So far, scientists have figured out that being male, elderly, and having underlying medical conditions can all raise risk factors for patients. But even patients who check all these boxes don't always experience serious symptoms. Scientists suspect that several factors influence severity, including pre-existing levels of inflammation, natural immunity levels, and the amount and strain of virus that starts the infection - along with variations in patients' genetic makeup.
As has been previously reported, many patients suffer the worst of the symptoms for COVID-19 due to an immune system overreaction called a "cytokine storm". As Dr. Fauci once explained, while "too little immunity is no good"..."too much immunity is really, really bad".
Now, researchers have discovered the role of a critical protein which could open the door to a new potential COVID-19 treatment.
Studies comparing reactions to COVID-19 in siblings have unearthed an interesting detail: the availability of a substance called interferon. Interferons are signaling proteins that help orchestrate the body’s defense against viral pathogens; they're used to treat diseases like Hepatitis C.
A growing body of evidence, including twin landmark studies published Thursday in the journal "Science" showed that "insufficient" interferon levels may be a dangerous precursor to a serious infection. As one researcher explained, the data suggest the virus uses this "one big trick" to slip past the body's initial defense systems.
"It looks like this virus has one big trick," said Shane Crotty, a professor in the Center for Infectious Disease and Vaccine Research at the La Jolla Institute for Immunology in California. "That big trick is to avoid the initial innate immune response for a significant period of time and, in particular, avoid an early type-1 interferon response."
The research highlights the potential for interferon-based therapies to expand a range of non-vaccine-related treatments, like Gilead's remdesivir and convalescent plasma.
Research shows the timing of medical intervention is also critical.
"We think timing may be essential because it’s only in the very early phase one can really battle the virus particles and defend against infection," said Alexander Hoischen, head of the genomic technologies and immuno-genomics group at Radboud University Medical Center in Nijmegen that analyzed the DNA of the two sets of brothers.
Then again, some people are believed to have trouble fighting infections because they make antibodies that deactivate their own interferon. On Thursday, a global consortium of researchers said such immune reactions to the protein could account for life-threatening pneumonia in at least 2.6% of women and 12.5% of men that causes inflammation in the patient's lungs.
Findings from the research offer the first explanation for the significantly higher mortality rate seen in male and elderly COVID-19 patients.
Interferon-blocking antibodies appeared in 101 of 987 patients with severe disease, but none of the 663 people with an asymptomatic or mild case, according to the research being published in "Science". Patients over 65 were also more likely than younger ones to have the autoimmune abnormality, which was "clinically silent until the patients were infected with SARS-CoV-2," said a group of more than 100 scientists said.
Researchers estimated that Inteferon issues might underlie as many as 14% of fatalities and the most severe cases.