What happens to the immune system when Covid-19 strikes

Dr Eddie McAteer is a retired paediatric anaesthetist, with a strong interest in immunology. Dr Yvonne Bordon is a Senior Editor with Nature Reviews Immunology, the world’s top immunology journal and one of Nature’s scientific journals. Here they explore what happens to the immune system when Covid-19 strikes.

Imagine a farmer with a field of wheat. The farmer is our immune system and the field of wheat represents the cells and organs of our body.

The farmer continuously inspects the field. If he spots any weeds or abnormal sheaves of wheat, he removes these; the field remains healthy. If the farmer ceases his inspections, pests can invade and weeds will grow. Eventually destroying the crop.

The weeds and pests are like infections in our bodies, such as bacteria and viruses.The abnormal wheat sheaves are cancerous cells. At the other extreme, if the farmer becomes over-zealous and starts removing the healthy wheat sheaves, the field will also be destroyed.

The virus that causes COVID-19 is the pest infecting the field. In the majority of cases, the pest infects some of the wheat sheaves, but the farmer goes about his job effectively and removes the damaged crops. The pest is cleared in the process and the field returns to full health (often after a nasty fever, cough and fatigue).

However, if the farmer doesn’t manage to clear the damaged wheat sheaves in time, the pest can infect more and more healthy sheaves. The farmer becomes overwhelmed trying to clear all of the damaged plants. He recruits more farmhands to help him protect the field, but in the process they also cut down the healthy stalks and the field of wheat is destroyed.

This represents the situation that occurs in the roughly 5–14% of people who develop severe disease after being infected by the new coronavirus. Immunologically, it seems that these individuals are developing an excessive immune response, something known medically as ‘cytokine release syndrome’, or ‘CRS’ for short.

Cytokines are the ‘messengers’ of the immune system ― the commands that the farmer sends to his farmhands to cut down stalks. If he sends too many orders like this, the farmhands start to remove healthy plants as well as defective crops. Some cytokines can be viewed as messages to the farmhands to ‘burn the crops’ ― these cytokines are particularly dangerous. CRS is the farmer sending too many orders to the farmhands to burn the field — the fire can quickly get out of control and kill the whole field.

However, doctors already have drugs that can block the dangerous cytokines associated with CRS. One such drug (called Tocilizumab, or Actemra) blocks the receptor for a cytokine called interleukin-6 (IL-6) and is currently in trials for use in severe COVID-19. It is used to treat CRS in other clinical settings, such as in cancer patients who develop CRS after receiving immunotherapies. The farmhands have switched off their mobiles and no longer receive the farmer’s messages to burn the field.

Another tactic the farmer can use is to treat the field with a pesticide. Many scientists are working on anti-viral therapies for COVID-19. One potential strategy, that has received a lot of media attention, is combined treatment with hydroxychloroquine and the antibiotic azithromycin. This approach is like blocking the messages to the farmhands and simultaneously treating the field with a pesticide.

However, despite a few initially hopeful small-scale studies, several subsequent studies have failed to find good evidence that this strategy is effective in COVID-19. And a worrying consequence of the initial media hype could be that patients who need hydroxychloroquine for other diseases (including lupus, rheumatoid arthritis and malaria) will not be able to access this vital drug if the existing stocks are stockpile.

There’s another interesting strategy that scientists are looking at just now. Believe it or not, the BCG vaccine that is used to protect against the bacteria that causes tuberculosis might offer some protection against the new coronavirus. It’s like the farmer having recruited some trained farmhands who have helped clear different weeds or pests in the past. These farmhands are more vigilant and will chop down any sheaths of wheat that look slightly unhealthy. The new pest never gets the chance to spread and the farmer does not have to resort to burning the field.

Continuing with the farmhand analogy, if the farmer can recruit specialist farmhands who have previous experience with the pest, they will be more effective in spotting the infected crops and clearing them quickly. This could be likened to another strategy that is being trialled in patients with COVID-19, known as ‘passive antibody therapy’. Here, blood plasma is taken from those who have tested positive for the COVID-19 virus and whose immune system has now eliminated the infection. These individuals have antibodies that help clear the virus and transferring these antibodies to patients who currently have COVID-19 could help them to recover.

Finally, the best solution for the farmer would be if he can spray his field with a safe, long-lasting protective pesticide before the pest even shows up. This is akin to the vaccines that are being developed. However, there are many challenges involved in vaccine development and it is unlikely that we will have an effective vaccine for SARS-CoV-2 any time soon.

It’s still too early to know which of the treatment strategies (if any of them) will prove to be most useful in helping to manage the disease until we have an effective vaccine. The NHS is currently trialling many new approaches to treat COVID-19 patients.

What has been particularly encouraging has been the way in which scientists throughout the world have come together to tackle the pandemic. This will undoubtedly speed up our efforts to develop successful therapies for the disease.