Research Roundup: Predicting COVID-19 Cytokine Storm and More
Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones.
Predicting the Cytokine Storm in COVID-19 Patients
One of the deadly aspects of COVID-19 is the cytokine storm, a chaotic and severe immune response. This occurs in about 20% to 30% of hospitalized COVID-19 patients. Researchers at Temple University Health System developed and validated predictive criteria that can be used for early identification of COVID-19 patients likely to develop hyperimmune responses that could lead to a cytokine storm. The research was published in the Annals of the Rheumatic Diseases.
“If we can anticipate cytokine storm, we can apply treatment sooner and possibly decrease mortality,” said Roberto Caricchio, chief of the Section of Rheumatology, director of the Temple Lupus Program, professor of Medicine and Microbiology and Immunology at the Lewis Katz School of Medicine at Temple University, and lead author of the study.
Since March, every patient admitted to Temple University Hospital (TUH) had more than 60 different lab variables collected daily until they either recovered or died. These include WBC counts, metabolic enzyme activity, and markers of inflammation and respiratory function. The researchers then ran statistical studies on the data for 513 COVID-19 patients hospitalized in March and April, 64 that developed cytokine storm. They then developed a genetic algorithm and identified six predictive criteria made up of three groups of lab result clusters related to inflammation, cell death and tissue damage, and electrolyte imbalance. They then validated the data in a subsequent cohort of 258 patients admitted to TUH for COVID-19 infection.
“The algorithm correctly predicted cytokine storm in almost 70% of patients,” Caricchio said. “The ability to reproduce our results in a second cohort of patients means that our group of variables are effective criteria for cytokine storm diagnosis in COVID-19 patients.”
Next COVID-19 Drug Target May be Virus Molecular Scissor
Researchers at the University of Texas Health Science Center at San Antonio and the Wroclaw University of Science and Technology in Poland described a novel rationale for designing drugs against COVID-19. They suggest blocking a molecular “scissor” in the SARS-CoV-2 virus that it uses for virus production. The enzyme in question is SARS-CoV-2-PLpro, which senses and processes viral and human proteins, which then promotes infection. The researchers have developed two molecules that inhibit the enzyme.
3 Possible Existing Drugs to Battle COVID-19
By screening a library of previously approved drugs, investigators at the University of New Mexico believe they have identified three drugs that could accelerate a patient’s recovery from COVID-19. They evaluated about 4,000 approved drugs. One was an older antimalarial drug, amodiaquine, which was effective in killing the virus in a test tube. The other two were zuclophentixol, an anti-psychotic, and a blood pressure drug, nebivolol. In lab experiments, they cleared the virus, although that is a significantly different thing than doing so in animals and human beings.
Mouthwashes and Oral Rinses May Inactivate Human Coronaviruses
Researchers from Penn State College of Medicine conducted a study suggesting that certain oral antiseptics and mouthwashes may be able to inactivate human coronaviruses, such as the one that causes COVID-19. They tested several oral and nasopharyngeal rinses in a lab setting for their ability to inactivate human coronaviruses that have a similar structure to SARS-CoV-2, the virus that causes COVID-19. They included a 1% solution of baby shampoo, a neti pot, peroxide sore-mouth cleansers, and mouthwashes. The baby shampoo inactivated more than 99.9% of human coronavirus after two minutes, but several of the mouthwashes and gargle products were similarly effective as well, inactivating more than 99.9% of virus after only 30 seconds of contact time.
Brain Imaging Biomarker May Help Diagnose PTSD and Major Depression
Cohen Veterans Bioscience (CVB), a non-profit research biotech, published data of brain imaging biomarker studies that looked at patient subtypes found in post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). The patient subtypes did not show differences in terms of clinical symptom severity before treatment but did respond differently to treatment. The subtypes were identified based on functional connectivity patterns, i.e., neural signatures, identified through electroencephalography (EEG). One of the subtypes did not respond well to psychotherapy or antidepressants, but both subtypes responded about the same to noninvasive transcranial magnetic brain stimulation (TMS).
Researchers Map the Human Proteome
The Human Proteome Organization (HUPO) published the first draft sequence of the human proteome in Nature Communications. This maps over 90% of the proteins in the human body and occurs 20 years after the release of the human genome. Chris Overall, from the University of British Columbia, said, “Humans share 99% of their DNA between individuals, yet deficiencies in the proteome ‘parts’ stemming from inherited genetic mutations can lead to genetic diseases, or defective or inadequate immune and cellular responses to environmental, nutritional and infection stressors. Knowing which proteins are key to protecting from disease, and the deficiencies in expression or activity that are hallmarks of disease, can inform individualized medicine and the development of new therapies.”
Experimental Drug Prolongs Patient Survival in ALS
A clinical trial by Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital (MGH) and Amylyx Pharmaceuticals demonstrated that a drug, AMX0035, could prolong survival in patients with amyotrophic lateral sclerosis (ALS). ALS is a degenerative disease that attacks brain and spinal cord nerve cells, affecting the patient’s ability to move, speak, eat and breathe. The drug is a combination of sodium phenyl-butyrate and taurusodiol, which target oxidative stress in the mitochondria and endoplasmic reticulum to prevent neurodegeneration. In the CENTAUR trial, 137 patients with ALS were randomized 2:1 to receive AMX0035 or placebo. They found that patients who received AMX0035 lived a median of 6.5 months longer than the ones originally randomized to receive the placebo.
“These findings are an important step forward because, in this trial, early treatment with AMX0035 was associated with longer survival in people with ALS,” said Sabrina Paganoni, the study leader and investigator at the Healthy & AMG Center for ALS. “These results provide substantial evidence supporting the role of AMX0035 for the treatment of ALS. Next steps will depend on ongoing discussions with regulatory agencies.”