In the United States and other leading nations, 

 vaccinations have been steadily increasing, driving infections down to numbers that haven’t been seen since the beginning of the pandemic.

Approved vaccines, like the mRNA platforms of Pfizer and Moderna and the adenovirus platform of Johnson & Johnson, have already mostly filled the need.

However, many poorer nations around the globe have been facing numerous issues with obtaining and administering doses that could significantly improve their situation.

Novavax’s investigative COVID-19 vaccine, NVX-CoV2373, has recently shown extremely promising results from the company’s 

. The biotechnology company soon plans to file for regulatory authorizations upon completing the final process qualification and assay validation phases.

The vaccine, a protein-based recombinant nanoparticle therapy designed from the genetic sequence of the first SARS-CoV-2 strain, showed an overall vaccine efficacy of 90.4% 7 days post-second dose among participants previously not infected with SARS-CoV-2.

With such an impressive efficacy and safety profile, NVX-CoV2373 could aid in the global fight against COVID-19, especially in areas where they are struggling to get it under control.

 recently sat down with Lisa Dunkle, global medical lead for Novavax’s COVID-19 vaccine initiative, to discuss the therapy, the trial and what role it will play in the global fight.

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A discussion surrounding Novavax’s NVX-CoV2373 with Lisa Dunkle, MD.

What Role Will Novavax’s Vaccine Play in the Global COVID-19 Effort?

Earlier today, Novavax announced data from its phase 3 PREVENT-19 trial for its NVX-CoV2373 COVID-19 vaccine. The results showed it was 90.4% overall for prevention of symptomatic disease.

While these results demonstrate a highly effective vaccine, what does the potential addition of this vaccine to the fold mean both here in the US and internationally?

From a big picture standpoint, the US has had enough COVID-19 vaccine supplies for some time, but one of the international concerns has been that many countries are desperately in need of vaccines. And the situation is becoming more direr as the emergence of the Delta variant has become a serious threat. Starting in India and making its way westward to the UK and now in the states, there is concern the Delta variant might become the dominant strain in this country. There have also been discussions by the medical community that a booster vaccination might be needed to address new variants or waning immunity. 

With these troublesome trends, the authorization of another vaccine could help ease these burdens. 

 spoke with Jonathan Baktari, MD, CEO of 

 about the importance of having another COVID-19 vaccine, some of the advantages of the Novavax vaccine, and the possibility of having an mRNA vaccine the first go around and then moving towards another vaccine platform.

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With the company reporting its data today and it applying for authorization with regulatory bodies internationally, and later this year with the US Food and Drug Administration (FDA), what does the prospect of this new vaccine mean to people in the US and internationally? 

What Does the Addition of a Novavax COVID-19 Vaccine Mean?

Before COVID-19, the mortality rate for ARDS was relatively high. In 1 study looking at hospitalized patients with ARDS they reported that mortality up to 1 year was found to be 41%.

And with the introduction of the SARS-CoV-2 pandemic, ARDS became a more common complication for COVID-19 patients with severe disease. COVID-19-related ARDS exacerbated the severity of the complication, and has been reported to have a mortality rate between 39% and up to 73% in a few studies. 

Gaithersburg, Maryland-based Cartesian Therapeutics, a small clinical-stage biopharmaceutical company, has created its RNA cell therapy, Descartes-30, the first such therapy for ARDS. Descartes-30 is part of the company’s proprietary RNA Armory combination therapy platform.

“The overarching vision behind the Armory is to be able to RNA engineer any cell to deliver to any part of the body any combination of therapies where we are using the cell both as a factory for producing as well as a vehicle for delivering not just one therapeutic but multiple—right to the site of disease,” Murat Kalayoglu, MD, PhD, president and chief executive officer at Cartesian Therapeutics, said.

Descartes-30 is a mesenchymal stem cell (MSC) therapy engineered to secrete 2 DNases that degrade neutrophil extracellular traps (NETs), which are key drivers of several respiratory, autoimmune and cardiovascular diseases. The MSC acts both as a protein factory, by producing therapeutic DNases for an extended period, and as a vehicle to deliver those therapeutics directly to the lungs, where NETs accumulate.

Last month, Cartesian announced a $2 million competitive research and development award from the National Heart, Lung, and Blood Institute of the National Institutes of Health to support its clinical development for Descartes-30, the first RNA cell therapy for respiratory diseases.

The company is enrolling patients with moderate-to-severe ARDS, including those with COVID-19, for a phase 1/2 clinical trial.

 spoke to Kalayoglu to understand the differences in the RNA vs DNA engineered therapies, insights into the company’s RNA Armory combination therapy platform, and progress on their clinical trial.

1 Chen Yu Wang Carolyn S Calfee, et al. One-year mortality and predictors of death among hospital survivors of acute respiratory distress syndrome. 

 2014 Mar;40(3):388-96. doi: 10.1007/s00134-013-3186-3

2 Syed Shahzad Hasan,Toby Capstick, et al. Mortality in COVID-19 patients with acute respiratory distress syndrome and corticosteroids use: a systematic review and meta-analysis. 

 2020;1-15. doi: 10.1080/17476348.2020.1804365

Cartesian Therapeutics has created its therapy, Descartes-30, the first RNA cell therapy for acute respiratory distress syndrome (ARDS), and the company is now recruiting for a clinical trial.

RNA Cell Therapy for COVID-19 Related ARDS in Development

 pandemic brought vaccine research and development to the forefront of the global conversation. Investigators worked tirelessly to create therapies that would aid in, and hopefully bring to an end, one of the worlds worst public health crises in recent memory.

Messenger RNA (mRNA) vaccines, like those developed by 

, were some of the first and most successful to be adopted and rolled out into inoculation efforts.

However, other platforms have also been heavily researched and developed into efficacious, safe vaccines. The two most notable are perhaps adenovirus vaccines, like the one created by 

, and nanoparticle vaccines, like the one created by 

To gain a more thorough understanding of these two vaccine platforms, 

 sat down with Doctors Daniel Kulp and Hildegund C.J. Ertl, professors in the Vaccine & Immunotherapy center at the Wistar Institute.

, based in Philadelphia, is a global leader in biomedical research with special expertise in cancer, immunology, infectious diseases and vaccine development.

In the discussion, we talk about the mechanisms of action of the adenovirus and nanoparticle vaccines, the properties of the vaccines, efficacies, immunogenicity, associated risks, lessons learned from their development and implementation and other diseases the platforms are being developed for.

A Q&A surrounding the two technologies with investigators from the Wistar Institute.

Discussing Nanoparticle and Adenovirus Vaccine Platforms

Welcome to our series, 1 Big Question, which asks 1 question to the medical community and we get their feedback on an important infectious disease topic.

In this episode, our 1 Big Question is: With regards to the recent CDC guidance on masks, how would you characterize the way it was rolled out, and what would you have liked to have seen more of from that?

We interviewed Jonathan Baktari, MD, CEO of 

, Jeanne Marrazzo, MD, MPH, FIDSA director of the Division of Infectious Diseases and professor of medicine at the University of Alabama, Birmingham, and an Infectious Diseases Society of America (IDSA) board member, and Anurag Malani, MD, infectious diseases specialist, St. Joseph Hospital, and a fellow of IDSA.

Check out our video to hear their insights.

With the US Centers for Disease Control and Prevention's recent change to mask guidance for vaccinated people, some confusion ensued and left state governments and businesses scrambling to react to the update.

Was CDC's Approach to Mask Guidance Less Than Ideal?

In the late winter and early spring of 2020, a shift occurred in healthcare to address the impending COVID-19 pandemic. Cases began to increase significantly, and almost overnight in March, the entire United States began to focus solely on SARS-CoV-2.

Screenings and elective surgeries were cancelled and reporting for healthcare-associated infections (HAI) became optional. At the Veterans Administration hospital in Ann Arbor, Michigan a small team took up a study looking to see if CDI testing and infection rates changed during this first surge of the pandemic.

The study was led by Armani Hawes, MD, and Payal K. Patel, MD, MPH, Division of Infectious Diseases assistant professor, University of Michigan Health System Medical Director of Antimicrobial Stewardship, VA Ann Arbor. They presented a poster virtually at The Society for Healthcare Epidemiology of America (SHEA) back in April and the work was just published in 

“As the pandemic started to get into full swing, we started to think about how all these healthcare-associated infections might be affected,” Hawes said about the study team’s motivation for the study. She said there were other variables including additional infection prevention factors in place because of COVID-19 and the Centers for Medicare and Medicaid's decision to stop mandatory reporting on all HAI including C diff.

The investigators conducted a single center, retrospective, observational study at the VA Hospital in Ann Arbor between January 2019 and June 2020. They compared data from CDI tests from January 2019 through February 2020 to data from March 2020—the first admission of patient with COVID-19 at the VA—through June 2020.

Between January 1, 2019 and June 30, 2020 there were 6525 total admissions and 34,533 bed days. There were 900 enzyme immunoassay (EIA) tests obtained and 104 positive cases of CDI between January 2019 and June 2020.

In terms of testing, there were some noted differences. “There was a statistically significant decrease in EIA tests after March 1, 2020 (the COVID-19 peak in their region), compared to January 1, 2019-March 1,2020,” the investigators wrote in the poster. “After March 1, 2020 the number of EIA tests obtained decreased by 10.2 each month (95% Confidence Interval [CI] -18.7 to -1.7; p=0.02).”

They reported no statistical significant change in the incidence rate of CDI.

“This was a single center study but some of the work that is coming out—not just nationally, but internationally—seems to support that was what others saw in their institutions and large regions as well,” Patel stated.

 spoke to Patel and Hawes about the study, further insights from their findings, and the importance of learning from COVID-19 and being able to apply this knowledge if need be for future pandemics.

During the COVID-19 surge last year, the federal government stopped the required reporting on healthcare-associated infections (HAI) thus leaving an absence of data and important information on HAI. One study examined the effect the initial pandemic surge had on Clostridioides Difficile infection (CDI) in one hospital. 

How Did COVID-19 Affect Clostridioides Difficile Testing and Incidence Rates?

As Americans honor military personnel who have died in the performance of their military duties while serving in the United States Armed Forces today, it is a reminder of the freedoms the country has earned. The question becomes does this freedom give people too much choice and is detrimental when thinking about health guidance that can help not only individuals but their fellow Americans?

If anything the pandemic has shown that people’s choices can greatly affect how a deadly virus can travel quickly or be mitigated.

As the US Centers for Disease Control and Prevention (CDC) recently changed its mask guidance for those who are fully vaccinated, the United States is learning to adapt to these changes. We are emerging from this pandemic and beginning to shed masks. If you walk into any business without a mask, it might feel slightly odd at first, like we forgot something. Turn on any sporting event on TV and we are starting to see more people in the crowd. 

Everyone should enjoy this return to a semblance of normalcy we are experiencing.

However, it is still undetermined if COVID-19 will be eliminated or become endemic. If it is the latter, and it becomes like influenza with an annual season, and the CDC were to recommend everyone wear masks in the winter, would Americans be willing to heed this advice?

Future COVID-19 mitigation strategies could not only help decrease COVID-19 transmission but other respiratory viruses as well. This past influenza season was greatly diminished due to heightened hygiene measures and mask wearing.

In some Asian cultures, they have been wearing masks in public for years to prevent respiratory viruses. Could this type of widespread mask wearing translate to the United States?

 spoke to Jeanne Marrazzo, MD, MPH, FIDSA, director of the Division of Infectious Diseases and professor of medicine at the University of Alabama, Birmingham, and an IDSA board member about a potential COVID-19 endemic scenario including the use of masks, some of the ancillary health benefits COVID-19 mitigation strategies provided, and the prospects of an American cultural shift towards using masks again.

Do the very freedoms Americans enjoy allow us to make less than optimal choices? And will it prevent us from doing what medical science says is best if needed again? 

What If We Are Asked to Wear Masks Again?

Across the world there are 38 million people living with the 

 (HIV) or Acquired Immunodeficiency Syndrome (AIDS). While numbers are on the decline, 1.7 million people acquired the HIV virus in 2019.

Treating HIV comes with several challenges and barriers, including a high cost of treatment, access to care, retention in care and transition from inpatient to outpatient care.

Contagion recently sat down with Melissa Badowski, PharmD, MPH, a clinical associate professor in the department of pharmacy practice at the University of Illinois at Chicago to discuss the issue of challenges in HIV management

Annual Making a Difference in Infectious Disease Meeting 2021 virtual sessions

“Were very stringent with our medical appointments. If you miss it by 10 or 15 minutes, a lot of patients will get turned away,” Badowski said. “Where in HIV care, it’s just the opposite. We try to remove any barriers; we try to meet the patient where they’re at.”

Patients face many barriers, from the ability to get their medication to being stigmatized from having HIV.

“HIV has been around for a long time, but I still think of it as being stigmatized,” Badowski said. “If we can just reduce the ‘Oh, this is just an infectious disease.’ I think that would help a lot of our patients with reducing that stigma.”

A discussion on issues surrounding the treatment of HIV with Melissa Badowski, PharmD, MPH.

Challenges in HIV Management and Therapy

Healthcare associated infections (HAI) can be a tremendous burden on hospital systems, patients, and clinicians. Within (HAI), rCDI can be a particularly challenging burden having patients deal with the same ongoing health issue. One study looked at the number of hospital admissions of Medicare patients and saw 20% of inpatients had rCDI as the primary diagnosis.

The findings were presented virtually at the 

23rd Annual Making a Difference in Infectious Disease Meeting 2021 virtual sessions

Investigators performed a large retrospective analysis looking at Medicare patient hospital admissions. They looked at Part A Medicare claims from January 2018 to June 2019. They had a total of 43,039 patients with 47,115 CDI-related hospital admissions, and 9472 of these admissions had rCDI.

They studied a variety of factors in 2 groups: CDI-related hospital admissions and non-CDI admissions. They looked at the length of stay (LOS), costs per admission, discharge status, outcomes, and in-hospital mortality.

The results did show differences in each patient group. For example, rCDI admissions resulted in higher inpatient costs than non-rCDI admissions. Investigators also found patients’ LOS was slightly longer for rCDI than non-rCDI admissions: 6.0 (5.7) vs 5.5 (5.1) days.

 spoke to principal investigator Meg Franklin, PharmD, PhD, president of Franklin Pharmaceutical Consulting who provided some insights into the understanding of the analysis including the patient implications and financial burden these challenging infections cost.

A study looked at hospital admissions of Medicare patients and saw a large percentage of recurrent Clostridioides difficile infections (rCDI) as the primary diagnosis.

The Burden of Clostridioides Difficile

Assessing the severity of COVID-19 is difficult and in the absence of any diagnostics to gain a better understanding of disease progression makes clinical care challenging. 

A new study used an analyzer to look at host proteins to help identify the severity of COVID-19. According to the investigators, it was found to outperform other candidate severity biomarkers including Interleukin 6 (IL-6).

The analyzer looked at TNF-related apoptosis-induced ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP). The investigators employed machine learning to integrate TRAIL, IP-10 and CRP levels into a score (0-100). They created 4 To render the model clinically intuitive, 4 score bins were developed.

“In area under the receiver operating characteristic curve (AUC) analysis, the score with AUC 0.86 (95% confidence interval, CI: 0.81-0.91) outperformed other candidate severity biomarkers, including IL-6 (n=139; AUC 0.77 (95%CI: 0.67-0.87); p=0.03),” the investigators reported. “Performance was also assessed by demonstrating a significant trend in likelihood of severe outcome going from low to high score bins (p<0.01). This trend was significant in the sub cohort of severe patients meeting outcome on day of/after blood sampling (n=339; p<0.01).”

The analyzer was developed by Haifa, Israel-based MeMed. 

 spoke to Tanya Gottlieb, PhD, MBA, vice president, Scientific Affairs, MeMed about the analyzer including how it can help identify what is going on in the immune system and the potential role that machine learning has in clinical care.

A diagnostic analyzer was studied looking at 3 biomarkers to predict the level of COVID-19, and could potentially serve as a risk stratification tool.