The role of animal studies in Covid-19 research

The Covid-19 pandemic has required international collaboration by the biomedical community on an unprecedented scale. Animal research has played a critical role in helping researchers understand the virus itself, the mechanics of its transmission, and the safety and efficiency of all the vaccines so far produced to bring the end of the pandemic a step closer.

EARA has produced a global interactive map to show what biomedical research was conducted using animal models, the species used and its location, including in 24 European countries.

How were animals used in the lead up to Covid-19?

The vaccines for Covid-19 were developed in record time, with three successful vaccines available within a year of the disease emerging. This was because animal research had already paved the way for basic research and drug development to go ahead without delay once the genome of SARS-CoV-2 had been established.

Mouse models used to study the disease had already been generated years previously, for the study of other coronaviruses such as Middle Eastern Respiratory Disease (MERS). As mice are not directly affected by the coronavirus themselves, the availability of this model meant that the disease could quickly be studied in the context of how the virus would affect human cells, without the need to breed a mouse with the specific mutation.

Vaccine research was also already in progress before the emergence of Covid-19. mRNA vaccines have been under development for many years thanks to initial research in mice and the understanding the mRNA could be manipulated to produce an immune response in the body. The Oxford/AstraZeneca vaccine also relied on previous generation of part of the vaccine which had been trialled as a candidate for vaccines against coronaviruses. Once the SARS-CoV-2 genome was available, the researchers could add this to their existing knowledge to generate a vaccine more quickly.

Which animals were used to help us understand Covid-19?

Before a vaccine can be developed, scientists first had to understand how to stop the spread of the virus in the body and how it interacts with cells and tissues. To do this, an animal model was often studied to help improve understanding of the biology of the viral infection. See also, the key stages in Covid-19 vaccine development and the role of animals.

Key animal species used in this research included:

Mice and rats – play an essential role in both vaccine and drug development for Covid-19. Ordinary mice are not susceptible to the disease, so scientists breed genetically altered mice to make them susceptible to Covid-19.
Ferrets – research has shown that ferrets and other members of the weasel family (e.g. mink) can be infected by coronaviruses and exhibit similar symptoms to humans. This makes them a useful tool to study the symptoms of infection, as well as how the virus can spread from animal to animal. They are often used in studies of influenza for similar reasons.
Monkeys – as they have a similar immune system to humans, monkeys are a valuable model to understand how the virus will affect the body. While most research is conducted with rhesus macaques to understand the workings of the virus, baboons have also been used to study the potential consequences of Covid-19 infection in an older population, or in patients with underlying diseases.
Hamsters – these animals are also susceptible to infection by coronaviruses, and were used extensively in SARS research in the early 2000s. Hamsters are being used to study the effects of Covid-19 as they can display similar symptoms to humans when infected. This similarity makes also them a good model for studying transmission, the effects of the virus (particularly on the lungs), and suitable treatments.
Pigs are used in Covid-19 vaccine testing to help scientists better understand how safe and effective a new vaccine is and therefore whether it is suitable for human trials. These animals have also been used to test the effectiveness of new types of ventilators before they are used on humans.

How are animals used while developing a vaccine?

When researchers have a vaccine candidate, it must first go through preclinical testing to ensure that the vaccine is safe and effective. This is often first conducted in mice to investigate whether an appropriate immune response can be generated, and later in monkeys to see how well the vaccine can protect an individual from infection.

Were animal tests skipped while developing Covid-19 vaccines?

During the Covid-19 pandemic, the European Medicine’s Agency issued new advice which allowed researchers to conclude efficacy trials in animals alongside the first Phase I clinical trials in humans, speeding up the vaccine development process. This article from AP News gives an excellent overview.

However, no animal testing stages were actually skipped in this process. The initial preclinical safety testing in mice and monkeys is necessary before progressing to clinical trials, to ensure that the vaccine is safe, and will not make the infection worse or have unwanted side effects. This overlapping of the early phases, rather than sequentially, was due to data evidence from the animal trials that this was safe to do so.

How is animal research used to develop other treatments for Covid-19?

A variety of animal species have been used during the search for treatments to help reduce symptoms for those who have been infected with the virus. Research in Belgium into potential antibody treatments has involved the use of llamas and alpacas, thanks to their ability to produce smaller forms of antibodies, known as nanobodies that are effective in blocking the SARS-CoV-2 route of entry into cells.

Large mammals such as pigs and sheep have also been valuable in Covid-19 research, for the production and development of ventilators which have been essential for patients with severe Covid-19 infections.