COVID-19 (SARS-CoV-2) OVERVIEW OF VIROLOGY RESEARCH
- Development of COVID-19-diagnostics. Identification of COVID-19 cases needs to be fast and broad to identify and isolate infected people. Multiple testing approaches are currently under development.
- Development and testing of antivirals. Both known and new molecules are screened for their potential to treat COVID-19 patients. The first clinical trials are starting in Helsinki.
- Development of vaccines.
- To follow virus evolution by molecular epidemiology. Genomes of SARS-CoV-2 strains of Finnish patients are sequenced in order to produce evolutionary information.
Covid-19 TESTING & ONGOING RESEARCH ACTIVITIES
A. Virus tests: detection of infected people
Societal impact: Enables isolation of infected people, which helps to stop virus spreading.
Lead: Olli Vapalahti / Tarja Sironen / Eili Huhtamo, Dept. Virology
Goal: Increase the capacity of Finland for virus tests
State: Laboratory facilities ready for sample testing in Viikki, current capacity about 200 samples/day. Next step: To up-scale testing capacity significantly.
Collaborators: Dept. Virology, FIMM
Comments: Vapalahti/Sironen/Huhtamo laboratory aims at studying and developing inactivation processes and alternative testing methods. Markus Vähä-Koskela (FIMM) maps availability of BSL2/3 labs in Meilahti. Pirkko Mattila/ Maija Puhka (FIMM) map RNA extraction capacity, Outi Monni (Faculty of Medicine)/Petri Auvinen (Institute of Biotechnology) map PCR capacity. Pre- and post-analytics are main bottlenecks. It is essential to ensure that testing resources (sampling equipment, reagents, etc.) are strategically and socially targeting the right activities in terms of controlling the pandemic.
B. Serological tests: detection of people who already have protective antibodies against SARS-CoV-2-virus
Societal impact: Mapping the spread of the pandemic (number of infected people) and already recovered patients – a reliable indicator of immunity. Could help to identify people who can go back to work.
Lead: Jussi Hepojoki / Tarja Sironen / Olli Vapalahti, Dept. Virology
Goal: Increase the testing capacity of serological tests of COVID-19 in Finland, and develop reliable serological tests in order to indicate immunity.
State: Testing is running in small-scale (10s of samples / day) in different methods: immunofluorescence assays (IFA), virus neutralization and recombinant pseudovirus tests in BSL2/3 labs. Several recombinant antigens are already developed and ready for expression. Serology panels are collected in co-operation with other agents.
Next step: Up-scaling testing capacity (to 1000s of samples / day) enables e.g. population screening if needed.
- New blood tests for antibodies could show true scale of coronavirus pandemic
- Serological and molecular findings during SARS-CoV-2 infection: the first case study in Finland, January to February 2020
C. Drug development 1
Societal impact: New drugs to treat COVID-19-patients reduces deaths and need of ICU
Lead: Anu Kantele (HUS, UH) / Olli Vapalahti and Suvi Kuivanen (Dept. Virology), Päivi Tammela / Vilja Pietiäinen (FIMM)
Goals: Find new molecules to treat COVID-19-infection and to test existing drugs used for other purposes in clinical trials.
State: First clinical trials are starting. Drug screening with cell lines (e.g. 200 drugs screened with lung cell lines)
Next step: Recruit patients to clinical trials, scaling up the capacity for drug screening, utilizing new cell lines for screening.
Collaborators: FIMM, HUS, University of Tarto (Denis Kainov, Tambet Teesalu); Dept of Pharmacy, European Cell-Based Assay Interest Group.
Drug development 2
Societal impact: New drugs to treat COVID-19-patients reduces deaths and need of ICU
Lead: Päivi Saavalainen (Fac. Med.) / Tomas Strandin (Dept. VIrology) / Ville Paavilainen (BI, Viikki)
Goals: To clone human monoclonal antibodies from COVID-19 recoveree cells
State: Memory cells binding to viral receptor binding domain from a patient sorted and sequenced.
Next step: To study patient samples more deeply, to sequence memory cells, to produce antibodies and testing.
Collaborators: HUS, VTT, FIMM, SPR
Comment: Human monoclonal antibodies are also applicable as tools in rapid antigen tests. Awaiting production of monoclonals, it is important to organize the collection of plasma and hyperimmunoglobulin samples from recoverees.
Drug development 3
Societal impact: Identification and development of protease inhibitors to inhibit SARS-CoV-2 entry
Lead: Juha Klefström (Research Programs Unit, CAN-PRO)
Goals: Identify, validate and repurpose serine protease inhibitors for inhibition of SARS-CoV-2 entry into human lung epithelial cells.
State: A panel of potential TMPRSS2 (a known regulator of SARS-CoV-2 cellular entry; Hoffmann Cell 2020) inhibitors have been identified in the team’s earlier work on TMPRSS proteases. Molecular modeling approaches and cell-based assays for protease activity already established. Lead molecules ready for validation.
Next step: Assess the interaction of TMPRSS2-related proteases on SARS-CoV-2 spike proteins and the effect of lead inhibitors. Molecular modeling and in silico screening of analogs. The inhibition on SARS-CoV-2 entry in collaboration with Dept Virology at University of Helsinki.
Collaborators: HY, UEF
Comments: Human trials with a TMPRSS2 inhibitor were started weeks after publication showing that a class of small molecule inhibitors interfere with SARS-CoV-2 cellular entry. There is urgent need for safe and clinically already tested drugs which could be imminently repurposed as antivirals.
Vaccine development 4
Lead: Vincenzo Cerullo
Goal: development of a prophylactic and therapeutic vaccine for SARS-COV-2 and go to clinical use within months
State: MTA has been signed, material has been purchased, preclinical testing starting soon
Collaborators: VALO therapeutics, Reithera,
Comments: We aim to use non-human adenoviruses encoding for SARS-COV-2 structural proteins to elicit antibodies response and coated with MHC-I-restricted peptides from non-structural proteins to boost the T cell response.
D. Using human genetics to understand the individual progress of COVID-19-disease
Societal impact: To support drug and vaccine development. To study whether some persons have genetically a higher risk of severe symptoms from COVID-19-infection.
Lead: Markus Perola (THL) / Mark Daly and Andrea Ganna (FIMM)
Goals: To identify possible genetic differences between people having severe vs. mild symptoms
State: Global sample collection ongoing
Next step: THL starts collecting samples and extracts DNA from patient samples in Finland. FIMM will genotype Finnish and a subset of international samples on Illumina GSA array in batches of 500 samples. Summary data will be made publicly available, at a weekly basis (https://www.covid19hg.com/)
Collaborators: FIMM, THL, Health Care Districts, International partners.
E. Virus sequencing and analysis
Societal impact: Helps to follow virus transmission chains (local vs. imported infections) and to estimate the prevalence of the virus, to quantify the degree to which social distancing efforts are slowing the transmission, potential to detect possible clinically relevant changes in virus genome.
Lead: Teemu Smura, Ravi Kant (Dept. Virology), Pekka Ellonen (FIMM), Lars Paulin, Petri Auvinen (Institute of Biotechnology)
Goals: To trace the transmission chains and geographical spread of the virus, estimate the extent of virus transmission in the Finnish population and detect functionally significant changes in the virus (antigenic drift and pathogenetic determinants).
State: So far, >40 SARS-CoV-2 genomes from Finland have been sequenced. The virus strains sequenced in February and the first week of March, showed no clear clustering, supporting between-country transmission in Europe. By the second week of March, clear evidence of local transmission was detected in Finland. (https://www.helsinki.fi/en/news/health-news/open-sesame-coronavirus-rese...)
Next step: Upscaling the effort with sequencing laboratories. Potential to sequence hundreds of virus genomes per month.
Collaborators: Dept.Virology, FIMM, Institute of Biotechnology
Comment: FIMM will double the sequencing capacity immediately. Ravi Kant will assist in sequence analysis. Additionally, Outi Monni and Petri Auvinen have suitable equipment to multiply capacity further. Important also to follow development of virus evolution during the course of an individual infection.
F. Platforms to exchange expertise, material, facilities, equipment and personnel
Impact: Get together different expertise in order to develop new study ideas and establishment of effective collaborations, and to test hypotheses
Lead: Ravi Kant, Tarja Sironen (Dept. Virology), Pirta Hotulainen (Minerva), Katja Kivinen and Vilja Pietiäinen (FIMM)
Goal: To create a platform for exchange of equipment, reagents, expertise, personnel. To enable efficient core-like use of UH biosafety-level 3 laboratories for infectious virus work to increase research output.
State: Webpage for general information and slack channels for idea change have been created, Meilahti BSL-3 (jointly with HUSLAB) is in use for virus work (2-3 persons trained to work with coronavirus + equipment available)
Next step: To increase capacity for Tasks A and B, to secure the availability of reagents, protective equipment etc. in order to implement large-scale testing.
Comment: HUS has requested that all interested to volunteer contact firstname.lastname@example.org .
G. Communication and effort facilitation, problem solving
Societal impact: Get all efforts to work, bring researchers' view to decision making
Lead: Pirta Hotulainen (Minerva), Mari Kaunisto (FIMM), Tarja Sironen, Ravi Kant, Olli Vapalahti (Dept. virology)
State: Active Tweeting to public, reporting in media, efforts reported to the Ministry of Social Affairs and Health and the Ministry of Education and Culture.
Next step: Facilitate up-scaling of Tasks A and B, secure reagents, equipment, face masks, people.
Comment: Pirta Hotulainen leads coordination and communication with the government, Tarja Sironen, Olli Vapalahti, Andrea Ganna and others give interviews, Ravi Kant and Mari Kaunisto work in collaboration with the University´s communication team.
H. Socio-economic and policy analysis
Societal impact: To provide science-based advice for managing the accumulation of multi-hazard risks from crisis decisions in pandemics
Lead: Janne I. Hukkinen, Sakari Kuikka
Goal: To provide probabilistic estimates of COVID19 policy on health and socio-economic risks, and to improve multi-level crisis governance with a diagnosis of the cascades of socio-environmental impacts of the pandemic.
State: The approaches have been developed in WISE project (STN funding). Decision analysis models enable the use of epidemiological knowledge and weighting of alternative aims and their impact on socio-economic risks, including the uncertainty from human reactions to alternative policies. Novel decision-making platforms are being developed that facilitate consideration of the long-term consequences of crisis decisions.
Next step: The structure of the model will be developed; probability estimates are obtained from experts, to be updated later with raw data and simulation models; novel decision-making platforms will be piloted further.
Collaborators: Ongoing planning with THL, UEF, Aalto, U Tampere, U Turku, BIOS
Comments: In addition to policy advice, we aim to reveal the challenges of value-laden policy decisions to the whole society: What are the trade-offs when we aim for specific outcomes?