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Article ; Online: A case of parotitis caused by hMPX virus.

de Regt, Marieke / Ooijevaar, Rogier / Jonges, Marcel / Welkers, Matthijs R A / Wagemakers, Alex

2023 Volume 401, Issue 10374, Page(s) e17

MeSH term(s)	Humans ; Parotitis/drug therapy ; Parotitis/etiology ; Mpox (monkeypox)/complications ; Monkeypox virus
Language	English
Publishing date	2023-01-16
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	3306-6
ISSN	1474-547X ; 0023-7507 ; 0140-6736
ISSN (online)	1474-547X
ISSN	0023-7507 ; 0140-6736
DOI	10.1016/S0140-6736(23)00047-8
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Article ; Online: Clinically relevant DNA viruses in pregnancy.

Linthorst, Jasper / Welkers, Matthijs R A / Sistermans, Erik A

Prenatal diagnosis

2022 Volume 43, Issue 4, Page(s) 457–466

Abstract: Infections by DNA viruses during pregnancy are associated with increased health risks to both mother and fetus. Although not all DNA viruses are related to an increased risk of complications during pregnancy, several can directly infect the fetus and/or ... ...

Abstract	Infections by DNA viruses during pregnancy are associated with increased health risks to both mother and fetus. Although not all DNA viruses are related to an increased risk of complications during pregnancy, several can directly infect the fetus and/or cause placental dysfunction. During Non-Invasive Prenatal Testing analysis, the presence of viral DNA can be detected, theoretically allowing screening early in pregnancy. Although treatment options are currently limited, this might rapidly change in the near future. It is therefore important to be aware of the potential impact of these viruses on feto-maternal health. In this manuscript we provide a brief introduction into the most commonly detected DNA viruses in human cell-free DNA sequencing experiments and their pathogenic potential during pregnancy.
MeSH term(s)	Pregnancy ; Humans ; Female ; Placenta ; Fetus ; DNA Viruses/genetics ; Prenatal Diagnosis/adverse effects
Language	English
Publishing date	2022-03-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	82031-3
ISSN	1097-0223 ; 0197-3851
ISSN (online)	1097-0223
ISSN	0197-3851
DOI	10.1002/pd.6116
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Article ; Online: The cell-free DNA virome of 108,349 Dutch pregnant women.

Linthorst, Jasper / Baksi, Moezammin M M / Welkers, Matthijs R A / Sistermans, Erik A

Prenatal diagnosis

2022 Volume 43, Issue 4, Page(s) 448–456

Abstract: Objective: Viral infections during pregnancy are a major health concern to mother and fetus. By repurposing cell-free Non Invasive Prenatal Testing (NIPT) sequencing data, we investigated prevalence and abundance of viral DNA in a cohort of 108,349 ... ...

Abstract	Objective: Viral infections during pregnancy are a major health concern to mother and fetus. By repurposing cell-free Non Invasive Prenatal Testing (NIPT) sequencing data, we investigated prevalence and abundance of viral DNA in a cohort of 108,349 pregnant women. Method: Cell-free DNA (cfDNA) sequencing reads that did not map to any of the human chromosomes or mitochondrial DNA of the human reference genome build GRCh38 were aligned to 224 DNA viruses selected from the NCBI refseq viral database. Results: In total 443,665 reads of viral origin were detected across 42,273 samples representing 165 viral species. Several are known to be potentially harmful during pregnancy and/or childbirth, including Cytomegalovirus, Parvovirus B19 and Hepatitis B. Viral sequences were mostly detected at very low abundance. However, several cases had exceptionally high viral loads for Parvovirus B19, Hepatitis B and others. We found statistically significant associations between presence of viral DNA and gestational age, maternal age, fetal fraction, cfDNA concentration and others. Conclusion: We demonstrate the feasibility to detect viral DNA from typical genome-wide NIPT cfDNA sequencing and describe the main characteristics of the viral DNA in our cohort. Our dataset of detected viral sequence reads is made publicly available to guide future clinical implementations.
MeSH term(s)	Pregnancy ; Humans ; Female ; DNA, Viral ; Pregnant Women ; Cell-Free Nucleic Acids/genetics ; Virome ; Hepatitis B ; Prenatal Diagnosis
Chemical Substances	DNA, Viral ; Cell-Free Nucleic Acids
Language	English
Publishing date	2022-04-27
Publishing country	England
Document type	Journal Article
ZDB-ID	82031-3
ISSN	1097-0223 ; 0197-3851
ISSN (online)	1097-0223
ISSN	0197-3851
DOI	10.1002/pd.6143
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Article ; Online: Development of Resistance-Associated Mutations After Sotrovimab Administration in High-risk Individuals Infected With the SARS-CoV-2 Omicron Variant.

Birnie, Emma / Biemond, Jason J / Appelman, Brent / de Bree, Godelieve J / Jonges, Marcel / Welkers, Matthijs R A / Wiersinga, W Joost

JAMA

2022 Volume 328, Issue 11, Page(s) 1104–1107

MeSH term(s)	Antibodies, Monoclonal, Humanized/adverse effects ; Antibodies, Monoclonal, Humanized/pharmacology ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antibodies, Neutralizing/adverse effects ; Antibodies, Neutralizing/pharmacology ; Antibodies, Neutralizing/therapeutic use ; COVID-19/genetics ; COVID-19/virology ; Drug Resistance, Viral/drug effects ; Drug Resistance, Viral/genetics ; Humans ; Mutation ; SARS-CoV-2/drug effects ; SARS-CoV-2/genetics ; COVID-19 Drug Treatment
Chemical Substances	Antibodies, Monoclonal, Humanized ; Antibodies, Neutralizing ; sotrovimab (1MTK0BPN8V)
Language	English
Publishing date	2022-08-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2958-0
ISSN	1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
ISSN (online)	1538-3598
ISSN	0254-9077 ; 0002-9955 ; 0098-7484
DOI	10.1001/jama.2022.13854
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Article: Possible host-adaptation of SARS-CoV-2 due to improved ACE2 receptor binding in mink.

Welkers, Matthijs R A / Han, Alvin X / Reusken, Chantal B E M / Eggink, Dirk

Virus evolution

2021 Volume 7, Issue 1, Page(s) veaa094

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on mink farms are increasingly observed in several countries, leading to the massive culling of animals on affected farms. Recent studies showed multiple (anthropo)zoonotic ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on mink farms are increasingly observed in several countries, leading to the massive culling of animals on affected farms. Recent studies showed multiple (anthropo)zoonotic transmission events between humans and mink on these farms. Mink-derived SARS-CoV-2 sequences from The Netherlands and Denmark contain multiple substitutions in the S protein receptor binding domain (RBD). Molecular modeling showed that these substitutions increase the mean binding energy, suggestive of potential adaptation of the SARS-CoV-2 S protein to the mink angiotensin-converting enzyme 2 (ACE2) receptor. These substitutions could possibly also impact human ACE2 binding affinity as well as humoral immune responses directed to the RBD region of the SARS-CoV-2 S protein in humans. We wish to highlight these observations to raise awareness and urge for the continued surveillance of mink (and other animal)-related infections.
Language	English
Publishing date	2021-01-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2818949-8
ISSN	2057-1577
ISSN	2057-1577
DOI	10.1093/ve/veaa094
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Article ; Online: Reptile-associated Salmonella urinary tract infection: a case report.

Bruning, Andrea H L / Beld, Maaike van den / Laverge, Jeroen / Welkers, Matthijs R A / Kuil, Sacha D / Bruisten, Sylvia M / van Dam, Alje P / Stam, Arjen J

Diagnostic microbiology and infectious disease

2023 Volume 105, Issue 4, Page(s) 115889

Abstract: We present an 18-year-old woman with a urinary tract infection caused by Salmonella Oranienburg. S. Oranienburg was isolated from her pet snake and confirmed as the source of infection using whole genome sequencing. Our case demonstrates the risk of ... ...

Abstract	We present an 18-year-old woman with a urinary tract infection caused by Salmonella Oranienburg. S. Oranienburg was isolated from her pet snake and confirmed as the source of infection using whole genome sequencing. Our case demonstrates the risk of acquiring reptile-associated salmonellosis and stretches the need for awareness to prevent these infections.
MeSH term(s)	Humans ; Animals ; Female ; Adolescent ; Zoonoses/prevention & control ; Salmonella Infections, Animal/diagnosis ; Salmonella/genetics ; Reptiles ; Urinary Tract Infections/diagnosis ; Urinary Tract Infections/drug therapy
Language	English
Publishing date	2023-01-04
Publishing country	United States
Document type	Case Reports
ZDB-ID	604920-5
ISSN	1879-0070 ; 0732-8893
ISSN (online)	1879-0070
ISSN	0732-8893
DOI	10.1016/j.diagmicrobio.2022.115889
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Article: Optimizing Antiviral Dosing for HSV and CMV Treatment in Immunocompromised Patients.

Huntjens, Daan W / Dijkstra, Jacob A / Verwiel, Lisanne N / Slijkhuis, Mirjam / Elbers, Paul / Welkers, Matthijs R A / Veldkamp, Agnes I / Kuijvenhoven, Marianne A / de Leeuw, David C / Abdullah-Koolmees, Heshu / Kuipers, Maria T / Bartelink, Imke H

Pharmaceutics

2023 Volume 15, Issue 1

Abstract: Herpes simplex virus (HSV) and cytomegalovirus (CMV) are DNA viruses that are common among humans. Severely immunocompromised patients are at increased risk of developing HSV or CMV disease due to a weakened immune system. Antiviral therapy can be ... ...

Abstract	Herpes simplex virus (HSV) and cytomegalovirus (CMV) are DNA viruses that are common among humans. Severely immunocompromised patients are at increased risk of developing HSV or CMV disease due to a weakened immune system. Antiviral therapy can be challenging because these drugs have a narrow therapeutic window and show significant pharmacokinetic variability. Above that, immunocompromised patients have various comorbidities like impaired renal function and are exposed to polypharmacy. This scoping review discusses the current pharmacokinetic (PK) and pharmacodynamic (PD) knowledge of antiviral drugs for HSV and CMV treatment in immunocompromised patients. HSV and CMV treatment guidelines are discussed, and multiple treatment interventions are proposed: early detection of drug resistance; optimization of dose to target concentration by therapeutic drug monitoring (TDM) of nucleoside analogs; the introduction of new antiviral drugs; alternation between compounds with different toxicity profiles; and combinations of synergistic antiviral drugs. This research will also serve as guidance for future research, which should focus on prospective evaluation of the benefit of each of these interventions in randomized controlled trials.
Language	English
Publishing date	2023-01-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15010163
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Article ; Online: Circulation, viral diversity and genomic rearrangement in mpox virus in the Netherlands during the 2022 outbreak and beyond.

Schuele, Leonard / Boter, Marjan / Nieuwenhuijse, David F / Götz, Hannelore / Fanoy, Ewout / de Vries, Henry / Vieyra, Bruno / Bavalia, Roisin / Hoornenborg, Elske / Molenkamp, Richard / Jonges, Marcel / van den Ouden, Anton / Simões, Margarida / van den Lubben, Mariken / Koopmans, Marion / Welkers, Matthijs R A / Oude Munnink, Bas B

Journal of medical virology

2024 Volume 96, Issue 1, Page(s) e29397

Abstract: Mpox is an emerging zoonotic disease which has now spread to over 113 countries as of August 2023, with over 89,500 confirmed human cases. The Netherlands had one of the highest incidence rates in Europe during the peak of the outbreak. In this study, we ...

Abstract	Mpox is an emerging zoonotic disease which has now spread to over 113 countries as of August 2023, with over 89,500 confirmed human cases. The Netherlands had one of the highest incidence rates in Europe during the peak of the outbreak. In this study, we generated 158 near-complete mpox virus (MPXV) genomes (12.4% of nationwide cases) that were collected throughout the Netherlands from the start of the outbreak in May 2022 to August 2023 to track viral evolution and investigate outbreak dynamics. We detected 14 different viral lineages, suggesting multiple introductions followed by rapid initial spread within the country. The estimated evolutionary rate was relatively high compared to previously described in orthopoxvirus literature, with an estimated 11.58 mutations per year. Genomic rearrangement events occurred at a rate of 0.63% and featured a large deletion event. In addition, based on phylogenetics, we identified multiple potential transmission clusters which could be supported by direct source- and contact tracing data. This led to the identification of at least two main transmission locations at the beginning of the outbreak. We conclude that whole genome sequencing of MPXV is essential to enhance our understanding of outbreak dynamics and evolution of a relatively understudied and emerging zoonotic pathogen.
MeSH term(s)	Humans ; Monkeypox virus ; Netherlands/epidemiology ; Genomics ; Disease Outbreaks ; Europe
Language	English
Publishing date	2024-01-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.29397
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Article ; Online: Uitbraak van monkeypox: een nieuwe pandemie?

de Stoppelaar, Sacha F / Hoornenborg, Elske / van Rijckevorsel, Gini / Vollaard, Albert / Brandwagt, Diederik A H / de Vries, Henry J C / Schinkel, Janke / Welkers, Matthijs R A / Goorhuis, A

Nederlands tijdschrift voor geneeskunde

2022 Volume 166

Abstract: Monkeypox (MPX) is a disease caused by the monkeypox virus. It is a viral zoonotic disease, endemic in Central and West Africa. Human-to-human spread also occurs and is a feature of the current global outbreak. As far as we know, exponential transmission ...

Title translation	Monkeypox, a new pandemic?
Abstract	Monkeypox (MPX) is a disease caused by the monkeypox virus. It is a viral zoonotic disease, endemic in Central and West Africa. Human-to-human spread also occurs and is a feature of the current global outbreak. As far as we know, exponential transmission during this outbreak is not related to changed viral characteristics but due to multiple high-risk contacts in a subset of people that have contracted the virus, so far almost exclusively affecting men who have sex with men (MSM). Appropriate public health measures and increased alertness of all health care providers is needed to increase case-finding and decrease transmission. There is a real chance of MPX to become endemic in large parts of the world.
MeSH term(s)	Male ; Humans ; Mpox (monkeypox)/epidemiology ; Homosexuality, Male ; Pandemics ; Sexual and Gender Minorities ; Monkeypox virus
Language	Dutch
Publishing date	2022-09-08
Publishing country	Netherlands
Document type	English Abstract ; Journal Article
ZDB-ID	82073-8
ISSN	1876-8784 ; 0028-2162
ISSN (online)	1876-8784
ISSN	0028-2162
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Article ; Online: Hyperimmune Globulin for Severely Immunocompromised Patients Hospitalized With Coronavirus Disease 2019: A Randomized, Controlled Trial.

Huygens, Sammy / Hofsink, Quincy / Nijhof, Inger S / Goorhuis, Abraham / Kater, Arnon P / Te Boekhorst, Peter A W / Swaneveld, Francis / Novotný, Věra M J / Bogers, Susanne / Welkers, Matthijs R A / Papageorgiou, Grigorios / Rijnders, Bart J / Heijmans, Jarom

The Journal of infectious diseases

2022 Volume 227, Issue 2, Page(s) 206–210

Abstract: Background: The aim of this randomized, controlled trial is to determine whether antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin (COVIG) protects against severe coronavirus disease 2019 (COVID-19) in severely immunocompromised, ... ...

Abstract	Background: The aim of this randomized, controlled trial is to determine whether antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin (COVIG) protects against severe coronavirus disease 2019 (COVID-19) in severely immunocompromised, hospitalized, COVID-19 patients. Methods: Patients were randomly assigned to receive COVIG or intravenous immunoglobulin (IVIG) without SARS-CoV-2 antibodies. Results: Severe COVID-19 was observed in 2 of 10 (20%) patients treated with COVIG compared to 7 of 8 (88%) in the IVIG control group (P = .015, Fisher's exact test). Conclusions: Antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin may be a valuable treatment in severely immunocompromised, hospitalized, COVID-19 patients and should be considered when no monoclonal antibody therapies are available.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Immunoglobulins, Intravenous/therapeutic use ; Treatment Outcome ; COVID-19 Serotherapy ; Immunization, Passive/adverse effects
Chemical Substances	Immunoglobulins, Intravenous
Language	English
Publishing date	2022-08-03
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiac334
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