Extracorporeal photopheresis in the treatment of the novel coronavirus disease COVID-19 (a case series)

Abstract

Rationale : Most people infected with SARS-CoV-2 have asymptomatic or minor clinical manifestations and recover without any aggressive therapy. However, there are patient categories in need of specific treatment and those at high risk of severe disease. Control of viremia with antiviral therapy may not be the best therapeutic strategy, since, in addition to substantial toxicity, antiviral agents can suppress the production of antiviral antibodies and disintegrate adoptive immunity against SARS-CoV-2. Due to a high correlation between the symptoms severity in patients with COVID-19 and inflammation, anti-inflammatory corticosteroids have been proposed to treat the disease. However, clinical data do not support the systemic administration of corticosteroids for the treatment of patients with severe COVID-19. Such treatment may have a negative effect due to suppression of the adoptive immune system. In this regard, the development or use of already available of agents that modulate inflammation without compromising the adoptive immune response could be the most effective therapeutic strategy. Aim: To evaluate clinical efficacy and safety of the cell biotherapy technique, the extracorporeal photopheresis (ECP), in the treatment of patients with moderately severe new coronavirus disease COVID-19. Materials and methods : The study included four patients (three women and one man, age 42 to 60 years), with SARS-CoV-2 infection confirmed by gene amplification. All patients had CT-confirmed bilateral multisegmental viral pneumonia (grades > 2, i.e. with 25 to 60% involvement of the lungs). Prior to admission, all patients received antibiotics (azithromycin 500 mg daily and levo-floxacin / amoxicillin clavulanate 500 mg BID) and antipyretics for torpid fever of up to 38.5-39 °C. The outpatient treatment lasted for 8 to 14 days, with signs of progressive respiratory failure. In addition to the moderately severe and torpid course of viral pneumonia, three patients showed hematology test abnormalities, such as hypochromic anemia, leukopenia, leukopenia/lymphopenia, and moderate thrombocytopenia. Three patients had high C-reactive protein (CRP) levels. Inpatient treatment consisted of azithromycin 500 mg daily, levofloxacin 500 mg BID, hydroxychloroquine 200 mg BID, and low molecular weight heparin (enoxaparin 0.4 ml, 4000 anti-Xa IU, s.c. BID). Despite the treatment, the patients showed signs of progressive respiratory failure, with increasing dyspnea and gradual decrease in saturation from 96% to 92%. Isolation of peripheral blood mononuclear cells was done in an intermittent blood separator "Haemonetics MCS+” (USA), with subsequent cell irradiation with an extracorporeal blood irradiator (OKUFKE 320/400-600/650-01 "Yulia”, ZAO NPKF "METOM”, Russia). Ammifurin (ZAO "Pharmcenter VILAR”, Russia) was used as a photosensitizer. Three patients had two ECP sessions with an interval of 24 hours, and one patient had one ECP session. Results: In three patients who had received two ECP sessions, there was a regression of radiographic signs of viral pneumonia from CT2 to CT1 (less than 25% of lung tissue involvement) during the next four days (96 hours). In one patient, the follow-up CT showed resolving pneumonia with less than 5% involvement of the lungs. The patients (n = 3) with baseline high CRP levels showed their normalization at 4 days after two ECP sessions. At 24 hours after a single ECP session, leukocyte count and differential, as well as platelets were restored. In three patients, viral RNA tests within 2 to 4 days after ECP were negative. These results were associated with normalization of body temperature, no further progression of respiratory failure, and a reduction in hospital stay. Conclusion: The use of ECP in 4 patients with moderately severe SARS-CoV-2 infection has contributed to the rapid relief of clinical symptoms, resolution of the inflammation and restoration of respiratory abnormalities in all of them. These observations allow us to consider ECP as an effective and safe method of treatment for moderately severe COVID-19 and a promising adjuvant method in the high-risk patients in order to prevent an unfavorable disease outcome.