Efficacy and tolerability of bevacizumab in patients with severe Covid-19

Abstract

On the basis of Covid-19-induced pulmonary pathological and vascular changes, we hypothesize that the anti-vascular endothelial growth factor (VEGF) drug bevacizumab might be beneficial for treating Covid-19 patients. From Feb 15 to April 5, 2020, we conducted a single-arm trial (NCT04275414) and recruited 26 patients from 2-centers (China and Italy) with 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) >100 mmHg and ≤300 mmHg, and diffuse pneumonia confirmed by chest imaging. Followed up for 28 days. Among these, bevacizumab plus standard care markedly improves the PaO2/FiO2 ratios at days 1 and 7. By day 28, 24 (92%) patients show improvement in oxygen-support status, 17 (65%) patients are discharged, and none show worsen oxygen-support status nor die. Significant reduction of lesion areas/ratios are shown in chest computed tomography (CT) or X-ray within 7 days. Of 14 patients with fever, body temperature normalizes within 72 h in 13 (93%) patients. Relative to comparable controls, bevacizumab shows clinical efficacy by improving oxygenation and shortening oxygen-support duration. Our findings suggest bevacizumab plus standard care is highly beneficial for patients with severe Covid-19. Randomized controlled trial is warranted.

Multilevel systems biology analysis of lung transcriptomics data identifies key miRNAs and potential miRNA target genes for SARS-CoV-2 infection

“…ICAM-1, a major cell adhesion molecule modulates the viral replication by inducing the NF-kB protein expression [ 66 ]. VEGF, a proangiogenic factor is known for its involvement in vascular leakiness and inflammation in COVID infected lung tissues [ 67 ]. Our findings confirm the recent miRNA studies in COVID patients [ 68 ] [ 69 ] [ 70 ].…”

A Multidisciplinary Approach to Coronavirus Disease (COVID-19)

“…It inhibits vascular endothelial growth factor A (VEGF-A), and it might be beneficial for treating COVID-19 patients [264]. Bevacizumab shows clinical efficacy by improving oxygenation and shortening oxygen-support duration in recent clinical trials [265].…”

Recent advances in potential drug therapies combating COVID-19 and related coronaviruses-A perspective

“…Preclinical for 2019-nCoV ( Beck et al, 2020 ) Bevacizumab (Avastin) Immunoglobulin G 1 C 6638 H 10160 N 1720 O 2108 S 44 SARS-CoV-2 VEGF inhibitor Approved in clinical oncotherapy Promising drug for COVID-19. Phase 2/3 trials (NCT04275414) ( Pang et al, 2021 ) Carmofur Pyrimidine analogue C 11 H 16 FN 3 O 3 SARS-CoV-2 Inhibits THE protease (M pro ) Induce leukoencephalopathy ( Jin et al, 2020 ) Chloroquine Aminoquinoline C 18 H 26 ClN 3 Broad spectrum: HCoV-229E HCoV-OC43, HIV, Ebola, SARS-CoV, MERS-CoV, SARS-CoV-2 S protein ACE2 inhibitor, Endosomal acidification Approved for malaria. Open-label trial for 2019-nCoV (ChiCTR2000029609) ( Zhang and Liu, 2020 ; Zumla et al, 2016 ) Chloroquine Phosphate Phosphate salt of chloroquine C 18 H 32 ClN 3 O 8 P 2 SARS-CoV-2 Inhibits autophagy and toll-like receptors (TLRs) An antimalarial drug, FDA approved drug for COVID.…”