We continue our Hope Behind the Headlines series by exploring the most recent — and most hopeful — findings in the field of COVID-19 research.
Hopefully, the COVID-19 pandemic will not last forever. Every 2 weeks, we round up the recently published evidence that reminds us of this.
In our last installment, we reported on a vaccine candidate that showed promise in monkeys and a new trial that tested an existing drug, among other innovations.
In this feature, we discover another existing drug that could treat the infection. We also learn about T cells and how a new blood test could speed up vaccine development and mass screening.
Furthermore, we zoom in on a class of immune-modifying drugs that may be the most effective treatment for severe forms of the disease.
Researchers have found that a drug that doctors currently use for treating conditions as varied as bipolar disorder and hearing loss also has antibacterial and anti-inflammatory properties. These properties make it a good candidate for treating COVID-19.
The drug is called Ebselen, and the fact that it is already in use indicates its safety. Furthermore, previous evidence has shown that Ebselen can block enzymes that the new coronavirus needs for replicating within healthy host cells.
This enzyme is called Mpro, and researchers have described this protease as “indispensable” for the replication of SARS-CoV-2. As a result, Mpro is an excellent drug candidate.
In the new study, Prof. Juan de Pablo, from the Pritzker School of Molecular Engineering at the University of Chicago, IL, and his colleagues set out to test whether Ebselen can indeed inhibit the Mpro protease.
To find out, they created computer models of both the drug and Mpro to see how they interact. They found that the drug’s action is two-pronged:
“In addition to binding at the catalytic site of the enzyme, Ebselen also binds strongly to a distant site, which interferes with the enzyme’s catalytic function by relying on a mechanism in which information is carried from one region of a large molecule to another region far away from it through subtle structural reorganizations.”
“These findings highlight the promise of Ebselen as a repurposed drug against SARS-CoV-2.”
– The study authors
In an exclusive interview for Medical News Today, James Hindley, Ph.D., explained how he and his collaborator Martin Scurr, Ph.D. — a research associate at Cardiff University’s School of Medicine in the United Kingdom — are working on a new test that measures a key component of the immune system: T cells.
Hindley, who is the Executive Director at Indoor Biotechnologies in Cardiff, told MNT that most of the existing tests focus on assessing antibodies to determine immunity to SARS-CoV-2.
“However, another critical component of our immune response to viruses is the T cell. These also provide memory immune responses and may even be more sensitive than antibodies,” said Hindley.
T cells are a type of lymphocyte, or white blood cell, that the bone marrow produces. Before neutralizing antibodies even come into play, different types of T cells have to collaborate to lead to antibody production.
“The test we have developed can provide quantitative results measuring the magnitude of an individual’s T-cell response to the SARS-CoV-2 virus. We can also run in parallel the same test for other human coronaviruses and viruses, such as influenza. This allows us to establish a person’s immune status.”
– James Hindley, Ph.D.
The researcher went on to explain that the test will be useful “for vaccine development; to determine whether a T-cell response to the vaccine has been generated and whether that is adequate to be protective from infection.”
“We also believe this test will enable public health bodies to perform much wider screenings of the population. [T]his would be carried out by laboratories in conjunction with antibody testing to determine what constitutes protective immunity.”
Finally, the researcher also explained how this test is more effective than others.
“Where we were innovative was looking at the minimum requirements to perform this test, to get the necessary data to answer the question of whether a person has specific T-cell responses.”
“By providing just these elements without the added complexity, we made this test much easier to perform in almost any lab.”
New research spearheaded by Marcus Buggert, an immunologist at the Karolinska Institutet in Sweden, also has T cells at its heart.
Buggert and his team found that 30 out of 31 people who recovered from a mild SARS-CoV-2 infection had memory T-cell responses to the new virus.
Out of the same sample, 27 had antibodies against the coronavirus. Such findings add to the newly emerging direction in research that uses T cells as an alternative path to COVID-19 immunity.
In the new study, T cell responses were still visible months after a mild infection, sometimes even in the absence of antibodies.
“In the absence of a protective vaccine,” says Buggert, “it is critical to determine if exposed or infected people, especially those with asymptomatic or very mild forms of the disease who likely act inadvertently as the major transmitters, develop robust adaptive immune responses against SARS-CoV-2.”
“Our findings suggest that the reliance on antibody responses may underestimate the extent of population-level immunity against SARS-CoV-2. The obvious next step is to determine whether robust memory T-cell responses in the absence of detectable antibodies can protect against COVID-19 in the long term.”
– Marcus Buggert
Finally, an observational study found a class of drugs called interleukin-6 (IL-6) receptor inhibitors to be the most effective for treating severe forms of COVID-19.
In fact, the new study found that these drugs are even more effective than remdesivir or dexamethasone — the other two treatments widely heralded as beneficial, based on clinical trial results.
Healthcare professionals typically prescribe IL-6 receptor inhibitors for conditions with an autoimmune component, such as rheumatoid arthritis, to dampen the immune system’s excessive response.
IL-6 receptor inhibitors — as their name suggests — block the receptors of IL-6, which is an immune signaling molecule, or cytokine.
In COVID-19, this action helps calm down the phenomenon known as the cytokine storm, which can lead to potentially fatal outcomes in people with the disease.
In the new paper, for which Dr. Pranay Sinha from the Section of Infectious Diseases at Boston University School of Medicine, MA, was the first author, the researchers explain that the participants who received the 1L-6 inhibitors “had considerably higher supplementary oxygen requirements, indicating more advanced disease, than patients in the remdesivir and dexamethasone trials and would have been expected to have a higher mortality rate.”
However, the IL-6 inhibitor “recipients had a lower mortality rate than patients in the intervention and control groups of those trials.”
Furthermore, the mortality rate for the participants who required ICU care was 22.9%. This rate was “considerably lower than the published 45–50% mortality in other ICU cohorts.”
“The majority of patients (85.5%) were also discharged alive, which is higher than the reported rate with standard of care (36–66%) over a similar time of follow-up.” Overall, the authors conclude:
“[IL-6 inihitor] use was associated with decreased mortality, decreased rate of intubation, higher likelihood of being discharged alive, and shorter length of stay.”
For live updates on the latest developments regarding the novel coronavirus and COVID-19, click here.