Background/Purpose: Severe and life threating COVID-19 pneumonia is often characterized by local and systemic immune-mediated hyperinflammation At the early disease stage activated monocytes are migrating to the lung and cause the typical opac infiltrates, which lead to an reduction of oxygen uptake. This was the rationale use this combination anti-inflammatory drugs in severe Covid-19 disease. Interleukin (IL)-6 and IL-1 blockade alone, respectively showed contradictory results in severe COVID-19 pneumonia that might be related to the differences is patient populations (early vs. late stage) and to the fact that blockade of just one cytokine might be not sufficient against the cytokine storm. Here we report results of an open-label treatment with a combination of an IL-6 receptor blocker tocilizumab and an IL-1 receptor antagonist anakinra in patients with early (up to 10 days since symptom onset) severe COVID-19 pneumonia with evidence of cytokine release.

Methods: Adult patients with, according to WHO criteria, severe to critical COVID-19 infection associated pneumonia and cytokine release, requiring oxygen supplementation and evidence of rapid deterioration and decrease of oxygen saturation to ≤ 95% hospitalized between May 2020 and April 2021 were treated with tocilizumab 8 mg/ kg up to 800 mg intravenously and anakinra 100 to 300 mg for 3 to 5 days, starting at the same day. We excluded patients with a symptom duration of > 10 days, patients with evidence of bacterial infection, indicated by an elevated procalcitonin serum level, patients with severe pre-existing lung disease such as severe COPD or heart failure of > II according to the NYHA classification and patients > 80 years. Laboratory parameters and chest CT were performed before and one month after treatment. A semi-quantitative CT score was calculated based on the extent of lobar pneumonia involvement (0:0%; 1, < 5%; 2:5-25%; 3:26-50%; 4:51-75%; 5, > 75%; range 0-5; global score 0-25) for each time point. All patients were informed about the off label use in reference to the statement of the German Robert Koch Institute regarding therapies in “off label use” in COVID-19 patients after carefull consideration of the individual risk-benefit ratio and written individual consents were obtained.

Results: Thirty-one adult patients with severe COVID-19 pneumonia and signs of cytokine release, mean age 54 (30-79) years, 5 female, 26 male, mean symptom duration 6 (3-10) days, were treated. Patients with more than > 10 days of symptoms, evidence of bacterial infection/ elevated procalcitonin and other severe lung diseases were excluded. Computed tomography (CT) scans of the lung were performed initially and after one month; inflammatory activity was assessed on a scale 0 to 25. Twenty-five patients survived without intubation and mechanical lung ventilation, two patients died. C-reactive protein decreased in 19/31 patients to normal ranges. The mean activity CT score decreased from 14 (8-20) to 6 (0-16, n=16).

Conclusion: In conclusion, most of our patients recovered fast and sustained, indicating that early interruption of cytokine release might be very effective in preventing patients from mechanical ventilation, death and long-term damage.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/successful-treatment-of-severe-covid-19-pneumonia-with-simultaneous-tocilizumab-and-anakinra-a-case-series/