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

Affiliation

Pang J(#)(1), Xu F(#)(1)(2)(3), Aondio G(#)(4), Li Y(5), Fumagalli A(4), Lu M(2), Valmadre G(4), Wei J(6), Bian Y(1), Canesi M(7), Damiani G(8), Zhang Y(2), Yu D(9), Chen J(10), Ji X(5), Sui W(3), Wang B(2), Wu S(1), Kovacs A(11), Revera M(12), Wang H(13), Jing X(1), Zhang Y(1), Chen Y(14)(15)(16), Cao Y(17).
Author information:
(1)Department of Emergency Medicine, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, Shandong, China.
(2)Clinical Research Center of Shandong University, Jinan, Shandong, China.
(3)Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Jinan, Shandong, China.
(4)Department of Medicine and Oncology, Moriggia-Pelascini Hospital, Gravedona ed Uniti, Gravedona, Italy.
(5)Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.
(6)Department of Emergency Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
(7)Department of Neurological Rehabilitation, Moriggia-Pelascini Hospital, Gravedona ed Uniti, Gravedona, Italy.
(8)Department of Radiology, Moriggia-Pelascini Hospital, Gravedona ed Uniti, Gravedona, Italy.
(9)Department of Radiology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
(10)Department of Radiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
(11)Department of Intensive Care Unit, Moriggia-Pelascini Hospital, Gravedona ed Uniti, Gravedona, 22015, Italy.
(12)Department of Cardiology, Moriggia-Pelascini Hospital, Gravedona ed Uniti, Gravedona, 22015, Italy.
(13)Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China.
(14)Department of Emergency Medicine, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, Shandong, China. [Email]
(15)Clinical Research Center of Shandong University, Jinan, Shandong, China. [Email]
(16)Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Jinan, Shandong, China. [Email]
(17)Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, 17177, Sweden. [Email]
(#)Contributed equally

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.