Research Roundup: COVID-19 Recovery & the Vaccine and More
Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones.
People Recovered from COVID-19 May Only Require One Dose of mRNA Vaccines
A study published on the preprint server medRxiv, meaning it has not yet been peer-reviewed, suggests that people who have had a strong case of COVID-19 may only require a single mRNA vaccine, such as that produced by Pfizer-BioNTech or Moderna, in order to generate sufficient immune response for protection. The study was conducted by scientists at Mount Sinai Hospital. The findings were partially described after noting that people who had previous cases of the disease appeared to have much more severe reactions to the first dose of the vaccines.
“I think one vaccination should be sufficient,” said Florian Krammer, a virologist at the Icahn School of Medicine at Mount Sinai and one of the study authors. “This would also spare individuals from unnecessary pain when getting the second dose and it would free up additional vaccine doses.”
It was supported by a second study published on medRxiv by researchers at the University of Maryland School of Medicine in healthcare workers. This study didn’t evaluate symptom response to the vaccine, but instead looked at antibody responses. In that study, they found that previously infected people generated high antibody levels after the first dose of the vaccines, comparable to the levels seen after second doses in individuals who had not previously had COVID-19.
Although the data is interesting, it’s a significantly long way from proving that the second doses should be abandoned in people already diagnosed with COVID-19. And there are cases where people with mild COVID-19 cases seemed to generate much lower antibody levels, which may not offer enough protection, particularly against the new more contagious variants.
Random DNA Change Reversed Rare Inherited Immune Condition
DOCK8 immunodeficiency is a rare autosomal recessive type of hyperimmunoglobulin E syndrome. It is caused by a mutation in the DOCK8 gene and is marked by elevated immunoglobulin E levels, eosinophilia, and recurrent staph and viral infections. Investigators at the Garvan Institute of Medical Research identified three patients whose bodies’ spontaneously repaired the mutation and restored normal immune function over time. Two of the patients were in France and one in Australia. Analyzing the genome of the patients’ immune cells, they observed that some cells had undergone somatic reversion, which is to say, they accumulated random mutations within the DOCK8 gene and when it was copied, they reverted to normal DNA code.
Why Some Psychiatric Drugs Help Some but Not Others
Scientists with the University of Colorado at Boulder found that a specific protein in the brain called AKT appears to function differently in males than females. AKT was identified in the 1970s and is known for causing cancer when mutated, but it was more recently found to be a key player in promoting “synaptic plasticity,” which is the brain’s ability to strengthen connections between neurons in response to experience. Mutations in the AKT gene are linked to schizophrenia, post-traumatic stress disorder, autism and Alzheimer’s. This research found that there are different forms of AKT that have different functions in the brain, for example, AKT2, which is implicated in brain cancer, is found only in the star-shaped astroglia. AKT3 is involved in brain growth and development, while AKT2 and AKT1 are critical for learning and memory. But the finding that there are sex differences, and it was a significant difference, they hope it will lead to more nuanced treatments for these diseases.
Subgroup of COVID-19 Patients at High-Risk for Severe Bleeding
A study by researchers at the University of Michigan published in Scientific Reports of a subgroup of COVID-19 patients found increased risk of bleeding. This is related to the well-known incidences of COVID-19 patients having high risk of blood clots, which could result in strokes or heart attacks. In this subgroup, they appear to have an unbalanced ability to break down blood clots, which is good for removing the clots, but then provides a greater risk of uncontrolled bleeding. The study included 118 COVID-19 patients and 30 healthy controls. The investigators expected to observe high levels of plasminogen activator-inhibitor-1 in the COVID-19 patients, which is associated with stabilizing blood clots. But, they found high levels of tissue-type plasminogen activator, a molecule responsible for removing clots.
How Exercise Improves Metabolism
Researchers with USC Leonard Davis School of Gerontology and the University of Ulsan College of Medicine in Seoul, South Korea, showed how moderate exercise stimulates cells in the hypothalamus to release a hormone called MOTS-c. The hormone is encoded in cells’ smaller mitochondrial genome. The hypothalamus is the part of the region that controls metabolism. The research suggests that low-grade stress in mitochondria promotes health and longevity, which is called mitohormesis. They conducted research on mice homodeficient in Crif1, which controls how cells use proteins encoded by mitochondria. The mice without Crif1 experienced severe mitochondrial stress and had metabolic problems at adulthood, such as weight gain and decreased energy expenditure. They also had insulin resistance and high blood sugar, similar to type 2 diabetes in humans. But mice that were heterodeficient in the Crif1 gene, meaning they produced some of the appropriate protein, had mild mitochondrial stress and protection against obesity or insulin resistance.
Super Responder Memory B Cells Attack COVID-19 Virus, but Not Necessarily the Spike Protein
Immunome, a biotech company in Exton, Pennsylvania, published preclinical research from its COVID-19 research program. The study found that 50% of the antibodies isolated from so-called super-responders are directed at non-Spike antigens. This suggests that non-Spike-related antibodies may play a big role in effectively clearing the virus. The most prevalent non-Spike targets were nucleocapsid proteins and the open reading frame-encoded (ORF) proteins, ORF8 and ORF10. They also found that the antibody response against both neutralizing and non-neutralizing epitopes—particular parts of the Spike protein—are committed to B-cell memory. The research is yet to be peer-reviewed but has been posted on the bioRxiv preprint server.
The company received a $13.3 million agreement from the U.S. Department of Defense’s Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), in collaboration with the Defense Health Agency, to support its COVID program.
“We believe that the broad response we observed to multiple viral proteins beyond just the Spike protein points towards an approach for developing an antibody cocktail, which could better mimic the natural human immune response against the SARS-CoV-2 infection,” said Purnanand Sarma, chief executive officer of Immunome. “Furthermore, an optimized combination of antibodies could potentially overcome the high level of mutational drift we are seeing in the Spike protein.”