Pro Inflammatory Cytokines Profiles of Patients With Long COVID Differ Between Variant Epochs

Area of Science:

• Immunology
• Infectious Diseases
• Virology

Background:

• Long COVID affects over 30% of COVID-19 patients, presenting persistent symptoms beyond 30 days.
• Elevated peripheral cytokines, including IL-6, IL-1β, and TNF-α, are linked to Long COVID.
• SARS-COV-2 variants have emerged, potentially influencing disease progression and outcomes.

Purpose of the Study:

• To investigate cytokine profiles in Long COVID patients.
• To analyze these profiles across different SARS-COV-2 variant epochs.
• To determine if cytokine signatures correlate with specific variants or epochs.

Main Methods:

• Clinical cytokine panels were analyzed in 390 Long COVID patients.
• Patients were stratified into four variant epochs: wild-type/alpha, alpha/beta/gamma, delta, and omicron.
• Time to cytokine testing and specific cytokine levels were compared across epochs.

Main Results:

• Tumor necrosis factor-α and interleukin-1β were significantly more elevated in earlier variant epochs (wild-type/alpha) compared to the omicron epoch.
• The time to cytokine panel testing was longer for earlier epochs.
• Nucleocapsid antibodies were consistently detected across all epochs.

Conclusions:

• Early epoch Long COVID patients exhibit persistently elevated pro-inflammatory cytokine levels compared to later epochs.
• Long COVID symptom clusters appear consistent across variant epochs.
• The underlying pathology of Long COVID may be independent of peripheral cytokine signatures, suggesting a complex multifactorial etiology.