Myotonic dystrophy type 1 (DM1), an inherited disease affecting muscles, was one of the first described “expanding repeat” disorders. In these 50…
5 COVID-19 Updates: Cats, Kids, Seniors, Blood, and an Old Vaccine
Times have been strange for us all, weird indeed for science journalists.
The initial manageable flow of news alerts to the media back in January quickly became an unceasing torrent. Every day now I receive dozens of news releases and heads-ups from science and medical journals. Many papers are preprints (not yet peer-reviewed) or embargoed, meaning we agree to not report findings until a certain date and time.
This is COVID article #42 for me. Today’s post covers 5 news releases that seemed intriguing. Cats first!
Cats Get COVID From Owners
When four-year-old Negrito’s human died of COVID-19, relatives took in the bereft European/Persian mix, who lived in Barcelona. Then Negrito developed difficulty breathing, so the new owners, who also had COVID, took him to the vet. Negrito’s shortness of breath was due to an enlarged heart from a pre-existing condition, and he humanely crossed the rainbow bridge. But his bloodwork revealed a low viral load of SARS-CoV-2, although the cat had no other symptoms of COVID-19.
Negrito’s housemate, Whisky, had neither symptoms nor virus. But both kitties had antibodies to SARS-CoV-2. The cats passed the virus to each other, because neither went outdoors, or the owner infected both.
Investigators at the IrsiCaixa AIDS Research Institute wondered how antibodies kept the cats healthy – which we still don’t know – but they found that the virus from the cats exactly matched that from the owner. The researchers deem the situation a “reverse zoonosis,” because cats are unwittingly infected but not affected as the virus jumps species. The findings are published in the Proceedings of the National Academy of Sciences.
Kids Have Better Innate Immunity
The two main branches of the human immune response are innate immunity, which attacks a broad bunch of pathogens, and the highly-targeted adaptive response, which consists of antibodies (produced by B cells) and several types of T cells. B and T cells (lymphocytes) are types of white blood cells.
Kids mount a more powerful innate immune response, according to several investigations.
A study published in Science Translational Medicine, from researchers at Albert Einstein College of Medicine, Children’s Hospital at Montefiore, and Yale University, compared blood test findings to clinical outcomes among 60 adults and 65 kids (under 24) hospitalized with COVID-19 between mid-March and mid-May. They probed the blood for the telltale cells, antibodies, and inflammatory cytokines that constitute the immune response.
The kids were alright. Only 8% of them required a ventilator compared to 37% of the adults, and only two – 3% – died, compared to 17 (28%) of the adults. The reason? Better innate immunity, particularly lots of one cytokine, interleukin-17. “The high levels of IL-17A that we found in pediatric patients may be important in protecting them against progression of their COVID-19,” said co-author Kevan Herold, MD, of Yale.
Kids and adults made neutralizing antibodies against the virus’s spike protein, but the levels were too high in the adults who died or required ventilation – kids had much lower levels. That finding also supports the idea that innate immunity, and not adaptive immunity, protects kids.
“These results suggest that the more severe COVID-19 disease seen in adults is not caused by a failure of their adaptive immunity to mount T-cell or antibody responses. Rather, adult patients respond with an over-vigorous adaptive immune response,” said K. Herold. The flood of antibodies in the sickest adults also suggests that convalescent plasma may not help in advanced infection. Instead, “therapies that boost innate immune responses early in the course of the disease may be especially beneficial,” said co-author Betsy Herold, MD, of Montefiore.
Seniors Have Too Few Killer T Cells
Antibodies make headlines, but T cells call the shots. They signal each other and other cells, activate B cells to churn out antibodies, and destroy cells about to spew viruses.
“Killer” (aka cytotoxic) T cells are particularly vital. They recognize infected cells and release perforins, proteins that poke holes in the doomed cells. Then the killers release proteins called cytotoxins that enter the holes and then shatter the cell from within. Meanwhile, some killer T cells spawn memory cells that enable resistance to re-infection.
A new study published in mBio profiled T cells in 30 people with mild cases of COVID who ranged in age from the mid-20s to the late 90s. In all of them, infection lowered the numbers of T cells in the blood as well as the biochemicals released, compared to healthy individuals. And the numbers of killer T cells dropped sharply in people over age 80.
Killer T cells are particularly important at the start of infection, when the virus attaches to cells in the nose or mouth, before descending to the lungs. Too few and inadequately armed killer T cells sets the stage for more severe disease.
Clues in Blood
The mantra that having type O blood protects against COVID-19 infection and severity has been around for a few months, echoing past associations of the blood type and resistance to infections. The red blood cells of people with type O blood are bare of the A and/or B antigens (surface proteins) that mark the other ABO blood types. (ABO is one of about three dozen blood types.)
Probing an effect of ABO blood type means accruing data: if an association emerges and grows into a correlation, then researchers deduce a plausible mechanism. That’s about where we are with type O blood and COVID-19. Two recent studies come to mind.
Back in March, the media glommed onto a preprint touting type O’s apparent protection, the findings officially published in August in Clinical Infectious Diseases. In the study, researchers compared ABO blood types among 2,173 COVID-19 patients with people living in the same neighborhoods who weren’t infected. Having type A blood was associated with increased risk of infection, but type O with decreased risk.
In the second study, the Severe Covid-19 GWAS Group took a different approach, scrutinizing genomes for regions harboring gene variants that are more or less common in people who are infected. Their report, published in The New England Journal of Medicine on June 17, zeroed in on part of chromosome 9 that differs in sequence between the infected and uninfected. That region harbors the gene that confers ABO blood type and a gene that encodes an immune system protein, interleukin-6 (IL-6).
How might one blood type lower risk and others raise it? A few hypotheses have emerged:
• A study on SARS from 2005 showed that people with blood types B and O make antibodies that block the binding of the SARS virus’s spikes to ACE2 receptors on human cells growing in culture.
• The close link on chromosome 9 between the ABO gene and the IL-6 gene suggests how the blood types may affect immunity, because genes that are neighbors on a chromosome tend to be inherited together.
• People with type A blood have stickier cells, increasing the likelihood that cells adhere to blood vessel linings, raising risk of the heart problems associated with COVID-19.
All of that sounds logical, but I can’t yet relax because I’m type O. Several experts told Rita Rubin, MA, in a short news article in JAMA Network Open September 16 that it’s too soon to tell if being type O protects against SARS-CoV-2.
Readers chimed in that the data to answer the question are readily available. Wrote ophthalmologist Stephen Orr, “With millions and millions of identified cases as the numerator and billions of people worldwide as the denominator I would think that a research group could mine these enormous data sets and develop some degree of consensus and identify associations and trends that have some degree of scientific validation.”
Meanwhile, another blood characteristic may predict COVID-19 severity.
A team at Massachusetts General Hospital scrutinized blood from 1,641 patients in March and April. “We were surprised to find that one standard test that quantifies the variation in size of red blood cells – called red cell distribution width, or RDW – was highly correlated with patient mortality, and the correlation persisted when controlling for other risk factors like age, other lab tests, and pre-existing illnesses,” said co-author Jonathan Carlson, MD, PhD. Their paper appears in JAMA Network Open.
Patients who had above-normal RDW values when admitted with COVID symptoms had a 2.7-times higher risk of dying, and their mortality rate was 31% compared to 11% among patients with normal RDWs. And if RDW increased after admission, risk of death rose further. Tracking RDW could help clinicians identify high-risk patients early and guide interventions, and monitor response to treatment.
An Old TB Vaccine, BCG
ClinicalTrials.gov lists 241 entries for COVID-19 vaccines, and 22 of them are testing a century-old vaccine called Bacille Calmette-Guérin, aka “BCG.” In some nations it’s given at birth or during childhood to protect against tuberculosis and other respiratory infections.
The vaccine prompts monocytes, a type of white blood cell, to release cytokines that build innate immunity, the type that gives kids an edge. Might such a boost protect against COVID-19? One study taking an historical approach suggests it might.
Researchers at the University of Michigan compared the spread of COVID in nations that mandated BCG vaccination until at least 2000 to nations that didn’t (like the US). According to the paper published in Science Advances, using the vaccine tracks with countries that flattened the COVID curve.
In a “what might have happened” calculation, the investigators picked a date – March 29. They deduced that the 2,467 COVID deaths in the US that day might have been 468 – 19% of reality – if we’d widely administered BCG past the year 2000. So “hindsight is 2020” is literally true. Might BCG vaccine supplement the waning innate immunity that puts older people at elevated risk for COVID?
The pace of publication of the research into the past, present, and future of COVID-19 is truly unprecedented. I so appreciate the rapid availability of new papers to the media and the frequent webinars to update us. Although I could write a blog post on 5 randomly chosen studies every day, I look forward to putting the pandemic in the past.