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COVID-19 and Its Disproportionate Impact on Racial and Ethnic Minorities in the United States

Infectious diseases clinicians turn to Twitter as a tool for education and collaboration.
 

Teaching Old Dogs New Tricks: Make the Most of Twitter to Boost ID Education, Engagement, and Advocacy

Along with a 1 reported case in Massachusetts, the

New Hampshire Department of Health and Human Services (DHHS) has confirmed a person infected with eastern equine encephalitis (EEE) has died. The public health agency said the person was hospitalized due to severe central nervous system disease. The last reported human EEEV infection in New Hampshire was in 2014, when DHHS identified 3 human infections, including 2 fatalities. In the same statement, DHHS mentions there has been 1 confirmed case in Vermont this summer.

On August 16, the Massachusetts Department of Public Health (MDPH) released a statement discussing the confirmation of the first human case of EEE in the state this year. The confirmed case was discovered in an 80 year old man who was exposed to the vector borne disease in Worcester County. As a result, the risk level in the local communities of Douglas, Oxford, Sutton, and Webster has been raised to critical, and in Dudley, Northbridge, and Uxbridge the risk is increased to high.

Additionally, the neighboring communities of Auburn, Charlton, Grafton, Leicester, Mendon, Millbury, Millville, Southbridge, and Upton are now considered at moderate risk according to MDPH.

“This is the first time we have seen a person infected with EEE in Massachusetts since 2020,” Public Health Commissioner Robbie Goldstein, MD, PhD, said in a statement. “EEE is a rare but serious disease and a public health concern. We want to remind residents of the need to protect themselves from mosquito bites, especially in areas of the state where we are seeing EEE activity.

Though very rare, EEE is serious and a potentially fatal disease that can affect people of all ages. EEE is generally spread to humans through the bite of an infected mosquito. There were 12 human cases of EEE in Massachusetts in 2019 with 6 deaths, and 5 human cases with 1 death in 2020. There were no human cases of EEE in Massachusetts in 2021, 2022, or 2023.

EEE has a fatality rate of 33% to 70%, with most deaths occurring 2–10 days after the onset of symptoms.

In addition to a high mortality rate, long-term physical and mental complications, including permanent neurological deficits have been identified in many people who survive EEE.

Plymouth is approximately 40 miles south of Boston along the coast, and Worcester County is in the middle of the state, so the 2 areas are not in close proximity, but due to the elevated risk locally, the town of Plymouth decided to take action in response to outdoor parks. As of last Friday, all town public parks and fields are close daily from dusk until dawn.

“As Mass DPH has now elevated Plymouth’s EEE risk status to high, it is important to take extra precautions when outdoors and follow state and local health guidelines to avoid unnecessary risk to exposure to EEE. The health and safety of our community, residents, and visitors remain our priority,” Plymouth’s Commissioner of Health and Human Services, Michelle Bratti, said in a statement.

According to the Centers for Disease Control and Prevention (CDC) most people who are infected with the virus do not develop symptoms; however, for those that do, the date from the bite to the onset of the illness is 4 to 10 days. EEE can also result in fever or neurologic disease. The type of illness will depend on the age of the person and other factors. Those who are infected can develop meningitis.

There are no FDA-approved treatments for EEE and for patients who develop severe cases, they can be hospitalized to receive supportive treatment.

Over the weekend, MDPH detailed plans of spraying for mosquitos including aerially in areas of Plymouth County, and truck-mounted spraying in parts of Worcester County. As of Saturday, 10 communities in Massachusetts were raised to high or critical risk for EEE virus.

“The risk from EEE is high in parts of Plymouth County and critical in parts of Worcester County,” State Epidemiologist Catherine M. Brown, DVM, said in a statement. “In addition to recommending that people use mosquito repellent with an EPA-registered active ingredient and clothing to reduce exposed skin, we also recommend that evening outdoor events be rescheduled to avoid the hours between dusk and dawn. The mosquitoes most likely to spread EEE are most active during the dusk to dawn hours.”

There are preventative strategies to avoid EEE, and the MDPH has listed such measures 

For those who live in Massachusetts and want more information on EEE, it can be found 

 or by calling the DPH Division of Epidemiology at 617-983-6800.

1.NH DHHS Identifies Person Infected with Eastern Equine Encephalitis Virus in New Hampshire.The New Hampshire Department of Health and Human Services. August 27, 2024. Accessed August 28, 2024.
https://www.dhhs.nh.gov/news-and-media/nh-dhhs-identifies-person-infected-eastern-equine-encephalitis-virus-new-hampshire
2. State health officials announce season’s first human case of Eastern Equine Encephalitis in Massachusetts. MDPH. August 16, 2024. Accessed August 27, 2024.
https://www.mass.gov/news/state-health-officials-announce-seasons-first-human-case-of-eastern-equine-encephalitis-in-massachusetts
3.Plymouth to Close all Public Parks and Fields from Dusk to Dawn. Town of Plymouth. August 23, 2024. Accessed August 27, 2024. PDF.
4. Eastern Equine Encephalitis: Symptoms, Diagnosis, and Treatment. CDC. May 15, 2024. Accessed August 27, 2024.
https://www.cdc.gov/eastern-equine-encephalitis/symptoms-diagnosis-treatment/index.html
5. State officials announce plans to spray for mosquitoes in sections of Worcester and Plymouth counties due to EEE. MDPH. August 24, 2024. Accessed August 27, 2024. 
https://www.mass.gov/news/state-officials-announce-plans-to-spray-for-mosquitoes-in-sections-of-worcester-and-plymouth-counties-due-to-eee



The town of Plymouth decided to prohibit people from using the parks from dusk to dawn due to concerns over eastern equine encephalitis after a man contracted the rare disease in the state.

Concerns Over Mosquito-Borne Illness Causes Massachusetts Town to Create Curfew for Parks, Spraying in Counties

Ami Patel discusses the work of Wistar Institute

Differentiating Between DNA and mRNA Platforms

 in Philadelphia, Pa, is involved in cancer, immunology and infectious disease research, and vaccine development. The research center advances basic research, translating fundamental discoveries into future therapies to benefit global health and training the next generation of scientific leaders.

Ami Patel, PhD, assistant professor, Vaccine & Immunotherapy Center, Wistar Institute, leads a laboratory team at the center. A major area of study with her team has been around employing non-viral DNA vectors for vaccine and antibody delivery. Patel’s most recent studies include DNA vaccine development against Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and multiple studies in the rapidly advancing field of DNA-encoded monoclonal antibodies (DMAbs).

Of course, everyone is familiar with the mRNA platform from the pandemic and the subsequent COVID-19 vaccines. However, not much is known to the public about how DNA vaccines and monoclonal antibodies work.

“DNA itself is a very inherently stable molecule. It has a very large coding capacity, and so that allows us to put very large synthetic genes inside DNA,” Patel said. “mRNA is really kind of an in-between step between DNA and protein synthesis. And when you have an mRNA platform, you get very rapid protein production. It's kind of an in-between way to kick start that process. And so, it's very rapid; it's a very burst of expression. But then it's finished with synthetic DNA. It mostly takes place in the nucleus, and you get multiple copies of mRNA coming off of that DNA molecule. And so, you can have a longer period of expression, and a longer period of protein expression afterwards, following translation. This allows us to encode genes in a different way and to get different types of immune responses, for example, or different types of protein production than you would get from a short burst from an mRNA platform.”

One of the interesting differences in DNA and mRNA is that the former is temperature stable, and it allows it to be used internationally more easily. “Being temperature stable, it helps enable some of these properties for delivery to resource limited settings, such as low and middle income countries, because it doesn't necessarily have to have the cold chain that's attached to it like mRNA,” she said.

Patel spoke at last week’s World AMR Congress, and her presentation, “Tackling Pandemic Pathogens: Gene-Encoded Antibodies as Pre-Exposure Prophylaxis,” discussed some of her work around the DNA platform.

Whereas, vaccines have been a long established modality to prevent diseases and viruses; monoclonal antibodies (DMAbs) are a newer area of study with the hope of bringing immunization of diseases. One example Patel points out is the monoclonal antibody, 

, to prevent RSV in the infant population. It was FDA approved last year. In fact, it is the first-ever prophylactic product indicated for the prevention of RSV lower respiratory tract disease (LRTD) in newborns and infants born during or entering their first RSV season, and for children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. Patel says the approval of this immunization has really opened the door to this line of research.

Although monoclonal antibodies might be a newer area of interest, it is not one that will likely reduce vaccines' roles in reducing illness. Patel sees vaccines and monoclonal antibodies as complementary, and not competing, prophylactic modalities.

“I like to think of vaccines as a way to induce active immunity. So basically you're delivering this protein or this coding sequence, and your body's developing its own immune response to it and its own antibodies and own T cells in an active form. So it's really requiring active engagement of your body," Patel said. "Something like DNA encoded antibodies, you're delivering the antibody already in almost a passive form, so your body doesn't have to develop its own immune response. It now has that end product antibody already, and so you can think of them working hand in hand together.”

She mentions there are some groups that do not respond well to vaccines and monoclonal antibodies are a way of delivering that type of passive immunity and a way to supplement their immune responses.



Ami Patel, PhD, provides insights on both technologies and how her research center, the Wistar Institute, is involved in DNA vaccine and monoclonal antibody research. 

 In response to the ongoing events in Africa related to mpox, Africa CDC has also signed a partnership agreement with the European Commission’s Health Emergency Preparedness and Response Authority (HERA) and Bavarian Nordic to provide over 215,000 doses of the MVA-BN (Jynneos) vaccine—the only FDA and EMA-approved mpox vaccine. Africa CDC will oversee the equitable distribution of these vaccines, prioritizing local needs across the affected Member States.

Back in May, the Centers for Disease Control and Prevention's (CDC) 

 published data around the mpox vaccine, MVA-BN (Jynneos), manufactured by Bavarian Nordic. Investigators reported the vaccine is highly effective in preventing mpox virus infection after receipt of 2 Jynneos doses. In fact the estimated incidence rate to have occurred is less than 0.8% in fully vaccinated persons.

In the period from May 2022 – May 2024, 271 mpox cases in fully vaccinated persons were reported to CDC from 27 US jurisdictions. The CDC data shows that among 32,819 probable or confirmed mpox cases during this time period, a total of 24,507 (75%) occurred in unvaccinated persons.

“Of these 271 cases, 51 (19%) occurred during 2024. Vaccination status was missing for 3737 (11%) cases; an additional 4304 (13%) cases were excluded from analysis because the patient had received only 1 Jynneos vaccine dose or had received the second dose <14 days before illness onset, or because other exclusion criteria were met.

They pointed out that compared with unvaccinated cases, a higher proportion of fully vaccinated cases occurred among non-Hispanic White individuals (59%) and people aged 30–39 years (47%).


In the spring of 2023, the city of Chicago had an mpox cluster amongst fully vaccinated (FV) individuals. During this outbreak, from March 18-June 27, 2023, investigators identified 49 mpox cases with 57% of these cases coming from fully vaccinated individuals.

“Our investigation indicated that cases were likely due to frequent behaviors associated with mpox transmission, even with relatively high vaccine effectiveness and vaccine coverage. Cases after vaccination might occur in similar populations,” the investigators concluded.

Bavarian Nordic announced the Jynneos vaccine

 was available for commercial purchase in the US. Health care providers can order the vaccine through wholesalers and distribution partners, making it accessible at pharmacies, physician offices, and public health clinics.

References
1. Africa CDC Declares Mpox A Public Health Emergency of Continental Security, Mobilizing Resources Across the Continent. Africa CDC. August 13, 2024. August 14, 2024.
https://africacdc.org/news-item/africa-cdc-declares-mpox-a-public-health-emergency-of-continental-security-mobilizing-resources-across-the-continent
2. Guagliardo SA, Kracalik I, Carter RJ, et al. Monkeypox Virus Infections After 2 Preexposure Doses of JYNNEOS Vaccine — United States, May 2022–May 2024. MMWR Morb Mortal Wkly Rep 2024;73:460–466. DOI: http://dx.doi.org/10.15585/mmwr.mm7320a3
3. Faherty EAG, Holly T, Ogale YP, et al. Investigation of an mpox outbreak affecting many vaccinated persons in Chicago, IL–March 2023–June 2023. Clin Infect Dis 2024;ciae181.


https://doi.org/10.1093/cid/ciae181 PMID:38567460


4. Abene S. FDA-Approved Mpox Vaccine Now Commercially Available in the US. 

. April 2, 2024. May 23, 2024.
https://www.contagionlive.com/view/fda-approved-mpox-vaccine-now-commercially-available-in-the-us

The vaccine, Jynneos, manufactured by Bavarian Nordic, is being shipped to Africa to address the ongoing mpox outbreak. 

In Response to African Mpox Outbreak, Vaccine is Being Made Available

Jason Roberts, PhD, discusses insights from the BLING III trial, outlining its study design and primary outcomes. 

Continuous β-Lactam Infusions Show Promise in the Battle Against Sepsis

In critical care settings, the optimal method of administering β-lactam antibiotics to septic patients has been a topic of ongoing contention. The international BLING III trial addressed this debate by comparing continuous and intermittent infusions of these antibiotics in 7,031 adult septic patients. The primary analysis revealed no statistically significant difference in 90-day mortality rates between the 2 infusion methods (24.9% vs. 26.8%, respectively; odds ratio (OR), 0.91). Although, the confidence interval suggests a potential for both no significant effect and a beneficial clinical impact with continuous infusions. These findings highlight the complexities in antibiotic administration strategies for critically ill patients.

Researcher Jason Roberts, PhD, started his career in critical care units at the Royal Brisbane Women's Hospital and transitioned to health and medical research over the past 15 years. He specializes in optimizing antimicrobial doses and is currently the director at the University of Queensland Centre for Clinical Research. Since beginning his PhD in 2005, Roberts has been deeply involved in the BLING research program (Beta Lactam Infusion Group), demonstrating his long-term dedication and expertise in this field.

This international, open label randomized clinical trial took place across 104 intensive care units in Australia, Belgium, France, Malaysia, New Zealand, Sweden, and the United Kingdom. Recruitment spanned from March 26, 2018, to January 11, 2023, with follow-up completed by April 12, 2023. Critically ill adults (≥18 years) treated with piperacillin-tazobactam or meropenem for sepsis were included.

What factors led to the decision to conduct an international, open-label trial across multiple countries? How did the diversity of ICUs and patient populations affect the study outcomes and generalizability?

To achieve adequate recruitment across multiple countries, the study organizers opted to conduct the research in an open-label format. This pragmatic decision aimed to involve a broad spectrum of ICUs and meet the study's recruitment needs effectively. The collaboration and support from investigators across different countries were pivotal and highly valued. Throughout BLING 2, strict adherence to specific patient inclusion criteria shaped the study's methodology and influenced its outcomes significantly.

Roberts explains how the diversity of ICUs and patient populations affected the study outcomes and generalizability,

“We deliberately aimed to be very broad with the types of ICUs that would be included from the countries, thinking that that would improve the generalizability of the results. And the patient population was still sepsis, people still had to align with that definition. Even if the individual case mix within the different ICUs could have been different, it's still more likely to be representative of the broader global sepsis population.”

Roberts reflects on the previous BLING I and BLING II study outcomes that influenced the outline of the BLING III trial because they were key factors in building the setting for BLING II to be successful.

BLING 1 and BLING 2 were pivotal randomized controlled trials conducted across multiple centers in Australia and Hong Kong. BLING 1, which involved four ICUs, aimed to assess the feasibility of a double-blind, double-dummy design in evaluating pharmacokinetic outcomes associated with continuous versus intermittent antibiotic infusion. BLING 2 expanded the scope to 26 ICUs, retaining the same design while focusing on ventilator-free days as the primary endpoint and examining clinical cures. These trials laid the groundwork for further investigation into continuous antibiotic infusion among critically ill patients.

“I think that the randomized control trial is very important but equally important is the systematic review and meta-analysis, and they should be both read together. And the cumulative evidence across all of the studies within the systematic review and meta-analysis is very consistent, favoring the use of prolonged infusions. We see the same results in the randomized control trial,” says Roberts.

The primary outcome of 90-day mortality showed a trend towards lower mortality with continuous infusion, although not statistically significant. How should clinicians interpret this finding, especially considering the confidence interval that suggests potential clinical benefit?

“Up until this point, for us to be able to randomize patients in our own intensive care units to continuous infusion, we couldn't have our own belief that intermittent infusion must be inferior because that would be unethical. So we were always very open-minded about this. I think that the nature of the point estimates for the odds ratio in the context of the confidence interval suggests that the likelihood is, is that this is a valuable intervention, which can save lives on certainly from a probabilistic perspective,” according to Roberts' perspectives

Out of 7202 participants randomly assigned, 7031 met the consent criteria for inclusion in the primary analysis (97.6%). Within 90 days, mortality rates were 24.9% (864 out of 3474) for patients receiving continuous infusion compared to 26.8% (939 out of 3507) for those receiving intermittent infusion, resulting in an absolute difference of -1.9% (95% CI, -4.9% to 1.1%) and an odds ratio of 0.91 (95% CI, 0.81 to 1.01; P = .08).

Roberts continues, “The final statistical evidence which comes through is through the posterior probabilities that came through from the systematic review and meta-analysis which said that there's a 99.1% probability that you're giving the drug by prolonged infusion because the systematic review is looking at continuous infusion and extended infusion studies, that there's a 99.1% likelihood that this intervention can reduce sepsis mortality.”

Clinical cure rates were higher in the continuous infusion group (55.7% (1930 out of 3467) compared to the intermittent infusion group (50.0% (1744 out of 3491), with an absolute difference of 5.7%. The primary outcome was all-cause mortality within 90 days after randomization.

Secondary Outcomes and Clinical Implications of β-lactam Infusion Strategies in Critically Ill Patients with Sepsis 

Roberts, J, Dulhunty JM, Brett SJ, De Waele JJ, et al. Continuous vs Intermittent β-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis. 

Published June 12, 2024. Accessed June 24, 2024. doi:10.1001/jama.2024.9779

Jason Roberts, PhD, discusses insights from the BLING III trial, outlining its study design and primary outcomes. His analysis centers on the clinical benefits of continuous infusions while addressing the complexities of antibiotic administration in critical care. This is part 1 of a 2-part series.

Peggy Lillis Foundation CEO Christian Lillis talks about how he became involved in advocacy around C diff and his motivation 

The Genesis of C diff Advocacy 

When Christian Lillis’ mother passed away suddenly at the age of 56 in 2010 from 

, he had to go through the process of getting her affairs in order. She did not have a will, and Christian had to go through the courts to become the executor of her will.

During the process he had spoken to someone within the pathologist’s department, and Christian naturally inquired about if his mother’s infection was reported to the state or federal agency.

“I'll never forget the person said: ‘people die from 

 every day in New York, it's not unusual. We don't report it to the state or the CDC.’ And my response to that was, a healthy 56-year-old woman going to the dentist and dying 6 days later isn't unusual to you?” Lillis said to the person. “And so that really is what made me dig into how 

 was reported, and to whom it was reported, and how easily the public could access that data and have that knowledge…I'm still angry over that conversation.”

The conversation stuck with him and motivated him into putting a spotlight on 

. That same year, Christian and his brother, Liam, started the 

Peggy Lillis Foundation (PLF) for C diff Education and Advocacy

. Over the years, PLF has worked to help serve 

Fast forward to last month, and congresswoman Yvette Clark (D-NY)—who is Christian’s representative—introduced legislation, the Peggy Lillis 

 Inclusion Act, into the House of Representatives. The act calls for 

nationally notifiable infectious disease and condition

PLF was instrumental in getting the bill introduced. As part of its governmental advocacy, PLF have a Lobby Day in Washington DC every year where they speak to Congressional representatives and their aides.

“We have been meeting with her [Clark] over the years, keeping her up to date on what was going on with 

,” Lillis said. He also said there was a health inequity aspect that appealed to Clark and helped in getting her involved and sponsoring the bill.

“There's research showing that people of color, in particular, Black Americans get 

 at slightly lower rates than White Americans, but they have worse outcomes. And Congresswoman Clark has always been very interested in health equity and ensuring that people have access to treatment.”

The Prospective Bill and Getting it Passed

The bill as written, and if passed, would:

Require states to collect and report data on confirmed cases of 

Require Health and Human Services (HHS) to establish standardized data elements, including demographic information, clinical information, and laboratory results, for the reporting of cases of 


While getting the bill introduced is a very important step, it must goes through a long process in order to get passed and they still need congressional help to have a chance of doing so.

“We're looking at republican congressional representatives to find a republican cosponsor,” Lillis said. “In these partisan times, having an all-democratic bill or an all-republican bill doesn't tend to work, so our volunteers and board members who live in republican districts are in communication with their representatives, and now talking to them about the bill. We're hoping that we can announce a cosponsor in the next month or 2.”

Anyone can get involved in advocating for the bill by contacting their local representatives. For anyone interested in contacting Congress, people can go to 

 and send a message directly to their representative’s office.

This is part 1 of a 2-part conversation with Lillis. We will be publishing the next part of the conversation in the coming days.

Peggy Lillis Foundation CEO Christian Lillis talks about how he became involved in advocacy around C diff and his motivation in helping to  bring a bill to Congress to make the healthcare-associated infection a nationally notifiable infectious disease and condition.

The impact of including patients with advanced disease and the role of comprehensive care in the PALM 007 clinical trial, which evaluated the antiviral tecovirimat for treating monkeypox in the Democratic Republic of the Congo.

SIGA Technologies' Trial Results Benefits Mpox Treatment Despite Not Meeting Primary Endpoint

Early this morning, SIGA Technologies announced the results of the PALM 007 clinical trial, which assessed antiviral tecovirimat for treating monkeypox (mpox) in the Democratic Republic of the Congo (DRC) did not achieve its primary objective of showing a statistically significant improvement in lesion resolution compared to a placebo. Regardless, tecovirimat's safety profile was consistent with the placebo's and aligned with previous studies' findings.

Jay Varma, MD, Chief Medical Officer at SIGA Technologies, discussed findings from the trial with 

. He acknowledged that although the primary goal was not met, he explained that the trial showed benefits in patients treated early or those with severe disease. Varma elaborated on a few reasons supporting this:

“Firstly, regarding early treatment, this study was designed with certain humanitarian considerations in mind. Instead of targeting the study solely towards those most likely to show a benefit from the drug, it included patients who could present much later in the course of their illness. For example, about 20 to 30% of patients presented more than seven days after the rash began. This significantly diluted the impact of the study findings. So, including patients who were unlikely to benefit much was a major reason why the primary endpoint wasn’t met,” Varma said.

Varma compared tecovirimat to other antivirals for infections like flu or COVID-19, noting that these drugs don’t kill viruses but prevent them from spreading through the body. He continued with his second point about patient benefits:

“The study was initially designed based on historical data about how quickly lesions resolve, under routine conditions. In this study, all patients were hospitalized, provided with food, nutrition, and treatment for other illnesses. This comprehensive care improved their outcomes by about 25 to 50%, with patients resolving their illnesses approximately two days faster than historically. This created a challenge in demonstrating a benefit in patients who might have had milder disease, which is why the treatment benefit was mainly observed in patients with severe disease or those treated early.”

Varma made an analogy of how regulatory agencies and clinical or public health agencies evaluate a drug. “Regulatory agencies, like referees in a sports game, focus on rule adherence. In contrast, doctors and public health agencies consider the broader performance and value. When evaluating the total data, it’s clear that the drug has value, particularly for patients treated early or those with severe disease.”

Regarding the new mpox strain, clade I, Varma commented on its transmission modes. 

Everything we know about the mpox strain circulating in the DRC, known as clade I, shows it’s still quite similar to the clade 2 strain spreading elsewhere. We don’t think respiratory transmission is a major factor at present, viruses evolve, and anything is possible, but respiratory transmission isn’t considered a primary driver right now,” Varma said. “The main difference between the two clades is the severity of illness. Clade I generally causes more severe disease compared to clade II, which can be less severe or occur in people with advanced AIDS or other immune suppression. Smallpox, a related virus, represents the most severe end of this continuum.”

Future research is ongoing with trials such as STOMP, UNITY, Platinum-CAN, and EPOXI to assess tecovirimat’s efficacy under various conditions. It’s essential to use lessons from this trial to improve these ongoing studies. Varma highlighted key factors for future research:

The impact of including patients with advanced disease and the role of comprehensive care in the PALM 007 clinical trial, which evaluated the antiviral tecovirimat for treating monkeypox in the Democratic Republic of the Congo.



CARLOS DEL RIO, MD

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