ABSTRACT
On the basis of Covid-19-induced pulmonary pathological and vascular changes, we hypothesized that the anti-VEGF drug bevacizumab might be beneficial for treating Covid-19 patients. We recruited 26 patients from 2-centers (China and Italy) with confirmed severe Covid-19, with respiratory rate [≥] 30 times/min, oxygen saturation [≤] 93% with ambient air, or partial arterial oxygen pressure to fraction of inspiration O2 ratio (PaO2/FiO2) >100mmHg and [≤] 300 mmHg, and diffuse pneumonia confirmed by chest radiological imaging. This trial was conducted from Feb 15 to April 5, 2020, and followed up for 28 days. Relative to comparable control patients with severe Covid-19 admitted in the same centers, bevacizumab showed clinical efficacy by improving oxygenation and shortening oxygen-support duration. Among 26 hospitalized patients with severe Covid-19 (median age, 62 years, 20 [77%] males), bevacizumab plus standard care markedly improved the PaO2/FiO2 ratios at days 1 and 7 (elevated values, day 1, 50.5 [4.0,119.0], p<0.001; day 7, 111.0 [85.0,165.0], p<0.001). By day 28, 24 (92%) patients showed improvement in oxygen-support status, 17 (65%) patients were discharged, and none showed worsen oxygen-support status nor died. Significant reduction of lesion areas and ratios were shown in chest CT or X-ray analysis within 7 days. Of 14 patients with fever, body temperature normalized within 72 hours in 13 (93%) patients. Lymphocyte counts in peripheral blood were significantly increased and CRP levels were markedly decreased as shown in available data. Our findings suggested bevacizumab plus standard care was highly beneficial for treating patients with severe Covid-19. Clinical efficacy of bevacizumab warrants double blind, randomized, placebo-controlled trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04275414, URL: https://clinicaltrials.gov/ct2/show/NCT04275414.