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

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.