COVID-19 is a global crisis that has infected more than 21 million people worldwide. While most infected individuals only experience mild symptoms of the virus, 15% of all reported cases required hospitalization, 2% were admitted to an intensive care unit (ICU) and 5% resulted in death. Why is it that some people get really sick from COVID-19, and others don’t? The answer may lie in a weakened innate immune response — our body’s natural defense mechanism against viruses and pathogens.

A group of scientists from Stanford University and University of Hong Kong led a study analyzing the blood samples from 76 COVID-19 patients and 69 healthy individuals. They treated the blood samples with viral particles and found that the white blood cells of infected patients were less able to produce IL-6, a type of cytokine. Cytokines are small signaling proteins secreted by the immune system that call on an army of white blood cells to combat viruses and other foreign particles. This means that COVID-19 infected individuals were less able to respond to viruses —and thus have a crippled innate immunity— in their blood. The sicker the patient is from COVID-19, the more suppressed the immune response is.

However, IL-6 is a pro-inflammatory cytokine, meaning that when it signals for white blood cells to attack tissues infected with viruses, it drives inflammation to the site of infection and contributes to the severity of COVID-19 symptoms. Therefore, it seemed counterintuitive that in a severe COVID-19 case, the white blood cells would secrete less cytokines. Indeed, when the team analyzed levels of cytokines in the blood, they found that cytokines were increased in infected patients, even more so in severely infected individuals. If the innate immune system in an infected individual is weakened, where did all the cytokines come from? They must have originated somewhere else in the body.

Digging further for more clues, the researchers found increased amounts of bacterial DNA in the blood of infected patients. They also found higher levels of proteins that are indicators of lung inflammation. Therefore, they postulated that the virus, and possibly bacteria, in the lungs caused the lungs to secrete high levels of cytokines in the blood, driving lung inflammation and severity of the disease. Meanwhile, the innate immune system of infected patients are still suppressed in the blood, undermining their ability to fight off the virus.

There have been many studies showing the increase in cytokines in patients infected with COVID-19, but no one has properly understood why that is. This study shows, for the first time, that people with severe COVID-19 infections have a much weaker innate immunity in their blood, and thus the increase in cytokines most likely originated from the lungs, not from their blood. This new understanding of the mechanism of COVID-19 infection would hopefully allow us to better develop therapeutics to target severe COVID-19 infection in the future.

The three co-authors of this paper are Prabhu S. Arunachala and Florian Wimmers, both postdoctoral scholars in Stanford University School of Medicine, and Chris Mok Ka Pun, a research assistant professor in Hong Kong University School of Public Health.

Managing Correspondent: Wei Li

Press Article: Study reveals immune-system deviations in severe COVID-19 cases. Stanford Medicine News Center.

Original Scientific Article: Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans. Science.

Image Credit: Gerd Altmann from Pixabay

4 thoughts on “Severe vs Mild COVID-19 infections: differences in immune responses

  1. For almost 4 years, our family tried to keep our elderly parents from contracting the covid virus.
    Unfortunately, my father passed away last week because of a covid disease.
    At an old age and with diabetes and high blood pressure, he got severe symptoms with a high fever, lost taste…
    When he was in the hospital, I came and cared for him for 1 day.
    Two days later, I tested positive.
    I was worried because I’m pre-diabetic and I usually catch a cold or flu easily, so maybe my immune system is not strong enough to deal with the covid virus.
    But by surprise, I only had mild symptoms.
    I think it was because I found a home remedy for coughing that works for me wonder (lemon, ginger and honey) and was able to control my coughing at the beginning.
    I think when it comes to a cold, flu or covid, a cough could make the sickness get worse.
    But on the other hand, I’m worried that if I just had mild covid, my body won’t produce enough immune to keep me strong enough and can easily contract with the virus again.

  2. Since taking fermented brewer’s yeast daily beginning about five years ago, I have not had a single cold or flu. I was getting sick about three times a year before that. This is why I found this article. I have looked and looked for information regarding how people can strengthen their immunity during this pandemic, but, let me tell you, it’s hard to find! I suppose the CDC wouldn’t want people thinking they don’t need a vaccine if they are doing things to prevent themselves from getting sick from viruses. Too bad!

  3. Every human has a natural bell curve of birth, life, and death. Within this time frame the exact state of the health of every single system in the body ( cardiopulmonary,cardiovascular,musculo/skeletal,digestive,neuro/physiological,lymph,etc), is influenced by many variables, (genetics,lifestyle, comorbidities,age and several others) and unfortunately puts millions of people generally left with a seriously compromised immune system which a moderate or even mild infection ends in death.There are 330,000,000 people in the US and just estimating 300,000,000 are under 70 and may have fairly healthy immune systems.( Just an opinion )-Thanks for the comment field.

  4. Hello have you looked at kancera candidate 567 who will be tested on Covid 19 patients at St Göran’s Hospital this September when they start phase 2? if not, it’s incredibly interesting.

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