New study reveals the surprising reason why young, healthy people die of COVID-19

When we narrow in on aggressive viral activity, we get a sense of how complex the human immune system really is.

The vast majority of individuals who succumb to COVID-19 suffer from conditions that in some way compromise their immune system. However, a smaller portion of otherwise healthy patients achieves critical status due to a miscalculated immune response. 

Recently, Ladders reported on a growing number of COVID-19 deaths that result from an abundance of immune system proteins called cytokines. A cytokine storm occurs when these proteins begin to attack healthy cells in order to eliminate a pathogen. 

This process is common in autoimmune conditions, arthritis, and viral infections. In fact, 81% of participants who died while under review in a recent H1N1 study did so because of cytokines storms.

Although the literature on the adaptive immune response is ample, SARS-CoV-2 has defied much of the canon. Its incubation cycle is as inconsistent as the recovery windows evidenced by those infected, saying nothing of the lengthening list of symptoms once thought to be atypical that are now officially recognized as instructive.

This means targeted immunogen development and synthetic immune system suppression are concurrently being surveyed with a comparable degree of seriousness.

After extensive mathematical modeling, a new study published in the Journal Medical Virology determined that subduing the human immune system in the early stages of SARS-CoV-2 infection might dramatically reduce the likelihood of fatal outcomes in young healthy carriers.

“We have applied mathematical modeling to investigate the infections of the ongoing COVID‐19 pandemic caused by SARS‐CoV‐2 virus. We first validated our model using the well‐studied influenza viruses and then compared the pathogenesis processes between the two viruses,” the author wrote in the new paper. “The interaction between host innate and adaptive immune responses was found to be a potential cause for the higher severity and mortality in COVID‐19 patients. Specifically, the timing mismatch between the two immune responses has a major impact on disease progression. Suppressing the adaptive immune response temporarily and avoiding its interference with the innate immune response may allow the innate immunity to more efficiently clear the virus.”

Interaction between Innate and Adaptive Immune Responses in COVID‐19 and Implications for Viral Pathogenesis

The innate immune response is initiated as soon as our bodies become aware of the presence of a pathogen.

To eradicate it, our immune system deploys agents to attack viral material as well as host cells that the virus has successfully impregnated with genetic material. T cells and B cells are subsequently recruited to finish the job. Although this course of action is a thorough one, it isn’t exactly methodical. It’s more like programming.

What happens if a virus’s incubation cycle is not congruent with our body’s clean up procedure? Sadly, our latest pandemic has supplied a disconcerting answer.

The innate immune response and the adaptive immune response arrive at the scene at the same time, delaying viral clearance by sending protective biological measures into overdrive.

“Some COVID-19 patients may experience a resurgence of the disease after an apparent easing of symptoms. It’s possible that the combined effect of the adaptive and the innate immune responses may reduce the virus to a low level temporarily. However, if the virus is not completely cleared, and the target cells regenerate, the virus can take hold again and reach another peak,” explains the study’s lead author, Dr. Sean Du. “The danger is, as the infection keeps going on, it will mobilize the whole of the adaptive immune response with its multiple layers. This longer duration of viral activity may lead to an overreaction of the immune system, called a cytokine storm, which kills healthy cells, causing tissue damage.”

These findings are observable here and there in preceding literature, across similar scenarios. Every year the majority of the minority of healthy individuals who die of the common flu evidence an overactive immune response. Of course, there are pharmaceutical countermeasures in place for pedestrian influenza strains to ensure these outcomes remain fairly scarce in developed nations.

Without antiviral treatment for SARS-CoV-2 researchers have to devise unique therapeutics for every impacted population.

For the immune-compromised, medical facilities have to invest in supportive care for any and all aggravating factors. For the elderly, officials have to limit exposure by enforcing social distancing mandates. For essential workers, technology, caution, and funding have to be exercised by parties involved to temper high-risk situations. And finally, for the demographic initially thought to be safe from fatal COVID-19 manifestations, academicians are trying to anticipate when youth and vigor are actually liabilities in disguise.

“Based on the results of the mathematical modeling, we proposed a counterintuitive idea that a short regimen of a proper immunosuppressant drug applied early in the disease process may improve a patient’s outcome,” says Du. “With the right suppressive agent, we may be able to delay the adaptive immune response and prevent it from interfering with the innate immune response, which enables faster elimination of the virus and the infected cells.”

CW Headley is a reporter for the Ladders and can be reached at cheadley@theladders.com.