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IDWeek 2023: COVID-19
Key Takeaways From IDWeek 2023 on COVID-19 Risk Factors, Clinical Outcomes, and Future Therapeutics

Released: November 06, 2023

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Key Takeaways
  • The COVID-19 pandemic isn’t over, particularly for people with immunocompromise.
  • Novel COVID-19 therapies are being developed to meet future therapeutic needs.

IDWeek 2023 provided a program overflowing with data related to the COVID-19 pandemic, demonstrating how the past 3-plus years have focused so many infectious disease healthcare professionals, researchers, and policymakers on the SARS-CoV-2 virus. Several presentations demonstrated the current state of the COVID-19 pandemic, almost 2 years into the omicron era.

Here, I discuss data regarding who remains at risk for severe consequences of COVID-19 infections, which antivirals remain active against current SARS-CoV-2 variants, and what the future COVID-19 therapeutic landscape looks like. 

COVID-19: It Ain’t Over ’Til It’s Over
Two presentations from the INFORM study group identified risk factors for COVID-19 hospitalization in a large National Health Service database in England. The study period was the calendar year 2022, which coincided with the first omicron waves during a time when much of the population had been vaccinated.

When examining patients with 3 or more COVID-19 vaccine doses, people with immunocompromise accounted for 21.9% of hospitalizations and 23.8% of deaths, despite comprising only 3.9% of the English population. Patients with the highest risk for hospitalization included those who had received stem cell transplants within the prior 2 years or organ transplants within the prior 5 years.

A parallel presentation noted that despite individuals with end-stage renal disease comprising only 0.2% of their study population, they accounted for 2.8% of all COVID-19 hospitalizations and 3.0% of all COVID-19 deaths. Of note, older age and other comorbidities are also likely strong risk factors for developing severe COVID-19.

The patients in this study, recently published in The Lancet Regional Health—Europe, parallel patients who are currently hospitalized at my institution with COVID-19 and the primary groups who suffer from COVID-19‒related consequences in the omicron era.

Therefore, although the overall burden of COVID-19 remains lower in this era of widespread immunity, patients with immunocompromise and patients with end-stage renal disease may benefit the most from preventive and therapeutic COVID-19 strategies. 

Igho Ofotokun, MD, MSc, FIDSA, from Emory University, provided an update on the US-based RECOVER study on long COVID. This presentation reminded me that the largest burden of SARS-CoV-2 has shifted from the inpatient to the outpatient setting, where COVID-19 continues to cause significant morbidity and disability.

I predict that long COVID will be a major topic of discussion at future IDWeek meetings, where further insights will elucidate whether COVID-19 vaccination and/or antivirals may prevent this post-COVID syndrome and perhaps reveal breakthroughs for patients suffering from long-term consequences after other infections.

Insights From Sequencing Omicron: You Can Observe A Lot by Just Watching 
An abstract presented by Zoe M. Raglow, MD, shed light on the SARS-CoV-2 mutation rates in people with immunocompromise who have evidence of prolonged SARS-CoV-2 infection during the omicron era. Embedded in the IVY study across 5 states, investigators enrolled patients with various immunocompromising conditions. Study investigators collected and tested patients’ nasal specimens every 2-4 weeks until these patients tested negative on 2 consecutive specimens.

The bad news is that some patients tested positive for months, particularly those with B-cell dysfunction. This does not surprise me because patients exposed to B-cell‒depleting agents are indeed some of the more clinically challenging patients whom I have encountered.

However, the good news is that the prevalence of prolonged viral shedding overall was fairly low, and only rarely were there mutations associated with resistance or positive viral cultures. It has been hypothesized that novel strains of SARS-CoV-2 with enhanced immune evasion capabilities or resistance to antivirals can arise because of viral mutation in the people with immunocompromise, so these data were reassuring to me because we did not see this occur on a widespread basis.

Other work presented at this conference suggested that resistance mutations associated with reduced susceptibility to protease inhibitors (eg, nirmatrelvir plus ritonavir) and polymerase inhibitors (eg, remdesivir) are not emerging, preserving our most effective therapeutic options.

The Future of COVID-19 Therapeutics: If you don't know where you are going, you might wind up someplace else
Presenters at IDWeek 2023 described agents that may meet future therapeutic needs of people with COVID-19. Ensitrelvir is a novel 3CL protease inhibitor that is already deployed in Japan. Although drug‒drug interactions will still be a concern with this agent, they should be milder than those associated with nirmatrelvir plus ritonavir because of the absence of a boosting agent such as ritonavir.

Obeldesivir—an orally administered polymerase inhibitor—will be welcomed into our arsenal, as well. Other agents are in development that target conserved regions, such as the S2 subunit of the SARS-CoV-2 spike protein. Such agents may be less prone to mutational escape than those targeting the receptor-binding domain, which was the downfall of the original monoclonal antibodies that served us well until the omicron era.

Pharmaceutical manufacturers are developing long-acting monoclonal antibodies that retain activity against current and future SARS-CoV-2 variants to provide passive immunity. This is an important preventive strategy, especially for people who have suboptimal responses to COVID-19 vaccination

The COVID-19 pandemic isn’t over, and more therapeutic options are welcomed—especially if they are safe, efficacious, and accessible from both cost and logistical standpoints. 

Your Thoughts? 
What do you see as the primary COVID-19 obstacle to overcome currently and moving forward? What are the gaps in our COVID-19 therapeutic armamentarium? Join the discussion by posting a comment.