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1.
Nat Commun ; 12(1): 814, 2021 02 05.
Article in English | MEDLINE | ID: covidwho-1065864

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.


Subject(s)
Bevacizumab/therapeutic use , COVID-19/drug therapy , SARS-CoV-2/drug effects , Aged , Angiogenesis Inhibitors/therapeutic use , Body Temperature/drug effects , COVID-19/virology , China , Female , Fever/prevention & control , Humans , Italy , Male , Middle Aged , SARS-CoV-2/physiology , Treatment Outcome
2.
Nat Commun ; 11(1): 6385, 2020 12 14.
Article in English | MEDLINE | ID: covidwho-977267

ABSTRACT

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Immunity, Humoral/drug effects , SARS-CoV-2/drug effects , Adenosine Monophosphate/therapeutic use , Adult , Alanine/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/virology , Fever/prevention & control , Humans , Immunity, Humoral/immunology , Lymphocyte Count , Male , SARS-CoV-2/immunology , SARS-CoV-2/physiology , Treatment Outcome
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