Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more

Reddit as window into opioid withdrawal strategies

Drug abuse researchers are using the social media site Reddit as a window into the experiences of people living with opioid addiction. Abeed Sarker in Emory's Department of Biomedical Informatics has a paper in Clinical Toxicology focusing on the phenomenon of “precipitated withdrawal,” in collaboration with emergency medicine specialists from Penn, Rutgers and Mt Sinai. Precipitated withdrawal is a more intense form of withdrawal that can occur when someone who was using opioids starts medication-assisted treatment Read more

CROI: HIV cure report and ongoing research

The big news out of CROI (Conference on Retroviruses and Opportunistic Infections) was a report of a third person being cured of HIV infection, this time using umbilical cord blood for a hematopoetic stem cell transplant. Emory’s Carlos del Rio gave a nice overview of the achievement for NPR this morning. As del Rio explains, the field of HIV cure research took off over the last decade after Timothy Brown, known as “the Berlin patient,” Read more

Mehul Suthar

Report on first Omicron case detected in GA

The first Omicron case detected in Georgia through SARS-CoV-2 genomic surveillance probably became infected during a visit to Cape Town, South Africa, according to a recent case report in Clinical Infectious Diseases.

The patient was a woman in her 30s, who was fully vaccinated with Pfizer/BioNTech twice, then a booster in October 2021 – about six weeks before becoming sick. She had a negative PCR test shortly before traveling back to Georgia but developed symptoms around the time of her return flight.

The woman was diagnosed with COVID-19 at the end of November, a few days after her return to Georgia — just after Omicron was declared a Variant of Concern by the WHO.

This single case report is not representative of the overall severity of Omicron, which is generating a large number of infections, burdening hospitals in Georgia and elsewhere. The patient experienced muscle aches, nausea, fatigue and cough, but did not have a fever or shortness of breath and did not require hospitalization.

A view of Cape Town’s Table Mountain

The lead authors of the case report were Marybeth Sexton, chief quality officer for the Emory Clinic, and infectious disease specialist Jesse Waggoner. The senior author was viral geneticist Anne Piantadosi.

The authors note: “Identifying this case required eliciting an appropriate travel history and being able to identify and perform sequencing for COVID patients in the community, since the patient had mild symptoms and did not seek clinical care.”

To speed detection of SARS-CoV-2 variants such as Omicron, the case report contains information about how to customize the “Spike SNP” PCR assay to give results within a few hours, rather than waiting for full viral sequencing taking 72 hours.

With the help of virologist Mehul Suthar’s lab, the authors were also able to report that the patient developed high levels of antiviral antibodies capable of neutralizing the Omicron variant. Currently available booster shots can elicit measurable antiviral antibody activity (see our recent post Thrice is nice), but actual Omicron infection generates way more.

Posted on by Quinn Eastman in Immunology Leave a comment

Booster COVID-19 vaccine vs Omicron: thrice is nice

A third dose of an mRNA COVID-19 vaccine is necessary to give someone robust neutralizing antibody activity against the Omicron variant, according to data from Emory researchers posted on the preprint server Biorxiv.

The findings support public health efforts to promote booster vaccination as a measure to fight Omicron, which is currently overwhelming hospitals around the world. They also explain why more breakthrough infections are occurring with the Omicron variant in people who have been vaccinated twice, and are in line with what other investigators have observed.

Compared with the 2020 Wuhan strain, the Omicron variant of SARS-CoV2 has more than 30 mutations in the viral spike protein, which is the primary target of neutralizing antibodies generated by vaccination. 

“Our findings highlight the need for a third dose to maintain an effective antibody response for neutralizing the Omicron variant,” says lead author Mehul Suthar, a virologist based at Emory Vaccine Center and Yerkes National Primate Research Center.

Vaccinated individuals who develop breakthrough Omicron infections are likely to experience less severe symptoms, and it is possible for Omicron to infect people even after receiving a booster, Suthar notes. Still, a majority of patients now coming into hospitals continue to be those who are unvaccinated.

In the preprint, Emory researchers tested blood samples from people who participated in Pfizer/BioNTech or Moderna vaccine studies in the laboratory for their ability to smother SARS-CoV-2 variants in culture. The preprint does not include clinical outcomes from infection, and also does not cover other aspects of vaccine-induced antiviral immunity, such as T cells.

In people who were vaccinated twice with mRNA vaccines, either Pfizer/BioNTech or Moderna, none showed measurable neutralizing antibody activity against Omicron six months after vaccination. But 90 percent displayed some neutralizing activity against Omicron a few weeks after a third dose.

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COVID-19 vaccine-generated antibodies last at least 6 months

How long does COVID-19 vaccine-generated immunity last? New laboratory results provide a partial answer to that question.

Antibodies generated by a currently available COVID-19 vaccine declined over time, but remained at high levels in 33 study participants 6 months after vaccination, according to data published Tuesday in the New England Journal of Medicine.

The results could begin to inform public health decisions about COVID-19 booster vaccinations and how frequently people should receive them. In older study participants, antiviral antibody activity tended to decay more rapidly than in those aged 18-55.

From Doria-Rose et al (2021). Note that neutralizing antibody activity was (on average) higher at day 209 than on day 29, when the second vaccine dose was administered. It takes two weeks for the immune system to kick into high gear after the second shot.

Emory Vaccine Center’s Mehul Suthar, co-lead author of the brief report, said that the “correlates of protection” are not yet known from COVID-19 vaccine studies – that is, what levels of antiviral antibodies are needed to fend off infection. Other forms of immunity, such as T cells, could be contributing to antiviral protection as well.

He cautioned that the decay in antibody activity over time – not surprising in itself – may combine with increased prevalence of emerging SARS-CoV-2 variants that may allow viruses to escape the immune system’s pressure.

“Still, these are encouraging results,” Suthar says. “We are seeing good antibody activity, measured three different ways, six months after vaccination. There are differences between age groups, which are consistent with what we know from other studies.”

The findings come from analysis of samples from the Moderna mRNA-1273 phase I clinical trial, which began last year. Reports of clinical outcomes from Pfizer/BioNTech also indicate that their vaccine remains effective after six months.

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Strengthening SARS-CoV-2 genomic surveillance: support from CDC, private foundations

As part of an effort to strengthen genomic surveillance for emerging strains of SARS-CoV-2, the Centers for Disease Control and Prevention (CDC) has awarded a contract to Emory University researchers to characterize viral variants circulating in Georgia.

The two-year contract is part of the SPHERES (SARS-CoV-2 Sequencing for Public Health Emergency Response, Epidemiology and Surveillance) initiative, with roughly $620,000 in total costs. The principal investigator is Anne Piantadosi, MD, PhD, assistant professor of pathology and laboratory medicine, with co-investigator Mehul Suthar, PhD, assistant professor of pediatrics (infectious diseases).

Both Piantadosi and Suthar are affiliated with Emory University School of Medicine and Emory Vaccine Center. Additional Emory partners include assistant professor of medicine Ahmed Babiker, MBBS, assistant professor of medicine Jesse Waggoner, MD and assistant professor of biology Katia Koelle, PhD.

“We are analyzing SARS-CoV-2 genomes from patients in Georgia to understand the timing and source of virus introduction into our community,” Piantadosi says. “We want to know whether there have been population-level changes in the rates of viral spread, and whether there are associations between viral genotype, viral phenotype in vitro, and clinical phenotype or clinical outcome.”

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Posted on by Quinn Eastman in Immunology, Uncategorized 1 Comment

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.

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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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Zika virus blindfolds immune alarm cells

Important immune alarm cells — dendritic cells — are fighting Zika virus with an arm tied behind their backs, scientists from Emory Vaccine Center report.

Dendritic cells are “sentinel” cells that alert the rest of the immune system when they detect viral infection. When Zika virus infects them, it shuts down interferon signaling, one route for mustering the antiviral troops. However, another antiviral pathway called RIG-I-like receptor (RLR) signaling is left intact and could be a target for immunity-boosting therapies, the researchers say.

Mehul Suthar, PhD in the lab with graduate students Kendra Quicke and James Bowen

The findings were published on Feb. 2 in PLOS Pathogens.

Zika was known to disrupt interferon signaling, but Emory researchers have observed that it does so in ways that are distinct from other related flaviviruses, such as Dengue virus and West Nile virus. The findings give additional insight into how Zika virus is able to counter human immune defenses. Read more

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Antiviral success makes some immune cells stickier

As they succeed in clearing a viral infection from the body, some virus-hunting T cells begin to stick better to their target cells, researchers from Emory Vaccine Center and Georgia Tech have discovered.

The increased affinity helps the T cells kill their target cells more efficiently, but it depends both on the immune cells’ anatomic location and the phase of the infection.

The results were published this week in the journal Immunity.

Arash Grakoui, PhD

Arash Grakoui, PhD

After the peak of the infection, cells within the red pulp of the spleen or in the blood displayed a higher affinity for their targets than those within the white pulp. However, the white pulp T cells were more likely to become long-lasting memory T cells, critical for vaccines.

“These results provide a better understanding of how memory precursor populations are established and may have important implications for the development of efficacious vaccines,” the scientists write.

In the mouse model the researchers were using, the differences in affinity were only detectable a few days after the non-lethal LCMV viral infection peaks. How the differences were detected illustrates the role of serendipity in science, says senior author Arash Grakoui, PhD.

Typically, the scientists would have taken samples only at the peak (day 7 of the infection) and weeks later, when memory T cells had developed, Grakoui says. In January 2014, the weather intervened during one of these experiments. Snow disrupted transportation in the Atlanta area and prevented postdoctoral fellow Young-Jin Seo, PhD from taking samples from the infected mice until day 11, which is when the differences in affinity were apparent.

Seo and Grakoui collaborated with graduate student Prithiviraj Jothikumar and Cheng Zhu, PhD at Georgia Tech, using a technique Zhu’s laboratory has developed to measure the interactions between T cells and their target cells. Co-author Mehul Suthar, PhD performed gene expression analysis.

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