Why Do Some Experience Severe COVID-19 Infections and Others Do Not?

Author: Silvia DiPaola

Editors: Katelyn Ma, Shamsia Ahmed

Artist: Kaitlyn Stanton

We are all aware of the COVID-19 pandemic raging through the world right now.

Many lie in fear of acquiring serious illness because of certain risk factors the disease may harbor. Some risk factors for severe COVID-19 complications are rather obvious: obesity, poor diet, hypertension, a compromised immune system, and diabetes. Other risk factors for severe coronavirus complications are not quite as obvious; these include features of the innate immune system which some people may have: interferon issues and autoantibodies.

In general, elderly people and those with underlying chronic illness are more likely to have a serious case of coronavirus. However, this does not account as to why young people are beginning to fall seriously ill as well. Recent studies from mid-September have shown that interferons, a type of immune system protein, may be involved. Interferons disrupt the replication of viruses, and thus they are one of the first lines of immune defense against viruses such as SARS-CoV-2 (the virus that causes the coronavirus disease.)

A study was done by Jean-Laurent Casanova and Helen Su of the National Institute of Allergy and Infectious Diseases to investigate this notion. DNA from 659 severely ill COVID patients was compared to that of 534 mildly ill COVID patients; researchers were searching for mutations that might be impairing the production of interferons. The results showed that 3.5% of the gravely ill patients had the mutations, while none in the control group did. Another one of their studies showed that 13.7% of the 987 severely-ill individuals tested had auto-antibodies; these are antibodies produced that attack the body’s own type I interferons instead of the pathogen. In 10.2% of the 987 patients, the auto-antibodies completely hindered the actions of the interferons. This may indicate a correlation between auto-antibody production and severe COVID complications. The auto-antibodies were found in 12.5% of the severely ill men but only 2.6% of clinically similar women. This may be a possible reason as to why men have higher COVID mortality rates. These results are surprising because auto-antibodies are highly rare in the general population, but they seem to be common amongst critically ill coronavirus patients. This discovery has raised red flags for use of convalescent plasma from those who have recovered from coronavirus. It is because if the recovered patient has these auto-antibodies, giving their plasma to a severely ill COVID patient may worsen their condition instead of alleviating it.

Interferons are also being investigated as a potential cause of severe coronavirus infections. SARS-CoV-2 has been seen to suppress the body’s natural interferon response. Genetic mutations on the X chromosome may also impair the interferon responses. However, interferons can have both positive and negative effects on the body’s response to infection; it can activate immune cells, but it may also enhance inflammation that increases the odds of a negative outcome. To have a positive effect, interferons would have to be administered to COVID patients early. This is because once a patient develops a severe immune reaction, interferons are likely to be of no help. Genetic factors combined with the nature of the virus may explain why some people have severe cases of the virus, and some never show any symptoms.

The National Institute of Allergy and Infectious Diseases is conducting studies to see how Remde Sivir compares to a combined therapy of the drug and interferon-beta. They are also running tests to see if giving interferons to family members of those infected with coronavirus will help prevent them from getting infected as well. Such developments related to coronavirus treatment through interferons may lead to the discovery of possible reasons why some people acquire severe infections, and some have no symptoms at all. One can hope to see interferons become part of regular treatment for coronavirus; with any luck, they might be key to producing effective treatments that will allow society to return to its normal, pre-COVID state faster.


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Fighters, Beat COVID-19?” Science, Science Mag, 21 July 2020,


Wallis, Claudia. "One in Seven Dire COVID Cases May Result from a Faulty Immune

Response." Scientific American, Scientific American, 30 Sept. 2020,


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