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

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 a few conclusions, such as: there was no “Patient Zero”, at least here.

According to sequence analysis in the paper, multiple early introductions of SARS-CoV-2 into Georgia occurred, probably coming from Asia, weeks before the first officially reported case in March 2020. The authors suggest that the early focus on returning international travelers was misplaced, as opposed to broader testing of patients with COVID-19 symptoms.

“SARS-CoV-2 was likely spreading within the state for approximately three weeks prior to detection in either diagnostic or sequencing data,” the authors write.

Tree showing relationships between SARS-CoV-2 genetic sequences from Georgia and other states/countries

In Georgia, the subclade, or swarm of related viruses, that was dominant early on (called 19B) disappeared by the end of April, eclipsed by variants carrying the D614G mutation. This was an early hint – even before the emergence of B117/Alpha and other variants such as Delta and Omicron — that SARS-CoV-2 would evolve through competition. 

Similarly, sequence analysis from Washington state – the site of the first COVID-19 case identified in the United States — has shown that the first official case did not lead directly to the initial wave of infections there. The first wave actually fizzled out as a result of public health interventions, but other undetected infections in Washington in February 2020 led to sustained downstream transmission. 

The co-first authors of the Viral Evolution paper are Emory infectious disease specialist Ahmed Babiker and graduate student Michael Martin, with co-authors from the Centers of Disease Control and Prevention. The paper analyzes sequences from Emory Healthcare patients along with previously available sequences.

In a few cases, scientists attempted to trace relationships between infected patients who had recently travelled to other countries (Italy, Switzerland) or other states (Louisiana, Colorado), but the available data did not confirm all of those connections. 

Keep in mind that SARS-CoV-2 testing was very limited at the start of the pandemic, because of short supplies as well as FDA policy. More extensive virus sequencing efforts at Emory did not begin until mid-March 2020. With respect to viruses, we only see what we look for, and scientists can’t analyze samples they don’t have. If more samples were available from January or February, what would we find? Also, this paper’s analysis does not include any (known) samples from a February 2020 funeral in Albany, GA that was considered a “super-spreader event.” 

Two years later, has SARS-CoV-2 genomic surveillance improved? Piantadosi says that her team’s paper should be viewed in combination with their recent paperon the detection of the first Omicron case in Georgia, a woman who became sick in November 2021 while visiting Cape Town, South Africa.

 “That’s an example of where we did better,” Piantadosi says. “It does speak to how much surveillance has improved. We were conducting routine surveillance – not focusing on returning travelers.”

In the Omicron case, the woman in question first went to a community testing site, and those samples were not available for sequence analysis.

Piantadosi says that “we’ve achieved Phase I” – in that large hospitals or health systems such as Emory are collecting SARS-CoV-2 sequences, and the state Department of Public Health and large diagnostic services companies are also doing so. But as more SARS-CoV-2 testing is performed at home – generally a good thing for convenience and public health — surveillance for new variants needs to continue, she says.

Posted on by Quinn Eastman in Uncategorized Leave a comment

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 with buprenorphine – and also when someone receives naloxone for an overdose.

Precipitated withdrawal is reported to occur more often when someone has a history of fentanyl use, possibly because fentanyl remains in the body’s peripheral tissues, even during periods of abstinence.

When it occurs prior to medication-assisted treatment, precipitated withdrawal is reported to occur more often when someone has a history of fentanyl use, possibly because fentanyl remains in the body’s peripheral tissues, even during periods of abstinence. The buprenorphine washes out remaining fentanyl or its relatives quickly, leading to symptoms such as diarrhea and vomiting, and sometimes to dehydration and hospitalization.

“From Reddit, we have found that people who use opioids had been talking about it [precipitated withdrawal] for a couple of years now and they have, as a community, come up with their own self-management strategies,” Sarker says.

The strategies are based on microdosing; one approach is called the “Bernese method.”

“These findings are important because this cohort is very difficult to follow, and therefore studying causes and solutions to precipitated withdrawal after buprenorphine initiation is challenging,” Sarker says. “We are essentially trying to give people who use opioids a voice.”

Read more

Posted on by Quinn Eastman in Neuro, Uncategorized Leave a comment

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,” was cured after receiving a stem cell transplant for acute myeloid leukemia. His transplant donor had a mutation that made incoming blood and immune cells resistant to HIV infection.

For several reasons – safety, expense, and lack of immune compatibility — it is not practical to do hematopoetic stem cell transplants for everyone infected with HIV. Such transplants, which replace the cells that generate blood and immune cells, pose considerable risk.

“This is not a scaleable intervention,” del Rio told interviewer Leila Fadel. “This is very fascinating science, very cool science that will advance the field of HIV research, but this is also a very rare phenomenon.”

The transplant option comes into consideration when someone living with HIV is diagnosed with leukemia or lymphoma. But the CCR5 delta32 mutation that makes donor cells HIV-resistant is rare and found mainly in people of Northern European descent, and the process of finding a match has limitations. People of color are under-represented in registries for matching donors and recipients.

Using more malleable umbilical cord blood as a source for stem cell transplant may allow the approach to be offered to a larger group of people, including more people of color. Emory’s Vince Marconi told WebMD that cord blood could also allow patients to undergo a less grueling experience.

During the COVID-19 pandemic, the CROI conference has morphed into a premier immunology meeting, including presentations on COVID-19 and SARS-CoV-2, as well as HIV and viral hepatitis. As usual, Emory/Yerkes scientists had a strong presence at CROI.

In particular, researchers such as Mirko Paiardini and Ann Chahroudi have been investigating approaches to HIV/SIV cure in non-human primate models that avoid stem cell transplants. Instead, cancer immunotherapy drugs and HIV “latency reversal” agents (one is called AZD5582) wake up lurking virus-infected immune cells and flush them out. While clinical trials

Paiardini’s upcoming CROI talk on “Novel Immunotherapy-based Cure interventions” is scheduled for this Wednesday. While we can’t reveal the details ahead of time, Paiardini’s colleagues were highly impressed when he gave a presentation about the results in November.

Posted on by Quinn Eastman in Immunology 1 Comment

Flowing toward potential CV therapeutic

It’s not a blockbuster cardiovascular drug – yet. But the pathway from bench to bedside is easy to see.

In a recent eLife paper, Hanjoong Jo’s lab characterizes a “flow-kine”: a protein produced by endothelial cells in response to healthy blood flow patterns. Unlike other atherosclerosis-linked factors previously identified by Jo’s team, this one – called KLK10 — is secreted. That means that the KLK10 protein could morph into a therapeutic.

Hanjoong Jo, PhD

We can compare KLK10 to PCSK9 inhibitors, which lower LDL cholesterol and have a proven ability to prevent cardiovascular events. KLK10 acts in a different way, not affecting cholesterol, but instead inhibiting inflammation in endothelial cells. KLK10 can protect against atherosclerosis in animal models, when delivered by injection.

“The most important clinical implication is that we were able to see that human atherosclerotic plaques have a low level of KLK10,” Jo says. “In a healthy heart, the expression level is OK.”

Jo sees similarities between KLK10 and myo