Therapeutic plasma exchange accelerates immune cell recovery in severe COVID-19.

Summary

In a registered randomized clinical trial, adding therapeutic plasma exchange to standard care in severe COVID-19 reduced anti-type I IFN autoantibodies and inflammatory mediators and improved lymphopenia and T-cell dysfunction. While ARDS parameters did not improve overall, a subset of patients with early favorable respiratory outcomes showed enhanced virus-specific T-cell responses.

Key Findings

• TPE reduced anti-type I IFN autoantibodies and circulating inflammatory mediators (e.g., IL-18, IL-7, CCL2, CCL3).
• TPE did not change ARDS parameters across the protocol compared with standard treatment.
• TPE reversed lymphopenia, prevented T-cell hyperactivation, reduced T-cell exhaustion, and increased memory and virus-specific T cells in patients with early favorable respiratory outcomes.

Clinical Implications

TPE should not be expected to improve ARDS metrics acutely but may be considered in biomarker-selected severe COVID-19 to reverse lymphopenia and T-cell exhaustion, particularly in patients with anti-type I IFN autoantibodies.

Limitations

• Sample size and blinding details are not provided in the abstract; likely underpowered for clinical outcomes.
• Lack of improvement in ARDS physiological parameters limits immediate clinical adoption.

Future Directions

Conduct larger, blinded RCTs stratified by anti-IFN autoantibody status to test whether immune recovery translates into improved clinical outcomes and to define optimal timing and dosing of TPE.