Over the course of the many months, it has become apparent that asymptomatic cases of COVID are common. Though estimations vary, some research suggests up to 45 percent of cases are completely without symptoms. These individuals have little to no awareness that anything is wrong. At the same time, symptomatic individuals can be severely affected and succumb to their illness. These reasons for these differences continue to baffle researchers and scientists.
The original explanation for variations among individuals exposed to the pandemic coronavirus focused on the immune system. Those who lacked symptoms were suspected of having a more robust response in fighting the virus. But this no longer appears to be the case. As additional research evolves, scientists are recognizing that this is often not the case. Instead, a feature known as disease tolerance seems to be more relevant among asymptomatic people. And this might just be important in efforts to develop better COVID immune treatments.
“Our traditional view has been to survive an infection, you have to kill it. We have a very disease-centric approach to biology.” – Janelle Ayres, Infectious Disease Physiologist, Salk Institute for Biological Studies
Explaining Disease Tolerance in COVID
Disease tolerance is a concept that differs from previous ideas about how we deal with infections. Disease tolerance describes how some people are resistant to a disease because of genetics, lifestyle, or some other facet they possess. While our immune system is important in fighting disease, it doesn’t appear to be the only one. The human body looks to have other ways of managing infections including some that allow them to coexist. Therefore, instead of trying to develop COVID immune treatments, scientists may be looking to boost disease tolerance. Both are likely to be important in our efforts to fight COVID and other pathogens.
Disease tolerance is a concept that has been well appreciated in plants. Rather than trying to kill a disease-causing agent, plants adapt to tolerate them. It’s quite probable that human beings have done the same, which can explain why many may be asymptomatic from COVID. Studies have now shown that asymptomatic people with COVID actually have a weaker immune response than those with symptoms. This undermines the theory that they lack symptoms because of a stronger immune system. It also gives weight to concepts like disease tolerance as well.
“With things like COVID, I think it’s going to be very parallel to TB, where you have this Goldilocks situation, where you need that perfect amount of inflammation to control the virus and not damage the lungs.” – Andrew Olive, Immunologist, Michigan State University
Existing COVID Immune Treatments
Since the early days of COVID, much has been learned by the medical and scientific community. This is especially true concerning COVID immune treatments. In general, symptomatic COVID patients range from mild to severe. But it became increasingly evident that severe didn’t necessarily have a worse case of the coronavirus. Instead, many became incredibly ill because of an exaggerated immune and inflammatory response. This led many physicians to try medications that “cooled off” the immune system in more severe individuals. Though this seems counterintuitive, it’s an approach that seems to have merit.
COVID immune treatments that suppress the immune system can be grouped into 3categories. The first group of COVID immune treatments is the steroid group. Drugs like dexamethasone appear to help more severe COVID patients if given early. In fact, the Recovery Trial out of the University of Oxford supported these findings. The second group of COVID immune therapies include various types of interferons. These occur naturally within the body, and they serve to modulate the immune system. Interferons early in the course of the coronavirus seem to be beneficial as well.
The final group of COVID immune treatments are getting the most attention, and they are called biologics. Many are monoclonal antibody drugs that are also designed to reduce the immune system’s response. Several companies and universities are exploring the benefits of these COVID immune treatments. For example, British biotech company Synairgen is testing the leronilimab in trials, which is a more recent HIV treatment innovation. Another biotech company’s drug, Kineret, is similarly undergoing trials to assess its potential benefit. Early data from both suggest these drugs may be quite helpful in more advanced patients with COVID.
“[Investigations have] all been focused on the pathogen as an invader that has to be eliminated some way. What we really should be thinking about is how do we keep the person from getting sick.” – Jeremy Luba, Virologist, University of Massachusetts Medical School
Shifting Perspectives to Disease Tolerance
The use of these COVID immune treatments are important in saving lives and reducing disease burden. But at the same time, many of the COVID patients that survive will have longstanding health issues. This may be particularly true of respiratory function. More intriguing, and potentially more effective, are disease tolerance mechanisms. If these could be elucidated, then protective efforts could be employed to reduce the severity of a COVID infection. The goal is to identify specific mechanisms that allow our bodies to tolerate COVID. Taking this approach may eliminate the need for these other COVID immune treatments altogether.
Unfortunately, this burgeoning research field is relatively young. While disease tolerance has been studied for years in plants, this is new for human health investigations. Some of the current pursuits related to COVID are trying to explain why bats are not affected by the coronavirus. Clearly, they harbor large quantities of the virus, yet they show no signs of illness at all. Researchers wonder if a mechanism of disease tolerance might underlie these phenomena. And if so, then perhaps similar strategies could be used to protect human beings also.
Current State of Knowledge About COVID
While much has been learned in a few short months, an enormous number of unknowns persist concerning COVID. Survival rates have improved among symptomatic COVID patients. However, these rates are nowhere near where physicians want them to be. New COVID immune treatments have provided new ways to address an overactive immune response. But no viral medications, including remdesivir, have been definitively proven to help. Technological advances are making progress regardless, and exploring disease tolerance offers a new direction to consider. Combining these efforts along with coronavirus vaccine development may be our best hope for the future.
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