Ricki Lewis

While antibodies have been the focus of testing for past infection with COVID-19, T cells will also provide some insights -- potentially better ones, experts say.

These lymphocytes are the first responders that then coordinate the immune response while building an imprint, a memory, so that subsequent infections fade quickly, often unnoticed.

T cell tests are more complex and typically reserved for research, but some may be coming to the clinic soon, with at least one company seeking FDA emergency use authorization (EUA). Recent studies indicate that assaying T cells can even improve diagnostic accuracy and possibly predict how COVID-19 will unfold.

"Testing T cell responses can accelerate detection of an infection by as much as a week. The cells come in on day 2 and they divide very quickly, to detectable levels as early as 3 or 4 days from infection," said Dawn Jelley-Gibbs, PhD, who investigated T cells in influenza at the Trudeau Institute in Saranac Lake, New York.

"Identifying people who have been infected and become immune could have huge benefits for enabling society to safely return to normalcy. Numerous antibody tests exist, but doubts remain about their reliability and about antibody longevity post-infection," said Maria Oliver, PhD, senior scientist at Indoor Biotechnologies in Great Britain, one of several companies developing clinical T cell tests.

T Cell Basics

To continue reading, please go to MEDPAGE TODAY, where this post first appeared.

Ominous headlines have been common in recent months declaring that antibodies against COVID-19 decline quickly. But the reports simply describe an expected phenomenon and are not evidence of waning immunity, experts say. And recent data show strong T-cell response in people who had mild or asymptomatic infections.

"A large number of investigators are reporting the antibody response in humans infected with COVID who recover tends to drop relatively quickly. To some people that's an alarm bell. Following recovery from an acute infection, a decline in antibodies is normal B-cell biology and is exactly what we predict," said Dan Barouch, MD, PhD, professor of medicine at Harvard Medical School in Boston, Massachusetts.

"Do titers stabilize? Do antibodies last a long time or not? It's an unknown area, but there are no alarm bells yet," Barouch told Medscape Medical News.

 
Researchers and clinicians use antibodies as a surrogate for an evolving adaptive immune response because they're far easier to assay than the T cells that drive the response and stimulate B cells to produce the antibodies.

In tracking the ups and downs of antibodies and T cells, researchers seek "correlates of protection." These are measurable signs that an individual is immune to a specific infection. For example, an antibody against the viral spike protein is a correlate of protection because it predicts neutralization of SARS-CoV-2.

The Immune Response to SARS-CoV-2

Both arms of adaptive immunity respond quickly to a viral infection. CD4 ("helper") T cells are activated by day 2 of infection and they stimulate B cells to make antibodies against the infective agent.

To continue reading go to Medscape Medical News, where this post first appeared.

My blog posts around Thanksgiving are predictably dull: Turkey Genetics 101, The Peaceable Genomes of Pumpkins.

But 2020 is like no other year. Humanity is at war with the novel coronavirus SARS-CoV-2.

Images of overwhelmed hospitals and mobile morgues that dominated reporting from New York City in March are now coming from everywhere.

A mutation that's entered the US a few times from Europe doubled transmission rate without affecting severity, which is one reason why the percentage of fatal cases has fallen. Still, it's a huge absolute number, because of the fact that nearly 12 million Americans (as of today) have been infected. More than a quarter of a million have died.

And yet, some people still deny reality. Nurses tell of patients on their deathbeds still insisting that the pandemic is a hoax, that they're suffering from something else.

A Dangerous Meme

To continue reading, please go to my blog DNA Science at Public Library of Science, where this post first appeared.

The components of certain things are meant to remain mysterious. The ingredients of sausage. A burger's slimy secret sauce. The recipe for Coke or Kentucky Fried Chicken.

Researchers from Stanford University are tackling the make-up of another entity, something rather new to our world: the stuff retrieved from swabs shoved up nostrils to sample genetic material from SARS-CoV-2, the virus behind COVID-19. A swab actually samples much more than the virus's RNA, required for diagnosis.

Super Swabs

John Gorzynski and colleagues describe the "multi-omic data repositories" from deployed swabs in a preprint (not yet peer-reviewed) and at the recent virtual annual meeting of The American Society of Human Genetics.

"A single nasopharyngeal swab can reveal substantial host and viral genomic information in a high-throughput manner that will facilitate public health pandemic tracking and research into the mechanisms underlying virus-host interactions," they write.

That's a mouthful. I'll just call them super swabs.

Amplifying Viral Sequences

Extracting clues from the stuff on the swabs is a little like collecting evidence at a crime scene. Several things happen.

To continue reading, please go to my blog DNA Science at Public Library of Science, where this post first appeared.

In the early weeks of the pandemic, as patients overwhelmed New York City hospitals, the clinical characteristics of the most vulnerable quickly became apparent: many of the sickest people were older or had "co-morbidities" like diabetes, hypertension, or respiratory conditions.

As weeks became months and the symptom spectrum widened and worsened, researchers began to focus on "host risk factors" to explain the increasingly apparent variability in the COVID-19 experience. According to Jack Kosmicki, PhD, of Regeneron Genetics Center, at the recent American Society of Human Genetics virtual annual meeting:

"Genetics is one avenue to better understand why outcomes of COVID are so different. Some patients have so few symptoms that they don't realize they're infected, yet the other end of the extreme is requiring hospitalization, or death. Genetic risk factors might influence the likelihood of becoming infected or requiring hospitalization."

So far, very few genes have been linked to COVID-19. Other factors like socioeconomic status, exposure to the virus in the workplace or in crowded housing conditions, being of Black or Asian ancestry and non-genetic pre-existing conditions are more important.

To continue reading, please go to Genetic Literacy Project, where this post first appeared.

People with Down syndrome who contract COVID-19 face a fivefold increased risk for hospitalization and a tenfold increased risk for death compared with infected individuals who do not have the syndrome, researchers report in the Annals of Internal Medicine.

Since the pandemic began, public health and infectious disease experts have identified comorbidities that elevate the risk for serious complications or death from COVID-19. In the United Kingdom and the United States, Down syndrome hasn't been on that list. The authors of the new report argue that it should be.

Down syndrome might be associated with more severe COVID-19, owing to "the immune dysregulation, such as differences in T cell function," said first author Ashley Kieran Clift, MA, MBBS, clinical research fellow at the University of Oxford, Oxford, United Kingdom. "People with Down syndrome have a higher risk of pneumonia and viral respiratory tract infections, which may also apply to this novel coronavirus. They have high rates of other conditions that may make them more vulnerable, such as heart and lung disease. There could also be a role for their environment, such as living in care homes or other institutions."

 
The researchers analyzed data from a UK government-sponsored cohort study of 8.26 million adults older than 19 years. The data included information on COVID-19 test results; records of associated hospitalizations and deaths; whether or not a person also had Down syndrome; and information on age, sex, ethnicity, alcohol intake, smoking status, body mass index (BMI), comorbidities, and medications.

The cohort included 4053 people with Down syndrome. Of those, during the study period, from January 24 until June 30, 2020, 68 died ―39.7% of COVID-19, 25.0% of pneumonia or pneumonitis, and 35.3% of other causes. By contrast, among the 8,252,105 people who did not have Down syndrome, 41,685 died; the cause of death was listed as COVID-19 for 20.3%, pneumonia or pneumonitis for 14.4%, and other causes for 65.3%.

The hazard ratio (HR) for death related to COVID-19 was 10.39 (CI, 7.08 – 15.23) and for hospitalization, 4.94 (CI, 3.63 – 6.73) after adjusting for age, sex, ethnicity, BMI, dementia diagnosis, living in a care home, congenital heart disease, and other comorbidities and treatments. For individuals who had learning disabilities but not Down syndrome, the adjusted HR for COVID-19–related death was only 1.27 (CI, 1.16–1.40).

Corresponding author Julia Hippisley-Cox, MD, professor of clinical epidemiology and general practice, St. Anne's College, University of Oxford, said that although the study was observational and did not identify reasons for the elevated risk, "we feel that clinicians, policymakers, and other healthcare workers should be aware of potential risks. These findings could be used by healthcare workers within the context of other factors to have a more nuanced risk assessment for their patients." 

That might entail weighing the relative risks and benefits of measures that protect against infection vs the values of socialization in day care programs and physical and occupational therapies. It's a balancing act, Hippisley-Cox said.

Preston McCormack, MD, assistant professor or internal medicine and pediatrics at the University of Arkansas for Medical Sciences College of Medicine, Little Rock, Arkansas, agreed that caution is warranted in navigating care during this challenging time.

"It's well known that Down syndrome patients are at increased risk. However, with these data surfacing, it may be a good time to reassess how we plan to move forward," McCormack said. "The risk, even after adjustment for age, sex, and associated comorbidities, remains impressive and demands attention as we approach another viral season this fall and upcoming winter.

"The fact that most in this population require more frequent medical follow-up, therapy, and other ancillary services further compounds this risk," he continued. "The decision to restrict patients from these care providers will likely have to be determined on an individual basis, though it is imperative that we are continually informed of the risks vs benefits of these decisions. Without a doubt, we are unable to optimize therapy and socialization in this pandemic landscape. However, this expense is offset with minimization of significant risk quantified in this recent study."

Originally published at Medscape Medical News

Antibodies are supposed to be the good guys. The proteins, built of distinctive Y-shaped pieces, enter the bloodstream early in infection, pouring out from plasma cells. They then latch onto molecules festooning pathogens and alert natural killer cells, which release a torrent of cytokines and complement, which are the biochemical weapons of an immune response.

Fighting infection is a complex business.

In a mysterious phenomenon called "antibody-dependent enhancement," the proteins actually make matters worse, intensifying symptoms. When a vaccine elicits the errant antibodies, the backfiring is called "vaccine enhancement of disease." We know these reactions exist, but still do not completely understand them.

The turncoat antibodies can be coaxed to appear in test tube experiments, but are elusive in a patient who is getting sicker. That is, there's no clinical way to distinguish antibody-dependent enhancement from just a severe case of an infectious disease. And that can complicate analysis of a candidate vaccine. "Vaccine enhancement of disease" would show up in a clinical trial as more people receiving a vaccine getting sick than the participants getting placebo.

Reportedly that hasn't happened for the candidate COVID-19 vaccines, but the data won't be published until the phase 3 trials are completed.

To continue reading, please go to my blog DNA Science at Public Library of Science.