Conference Coverage

Are Cytokines Such As IL-6 Associated With Post-COVID Conditions?

Yuriko Fukuta, MD, PhD

Although female sex and older age have been previously reported as risk factors for post-COVID conditions, and high IL-6 and C-reactive protein are associated with more severe COVID-19 infections, it remains unclear whether other cytokines are associated with post-COVID conditions. 

In their study, Yuriko Fukuta, MD, PhD, and her research team evaluated the risk factors, including cytokines, associated with post-COVID conditions. Dr Fukuta presented her research team's findings at IDWeek 2023 in Boston, MA.

Fukuta Y, Gebo K, Heath S, Zhu X, Tobian A, Sullivan D, et al. 
Risk of post-COVID conditions correlates with IL-6 plasma levels and is reduced by early antibody therapy. Paper presented at IDWeek 2023.

Consultant360: Please provide an overview of your presentation at IDWeek 2023 entitled, “Risk of Post-COVID Conditions Correlates with IL-6 Plasma Levels and Is Reduced by Early Antibody Therapy.”

Yuriko Fukuta, MD, PhD: This study evaluated the risk factors including cytokines associated with post-COVID conditions. It showed elevated baseline interleukin (IL)-6, female sex, and age 50 or older were associated with the development of post-COVID conditions and early COVID-19 convalescent plasma treatment lowered odds of post-COVID conditions significantly. 

Consultant360: Why is the risk of post-COVID conditions, especially cytokines, important to study at this time?

Dr Fukaua: The CDC reported that the prevalence of long COVID ranged from 6% to 18.9% and approximately 25% of people with long COVID had significant activity limitations. No specific treatment has been established yet.

Previous studies showed older age, female sex, and comorbidities as risk factors for post-COVID conditions. However, no study has evaluated the association between cytokines and COVID-19. In looking for potential therapeutic options, understanding the pathophysiology of post-COVID conditions is very important. 

Consultant360: What were the results of your study?

Dr Fukuta: More participants 50 years of age or older (40.1% vs. 30.8%, p < 0.001), more female participants (70.2% vs. 51%, p < 0.001), more participants with BMI of 30+ (41% vs. 33.9%, p = 0.042), and more participants with diabetes (11% vs. 6.8%, p = 0.045) were found in the post-COVID condition group compared with the non-post-COVID condition group. At day 90, 292 (33.1%) participants had post-COVID conditions. The most common symptoms were fatigue (14.5%), anosmia (14.5%), and ageusia (10%). Our research also showed that the levels of most cytokines decreased over time. Five cytokines among 16, especially IL-6, were elevated at baseline. In multivariable analysis, female sex (adjusted odds ratio [AOR] = 2.70 [1.93-3.81]), age 50 or older (AOR = 1.32 [1.17-1.50]), and elevated baseline IL-6 (AOR = 1.59 [1.02-2.47]) were associated with the development of post-COVID conditions.

Comparison of Cytokines at Screening Between Study Participants With PCC and Without PCC

Figure 1. Comparison of Cytokines at Screening Between Study Participants With PCC and Without PCC

Consultant360: How does the study contribute to existing literature on this topic?

Dr Fukuta: It is very interesting that previous studies found that high levels of IL-6 and C-reactive protein were associated with more severe COVID-19 infection, and our study showed elevated IL-6 at baseline was also associated with post-COVID conditions. 

IL-6 is a prototype cytokine, and it plays a major role in host defense. It is produced rapidly when infection and tissue damage occur. When SARS-CoV-2 infects the upper and lower respiratory tracts, it may induce the release of pro-inflammatory cytokines including IL-6, which can result in hyperinflammation and its subsequent severe organ damage. The FDA approved tocilizumab, an IL-6 modulator, for the treatment of in-patients with severe COVID-19. Our study results suggest the possibility that early treatment of IL-6 modulation could reduce post-COVID-19 conditions. 

Consultant360: What are the gaps in the research, and what’s next for research on this topic?

Dr Fukuta: Our study suggested the potential of early treatment to IL-6 modulation to reduce post-COVID-19 conditions, however, no clinical trial has been conducted yet on this. Future studies might evaluate the impact of anti-IL-6 agents and the development of post-COVID-19 conditions among outpatients. 

Consultant360: What are the overall take-home messages from this study and from our conversation today?

Dr Fukuta: Although the federal COVID-19 public health emergency declaration ended and life has mostly returned to normal, people still get infected with COVID-19 and there are substantial numbers of people who continue to suffer from post-COVID-19 conditions. We should continue updating COVID-19 information because it helps us provide good quality patient care. 

Consultant360: Is there anything else you’d like to add?

Dr Fukuta: I believe most Consultant360 readers are aware that the current COVID-19 vaccination rate is low. Although I understand people get less interested in vaccination, it is still the most important way to prevent COVID-19 and subsequent post-COVID-19 conditions. I would ask that we keep encouraging our patients to get vaccinated to help the community.