“No one has taken this fragment of protein, infected someone with it and proved that it causes disease.”

This is a direct quote from a letter sent to me by someone who is not convinced that COVID-19 is caused by the SARS-CoV-2 virus. As a science educator, I rather feel that the scientific community has failed somewhere along the line for people to question this; what I regard as a fairly fundamental point. So, I feel duty-bound to respond.

First, I’m going to split some hairs. The virus is a package consisting of RNA (rather like DNA inside human cells) and a shell made out of proteins. All of this is wrapped in an incredibly thin greasy layer. The virus is not simply a fragment of protein.

RNA is a substance that contains coded instructions for making copies of the virus. When the virus gets into a cell, it fools the cell into using these RNA instructions to make new viruses (rather than the cell continuing to use its own RNA to make new things for the cell). All viruses work like this.

What you refer to are ‘human challenge trials’. To my knowledge these have not been done for COVID-19. Trials like this are routinely done to test new vaccines but only when there is a cure for the disease that is being tested (in case the new vaccine doesn’t work). The cheery photo that I have posted above is of someone about to drink a liquid containing the bacteria that cause typhoid. The photo is from vaccine study a few years ago.

There was an application a couple of months ago to do human challenge trials for COVID-19 but this was rejected on ethical grounds.

However, macaque monkeys suffer from many of the same diseases as humans do, show the same symptoms and their bodies have a similar way of getting rid of bacteria and viruses (a similar immune system). So, scientists routinely use macaque monkeys to test treatments for human diseases, when human challenge trials are not deemed ethically sound. Hundreds of macaques have been infected with COVID-19 and when infected they start to show the same symptoms as humans. (I’m not getting into discussions about animal testing. This is just what happens.)

The problem with the macaques is that they are big animals with long life cycles and you don’t want to risk killing your macaques because then they won’t be available for other experiments. So, scientists also infect Syrian hamsters, which by chance are also infected by many human viruses and have immune systems that respond in a similar way as humans. Again, hundreds of the animals have been infected with SARS-CoV-2 in order to study the virus. When infected, the animals show “diffuse alveolar damage with extensive apoptosis”, which translates into English as ‘damage to wide areas of lung tissue with lots of dead cells’.

The usual target animal for such disease tests in animals are mice. However, mice can’t get COVID-19.

We are also able to grow human cells (of many different types) in bottles in labs. These cells are routinely infected with the SARS-CoV-2 virus, and the progress of infection can be followed. Some of these studies have used an electron microscope to take photos of this process, and you can see SARS-CoV-2 virus particles entering human cells, and then those cells becoming full of the virus particles. (As an aside, that’s one way in which scientists generate copies of the virus in order to study it – they infect human cells in a bottle and wait for the cells to be fooled into making millions of copies of the virus). These sorts of experiments have been repeated hundreds of times.

Scientists used bottles of human cells when working out how the virus gets into cells and why it infects cells of the respiratory tract in particular. They found that the virus latches onto a protein, called ACE2, that sticks out of these cells.

Having found the thing that the virus uses to get into human cells, scientists then genetically modified mice to have respiratory tract cells with the ACE2 protein on them. The scientists predicted that these GM mice would then get COVID-19 if infected with the virus. And this prediction was shown to be correct; these GM mice get COVID-19.

Ferrets and cats also get COVID-19 when infected with the SARS-CoV-2 virus. There are doubtless others, but these are the animals that I am aware of.

So, while human challenge trials have not been done, thousands of experiments in animals show that the virus that we call SARS-CoV-2 is the cause of COVID-19 in those animals. Scientists have also shown directly that the SARS-CoV-2 can enter human cells, and when it does so, it causes those cells to make thousands of copies of the virus.

Together with data that shows a direct correlation between having the SARS-CoV-2 virus in your body and having COVID-19, that is quite enough proof for me that the virus causes the disease in humans.

Doubtless, once we have a better understanding of the disease and how to prevent/treat it, human challenge trials will be done. For the moment, the only human trials are the vaccine trials, which revolve around people naturally being exposed to the virus.

Text: Mark Levesley   @marklevesley    levesley.com

Photo: Andrew Testa for The New York Times (permission being sought)