COVID-19

Publications related to COVID-19

A presentation of COVID-19 related publications from our researchers

• Buijsers B, Yanginlar C, de Nooijer A, Grondman I, Maciej-Hulme ML, Jonkman I, Janssen NAF, Rother N, de Graaf M, Pickkers P, Kox M, Joosten LAB, Nijenhuis T, Netea MG, Hilbrands L, van de Veerdonk FL, Duivenvoorden R, de Mast Q, van der Vlag J. Increased plasma heparanase activity in COVID-19 patients. Front Immunol 11:575047, 2020.

• Buijsers B, Yanginlar C, Maciej-Hulme ML, de Mast Q, van der Vlag J. Beneficial non-anticoagulant mechanisms underlying heparin treatment of COVID-19 patients. EBioMedicine 59:102969, 2020.

• Debisarun PA, Struycken P, Domínguez-Andrés J, Moorlag SJCFM, Taks E, Gössling KL, Ostermann PN, Müller L, Schaal H, ten Oever J, van Crevel R, Netea MG. The effect of influenza vaccination on trained immunity: impact on COVID-19. MetRxiv: 20212498, 2020.

• Dinmohamed AG, Visser O, Verhoeven RHA, Louwman MWJ, van Nederveen FH, Willems SM, Merkx MAW, Lemmens VEPP, Nagtegaal ID, Siesling S. Fewer cancer diagnoses during the COVID-19 epidemic in the Netherlands. Lancet Oncol S1470-2045: 30265-5, 2020.
   
• Gansevoort RT, Hilbrands LB. CKD is a key risk factor for COVID-19 mortality. Nat Rev Nephrol 16:705-706, 2020.

• Hilbrands LB, Duivenvoorden R, Vart P, Franssen CFM, Hemmelder MH, Jager KJ, Kieneker LM, Noordzij M, Pena MJ, Vries H, Arroyo D, Covic A, Crespo M, Goffin E, Islam M, Massy ZA, Montero N, Oliveira JP, Roca Muñoz A, Sanchez JE, Sridharan S, Winzeler R, Gansevoort RT. ERACODA Collaborators. COVID-19-related mortality in kidney transplant and dialysis patients: results of the ERACODA collaboration. Nephrol Dial Transplant 35:1973-1983, 2020.

• Meijers B, Hilbrands LB. The clinical characteristics of coronavirus-associated nephropathy. Nephrol Dial Transplant 35:1279-1281, 2020.

• Netea MG, Giamarellos-Bourboulis EJ, Domínguez-Andrés J, Curtis N, van Crevel R, van de Veerdonk FL, Bonten M. Trained immunity: a tool for reducing susceptibility to and the severity of SARS-CoV-2 infection. Cell 181:969-977, 2020.

• Noordzij M, Duivenvoorden R, Pena MJ, de Vries H, Kieneker LM; ERACODA Working Group. ERACODA: the European database collecting clinical information of patients on kidney replacement therapy with COVID-19. Nephrol Dial Transplant 35:2023-2025, 2020.

• Rother N, Yanginlar C, Lindeboom RGH, Bekkering S, van Leent MMT, Buijsers B, Jonkman I, de Graaf M, Baltissen M, Lamers LA, Riksen NP, Fayad ZA, Mulder WJM, Hilbrands LB, Joosten LAB, Netea MG, Vermeulen M, van der Vlag J, Duivenvoorden R. Hydroxychloroquine inhibits the trained innate immune response to interferons. Cell Rep Med 1: 100146, 2020.

• Schoot TS, Kerckhoffs APM, Hilbrands LB, van Marum RJ. Immunosuppressive drugs and COVID-19: A Review. Front Pharmacol 11:1333, 2020.

• van de Veerdonk F, Netea MG, van Deuren M, van der Meer, JW, de Mast Q, Bruggemann RJ, van der Hoeven H. Kinins and cytokines in COVID-19: A comprehensive pathophysiological approach. Preprints 2020040023, 2020.

• Van de Veerdonk FL, Kouijzer IJE, de Nooijer AH, van der Hoeven HG, Maas C, Netea MG, Brüggemann RJM. Outcomes associated with use of a kinin B2 receptor antagonist among patients with COVID-19. JAMA Netw Open 3:e2017708, 2020.

• van de Veerdonk FL, Netea MG, van Deuren M, van der Meer JWM, de Mast Q, Brüggemann RJ, van der Hoeven H. Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome. Elife 9:e57555, 2020.

• van der Made CI, Simons A, Schuurs-Hoeijmakers J, van den Heuvel G, Mantere T, Kersten S, van Deuren RC, Steehouwer M, van Reijmersdal SV, Jaeger M, Hofste T, Astuti G, Corominas Galbany J, van der Schoot V, van der Hoeven H, Hagmolen of ten Have W, Klijn E, van den Meer C, Fiddelaers J, de Mast Q, Bleeker-Rovers CP, Joosten LAB, Yntema HG, Gilissen C, Nelen M, van der Meer JWM, Brunner HG, Netea MG, van de Veerdonk FL, Hoischen A. Presence of genetic variants among young men with severe COVID-19. JAMA 324:1-11, 2020. PMID 32706371.

• Verweij PE, Gangneux J-P, Bassetti M, Brüggemann RJM, Cornely OA, Koehler P, Lass-Flörl C, van de Veerdonk FL, Chakrabarti A, Hoenigl M. Diagnosing COVID-19-associated pulmonary aspergillosis. The Lancet Microbe 1:e53-e55, 2020.

• Wagener FADTG, Pickkers P, Peterson SJ, Immenschuh S, Abraham NG. Targeting the heme-heme oxygenase system to prevent devere vomplications following COVID-19 infections. Antioxidants (Basel) 9:540, 2020.

Highlighted study Alexander Hoischen, Frank van de Veerdonk and Caspar van der Made

Genetic mutation reveals how coronavirus strikes TLR7 plays essential role in disease process. 

Studies on COVID-19

Some COVID-19 related studies from our researchers:

Investigating the presence of antibodies to SARS-CoV-2 in nasal mucous study from Dimitri Diavatopoulos and Marien de Jonge

Radboud university medical center has launched a study into the presence of antibodies to the coronavirus in nasal mucous. The aim is to show whether antibodies can be found in nasal mucous after a mild infection with few or no symptoms. The study focuses partly on children, because they often have few or no symptoms when infected with the coronavirus. This can provide important insights into herd immunity in the population. The study is complementary to the current coronavirus research at RIVM.

Much research is now being conducted into antibodies to the coronavirus. These antibodies are usually detected in the blood. These blood tests determine whether people have been infected with the coronavirus, which can provide insight into herd immunity in the population. High levels of antibodies in the blood are detectable in people who have recovered from a severe coronavirus infection. However, previous research with other respiratory infections has shown that mild infections, or infections without symptoms, can sometimes induce antibodies in the upper respiratory tract but not in the blood. It is unknown whether this also applies to the coronavirus.

Radboud university medical center researchers Dimitri Diavatopoulos and Marien de Jonge, both theme Infectious diseases and global health, have therefore started a clinical study into COVID-19 in 50 families: the MuCo study. It focuses primarily on whether antibodies can be measured in nasal mucous after a mild infection or exposure to the virus. In collaboration with Utrecht University, Radboud university medical center researchers are investigating whether these antibodies can inhibit infection with the virus. This is called 'virus neutralization'. The MuCo study focuses in part on families with children, because children often experience few or no symptoms.

Fifty hospital workers and their families

The research team, affiliated with the Center for Infectious Diseases of Radboud university medical center, visited over 50 families at home. The study began with hospital staff from Radboud university medical center, Canisius-Wilhelmina Hospital (both in Nijmegen) and Rijnstate hospital (in Arnhem) who have tested positive for the coronavirus and therefore were in home isolation. During the home visit, a sample of nose and throat mucous is taken from all members of the household to determine whether the virus is present. The 50 families were then followed for a month during which the participants themselves take nasal mucous samples at various times by means of an absorbent nasal strip. The also kept a symptom diary to distinguish between mild and more severe symptoms. The samples are then tested with a very sensitive method to determine whether antibodies to the coronavirus are present and whether they can neutralize the virus. 

RIVM and Utrecht University

This study is led by Radboud university medical center, but is coordinated with RIVM and is complementary to other ongoing studies at RIVM. Radboud university medical center is focusing primarily on immunity in the upper respiratory tract. The study involves a collaboration with Frank van Kuppeveld and Berend Jan Bosch of the Faculty of Veterinary Medicine at Utrecht University, which has substantial expertise about coronaviruses and extensive experience in measuring virus neutralization.

Two studies into better protection for healthcare workers and elderly people against COVID-19 infection. Mihai Netea

In absence of a coronavirus vaccine, Radboudumc and UMC Utrecht started in 2020 two studies to investigate whether health care workers and people above 60 are better protected against the coronavirus after a vaccination against tuberculosis (BCG vaccine). This vaccine does not directly protect against the coronavirus, but provides a boost to the immune system, which may lead to improved protection against the coronavirus and a milder infection.

Not directed against COVID-19

Radboudumc and UMC Utrecht investigated whether people can be protected by a vaccine against tuberculosis. This BCG vaccine (Bacillus Calmette-Guérin) does not directly target the coronavirus, but it boosts the immune system. This boost may provide additional protection against a coronavirus infection, which may result in fewer people to suffer from the virus and also make the infection milder.

More protection, less downtime?

Previous research shows that such a boost of the immune system with BCG provides some protection against influenza, but it is not known whether this also applies to other infections such as COVID-19. "That is exactly the reason for this research," says Mihai Netea, professor of experimental internal medicine. "If during this epidemic fewer people in the BCG-vaccinated group would drop out due to illness, this would be an encouraging result."

Thousand employees

Marc Bonten, professor of molecular epidemiology of infectious diseases at the UMC Utrecht, has initiated this research together with Netea. The study was quickly approved by the Medical Ethics Review Committee (METC). "We are in the middle of the outbreak, so we want to have the results of this study as soon as possible," says Bonten. “A total of 1000 employees can participate at Radboudumc, UMC Utrecht, but also in other hospitals. Half of them will receive the BCG vaccine, the other half a placebo. If it turns out that the vaccine does indeed provide extra protection, we can also offer it to other employees.”

1,600 elderly people

The elderly have a higher chance of becoming seriously ill as a result of the coronavirus. Also, if infected, they are more at risk of dying from the infection. This second study aims to discover whether the tuberculosis (BCG) vaccine reduces the risk of infection with the coronavirus in people aged 60 or older, or the severity of the symptoms in the event of infection. A total of 1,600 people may take part in the study, which starts today. Half of the study participants will be given the vaccine, the other half will not.

Scientific research

It is unclear whether the BCG vaccine can also provide some level of protection from the coronavirus. The aim of these studies is therefore to find out whether it does. The study should answer the question whether the BCG vaccine provides protection from the coronavirus and/or whether it reduces the severity of the symptoms in the elderly and in healthcare personnel. 

The vaccine

BCG is the most widely administered vaccine in the world and is used in many countries to prevent tuberculosis. For this study, the hospitals will obtain the BCG vaccine directly from the Dutch National Institute for Public Health and the Environment (RIVM). The study will therefore not affect the availability of the vaccine for regular use by the municipal public health service (GGD) in the Netherlands.

Grants related to COVID-19

A respresentation of some COVID-19 related grants of our researchers:

Consortium H2020

SC1-PHE-Coronavirus-2020: RECOVER - Rapid European COVID-19 Emergency research response. Frank van de Veerdonk, Infectious diseases and global health.
Total grant: 5,000 kEuro. Awarded Radboudumc: 188 kEuro.

ZonMw COVID-19 Second Wave call

A phase-2-study, pivotal for clinical development of lanadelumab for treatment of COVID-19. Frank van de Veerdonk, Infectious diseases and global health.
Total grant: 500 kEuro. Awarded Radboudumc: 500 kEuro.

Integrative analysis of multi-omics longitudinal data to identify effective strategies for the prediction and treatment of COVID-19. Vinod Kumar Magadi Gopalaiah, Infectious diseases and global health.
Total grant: 500 kEuro. Awarded Radboudumc: 500 kEuro.

ZonMW Health Holland grant

LSH-TKI EUREKA COVID-19 Network call: COVABELP. Development of an elastin-like peptide based theranostic platform technology to fight SARS-CoV-2.  William Leenders, Nanomedicine.
Total grant: 350 kEuro. Awarded Radboudumc: 140 kEuro.

Mihai Netea BCG vaccine, helpful against COVID-19?

Vlog Özlem Bulut about COVID-19 & stress

Jerusalema challenge Radboudumc