Extracorporeal Photopheresis as a Possible Therapeutic Approach to Adults With Severe and Critical COVID-19

A prospective, single-center investigational study is olanned to be performed at a tertiary referral center for COVID-19. Patients with COVID-19 are screened, and severe or critical COVID-19 cases fulfilling pre-defined clinical and biochemical criteria of non-response for >5 days despite remdesivir, dexamethasone and immunomodulation (tocilizumab, baricitinib, ruxolitinib) are consecutively enrolled. After inclusion, two ECP sessions on two consecutive days per week for 2 weeks are applied. Patients are followed up per protocol from study inclusion, and clinical, virological and radiological outcomes are assessed at end-of-treatment (EOT)+28 days.

Hospitalized adult (≥18 years at diagnosis) patients with diagnosed COVID-19 of any illness duration are eligible, and screened for inclusion during daily on-site investigator visits. Patients are consecutively enrolled.

Inclusion criteria

• severe or critical COVID-19,
• clinical and biochemical non-response for >5 consecutive days, despite remdesivir, dexamethasone and immunomodulatory therapies (tocilizumab, baricitinib or ruxolitinib), with or without COVID-19 reconvalescent plasmatherapy, in absence of other causes.

Exclusion criteria

• pregnancy or breastfeeding,
• allergy or contraindications to 8-methoxypsoralen,
• pre-COVID-19 ECP,
• written informed consent was not obtainable.

Clinical non-response is defined when ≥2 of the following are met, compared to baseline:

• persistent fever (non-contact tympanal measurement of >38.0°C) for ≥48 hours, despite antipyretics,
• persistent or failing COVID-19 severity, according to World Health Organization criteria, by ≥1 stratum after ≥48 hours,
• persistent or failing partial arterial oxygen tension (PaO2) / inspired oxygen fraction (FiO2), by ≥10% after ≥48 hours, despite respiratory support,
• radiological progression by infiltrate extension on chest computed tomography (CT), by ≥10% after ≥48 hours,
• novel requirement of invasive mechanical ventilation, as deemed necessary by an intensive care unit (ICU) team.

Biochemical non-response is defined when ≥2 of the following analytes show persistent or increasing levels by ≥20% after ≥48 hours, compared to baseline:

• serum lactate dehydrogenase (LDH),
• serum C-reactive protein (CRP),
• serum ferritin
• plasma interleukin-6 (IL-6),
• D-dimer.