Saliva-based SARS-CoV-2 antibody testing

As the Atlanta area recovers from Zeta, we’d like to highlight this Journal of Clinical Microbiology paper about saliva-based SARS-CoV-2 antibody testing. It was a collaboration between the Hope Clinic and investigators at Johns Hopkins, led by epidemiologist Christopher Heaney. Infectious disease specialists Matthew Collins, Nadine Rouphael and several colleagues from Emory are co-authors. They organized the collection of saliva and blood samples from Emory COVID-19 patients at several stages: being tested, hospitalized, and recovered. Read more

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Immune cell activation in severe COVID-19 resembles lupus

In severe cases of COVID-19, Emory researchers have been observing an exuberant activation of B cells, resembling acute flares in systemic lupus erythematosus (SLE), an autoimmune disease. The findings point towards tests that could separate some COVID-19 patients who need immune-calming therapies from others who may not. It also may begin to explain why some people infected with SARS-CoV-2 produce abundant antibodies against the virus, yet experience poor outcomes. The results were published online on Oct. Read more

COVID-19

Saliva-based SARS-CoV-2 antibody testing

As the Atlanta area recovers from Zeta, we’d like to highlight this Journal of Clinical Microbiology paper about saliva-based SARS-CoV-2 antibody testing. It was a collaboration between the Hope Clinic and investigators at Johns Hopkins, led by epidemiologist Christopher Heaney.

Infectious disease specialists Matthew Collins, Nadine Rouphael and several colleagues from Emory are co-authors. They organized the collection of saliva and blood samples from Emory COVID-19 patients at several stages: being tested, hospitalized, and recovered. Saliva samples were collected by having participants brush their gum line with a sponge-like collection device. More convenient than obtaining blood or sticking a swab up the nose!

Saliva collection instrument

The paper shows that antiviral antibody levels in saliva parallel what’s happening in patients’ blood. However, some forms of antibodies (IgM) appear less in saliva because of their greater molecular size. People who test positive do so by 10 days after symptom onset.

The authors conclude: “Saliva-based assays can be used to detect prior SARS-CoV-2 infection with excellent sensitivity and specificity and represent a practical, non-invasive alternative to blood for COVID-19 antibody testing…  A logical next step would be to perform a head-to-head comparison of this novel saliva assay with other antibody tests approved for clinical use.”

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Immune cell activation in severe COVID-19 resembles lupus

In severe cases of COVID-19, Emory researchers have been observing an exuberant activation of B cells, resembling acute flares in systemic lupus erythematosus (SLE), an autoimmune disease.

The findings point towards tests that could separate some COVID-19 patients who need immune-calming therapies from others who may not. It also may begin to explain why some people infected with SARS-CoV-2 produce abundant antibodies against the virus, yet experience poor outcomes.

The results were published online on Oct. 7 in Nature Immunology.

The Emory team’s results converge with recent findings by other investigators, who found that high inflammation in COVID-19 may disrupt the formation of germinal centers, structures in lymph nodes where antibody-producing cells are trained. The Emory group observed that B cell activation is moving ahead along an “extrafollicular” pathway outside germinal centers – looking similar to what they had observed in SLE.

Update: check out first author Matthew Woodruff’s commentary in The Conversation: “The autoimmune-like inflammatory responses my team discovered could simply reflect a ‘normal’ response to a viral infection already out of hand. However, even if this kind of response is ‘normal,’ it doesn’t mean that it’s not dangerous.”

B cells represent a library of blueprints for antibodies, which the immune system can tap to fight infection. In severe COVID-19, the immune system is, in effect, pulling library books off the shelves and throwing them into a disorganized heap.

Before the COVID-19 pandemic, co-senior author Ignacio (Iñaki) Sanz and his lab were focused on studying SLE and how the disease perturbs the development of B cells.

“We came in pretty unbiased,” Sanz says. “It wasn’t until the third or fourth ICU patient whose cells we analyzed, that we realized that we were seeing patterns highly reminiscent of acute flares in SLE.”

In people with SLE, B cells are abnormally activated and avoid the checks and balances that usually constrain them. That often leads to production of “autoantibodies” that react against cells in the body, causing symptoms such as fatigue, joint pain, skin rashes and kidney problems. Flares are times when the symptoms are worse.

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Several ways to survey for SARS-CoV-2 exposure

How many people out there have been exposed to SARS-CoV-2? It’s a tricky question, once you think about all the people who have experienced COVID-19 symptoms over the last several months, but didn’t go to the hospital. And there’s a murkier penumbra of people who may have fended off the virus with a minor immune skirmish.

A recent Emerging Infectious Diseases paper from Emory investigators includes antibody tests on a group of more than 100 adults in the Atlanta area who experienced mild flu-like symptoms this spring, but couldn’t get tested for SARS-CoV-2 itself.

A sizable fraction (22 to 48 percent, depending on when they provided blood samples) had elevated levels of IgM against the coronavirus. IgM is the “rookie” antibody produced when the immune system is first encountering something, as opposed to the more seasoned IgG, which appears later in an immune response and tended to rise only in people who were hospitalized. The Emory authors came to a conclusion that others are also reaching:

“Examining IgM and IgG against multiple SARS-CoV-2–related antigens may thus better inform natural history and vaccine studies than any one antibody.”

To answer these kinds of questions more comprehensively, investigators will need to go broader. For example, this week the American Red Cross published data on what proportion of its blood donors have antibodies against SARS-CoV-2. About 3 percent of first-time donors did, using their criteria.

For big answers, we can look to studies such as Emory’s COVID-Vu, a nationwide population-based study using antibody and virus tests taken at home. Rollins School of Public Health researchers received a $6.6 million grant to launch the study this summer. This type of study is designed to cover everyone, whether they were sick or not.

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High antiviral antibody levels may herald pediatric COVID-19 complication

Measuring blood antibody levels against SARS-CoV-2 may distinguish children with multisystem inflammatory syndrome (MIS-C), which appears to be a serious but rare complication of viral infection, say researchers at Emory University School of Medicine and Children’s Healthcare of Atlanta.  

Children with MIS-C had significantly higher levels of antiviral antibodies – more than 10 times higher — compared to children with milder symptoms of COVID-19, the research team found.  

The results, published in the journal Pediatrics, could help doctors establish the diagnosis of MIS-C and figure out which children are likely to need extra anti-inflammatory treatments. Children with MIS-C often develop cardiac problems and low blood pressure requiring intensive care.

More information about this research here.

Infographic showing CDC criteria for the diagnosis of MIS-C. From Nakra et al via Creative Commons.

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Posted on by Quinn Eastman in Immunology 2 Comments

In current vaccine research, adjuvants are no secret

Visionary immunologist Charlie Janeway was known for calling adjuvants – vaccine additives that enhance the immune response – a “dirty little secret.”

Charlie Janeway, MD, in a hat he wore often

Janeway’s point was that foreign antigens, by themselves, were unable to stimulate the components of the adaptive immune system (T and B cells) without signals from the innate immune system. Adjuvants facilitate that help.

By now, adjuvants are hardly a secret, looking at some of the research that has been coming out of Emory Vaccine Center. This week, an analysis by Ali Ellebedy, now at Washington University St Louis, and colleagues showed that in healthy volunteers, the AS03 adjuvant boosted otherwise poor immune responses to a limited dose of the exotic avian flu H5N1, recruiting both memory and naïve B cells. More on that here.

The Moderna SARS-CoV-2 vaccine, which has shown some activity in a small clinical trial here at Emory, has its own kind of adjuvant, since it’s made of both innate-immune-stimulating mRNA and clothed in lipid nanoparticles. Extra adjuvants may come into play later, either with this vaccine or others.

A question we’ve seen many people asking, and discussed on Twitter etc is this: how long does the immunity induced by a SARS-CoV-2 vaccine last? How can we make the immune cells induced by a vaccine stick around for a long time? Read more

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Study finds ‘important implications’ to understanding immunity against COVID-19

New research from Emory University indicates that nearly all people hospitalized with COVID-19 develop virus-neutralizing antibodies within six days of testing positive. The findings will be key in helping researchers understand protective immunity against SARS-CoV-2 and in informing vaccine development.

The test that Emory researchers developed also could help determine whether convalescent plasma from COVID-19 survivors can provide immunity to others, and which donors’ plasma should be used.

The antibody test developed by Emory and validated with samples from diagnosed patients has demonstrated that not all antibody tests are created equal – and that neutralizing antibodies, which provide immunity, have specific characteristics. Emory’s study focused on those neutralizing antibodies, which can stop the virus from infecting other cells.

The findings are now available on MedRxiv, the preprint server for health sciences, and are not yet peer-reviewed.

In the study, researchers looked at antibodies against the receptor-binding domain (RBD), part of the spike protein on the outside of the virus. The RBD is what grips on to human cells and allows the virus to enter them. The researchers focused on antibodies against the RBD because the sequence of the RBD in SARS-CoV-2 distinguishes it from other coronaviruses that cause the common cold.

The receptor-binding domain, or RBD, is what grips on to human cells and allows the virus to enter them.

The initial 44 patient blood samples used in this study were from patients being treated for COVID-19 at Emory University Hospital and Emory University Hospital Midtown.

“These findings have important implications for our understanding of protective immunity against SARS-CoV-2, the use of immune plasma as a therapy, and the development of much-needed vaccines,” says Mehul S. Suthar, PhD, co-lead author and assistant professor of pediatrics at Emory University School of Medicine and Emory Vaccine Center. This study serves as the initial step in a much larger serology effort.

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Emory launches study on COVID-19 immune responses

Emory University researchers are taking part in a multi-site study across the United States to track the immune responses of people hospitalized with COVID-19 that will help inform how the disease progresses and potentially identify new ways to treat it.  The study is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The study – called Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) – launched Friday. Investigators expect to enroll up to 2,000 individuals who have been hospitalized with the new coronavirus in 10 research locations across the country.

Participants will be followed for up to 12 months after their hospitalization to assess how well they recover and whether they develop durable immunity to the virus.

Nadine Rouphael, associate professor at Emory’s School of Medicine, is leading the investigation as part of NIAID’s Human Immunology Project Consortium (HIPC) and says the study aims to determine how certain immunological measures correspond to or even predict the clinical severity of COVID-19.

“The IMPACC study is a unique opportunity to leverage clinical data and samples with cutting edge technology,” Rouphael says. “By analyzing the immune responses of diverse participants enrolled in the study, we aim to better understand why some cases of COVID-19 worsen while other patients recover.”

As participants recover, investigators will continue evaluating their immune responses to see how they fare: Do they experience lingering symptoms, or do they get long-term protection against the virus? This effort is one of many clinical projects working to better understand how this novel disease affects people differently and determine optimal ways to treat COVID-19.

Researchers will recruit participants within 36 hours of their admission to the hospital and collect blood and nasal swabs throughout their hospitalization, and during follow-up clinic visits after discharge. When possible, researchers will also examine lower airway secretions collected from patients requiring a ventilator for breathing support. Participants can be co-enrolled in other studies, such as those evaluating experimental treatments for COVID-19.

Biologic samples from all study participants will be sent to a number of Core Laboratories for detailed analysis of various aspects of the immune response to the virus that causes COVID-19.

For more information on the U.S. government response to the COVID-19 pandemic, visit www.coronavirus.gov.

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Can blood from coronavirus survivors save the lives of others?

Donated blood from COVID-19 survivors could be an effective treatment in helping others fight the illness – and should be tested more broadly to see if it can “change the course of this pandemic,” two Emory pathologists say.

The idea of using a component of survivors’ donated blood, or “convalescent plasma,” is that antibodies from patients who have recovered can be used in other people to help them defend against coronavirus.

Emory pathologists John Roback, MD, PhD and Jeannette Guarner, MD, wrote about the prospects of using the donated blood in a commentary published in JAMA. Their article accompanied a small study in China of five patients on ventilators whose condition improved after they were treated with convalescent plasma.

“Deploying passive antibody therapies against the rapidly increasing number of COIVD-19 cases provides an unprecedented opportunity to perform clinical studies of the efficacy of this treatment against a viral agent,” the two wrote. “If the results of rigorously conducted investigations, such as a large-scale randomized clinical trial, demonstrate efficacy, use of this therapy also could help change the course of this pandemic.”

The patients in Shenzhen were also treated with other antiviral and antiinflammatory agents, and the study was too small to come to definite conclusions. Still, the Emory authors say, the Shenzhen study provides an example of an approach that should be tested on a larger scale. Read more

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