Bevacizumab in post-acute sequelae of COVID-19 : Efficacy and Safety (PilotStudy)

"In over 25% of cases of persistent dyspnea after COVID-19, an impaired diffusing capacity for carbon monoxide (DLCO) is observed. Our hypothesis is an uncontrolled angiogenic process that could give rise to respiratory dysfunction (1,2). We previously longitudinally assessed DLCO measurements in a cohort of long COVID patients at three time points: 1 month, 3 months, and 28 months post-initial COVID-19 diagnosis. DLCO, a critical measure of gas exchange efficiency in the lungs, serves as a proxy for pulmonary function. Our findings indicate a very low improvement in pulmonary function among long COVID patients, as evidenced by low increases in DLCO. Specifically, a comparison between 1 and 3 months post-diagnosis revealed a 5.6% increase in DLCO (95% CI: 0.2% to 10.9%). Furthermore, the analysis between 3 and 28 months demonstrated an additional 6.2% increase in DLCO (3). The observed enhancements in DLCO over time provide a low recovery for long COVID patients. Here we propose a pilot study using intravenous (IV) injection of bevacizumab in patients with impaired DLCO after COVID-19 infection. Our hypothesis is that IV bevacizumab during two months will be associated with an increase in the pulmonary function test evaluated by DLCO without side-effects. The main objective of this trial is to assess efficacy of bevacizumab injection in control of impaired DLCO (<75% of predicted value) within 3 months after the first bevacizumab injection. The positive criteria will be a 10% increase in DLCO or a normalized DLCO exceeding 75% at three months after the introduction of bevacizumab. The secondary objectives are to evaluate: • Modification of clinical evaluation at 1, 2, 3 and 6 months and in particular the clinical symptom of dyspnea and fatigue (evaluated by the mMRC dyspnea scale, Borg Scale, Epworth Sleepiness Scale, WHODAS 2.0), or other related clinical parameters of long-COVID patients. • Modification of other respiratory function markers: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, total lung capacity (TLC), residual volume (RV), and 6 minute walking distance at 1, 2 and 3-months after the initiation of Bevacizumab treatment. Modification of DLCO will also be evaluated at 1 and 2 months. • Decrease of circulating biomarkers of angiogenesis disorders or endotheliopathy at 1, 2 and 3 months after the initiation of Bevacizumab treatment. • Safety of bevacizumab in long-COVID patients during the 6 months of follow-up. "