Head of Erasmus University Medical Center Rotterdam
Department of Viroscience, Rotterdam, Netherlands
What efforts are you making on COVID-19 serology, and how would you assess the progress of current testing?
Serological assays are important as an adjunct to diagnosis of COVID-19, to assess the extent of circulation of SARS-CoV-2 in the community, and as measure or proxy of population immunity. Based on our knowledge of coronaviruses and building from work on MERS CoV we have developed initial serological assays based on S1, N and RBD as antigens, and using virus neutralization assays as gold standard (Okba et al 2020). This suite of assays is used as reference to compare performance of the currently available commercial assays and to provide guidance to public health authorities and WHO (Geurts van Kessel et al. 2020). An interesting observation has been the finding that virus cannot be cultured from RT-PCR positive patients as soon as neutralizing antibodies are found. We currently are comparing the kinetics of specific and cross-reactive serological responses in patients with mild and severe illness by using memory B cell cloning and antibody arrays with full-length spike (S), S1, receptor binding domain (RBD) and nucleocapsid (N) proteins from SARS-CoV-2, SARS, and the four seasonal coronaviruses. Finally, we are testing recovered patients as potential plasma donors. Plasma with high and low levels of neutralizing antibodies is tested in hamsters to titrate the possible protective titers, and to study potential adverse effects, in preparation of a clinical trial (Rockx, Haagmans et al. in preparation).
Earlier you spoke of zoonotic and emerging viruses, global reference database with samples and an 800 hospital network. Currently, you are running clinical animal vaccine trials and therapeutic antibody studies. Please, would you elaborate on these endeavors?
The work in our department is highly interdisciplinary, and involves teams working on basic virology, immunology, pathogenesis and diagnostic research, both pre-clinical and clinical, and involving humans and animals. From the first person diagnosed with COVID-19 in The Netherlands, we have systematically sequenced a large proportion of cases which now serves as a reference for the enhanced track and trace policy (Oude Munnink et al., 2020). We developed a protocol that allows a turnaround time of 1.5 day to be able to include the genomic data in the decision making. There are a lot of discussion about the possible modes of transmission in outbreaks that involved singing in church choirs, transmission among meat processors in the slaughterhouses, and spread in nursing homes. With careful evaluation of such outbreaks we do learn a lot that is immediately used. For instance, in the week after the first cases were diagnosed in our country, microbiologists from the Southern provinces alerted the national outbreak management team that they had the impression the incidence of “common cold” was high in their region. They did a screening of > 1000 healthcare workers with mild complaints over the weekend early March and found that 4,5% of them had ongoing infection. Sequencing analysis showed that this was not a single cluster from the carnival, as was suspected, but a diversity of viruses, indicating that the policy was missing a lot of introductions. That was used to support the decision for the first containment measures (Sikkema et al, 2020). The most recent example was the documentation of human to mink to human to human transmission in a farm. In addition to the studies above, we currently have worked on immunopathogenesis, transmission, assessing the role of aerosols, and testing monoclonal antibodies and plasma for therapeutic applications.
Relevant publications and preprints:
Munster et al., 2020 https://www.nejm.org/doi/full/10.1056/NEJMp2000929
Rockx et al., 2020 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164679/
Corman et al., 2020 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988269/
Lamers et al. 2020 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199907/
Okba et al., 2020 https://wwwnc.cdc.gov/eid/article/26/7/20-0841_article
Oude Munnink et al., 2020 https://www.biorxiv.org/content/10.1101/2020.04.21.050633v1 in press Nature Med
Kluytmans et al., 2020 https://www.medrxiv.org/content/10.1101/2020.03.23.20041913v3 in press JAMA
Weiskopf et al., 2020 https://www.medrxiv.org/content/10.1101/2020.04.11.20062349v2 Under review
Geurts van Kessel et al., 2020 https://www.medrxiv.org/content/10.1101/2020.04.23.20077156v2 revision Nature comm
Sikkema et al., 2020 https://www.medrxiv.org/content/10.1101/2020.04.26.20079418v1 revision Lancet
Richard et al, 2020 https://www.biorxiv.org/content/10.1101/2020.04.16.044503v1 in press Sci Rep
Oreshkova et al., 2020 https://www.biorxiv.org/content/10.1101/2020.05.18.101493v1 in press Eurosurveillance
Professor Marion Koopmans, DVM PhD focuses on global population level impact of rapidly spreading zoonotic virus infections, with special emphasis on foodborne transmission. Her research focuses on unravelling the modes of transmission of viruses among animals, between animals and humans, and among humans. She uses the pathogen genomic information to unravel these pathways and to signal changes in transmission or disease impact. Professor Koopmans is coordinator of VEO, a project funded by the European Commission’s Horizon 2020 program. VEO aims to develop approaches for early warning of risk of emerging disease emergence, through in depth ecological studies aimed at detecting indicators of changing risk. In addition, she is also a PI in the PREPARE project, an EU funded network for harmonized large-scale clinical research studies on infectious diseases, and in a dedicated COVID-19 funded project linked to PREPARE. Marion Koopmans is the director of the WHO- cooperation center for Emerging Diseases at the Erasmus MC and scientific director of Emerging Diseases of the Netherlands Centre for One Health
Overview of the Erasmus MC Department of Viroscience, Rotterdam
The Department of Viroscience of the Erasmus MC is an international centre of excellence for multidisciplinary, basic, translational and clinical research of viruses and virus infections at the molecular, patient and population level. The unique aspect of the Department of Viroscience is its translational approach, with expertise ranging from basic virology to clinical virology, connecting medical and veterinary health, public health and ecology. By combining these complementary areas of expertise, The Department of Viroscience is able to meet today’s and tomorrow’s societal challenges in diseases caused by common and newly emerging viruses.