therapy.
MeSH term(s)	Aged ; COVID-19/complications ; COVID-19/diagnosis ; Cohort Studies ; Female ; Humans ; Intensive Care Units ; Male ; Netherlands/epidemiology ; Polymerase Chain Reaction ; Prospective Studies ; Pulmonary Aspergillosis/complications ; Pulmonary Aspergillosis/epidemiology ; Pulmonary Aspergillosis/etiology ; Pulmonary Aspergillosis/mortality ; Respiration, Artificial ; Respiratory Insufficiency/etiology ; Respiratory Insufficiency/therapy ; SARS-CoV-2/genetics ; SARS-CoV-2/isolation & purification
Language	English
Publishing date	2021-02-16
Publishing country	Germany
Document type	Journal Article
ZDB-ID	392487-7
ISSN	1439-0507 ; 0933-7407
ISSN (online)	1439-0507
ISSN	0933-7407
DOI	10.1111/myc.13254
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Article: Vitamin K metabolism as the potential missing link between lung damage and thromboembolism in Coronavirus disease 2019

Janssen, Rob / Visser, Margot P. J / Dofferhoff, Anton S. M / Vermeer, Cees / Janssens, Wim / Walk, Jona

British journal of nutrition. 2021 July 28, v. 126, no. 2

2021

Abstract: Coronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2, exerts far-reaching effects on public health and socio-economic welfare. The majority of infected individuals have mild to moderate symptoms, but a ...

Abstract	Coronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2, exerts far-reaching effects on public health and socio-economic welfare. The majority of infected individuals have mild to moderate symptoms, but a significant proportion develops respiratory failure due to pneumonia. Thrombosis is another frequent manifestation of Covid-19 that contributes to poor outcomes. Vitamin K plays a crucial role in the activation of both pro- and anticlotting factors in the liver and the activation of extrahepatically synthesised protein S which seems to be important in local thrombosis prevention. However, the role of vitamin K extends beyond coagulation. Matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of soft tissue calcification and elastic fibre degradation. Severe extrahepatic vitamin K insufficiency was recently demonstrated in Covid-19 patients, with high inactive MGP levels correlating with elastic fibre degradation rates. This suggests that insufficient vitamin K-dependent MGP activation leaves elastic fibres unprotected against SARS-CoV-2-induced proteolysis. In contrast to MGP, Covid-19 patients have normal levels of activated factor II, in line with previous observations that vitamin K is preferentially transported to the liver for activation of procoagulant factors. We therefore expect that vitamin K-dependent endothelial protein S activation is also compromised, which would be compatible with enhanced thrombogenicity. Taking these data together, we propose a mechanism of pneumonia-induced vitamin K depletion, leading to a decrease in activated MGP and protein S, aggravating pulmonary damage and coagulopathy, respectively. Intervention trials should be conducted to assess whether vitamin K administration plays a role in the prevention and treatment of severe Covid-19.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus ; calcification ; coagulation ; liver ; lungs ; metabolism ; pneumonia ; proteolysis ; public health ; socioeconomics ; thrombosis ; tissues ; vitamin K
Language	English
Dates of publication	2021-0728
Size	p. 191-198.
Publishing place	Cambridge University Press
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	280396-3
ISSN	1475-2662 ; 0007-1145
ISSN (online)	1475-2662
ISSN	0007-1145
DOI	10.1017/S0007114520003979
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Article ; Online: Vitamin K metabolism as the potential missing link between lung damage and thromboembolism in Coronavirus disease 2019.

Janssen, Rob / Visser, Margot P J / Dofferhoff, Anton S M / Vermeer, Cees / Janssens, Wim / Walk, Jona

The British journal of nutrition

2020 Volume 126, Issue 2, Page(s) 191–198

Abstract	Coronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2, exerts far-reaching effects on public health and socio-economic welfare. The majority of infected individuals have mild to moderate symptoms, but a significant proportion develops respiratory failure due to pneumonia. Thrombosis is another frequent manifestation of Covid-19 that contributes to poor outcomes. Vitamin K plays a crucial role in the activation of both pro- and anticlotting factors in the liver and the activation of extrahepatically synthesised protein S which seems to be important in local thrombosis prevention. However, the role of vitamin K extends beyond coagulation. Matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of soft tissue calcification and elastic fibre degradation. Severe extrahepatic vitamin K insufficiency was recently demonstrated in Covid-19 patients, with high inactive MGP levels correlating with elastic fibre degradation rates. This suggests that insufficient vitamin K-dependent MGP activation leaves elastic fibres unprotected against SARS-CoV-2-induced proteolysis. In contrast to MGP, Covid-19 patients have normal levels of activated factor II, in line with previous observations that vitamin K is preferentially transported to the liver for activation of procoagulant factors. We therefore expect that vitamin K-dependent endothelial protein S activation is also compromised, which would be compatible with enhanced thrombogenicity. Taking these data together, we propose a mechanism of pneumonia-induced vitamin K depletion, leading to a decrease in activated MGP and protein S, aggravating pulmonary damage and coagulopathy, respectively. Intervention trials should be conducted to assess whether vitamin K administration plays a role in the prevention and treatment of severe Covid-19.
MeSH term(s)	COVID-19/complications ; COVID-19/pathology ; Calcium-Binding Proteins/metabolism ; Extracellular Matrix Proteins/metabolism ; Humans ; Lung/physiopathology ; Protein S/metabolism ; SARS-CoV-2 ; Thromboembolism/etiology ; Thromboembolism/prevention & control ; Thrombosis/etiology ; Thrombosis/prevention & control ; Vitamin K/antagonists & inhibitors ; Vitamin K/metabolism ; Vitamin K Deficiency/etiology ; Vitamin K Deficiency/metabolism ; Matrix Gla Protein
Chemical Substances	Calcium-Binding Proteins ; Extracellular Matrix Proteins ; Protein S ; Vitamin K (12001-79-5)
Keywords	covid19
Language	English
Publishing date	2020-10-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	280396-3
ISSN	1475-2662 ; 0007-1145
ISSN (online)	1475-2662
ISSN	0007-1145
DOI	10.1017/S0007114520003979
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Article ; Online: Azole-Resistant COVID-19-Associated Pulmonary Aspergillosis in an Immunocompetent Host: A Case Report.

Meijer, Eelco F J / Dofferhoff, Anton S M / Hoiting, Oscar / Buil, Jochem B / Meis, Jacques F

Journal of fungi (Basel, Switzerland)

2020 Volume 6, Issue 2

Abstract: COVID-19-associated pulmonary aspergillosis (CAPA) is a recently described disease entity affecting patients with severe pulmonary abnormalities treated in intensive care units. Delays in diagnosis contribute to a delayed start of antifungal therapy. In ... ...

Abstract	COVID-19-associated pulmonary aspergillosis (CAPA) is a recently described disease entity affecting patients with severe pulmonary abnormalities treated in intensive care units. Delays in diagnosis contribute to a delayed start of antifungal therapy. In addition, the emergence of resistance to triazole antifungal agents puts emphasis on early surveillance for azole-resistant
Keywords	covid19
Language	English
Publishing date	2020-06-06
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2784229-0
ISSN	2309-608X ; 2309-608X
ISSN (online)	2309-608X
ISSN	2309-608X
DOI	10.3390/jof6020079
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Article: Effects of Vitamin D and K on Interleukin-6 in COVID-19.

Visser, Margot P J / Dofferhoff, Anton S M / van den Ouweland, Jody M W / van Daal, Henny / Kramers, Cornelis / Schurgers, Leon J / Janssen, Rob / Walk, Jona

Frontiers in nutrition

2022 Volume 8, Page(s) 761191

Abstract: Background: Pathology during COVID-19 infection arises partly from an excessive inflammatory response with a key role for interleukin (IL)-6. Both vitamin D and K have been proposed as potential modulators of this process.: Methods: We assessed ... ...

Abstract	Background: Pathology during COVID-19 infection arises partly from an excessive inflammatory response with a key role for interleukin (IL)-6. Both vitamin D and K have been proposed as potential modulators of this process. Methods: We assessed vitamin D and K status by measuring circulating 25-hydroxyvitamin D (25(OH)D) and desphospho-uncarboxylated Matrix Gla-Protein (dp-ucMGP), respectively in 135 hospitalized COVID-19 patients in relation to inflammatory response, elastic fiber degradation and clinical outcomes. Results: Comparing good and poor disease outcomes of COVID-19 patients, vitamin 25(OH)D levels were not significantly different. IL-6 levels, however, were significantly higher in patients with poor outcome, compared to patients with good outcome (30.3 vs. 153.0 pg/mL; Conclusions: Dp-ucMGP associates with IL-6 as a central component of the destructive inflammatory processes in COVID-19. An intervention trial may provide insight whether vitamin K administration, either or not in combination with vitamin D, improves clinical outcome of COVID-19.
Language	English
Publishing date	2022-01-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2776676-7
ISSN	2296-861X
ISSN	2296-861X
DOI	10.3389/fnut.2021.761191
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Article: Corrigendum: Effects of Vitamin D and K on Interleukin-6 in COVID-19.

Visser, Margot P J / Dofferhoff, Anton S M / van den Ouweland, Jody M W / van Daal, Henny / Kramers, Cornelis / Schurgers, Leon J / Janssen, Rob / Walk, Jona

Frontiers in nutrition

2022 Volume 9, Page(s) 868324

Abstract: This corrects the article DOI: 10.3389/fnut.2021.761191.]. ...

Abstract	[This corrects the article DOI: 10.3389/fnut.2021.761191.].
Language	English
Publishing date	2022-03-08
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2776676-7
ISSN	2296-861X
ISSN	2296-861X
DOI	10.3389/fnut.2022.868324
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Article ; Online: Vitamin K metabolism as the potential missing link between lung damage and thromboembolism in Coronavirus disease 2019

Janssen, Rob / Visser, Margot P. J. / Dofferhoff, Anton S. M. / Vermeer, Cees / Janssens, Wim / Walk, Jona

British Journal of Nutrition

2020 , Page(s) 1–8

Abstract: Abstract Coronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2, exerts far-reaching effects on public health and socio-economic welfare. The majority of infected individuals have mild to moderate ... ...

Abstract	Abstract Coronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2, exerts far-reaching effects on public health and socio-economic welfare. The majority of infected individuals have mild to moderate symptoms, but a significant proportion develops respiratory failure due to pneumonia. Thrombosis is another frequent manifestation of Covid-19 that contributes to poor outcomes. Vitamin K plays a crucial role in the activation of both pro- and anticlotting factors in the liver and the activation of extrahepatically synthesised protein S which seems to be important in local thrombosis prevention. However, the role of vitamin K extends beyond coagulation. Matrix Gla protein (MGP) is a vitamin K-dependent inhibitor of soft tissue calcification and elastic fibre degradation. Severe extrahepatic vitamin K insufficiency was recently demonstrated in Covid-19 patients, with high inactive MGP levels correlating with elastic fibre degradation rates. This suggests that insufficient vitamin K-dependent MGP activation leaves elastic fibres unprotected against SARS-CoV-2-induced proteolysis. In contrast to MGP, Covid-19 patients have normal levels of activated factor II, in line with previous observations that vitamin K is preferentially transported to the liver for activation of procoagulant factors. We therefore expect that vitamin K-dependent endothelial protein S activation is also compromised, which would be compatible with enhanced thrombogenicity. Taking these data together, we propose a mechanism of pneumonia-induced vitamin K depletion, leading to a decrease in activated MGP and protein S, aggravating pulmonary damage and coagulopathy, respectively. Intervention trials should be conducted to assess whether vitamin K administration plays a role in the prevention and treatment of severe Covid-19.
Keywords	Nutrition and Dietetics ; Medicine (miscellaneous) ; covid19
Language	English
Publisher	Cambridge University Press (CUP)
Publishing country	uk
Document type	Article ; Online
ZDB-ID	280396-3
ISSN	1475-2662 ; 0007-1145
ISSN (online)	1475-2662
ISSN	0007-1145
DOI	10.1017/s0007114520003979
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Article ; Online: Few bacterial co-infections but frequent empiric antibiotic use in the early phase of hospitalized patients with COVID-19: results from a multicentre retrospective cohort study in The Netherlands.

Karami, Zara / Knoop, Bram T / Dofferhoff, Anton S M / Blaauw, Marc J T / Janssen, Nico A / van Apeldoorn, Marjan / Kerckhoffs, Angèle P M / van de Maat, Josephine S / Hoogerwerf, Jacobien J / Ten Oever, Jaap

Infectious diseases (London, England)

2020 Volume 53, Issue 2, Page(s) 102–110

Abstract: Background: Knowledge on bacterial co-infections in COVID-19 is crucial to use antibiotics appropriately. Therefore, we aimed to determine the incidence of bacterial co-infections, antibiotic use and application of antimicrobial stewardship principles ... ...

Abstract	Background: Knowledge on bacterial co-infections in COVID-19 is crucial to use antibiotics appropriately. Therefore, we aimed to determine the incidence of bacterial co-infections, antibiotic use and application of antimicrobial stewardship principles in hospitalized patients with COVID-19. Methods: We performed a retrospective observational study in four hospitals (1 university, 2 non-university teaching, 1 non-teaching hospital) in the Netherlands from March to May 2020 including consecutive patients with PCR-confirmed COVID-19. Data on first microbiological investigations obtained at the discretion of the physician and antibiotic use in the first week of hospital admission were collected. Results: Twelve (1.2%) of the 925 patients included had a documented bacterial co-infection (75.0% pneumonia) within the first week. Microbiological testing was performed in 749 (81%) patients: sputum cultures in 105 (11.4%), blood cultures in 711 (76.9%), pneumococcal urinary antigen testing in 202 (21.8%), and Conclusions: On presentation to the hospital bacterial co-infections are rare, while empiric antibiotic use is abundant. This implies that in patients with COVID-19 empiric antibiotic should be withheld. This has the potential to dramatically reduce the current overuse of antibiotics in the COVID-19 pandemic.
MeSH term(s)	Aged ; Anti-Bacterial Agents/administration & dosage ; Antimicrobial Stewardship ; Bacterial Infections/drug therapy ; Bacterial Infections/epidemiology ; Bacterial Infections/microbiology ; Blood Culture ; COVID-19/epidemiology ; COVID-19/virology ; Coinfection ; Drug Administration Routes ; Drug Administration Schedule ; Female ; Guideline Adherence/statistics & numerical data ; Hospitalization ; Humans ; Incidence ; Male ; Middle Aged ; Netherlands/epidemiology ; Pandemics ; Prescription Drug Overuse/prevention & control ; Prescription Drug Overuse/statistics & numerical data ; Retrospective Studies ; SARS-CoV-2/pathogenicity
Chemical Substances	Anti-Bacterial Agents
Keywords	covid19
Language	English
Publishing date	2020-10-24
Publishing country	England
Document type	Journal Article ; Multicenter Study ; Observational Study
ZDB-ID	2839775-7
ISSN	2374-4243 ; 2374-4235
ISSN (online)	2374-4243
ISSN	2374-4235
DOI	10.1080/23744235.2020.1839672
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Article ; Online: Prior use of therapeutic anticoagulation does not protect against COVID-19 related clinical outcomes in hospitalized patients: A propensity score-matched cohort study.

Spiegelenberg, Janneke P / van Gelder, Marleen M H J / Maas, Martje L / Hovens, Marcel M C / Esselink, Anne / Dofferhoff, Anton S M / Janssen, Rob / van de Maat, Josephine / Janssen, Nico / Blaauw, Marc / Hassing, Robert-Jan / van Apeldoorn, Marjan / Kerckhoffs, Angèle / Veerman, Karin / Hoogerwerf, Jacobien / Kramers, Cornelis / Leentjens, Jenneke

British journal of clinical pharmacology

2021 Volume 87, Issue 12, Page(s) 4839–4847

Abstract: The hypercoagulable state observed in COVID-19 could be responsible for morbidity and mortality. In this retrospective study we investigated whether therapeutic anticoagulation prior to infection has a beneficial effect in hospitalized COVID-19 patients. ...

Abstract	The hypercoagulable state observed in COVID-19 could be responsible for morbidity and mortality. In this retrospective study we investigated whether therapeutic anticoagulation prior to infection has a beneficial effect in hospitalized COVID-19 patients. This study included 1154 COVID-19 patients admitted to 6 hospitals in the Netherlands between March and May 2020. We applied 1:3 propensity score matching to evaluate the association between prior therapeutic anticoagulation use and clinical outcome, with in hospital mortality as primary endpoint. In total, 190 (16%) patients used therapeutic anticoagulation prior to admission. In the propensity score matched analyses, we observed no associations between prior use of therapeutic anticoagulation and overall mortality (risk ratio 1.02 [95% confidence interval; 0.80-1.30]) or length of hospital stay (7.0 [4-12] vs. 7.0 [4-12] days, P = .69), although we observed a lower risk of pulmonary embolism (0.19 [0.05-0.80]). This study shows that prior use of therapeutic anticoagulation is not associated with improved clinical outcome in hospitalized COVID-19 patients.
MeSH term(s)	Anticoagulants ; COVID-19 ; Cohort Studies ; Humans ; Propensity Score ; Retrospective Studies ; SARS-CoV-2
Chemical Substances	Anticoagulants
Language	English
Publishing date	2021-05-07
Publishing country	England
Document type	Journal Article
ZDB-ID	188974-6
ISSN	1365-2125 ; 0306-5251 ; 0264-3774
ISSN (online)	1365-2125
ISSN	0306-5251 ; 0264-3774
DOI	10.1111/bcp.14877
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