In this post we discuss two fresh articles that provide some good news (or do they? more on that in the end) regarding COVID-19 related research. Some leading researchers in the field of immunology called the new findings “remarkable” because they may provide immediate practical implications in our fight against the pandemic. We at Pretty Light Science made it our mission to break down the main findings of the studies and deliver them to you.
Two new papers published in Science confirm an earlier idea suggesting that a special molecule called a type I interferon (type I IFNs), which acts as a natural virus fighter in a human body, may be inactive in some individuals resulting in more severe COVID-19 infections. Why would it do that, why would it leave us defenseless? The researchers identified two reasons for this. In some cases, inborn genetic errors were to blame and in others interferon was attacked by our own faulty antibodies.
Auto-antibodies against type I IFNs in patients with life-threatening COVID-19
In one study, a team led by Jean-Laurent Casanova, a geneticist from Rockefeller University, studied blood samples from 987 patients hospitalized with life-threatening COVID-19 pneumonia. They also examined 663 individuals infected with SARS-CoV-2 who had mild symptoms or were asymptomatic, and 1227 healthy individuals who acted as a control group. In 101 of 987 patients (10.2%) with pneumonia the researchers identified antibodies that attack the patients’ own type I interferon. In contrast, these autoimmune antibodies were detected in only 4 out of 1227 (0.33%) healthy individuals and in none of the 663 patients who were asymptomatic or had only mild symptoms of the COVID-19 infection.
Almost half of the patients with interferon-attacking antibodies were older than 65 years old and 94% were male.
What these findings mean is that an autoimmune attack may explain 10% of all the critical COVID-19 cases. Taking into account that SARS-CoV-2 has already taken 800,000 lives, has been detected in at least 20 million people, and has infected many more, 10% is a soberingly high number. Other interesting results from this study may help explain the increased susceptibility to the infection by males and older people. Almost half of the patients with interferon-attacking antibodies were older than 65 years old and 94% were male! These results may be of incredible significance because it seems that the virus doesn’t select its victims randomly like a maniac in a bad horror movie but rather like a cold blooded killer who knows what he wants and has a plan. A direct practical implication from these findings is that we may be able to more accurately identify individuals who are more susceptible to a SARS-CoV-2 infection and protect them.
Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
In the second study the researchers took samples from 659 patients of various ancestries, aged between one month and 99 years old, with life-threatening COVID-19 pneumonia. As controls, they examined 534 individuals infected with SARS-CoV-2 who either remained asymptomatic or developed only a mild infection. They studied 13 human genes known to govern type I interferon immunity to influenza or other viral diseases. In 3.5% of the severely infected patients (23 out of 659) the researchers found rare inborn mutations in 8 out of these 13 genes. Interestingly, patients with mutations were of both sexes coming from different ancestries and belonging to various age groups. Interferon levels in those patients with mutations who had blood samples associated with them were extremely low.
The virus doesn’t select its victims randomly.
Why are these results exciting and thought provoking? Because this is the first study that conclusively demonstrates that mutations in certain genes may cause or contribute to severe cases of COVID-19. Furthermore, given the results from these few genes, it is reasonable to hypothesize that other human gene mutations may exist that influence the development of a coronavirus infection. Another interesting point is that none of the 23 patients with these mutations had type I interferon attacking antibodies described above. This suggests the independent nature of the two mechanisms weakening the interferon defence. Overall, the results from this article suggest that type I interferons play a more important role in our defence against SARS-CoV-2 than other viral infections. And thus, we should consider treatments aimed at boosting type I interferon responses in select patients infected with SARS-CoV-2.
A positive spin. Is this good news really all that good? (Yes, it is)
We read many research papers in our Pretty Light Science office but we also follow some news outlets to be aware how well (or badly, mostly badly) science is presented to the general public. From many articles and even more opinions and comments left by the readers, we understand that people are losing their patience with this pandemic. Which isn’t really surprising. We have to wear masks in public places; travel is fairly complicated; many museums, movie theaters, and gyms are working with restrictions or are simply closed. In some cities the government took things further and closed down bars, while not doing much to unload public transportation. So it is understandable that when we talk about the coronavirus, it seems like nothing good is happening and that we aren’t moving forward; that cases keep going up and those scientific results that were presented to us as breakthroughs aren’t really that but rather baby steps towards the final victory.
Every successful experiment that puts us a bit closer to the overall victory against the virus should be considered as good news.
Arguably, scientific findings from two fresh papers presented here may also fall into this category of not-that-much-of-a-discovery but rather a small step forward. However, we suggest taking a little bit more positive approach and reassess what good news actually is during the pandemic. The reality is that we are in the midst of an unprecedented situation affecting all branches of our society, including economy, politics etc (don’t forget that bars are closed in some places :-( ). Events of a similar magnitude to COVID-19 happened only a few times in history and even then the situation wasn’t quite the same. People were not flying around the world in planes, they were not taking packed public transportation to get to work, and the pace of life overall was not comparable to what we are blessed (or cursed) with to be enjoying now.
We should not expect good news in the form of “we beat the virus, the pandemic is over, let’s all go celebrate”, because it is not going to happen. The main goal that we keep hearing about on the news is a new vaccine that many countries are currently working on. However, even when this vaccine is created, the fight will still be far from over. It’ll take a considerable amount of time to vaccinate everyone, and then we’ll need to wait and see how the vaccine actually works in “the field”. So every little piece of information, every successful, scientifically proven experiment that puts us a bit closer to the overall victory should be considered as such. As good news that we should appreciate and build on. We believe that the potential to be able to explain 14% of the severe COVID-19 cases definitely qualifies as good news.
Glossary:
Type I interferons (type I IFNs)- special molecules that help regulate the activity of the immune system. They activate antimicrobial programs and influence the development of immune responses.
Mutation is a change in the nucleotide sequence of the genome of an organism.
References:
Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, Ogishi M, Sabli IK, Hodeib S, Korol C, Rosain J. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science. 2020. https://bit.ly/3nIiRjb
Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH, Zhang Y, Dorgham K, Philippot Q, Rosain J, Béziat V, Manry J. Auto-antibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020. https://bit.ly/3nHwpLQ
Hidden immune weakness found in 14% of gravely ill COVID-19 patients. https://bit.ly/2IhJ5Zw
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