By Marie Rosenthal
This week’s roundup might have you saying, “Lions and tigers and kitties, oh my!” Sorry, I could not resist. But SARS-CoV-2 is being found among wild and domestic animals, and there is concern about reservoirs, the development of variants and transmission. Several advisory organizations suggest that people who work with animals, hunters and others be careful. A group out of Columbia University took a deeper dive into the immune response of children with multisystem inflammatory syndrome in children and found some unique markers that might point to better diagnosis and treatment. Dr. David Ho looked at omicron’s effects on monoclonal antibodies and messenger RNA vaccines and affirmed that all of the subvariants of omicron reduce their effectiveness. Canadian researchers took a look at communication about COVID-19 risk and mitigation. Transparency appears to be the best course of action. And finally, apparently a genetic mutation handed down from the Neanderthals, which can cause a person to have severe COVID-19 infection, protects that person from HIV. It has the German researchers asking: What was its original purpose?
Wild Deer, Kitties: More SARS-CoV-2 in Animals
SARS-CoV-2 can infect animals, which may facilitate the emergence of new virus variants, according to a statement by the Food and Agriculture Organization of the United Nations (FAO), World Organization for Animal Health (OIE), and World Health Organization.
In addition to domestic animals, free-ranging, captive or farmed wild animals—such as big cats, mink, ferrets, North American white-tailed deer and great apes—have been infected with SARS-CoV-2, and farmed mink and pet hamsters are capable of human transmission. (The agencies are investigating a potential case of transmission be-tween white-tailed deer and a human.)
The introduction of SARS-CoV-2 to wildlife could result in the establishment of animal reservoirs. About one-third of wild white-tailed deer in the United States might have been infected with SARS-CoV-2, initially through human-to-deer transmission.
Ohio scientists detected infection by at least three variants of SARS-CoV-2 in free-ranging white-tailed deer in six northeast Ohio locations (Nature 2022;602[7897]:481-486).
They grew viral isolates in the lab, indicating viable samples of the SARS-CoV-2 virus and not only its genetic traces.
The concern, according to senior author Andrew Bowman, DVM, PhD, an associate professor at The Ohio State University, in Columbus, is “that we might actually have established a new maintenance host outside humans.”
Using polymerase chain reaction, the scientists detected genetic material from at least three different strains of the virus in 129 (35.8%) of the deer that were sampled.
More promising news from the University of Pennsylvania School of Veterinary Medicine and Perelman School of Medicine: For at least one example of apparent interspecies transmission, crossing the species boundary did not cause the virus to gain a significant number of mutations (Viruses 2022;14[2]:421).
The scientists identified an 11-year-old female domestic house cat, treated at Penn Vet’s Ryan Veterinary Hospital, with COVID-19.
The researchers did not have a sample from the infected owner, but a full genome sequence of the cat’s virus was similar to that circulating in the Delaware Valley region at the time (the AY.3 lineage of delta).
“SARS-CoV-2 has a really incredibly wide host range,” said Elizabeth Lennon, DVM, PhD, an assistant professor at Penn Vet, in Philadelphia. “What this means to me is that, as SARS-CoV-2 continues to be prevalent in the human population, we need to watch what’s happening in other animal species as well.”
The FAO, OIE and WHO suggested steps to reduce the risk for SARS-CoV-2 transmission between humans and wildlife:
- People working closely with wildlife should be trained to implement measures that reduce the risk for transmission between people and animals.
- Current evidence suggests that humans are not infected with the virus by eating meat. However, hunters should not track animals that appear sick or harvest those that are found dead.
- The FAO, OIE and WHO stress that the public should be educated about limiting contact with wildlife.
- It is also crucial to safely dispose of uneaten food, masks, tissues and any other human waste to avoid attracting wildlife, and if possible, keep domestic animals away from wildlife and their droppings.
- Encourage collaboration between national veterinary services and national wildlife authorities to promote animal health and safeguard human and environmental health.
- Promote monitoring and sampling wild animals known to be potentially susceptible to SARS-CoV-2.
- Share all genetic sequence data from animal surveillance studies through publicly available databases.
- Report confirmed animal cases of SARS-CoV-2 to the OIE through the World Animal Health Information System.
- Craft messages about SARS-CoV-2 in animals with care so that inaccurate public perceptions do not have a negative impact on conservation efforts. No animal found to be infected with SARS-CoV-2 should be abandoned, rejected or killed without providing justification from a country- or event-specific risk assessment.
- Suspend the sale of captured live wild mammals in food markets as an emergency measure.
Study Suggests How Post-COVID Syndrome, MIS-C, Starts in Children
Multisystem inflammatory syndrome in children (MIS-C) has unique features that could lead to faster diagnosis and better treatment, according to physicians at Columbia University Vagelos College of Physicians and Surgeons (J Allergy Clin Immunol 2022;149[3]:912-922).
“One of the major unanswered questions about MIS-C is how, immunologically, the disease evolves from the initial infectious episode to the final, immune-mediated assault,” said Mark Gorelik, MD, an assistant professor of pediatrics at Columbia, in New York City. “One way to study this could be to identify what is unique about the inflammatory/immunologic response in MIS-C.”
Although other studies have looked at the immune and inflammatory response in MIS-C patients, most have looked at patients after initiation of treatment and made comparisons with healthy controls. Here, the researchers compared eight MIS-C patients with 14 patients who had other febrile infections, by looking at the array of immune cells and responses in blood samples taken at the very first encounter with care in the emergency department, before treatments were initiated.
A clue to what causes MIS-C may lie in the different immune cells found in MIS-C patients compared with other patients.
“Only some cells were activated, which suggests that these cells are mistakenly directing the immune system to attack blood vessels in the body that had been damaged by the virus,” said Robert Winchester, MD, a professor of medicine, pathology and cell biology, and pediatrics at Columbia. “These cells are drawn to the blood vessels because of the presence of the virus, but they appear to misidentify the culprit when they alert the rest of the immune system.”
MIS-C also appears to drive patients’ natural killer cells to exhaustion. “They get to the point where they are no longer able to carry out their function properly,” Dr. Winchester said. “This is seen in some other inflammatory diseases, and may offer a clue to treatment similar to those diseases.”
Another finding may give physicians an easier way to diagnose MIS-C, which can be difficult to distinguish from other syndromes. Of note, interleukin-27 was very highly upregulated in patients with MIS-C but not in other febrile children.
Vaccine and Antibody Treatment Effectiveness Blunted by All 3 Omicron Subvariants
All omicron subvariants reduce the effectiveness of most authorized monoclonal antibodies (mAbs) and the messenger RNA (mRNA) vaccines (Nature 2022 Mar 3 https://doi.org/10.1038/s41586-022-04594-4).
Omicron is a highly transmissible variant of SARS-CoV-2 that has caused the biggest surge in COVID-19 cases so far in many countries. Researchers have identified three subvariants of omicron that share 21 mutations in the spike protein, and named them BA.1, BA.1.1 and BA.2.
When omicron was first identified in November 2021, the dominant subvariant was BA.1. Since December, BA.1 cases have declined, while BA.1.1 cases have risen and now make up around 40% of all omicron cases sequenced globally. The BA.2 subvariant currently represents only 10% of all omicron cases globally but is increasing in prevalence.
In laboratory experiments, David D. Ho, MD, the director of the Aaron Diamond AIDS Research Center and the Clyde ’56 and Helen Wu Professor of Medicine at Columbia University Vagelos College of Physicians and Surgeons, in New York City, and his team studied the ability of 19 mAbs and the sera from individuals immunized with one of two available mRNA vaccines to neutralize the three known subvariants of omicron.
Consistent with their previous study on the BA.1 subvariant, the researchers observed a similar loss of neutralization activity against BA.1.1 and BA.2 in blood samples from individuals who had received two mRNA shots. However, the decline in neutralization was less prominent in blood samples from individuals who had received three mRNA shots, reinforcing the importance of booster shots for sustaining immunity.
In neutralization experiments, all three subvariants exhibited a strong resistance to most of the mAbs tested. Of 19 antibodies, 17 were ineffective against the BA.2 subvariant. The researchers found that bebtelovimab, the latest mAb to receive FDA emergency use authorization, is the only available antibody therapy that can adequately treat all three omicron subvariants.
“The emergence of new variants is narrowing our treatment options and challenging the effectiveness of our current vaccines,” Dr. Ho said. “It is critical that we don’t relax prematurely and continue to devise novel strategies to contain this ever-evolving pathogen.”
—Dr. Ho and some of his colleagues are inventors of certain mAbs described in the paper.
Communicating COVID’s Impact
A new University of Toronto Scarborough study found that portraying COVID-19 data in a certain way can influence how seriously people view the pandemic, which in turn can affect their behavior (J Exp Psych Appl 2021;27[4]:657-668).
The study looked at two commonly used types of data: stock (total case counts since the pandemic started) and flow (number of new daily cases). Researchers found that people viewed the pandemic as riskier—and more deserving of caution—when they were shown total case counts.
To test the effect, participants were shown either total case counts since the pandemic began or new daily cases. They were then asked to rate the current level of risk associated with the pandemic and how it would affect their behavior, such as willingness to dine in restaurants or wear masks. Seeing the stock count makes people view the pandemic as more serious, which makes them less willing to engage in riskier behavior.
However, continuously doing so may be disingenuous. For example, if total case counts are shown while daily case counts remain consistently low, the data are not painting a complete picture of the current state of the pandemic.
At the same time, when people are presented with high numbers (in the millions for COVID-19 cases), the data can become abstract.
An effective way to get people’s attention might be to show the stock number along with a concrete example of an individual hospitalized with the infection.
There’s also no neutral way to present data. Whether it’s visualizing data or communicating science to a wider audience, those presenting the information are making decisions on what to show, which can influence how the audience interprets the message.
“It’s important to be transparent with data,” said Sam. J. Maglio, PhD, an associate professor at the University of Toronto Scarborough.
“If you’re only showing one side of the data, maybe direct your audience to where they can get all the data, or at the very least, some guidance on what’s missing.”
Neandertals Protecting Us Still
The major genetic risk variant for severe COVID-19, one inherited from Neandertals, is surprisingly common. A new study shows that the same gene variant that increases the risk for falling seriously ill with COVID-19 reduces a person’s risk for contracting HIV by 27%, according to Hugo Zeberg, a researcher at the Max Planck Institute for Evolutionary Anthropology, in Germany, and Karolinska Institutet, in Sweden (Proc Natl Acad Sci 2022;119[9]:e2116435119).
In addition to risk factors such as advanced age and chronic diseases, like diabetes, a person’s genetic heritage also contributes to their COVID-19 severity risk.
The researchers studied this variant in ancient human DNA and observed that its frequency has increased significantly since the last ice age. In fact, it has become unexpectedly common for inherited genetic variation from the Neanderthals.
Hence, it may have had a favorable impact on its carriers in the past. “This major genetic risk factor for COVID-19 is so common that I started wondering whether it might actually be good for something, such as providing protection against another infectious disease,” Dr. Zeberg said.
The genetic risk factor is located in a region on chromosome 3 that consists of many genes. There are several genes in its vicinity that encode receptors in the immune system. One of these receptors—CCR5—is used by the HIV virus to infect white blood cells. Dr. Zeberg found that people who carried the risk factor for COVID-19 had fewer CCR5 receptors. This led him to test whether they also had a lower risk for becoming infected with HIV. By analyzing patient data from three major biobanks (FinnGen, UK Biobank and Michigan Genomics Initiative), he found that carriers of the risk variant for COVID-19 had a 27% lower risk for contracting HIV.
“This shows how a genetic variant can be both good and bad news: bad news if a person contracts COVID-19, good news because it offers protection against getting infected with HIV,” he said.
However, since HIV only arose during the 20th century, protection against this infectious disease cannot explain why the genetic risk variant for COVID-19 became so common among humans as early as 10,000 years ago. Dr. Zeberg said it is probably protective against some other disease that increased its frequency after the last ice age.
