An open label trial of anakinra to prevent respiratory failure in COVID-19.
Background
It was studied if early suPAR-guided anakinra treatment can prevent severe respiratory failure (SRF) of COVID-19.


Methods
A total of 130 patients with suPAR ≥6 ng/ml were assigned to subcutaneous anakinra 100 mg once daily for 10 days. Primary outcome was SRF incidence by day 14 defined as any respiratory ratio below 150 mmHg necessitating mechanical or non-invasive ventilation. Main secondary outcomes were 30-day mortality and inflammatory mediators; 28-day WHO-CPS was explored. Propensity-matched standard-of care comparators were studied.


Results
22.3% with anakinra treatment and 59.2% comparators (hazard ratio, 0.30; 95% CI, 0.20-0.46) progressed into SRF; 30-day mortality was 11.5% and 22.3% respectively (hazard ratio 0.49; 95% CI 0.25-0.97). Anakinra was associated with decrease in circulating interleukin (IL)-6, sCD163 and sIL2-R; IL-10/IL-6 ratio on day 7 was inversely associated with SOFA score; patients were allocated to less severe WHO-CPS strata.


Conclusions
Early suPAR-guided anakinra decreased SRF and restored the pro-/anti-inflammatory balance.


Funding
This study was funded by the Hellenic Institute for the Study of Sepsis, Technomar Shipping Inc, Swedish Orphan Biovitrum, and the Horizon 2020 Framework Programme.


Clinical trial number
NCT04357366.
['Kyriazopoulou|Evdoxia|E|0000-0002-9585-517X', 'Panagopoulos|Periklis|P|', 'Metallidis|Symeon|S|', 'Dalekos|George N|GN|', 'Poulakou|Garyphallia|G|', 'Gatselis|Nikolaos|N|', 'Karakike|Eleni|E|', 'Saridaki|Maria|M|', 'Loli|Georgia|G|', 'Stefos|Aggelos|A|', 'Prasianaki|Danai|D|', 'Georgiadou|Sarah|S|', 'Tsachouridou|Olga|O|', 'Petrakis|Vasileios|V|', 'Tsiakos|Konstantinos|K|', 'Kosmidou|Maria|M|0000-0002-8618-9435', 'Lygoura|Vassiliki|V|', 'Dareioti|Maria|M|', 'Milionis|Haralampos|H|', 'Papanikolaou|Ilias C|IC|', 'Akinosoglou|Karolina|K|', 'Myrodia|Dimitra-Melia|DM|', 'Gravvani|Areti|A|', 'Stamou|Aliki|A|', 'Gkavogianni|Theologia|T|', 'Katrini|Konstantina|K|', 'Marantos|Theodoros|T|', 'Trontzas|Ioannis P|IP|', 'Syrigos|Konstantinos|K|', 'Chatzis|Loukas|L|0000-0002-2832-0116', 'Chatzis|Stamatios|S|', 'Vechlidis|Nikolaos|N|', 'Avgoustou|Christina|C|', 'Chalvatzis|Stamatios|S|', 'Kyprianou|Miltiades|M|', 'van der Meer|Jos Wm|JW|', 'Eugen-Olsen|Jesper|J|', 'Netea|Mihai G|MG|', 'Giamarellos-Bourboulis|Evangelos J|EJ|0000-0003-4713-3911']
D000368:Aged D000369:Aged, 80 and over D000893:Anti-Inflammatory Agents D015703:Antigens, CD D015214:Antigens, Differentiation, Myelomonocytic D000086382:COVID-19 D005260:Female D006801:Humans D015994:Incidence D007279:Injections, Subcutaneous D053590:Interleukin 1 Receptor Antagonist Protein D016753:Interleukin-10 D015850:Interleukin-6 D008297:Male D008875:Middle Aged D011956:Receptors, Cell Surface D055293:Receptors, Urokinase Plasminogen Activator D012121:Respiration, Artificial D012131:Respiratory Insufficiency D000086402:SARS-CoV-2 D059039:Standard of Care D016896:Treatment Outcome
anakinra COVID-19 severe respiratory failure suPAR SARS-CoV-2 human immunology inflammation interleukin-10 medicine