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

lungs

SARS-CoV-2 culture system using human airway cells

Journalist Roxanne Khamsi had an item in Wired highlighting how virologists studying SARS-CoV-2 and its relatives have relied on Vero cells, monkey kidney cells with deficient antiviral responses.

Vero cells are easy to culture and infect with viruses, so they are a standard laboratory workhorse. Unfortunately, they may have given people the wrong idea about the controversial drug hydroxychloroquine, Khamsi writes.

In contrast, Emory virologist Mehul Suthar’s team recently published a Journal of Virology paper on culturing SARS-CoV-2 in primary human airway epithelial cells, which are closer to the cells that the coronavirus actually infects “out on the street.”

Effect of interferon-beta on SARS-CoV-2 in primary human epithelial airway cells. Green = SARS-CoV-2, Red = F-actin, Blue = Hoechst (DNA). Courtesy of Abigail Vanderheiden

The Emory researchers found that airway cells are permissive to SARS-CoV-2 infection, but mount a weak antiviral response lacking certain interferons (type I and type III). Interferons are cytokines, part of the immune system’s response to viral infection. They were originally named for their ability to interfere with viral replication, but they also rouse immune cells and bolster cellular defenses.

In SARS-CoV-2 infection, the “misdirected” innate immune response is dominated instead by inflammatory and fibrosis-promoting cytokines, something others have observed as well.

“Early administration of type I or III IFN could potentially decrease virus replication and disease,” the authors conclude. We note that an NIH-supported clinical trial testing a type I interferon (along with remdesivir) for COVID-19 just started.

The first author of the paper is IMP graduate student Abigail Vanderheiden. As with a lot of recent SARS-CoV-2 work, this project included contributions from several labs at Emory: Arash Grakoui’s, Steve Bosinger’s, Larry Anderson’s, and Anice Lowen’s, along with help from University of Texas Medical Branch at Galveston.

Posted on by Quinn Eastman in Immunology Leave a comment

Immunologists identify T cell homing beacons for lungs

Scientists have identified a pair of molecules critical for T cells, part of the immune system, to travel to and populate the lungs. A potential application could be strengthening vaccines against respiratory pathogens such as influenza.

The findings were published online Thursday, September 26 in Journal of Experimental Medicine.

T cells in the lungs, courtesy of Alex Wein. Blue represents respiratory epithelium (EpCAM), while various T cells stain red, yellow or green.

Much research on immunity to influenza virus focuses on antibodies, infection- or vaccine-induced proteins in the blood that can smother viruses. But CD8 T cells, which survey other cells for signs of viral infection and kill infected cells, are an important arm of our defenses too. The epitopes – or bits of viral protein – they recognize generally do not change from year to year.

Researchers led by Jacob Kohlmeier, PhD, at Emory University School of Medicine wanted to learn more about what’s needed to get CD8 T cells into the lungs, since the lungs will often contain the first cells incoming virus will have a chance to infect. However, T cells don’t stick around in the lungs for extended amounts of time.

“The airways are a unique environment in the body,” says Alex Wein, a MD/PhD student who trained in Kohlmeier’s lab. “They’re high in oxygen but low in nutrients. Unlike other tissues, when T cells enter the airways, it’s a one-way trip and they have a half-life of a few weeks, so they must be continually repopulated.”

Wein, his fellow MD/PhD Sean McMaster, now at Boston Consulting Group, and Shiki Takamura at Kindai University are co-first authors of the paper. Kohlmeier is assistant professor of microbiology and immunology and part of the Emory-UGA Center of Excellence for Influenza Research and Surveillance.

The researchers showed that two molecules, called CXCR6 and CXCL16, are needed for CD8 T cells to reach the airways in mice. CXCR6 is found on T cells and CXCL16 is produced by the epithelial cells lining the airways of the lungs. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Biomarker may predict serious complications after lung transplantation

Researchers at Emory studying lung transplantation have identified a marker of inflammation that may help predict primary graft dysfunction (PGD), an often fatal complication following a lung transplant.

Primary graft dysfunction after a lung transplant

The results are published in the American Journal of Transplantation. First author Andres Pelaez, a pulmonary medicine specialist at Emory’s McKelvey Lung Transplant Center, and postdoc Patrick Mitchell led the research team.

“Despite major advances in surgical techniques and clinical management, serious lung transplant complications are common and often untreatable,” Pelaez says. “PGD is a severe lung injury appearing just a few days after transplantation. Unfortunately, predicting which lung transplant recipients go on to develop PGD has been so far unsuccessful. Therefore, our research has been directed towards identifying predictive markers in the donor lungs prior to transplantation.”

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