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

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: 1. severe or critical COVID-19, 2. 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: 1. pregnancy or breastfeeding, 2. allergy or contraindications to 8-methoxypsoralen, 3. pre-COVID-19 ECP, 4. written informed consent was not obtainable. Clinical non-response is defined when ≥2 of the following are met, compared to baseline: 1. persistent fever (non-contact tympanal measurement of \>38.0°C) for ≥48 hours, despite antipyretics, 2. persistent or failing COVID-19 severity, according to World Health Organization criteria, by ≥1 stratum after ≥48 hours, 3. persistent or failing partial arterial oxygen tension (PaO2) / inspired oxygen fraction (FiO2), by ≥10% after ≥48 hours, despite respiratory support, 4. radiological progression by infiltrate extension on chest computed tomography (CT), by ≥10% after ≥48 hours, 5. 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: 1. serum lactate dehydrogenase (LDH), 2. serum C-reactive protein (CRP), 3. serum ferritin 4. plasma interleukin-6 (IL-6), 5. D-dimer.