Researchers found a reason why COVID-19 may be life-threatening | University of Tartu

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Faculty of Arts and Humanities
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+372 737 5341
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Jakobi 2, rooms 116–121, 51005 Tartu
  • Dean's Office
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    Jakobi 2, rooms 116–121, 51005 Tartu
  • Institute of History and Archaeology
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    Jakobi 2, 51005 Tartu
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    Jakobi 2, 51005 Tartu
  • Institute of Philosophy and Semiotics
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    Jakobi 2, rooms 309–352, 51005 Tartu
  • Institute of Cultural Research
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    Faculty address: 
    Ülikooli 16, 51003 Tartu
  • School of Theology and Religious Studies
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    +372 737 5301
    Faculty address: 
    Ülikooli 18–310, 50090 Tartu
  • College of Foreign Languages and Cultures
    Faculty address: 
    J. Liivi 4, 50409, Tartu
  • Viljandi Culture Academy
    Faculty phone: 
    +372 435 5232
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    Posti 1, 71004 Viljandi
Faculty of Social Sciences
Faculty phone: 
+372 737 5957
Faculty address: 
Lossi 36, 51003 Tartu
  • Dean's Office
    Faculty phone: 
    + 372 737 5900
    Faculty address: 
    Lossi 36, 51003 Tartu
  • Institute of Education
    Faculty phone: 
    +372 737 6440
    Faculty address: 
    Salme 1a–29, 50103 Tartu
  • Johan Skytte Institute of Political Studies
    Faculty phone: 
    +372 737 5582
    Faculty address: 
    Lossi 36–301, 51003 Tartu
  • School of Economics and Business Administration
    Faculty phone: 
    +372 737 6310
    Faculty address: 
    Narva mnt 18, 51009 Tartu
  • Institute of Psychology
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    +372 737 5902
    Faculty address: 
    Näituse 2, 50409 Tartu
  • School of Law
    Faculty phone: 
    +372 737 5390
    Faculty address: 
    Näituse 20–324, 50409 Tartu
  • Institute of Social Studies
    Faculty phone: 
    +372 737 5188
    Faculty address: 
    Lossi 36, 51003 Tartu
  • Narva College
    Faculty phone: 
    +372 740 1900
    Faculty address: 
    Raekoja plats 2, 20307 Narva
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    Faculty phone: 
    +372 445 0520
    Faculty address: 
    Ringi 35, 80012 Pärnu
Faculty of Medicine
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+372 737 5326
Faculty address: 
Ravila 19, 50411 Tartu
  • Dean's Office
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    +372 737 5326
    Faculty address: 
    Ravila 19, 50411 Tartu
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    +372 737 4210
    Faculty address: 
    Biomeedikum, Ravila 19, 50411 Tartu
  • Institute of Pharmacy
    Faculty phone: 
    +372 737 5286
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    Nooruse 1, 50411 Tartu
  • Institute of Dentistry
    Faculty phone: 
    +372 731 9856
    Faculty address: 
    Raekoja plats 6, 51003 Tartu
  • Institute of Clinical Medicine
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    +372 737 5323
    Faculty address: 
    L. Puusepa 8, 50406 Tartu
  • Institute of Family Medicine and Public Health
    Faculty phone: 
    +372 737 4190
    Faculty address: 
    Ravila 19, 50411 Tartu
  • Institute of Sport Sciences and Physiotherapy
    Faculty phone: 
    +372 737 5360
    Faculty address: 
    Jakobi 5–205, 51005 Tartu
Faculty of Science and Technology
Faculty phone: 
+372 737 5820
Faculty address: 
Vanemuise 46–208, 51014 Tartu
  • Dean's Office
    Faculty phone: 
    +372 737 5820
    Faculty address: 
    Vanemuise 46–208, 51003 Tartu
  • Institute of Computer Science
    Faculty phone: 
    +372 737 5445
    Faculty address: 
    Narva mnt 18, 51009 Tartu
  • Estonian Marine Institute
    Faculty phone: 
    +372 671 8902
    Faculty address: 
    Mäealuse 14, 12618 Tallinn
  • Institute of Physics
    Faculty address: 
    W. Ostwaldi 1, 50411 Tartu
  • Institute of Chemistry
    Faculty phone: 
    +372 737 5261
    Faculty address: 
    Ravila 14a, 50411 Tartu
  • Institute of Mathematics and Statistics
    Faculty phone: 
    +372 737 5860
    Faculty address: 
    Narva mnt 18, 51009 Tartu
  • Institute of Molecular and Cell Biology
    Faculty phone: 
    +372 737 5027
    Faculty address: 
    Riia 23, 23b–134, 51010 Tartu
  • Tartu Observatory
    Faculty phone: 
    +372 737 4510
    Faculty address: 
    Observatooriumi 1, Tõravere, 61602 Tartumaa
  • Institute of Technology
    Faculty phone: 
    +372 737 4800
    Faculty address: 
    Nooruse 1, 50411 Tartu
  • Institute of Ecology and Earth Sciences
    Faculty phone: 
    +372 737 5835
    Faculty address: 
    Vanemuise 46, 51003 Tartu
Institutions
  • Library
    Faculty phone: 
    +372 737 5702
    Faculty address: 
    W. Struve 1, 50091 Tartu
  • Youth Academy
    Faculty phone: 
    +372 737 5581
    Faculty address: 
    Uppsala 10, 51003 Tartu
  • Institute of Genomics
    Faculty phone: 
    +372 737 4000
    Faculty address: 
    Riia 23b, 51010 Tartu
  • Museum
    Faculty phone: 
    +372 737 5674
    Faculty address: 
    Lossi 25, 51003 Tartu
  • University of Tartu Natural History Museum and Botanical Garden
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    Faculty address: 
    Vanemuise 46, 51003 Tartu
Support Units
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    Faculty phone: 
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    Faculty address: 
    Ülikooli 18a, 51005 Tartu
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    +372 737 4809
    Faculty address: 
    Narva mnt 18, 51009, Tartu
  • University Office in Tallinn
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    Faculty address: 
    Teatri väljak 3, 10143 Tallinn
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    Faculty address: 
    Ülikooli 18a, 51005 Tartu
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    Faculty address: 
    Jakobi 4, 51005 Tartu
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    Faculty address: 
    Raekoja plats 9, 51004 Tartu
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    Faculty phone: 
    +372 737 6000, IT-help: +372 737 5500
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Human Resources Office
    Faculty phone: 
    +372 737 5145
    Faculty address: 
    Ülikooli 18, rooms 302 and 304, 50090 Tartu
  • Internal Audit Office
    Faculty address: 
    Ülikooli 18-244, 51005 Tartu
  • Marketing and Communication Office
    Faculty phone: 
    +372 737 5687
    Faculty address: 
    Ülikooli 18, rooms 102, 104, 209, 210, 50090 Tartu
  • Office of Academic Affairs
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    +372 737 5620
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • Procurement Office
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    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Rector's Strategy Office
    Faculty phone: 
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    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • Student Council
    Faculty address: 
    Ülikooli 18b, 51005 Tartu
  • University of Tartu Press
    Faculty phone: 
    +372 737 5945
    Faculty address: 
    W. Struve 1, 50091 Tartu
Other Units
  • University of Tartu Academic Sports Club
    Faculty phone: 
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    Faculty address: 
    Ujula 4, 51008 Tartu
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    +372 740 9959
    Faculty address: 
    Narva mnt 25, 51013 Tartu
  • Tartu Students’ Club
    Faculty phone: 
    +372 730 2400
    Faculty address: 
    Kalevi 24, 51010 Tartu
  • Tartu University Hospital
    Faculty address: 
    L. Puusepa 1a, 50406 Tartu
  • University of Tartu Foundation
    Faculty phone: 
    +372 737 5852
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • View all other units

Contacts of UT units

Faculty of Arts and Humanities
Faculty phone: 
+372 737 5341
Faculty address: 
Jakobi 2, rooms 116–121, 51005 Tartu
  • Dean's Office
    Faculty phone: 
    + 372 737 5341
    Faculty address: 
    Jakobi 2, rooms 116–121, 51005 Tartu
  • Institute of History and Archaeology
    Faculty phone: 
    +372 737 5651
    Faculty address: 
    Jakobi 2, 51005 Tartu
  • Institute of Estonian and General Linguistics
    Faculty phone: 
    +372 737 5221
    Faculty address: 
    Jakobi 2, 51005 Tartu
  • Institute of Philosophy and Semiotics
    Faculty phone: 
    +372 737 5314
    Faculty address: 
    Jakobi 2, rooms 309–352, 51005 Tartu
  • Institute of Cultural Research
    Faculty phone: 
    (+372) 737 5223
    Faculty address: 
    Ülikooli 16, 51003 Tartu
  • School of Theology and Religious Studies
    Faculty phone: 
    +372 737 5301
    Faculty address: 
    Ülikooli 18–310, 50090 Tartu
  • College of Foreign Languages and Cultures
    Faculty address: 
    J. Liivi 4, 50409, Tartu
  • Viljandi Culture Academy
    Faculty phone: 
    +372 435 5232
    Faculty address: 
    Posti 1, 71004 Viljandi
Faculty of Social Sciences
Faculty phone: 
+372 737 5957
Faculty address: 
Lossi 36, 51003 Tartu
  • Dean's Office
    Faculty phone: 
    + 372 737 5900
    Faculty address: 
    Lossi 36, 51003 Tartu
  • Institute of Education
    Faculty phone: 
    +372 737 6440
    Faculty address: 
    Salme 1a–29, 50103 Tartu
  • Johan Skytte Institute of Political Studies
    Faculty phone: 
    +372 737 5582
    Faculty address: 
    Lossi 36–301, 51003 Tartu
  • School of Economics and Business Administration
    Faculty phone: 
    +372 737 6310
    Faculty address: 
    Narva mnt 18, 51009 Tartu
  • Institute of Psychology
    Faculty phone: 
    +372 737 5902
    Faculty address: 
    Näituse 2, 50409 Tartu
  • School of Law
    Faculty phone: 
    +372 737 5390
    Faculty address: 
    Näituse 20–324, 50409 Tartu
  • Institute of Social Studies
    Faculty phone: 
    +372 737 5188
    Faculty address: 
    Lossi 36, 51003 Tartu
  • Narva College
    Faculty phone: 
    +372 740 1900
    Faculty address: 
    Raekoja plats 2, 20307 Narva
  • Pärnu College
    Faculty phone: 
    +372 445 0520
    Faculty address: 
    Ringi 35, 80012 Pärnu
Faculty of Medicine
Faculty phone: 
+372 737 5326
Faculty address: 
Ravila 19, 50411 Tartu
  • Dean's Office
    Faculty phone: 
    +372 737 5326
    Faculty address: 
    Ravila 19, 50411 Tartu
  • Institute of Biomedicine and Translational Medicine
    Faculty phone: 
    +372 737 4210
    Faculty address: 
    Biomeedikum, Ravila 19, 50411 Tartu
  • Institute of Pharmacy
    Faculty phone: 
    +372 737 5286
    Faculty address: 
    Nooruse 1, 50411 Tartu
  • Institute of Dentistry
    Faculty phone: 
    +372 731 9856
    Faculty address: 
    Raekoja plats 6, 51003 Tartu
  • Institute of Clinical Medicine
    Faculty phone: 
    +372 737 5323
    Faculty address: 
    L. Puusepa 8, 50406 Tartu
  • Institute of Family Medicine and Public Health
    Faculty phone: 
    +372 737 4190
    Faculty address: 
    Ravila 19, 50411 Tartu
  • Institute of Sport Sciences and Physiotherapy
    Faculty phone: 
    +372 737 5360
    Faculty address: 
    Jakobi 5–205, 51005 Tartu
Faculty of Science and Technology
Faculty phone: 
+372 737 5820
Faculty address: 
Vanemuise 46–208, 51014 Tartu
  • Dean's Office
    Faculty phone: 
    +372 737 5820
    Faculty address: 
    Vanemuise 46–208, 51003 Tartu
  • Institute of Computer Science
    Faculty phone: 
    +372 737 5445
    Faculty address: 
    Narva mnt 18, 51009 Tartu
  • Estonian Marine Institute
    Faculty phone: 
    +372 671 8902
    Faculty address: 
    Mäealuse 14, 12618 Tallinn
  • Institute of Physics
    Faculty address: 
    W. Ostwaldi 1, 50411 Tartu
  • Institute of Chemistry
    Faculty phone: 
    +372 737 5261
    Faculty address: 
    Ravila 14a, 50411 Tartu
  • Institute of Mathematics and Statistics
    Faculty phone: 
    +372 737 5860
    Faculty address: 
    Narva mnt 18, 51009 Tartu
  • Institute of Molecular and Cell Biology
    Faculty phone: 
    +372 737 5027
    Faculty address: 
    Riia 23, 23b–134, 51010 Tartu
  • Tartu Observatory
    Faculty phone: 
    +372 737 4510
    Faculty address: 
    Observatooriumi 1, Tõravere, 61602 Tartumaa
  • Institute of Technology
    Faculty phone: 
    +372 737 4800
    Faculty address: 
    Nooruse 1, 50411 Tartu
  • Institute of Ecology and Earth Sciences
    Faculty phone: 
    +372 737 5835
    Faculty address: 
    Vanemuise 46, 51003 Tartu
Institutions
  • Library
    Faculty phone: 
    +372 737 5702
    Faculty address: 
    W. Struve 1, 50091 Tartu
  • Youth Academy
    Faculty phone: 
    +372 737 5581
    Faculty address: 
    Uppsala 10, 51003 Tartu
  • Institute of Genomics
    Faculty phone: 
    +372 737 4000
    Faculty address: 
    Riia 23b, 51010 Tartu
  • Museum
    Faculty phone: 
    +372 737 5674
    Faculty address: 
    Lossi 25, 51003 Tartu
  • University of Tartu Natural History Museum and Botanical Garden
    Faculty phone: 
    +372 737 6076
    Faculty address: 
    Vanemuise 46, 51003 Tartu
Support Units
  • Administrative Office
    Faculty phone: 
    +372 737 5606
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Centre for Entrepreneurship and Innovation
    Faculty phone: 
    +372 737 4809
    Faculty address: 
    Narva mnt 18, 51009, Tartu
  • University Office in Tallinn
    Faculty phone: 
    +372 737 6600
    Faculty address: 
    Teatri väljak 3, 10143 Tallinn
  • Estates Office
    Faculty phone: 
    +372 737 5137
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Finance Office
    Faculty phone: 
    +372 737 5125
    Faculty address: 
    Jakobi 4, 51005 Tartu
  • Grant Office
    Faculty phone: 
    +372 737 6215
    Faculty address: 
    Raekoja plats 9, 51004 Tartu
  • Information Technology Office
    Faculty phone: 
    +372 737 6000, IT-help: +372 737 5500
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Human Resources Office
    Faculty phone: 
    +372 737 5145
    Faculty address: 
    Ülikooli 18, rooms 302 and 304, 50090 Tartu
  • Internal Audit Office
    Faculty address: 
    Ülikooli 18-244, 51005 Tartu
  • Marketing and Communication Office
    Faculty phone: 
    +372 737 5687
    Faculty address: 
    Ülikooli 18, rooms 102, 104, 209, 210, 50090 Tartu
  • Office of Academic Affairs
    Faculty phone: 
    +372 737 5620
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • Procurement Office
    Faculty phone: 
    +372 737 6632
    Faculty address: 
    Ülikooli 18a, 51005 Tartu
  • Rector's Strategy Office
    Faculty phone: 
    +372 737 5600
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • Student Council
    Faculty address: 
    Ülikooli 18b, 51005 Tartu
  • University of Tartu Press
    Faculty phone: 
    +372 737 5945
    Faculty address: 
    W. Struve 1, 50091 Tartu
Other Units
  • University of Tartu Academic Sports Club
    Faculty phone: 
    +372 737 5371
    Faculty address: 
    Ujula 4, 51008 Tartu
  • Tartu Student Village
    Faculty phone: 
    +372 740 9959
    Faculty address: 
    Narva mnt 25, 51013 Tartu
  • Tartu Students’ Club
    Faculty phone: 
    +372 730 2400
    Faculty address: 
    Kalevi 24, 51010 Tartu
  • Tartu University Hospital
    Faculty address: 
    L. Puusepa 1a, 50406 Tartu
  • University of Tartu Foundation
    Faculty phone: 
    +372 737 5852
    Faculty address: 
    Ülikooli 18, 50090 Tartu
  • View all other units

Researchers found a reason why COVID-19 may be life-threatening

University of Tartu researchers participated in a study published in Science, indicating that about 10 per cent of young and healthy people who develop severe COVID-19 have misguided antibodies that attack not the virus, but the immune system itself. Another recently published study showed that another 3.5 per cent of such patients carry a specific kind of genetic mutation. In both cases, the patients did not have type I interferons that are essential in protection against viruses.

Interferons are part of the intrinsic and innate immunity, kicking in before the adaptive immune system mounts an antibody response. They are known to play an important role in immediately heightening the cells’ defences in response to several viruses.

However, researchers found that in some patients, auto-antibodies neutralise the effect of interferons, and in others, the production of interferons has been impaired due to gene defects. The upshot is the same: some COVID-19 sufferers whose severe form of the disease has so far been a mystery lack type I interferon.

The findings of the research published in participation with medical researchers of the University of Tartu help explain why some younger people develop a disease much more severe than others and require admission to the intensive care despite being free of underlying conditions such as cardiovascular disease and type 2 diabetes. The findings may also provide the first molecular explanation for why more men than women die from the disease.

Jean-Laurent Casanova, head of the St. Giles Laboratory of Human Genetics of Infectious Diseases at The Rockefeller University and a Howard Hughes Medical Institute investigator, said the first publications of the findings of the major international project COVID Human Genetic Effort provide compelling evidence that the disruption of type I interferon is often the cause of life-threatening COVID-19. “And at least in theory, such interferon problems could be treated with existing medications and interventions,” Casanova said.

The project led by Casanova and Helen Su from the US National Institute of Allergy and Infectious Diseases spans over 50 sequencing and research hubs and hundreds of hospitals around the world. The study included patients from several continents. “Nearly 15% of critical COVID-19 cases found an explanation in this research,” said Casanova.

Genetics of COVID-19 outliers

The way SARS-CoV-2 affects people differently has been puzzling. The virus can cause a symptom-free infection and go away quietly, or it can kill in a few days. Casanova’s research over the past two decades has shown that unusual susceptibility to certain infectious diseases can be traced to single-gene mutations that affect an individual’s immune response.

Since February, his team and their collaborators have been enrolling thousands of COVID-19 patients to find out whether something in their genetic make-up drives the disparate clinical outcomes the disease produces.

The research has now led to two publications. In one, the researchers studied more than 650 patients who had been hospitalized for life-threatening pneumonia due to SARS-CoV-2, 14 per cent of whom died. They also analysed samples from another group of over 530 people with asymptomatic or benign infection.

They initially searched for differences between the two groups across genes known to be related to severe influenza. These genes govern type I interferons. It soon became obvious that a significant number of people with a severe disease carried rare variants in these genes, and more than three per cent of them were, in fact, missing a functioning gene. Further experiments showed that immune cells from these patients did not produce any detectable type I interferons in response to SARS-CoV-2.

The cells that carried the studied gene variations were more sensitive to the virus: they died faster and in larger numbers compared to cells without the corresponding mutations.

A mysterious auto-immune condition

As it is known that susceptibility to some particular infectious agents can be caused by both a defective gene as well as auto-antibodies against the product of that gene, the team then checked for the possibility of a similar scenario.

Examining 987 patients with life-threatening COVID-19 pneumonia, they found that more than 10 per cent had auto-antibodies against interferons at the onset of their infection. The majority of them, 95%, were men.

Cell-based tests confirmed that these auto-antibodies are biologically active and neutralise the activity of type I interferons. In some cases, the team could analyse blood samples taken before patients became infected: these already had auto-antibodies. In others, auto-antibodies were found in the early stages of the infection, indicating that these auto-antibodies are actually the underlying reason some people get very sick and not the consequence of the infection. These auto-antibodies seem to be rare in the general population. Analysing the serum of 1,227 randomly selected healthy people, only four were found to have them.

“The findings point to new medical interventions to consider especially in the early stages of the infection,” Casanova said. For example, there are already interferons available as drugs and approved for use to treat certain conditions such as chronic viral hepatitis. 

Estonians’ contribution

An important contribution to the research into auto-antibodies was made by medical researchers of the University of Tartu, led by Research Professor of Cellular Immunology Kai Kisand, who was one of the co‑authors of the research article published in Science.

“Our research group has a long experience in research on interferons and this was very much appreciated by the consortium. We proved that the auto-antibodies of COVID-19 patients block all subtypes of interferon-alpha, 13 in total. As a result of neutralised interferons, antiviral barriers are weakened, leading to a facilitated and faster spread of the virus in the body,” described Kisand.

According to Kisand, the presence of auto-antibodies should be also taken into account in convalescent plasma transfer to the risk-group patients. “Fortunately, the risk is low, as plasma donors are mostly people who had moderate symptoms and did not need hospitalisation – many thanks to all of them. In such patients, we have not detected auto-antibodies against interferons so far.”

Researchers say that research in the field continues, as the genetic variants of other immune mediators or their receptors may also have a role in the development of the severe form of the disease. In parallel, the potential role of several other auto-antibodies in the onset of severe COVID-19 is studied.

Further information:
Kai Kisand
Research Professor of Cellular Immunology at the University of Tartu
+372 737 4186
kai.kisand [ät] ut.ee
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