RESUMEN
The emergence of SARS-CoV-2 Omicron variant has led to a complete reconfiguration of the therapeutic landscape, with all monoclonal antibodies having lost any neutralization activity. We report here a case series of 75 immunocompromised patients infected by the Omicron variant who benefited from COVID-19 convalescent plasma (CCP). At Day 28, the overall survival was 76% (95% CI 67-86) with no significant difference in the clinical outcome between patients with hematological malignancies, solid organ transplantation or autoimmune diseases. No safety concern was reported during the course of the study. These results showed that CCP is well tolerated and represents a treatment option for immunocompromised patients who remain highly impacted by the COVID19 epidemic.
Asunto(s)
COVID-19 , Humanos , COVID-19/terapia , Sueroterapia para COVID-19 , SARS-CoV-2 , Inmunización Pasiva , Huésped Inmunocomprometido , Anticuerpos Antivirales/uso terapéutico , Anticuerpos NeutralizantesRESUMEN
We highlighted in this current paper similar prolonged respiratory presentation with COVID-19 pneumonia in four severely immunocompromised patients currently being treated with anti-CD20 monoclonal antibodies (mAbs), such as ocrelizumab and rituximab, for multiple sclerosis or rheumatoid polyarthritis. Real-time reverse transcription-polymerase chain reaction on a nasopharyngeal swab specimen was negative in all patients. SARS-CoV-2 infection was confirmed from bronchoalveolar lavage fluid. A high titer of post-vaccine COVID-19 convalescent plasma was administered with complete recovery in all patients.
Asunto(s)
Antineoplásicos , COVID-19 , Humanos , COVID-19/diagnóstico , COVID-19/terapia , SARS-CoV-2/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sueroterapia para COVID-19 , Anticuerpos Monoclonales/uso terapéutico , Nasofaringe , Anticuerpos Antivirales , Prueba de COVID-19RESUMEN
PATHOGENESIS OF SARS-COV-2 INFECTION COVID-19 follows a rather stereotyped and reproducible course. While the first events are mediated by direct viral toxicity, resolution of the infection relies on a finely tuned immune response. In patients with severe forms, defects of the initial immune response have been reported, including insufficient type 1 interferon production or signaling, attenuated or skewed adaptative immune response, sometimes due to viral immune escape properties. These defects induce an hyperinflammatory state featuring hypersecretion of pro-inflammatory cytokines, excessive recruitment of immune cells in the lungs and parenchymal lesions, responsible for COVID-19 acute respiratory distress syndrome. Thus, COVID-19 is successively a viral and an inflammatory disease. Clarifying the chronology of these viral and immunological mechanisms allows us to identify a therapeutic logic, which sometimes involves contradictory treatments.
PATHOGENÈSE DE L'INFECTION PAR LE SARS-COV-2 L'infection par le SARS-CoV-2 suit une évolution relativement reproductible qu'il est possible de séparer en plusieurs étapes. Si les premières phases de la maladie sont le siège de cytotoxicité virale, les phases évolutives les plus tardives sont essentiellement la conséquence d'une réponse inflammatoire disproportionnée. Toxicité virale et hyperinflammation sont toutefois intimement liées. Les mécanismes d'évasion virale, l'affaiblissement de la réponse interféron et de la réponse immunitaire adaptative concourent à l'hypersécrétion des cytokines inflammatoires. L'infiltration exagérée des poumons par les macrophages, les neutrophiles et les lymphocytes surpasse les mécanismes de réparation tissulaire et conduit au syndrome de détresse respiratoire aiguë. L'infection par le SARS-CoV-2 est donc successivement une maladie virale puis une maladie inflammatoire. Préciser la chronologie de ces mécanismes viraux et immunologiques permet d'en dégager une logique thérapeutique, qui fait intervenir des traitements parfois contradictoires.
Asunto(s)
COVID-19 , SARS-CoV-2 , Citocinas/fisiología , HumanosRESUMEN
As the COVID-19 pandemic is still ongoing, and considering the lack of efficacy of antiviral strategies to this date, and the reactive hyperinflammation leading to tissue lesions and pneumonia, effective treatments targeting the dysregulated immune response are more than ever required. Immunomodulatory and immunosuppressive drugs have been repurposed in severe COVID-19 with contrasting results. The heterogeneity in the timing of treatments administrations could be accountable for these discrepancies. Indeed, many studies included patients at different timepoints of infection, potentially hiding the beneficial effects of a time-adapted intervention. We aim to review the available data on the kinetics of the immune response in beta-coronaviruses infections, from animal models and longitudinal human studies, and propose a four-step model of severe COVID-19 timeline. Then, we discuss the results of the clinical trials of immune interventions with regards to the timing of administration, and finally suggest a time frame in order to delineate the best timepoint for each treatment.
Asunto(s)
Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , COVID-19/terapia , Agentes Inmunomoduladores/administración & dosificación , Inmunosupresores/administración & dosificación , Inmunoterapia , SARS-CoV-2/efectos de los fármacos , Animales , Antivirales/efectos adversos , COVID-19/diagnóstico , COVID-19/inmunología , COVID-19/virología , Esquema de Medicación , Interacciones Huésped-Patógeno , Humanos , Agentes Inmunomoduladores/efectos adversos , Inmunosupresores/efectos adversos , Inmunoterapia/efectos adversos , SARS-CoV-2/inmunología , SARS-CoV-2/patogenicidad , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Artritis Reumatoide , Úlcera de la Córnea , Humanos , Inmunosupresores , Artralgia/etiologíaAsunto(s)
Infecciones Comunitarias Adquiridas , Esofagitis , Gastritis , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Esofagitis/diagnóstico , Exotoxinas , Gastritis/diagnóstico , Gastritis/tratamiento farmacológico , Humanos , Leucocidinas/genética , Reacción en Cadena de la Polimerasa , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológicoRESUMEN
The malaria parasite, Plasmodium, requires iron for growth, but how it imports iron remains unknown. We characterize here a protein that belongs to the ZIP (Zrt-, Irt-like Protein) family of metal ion transport proteins and have named ZIP domain-containing protein (ZIPCO). Inactivation of the ZIPCO-encoding gene in Plasmodium berghei, while not affecting the parasite's ability to multiply in mouse blood and to infect mosquitoes, greatly impairs its capacity to develop inside hepatocytes. Iron/zinc supplementation and depletion experiments suggest that ZIPCO is required for parasite utilization of iron and possibly zinc, consistent with its predicted function as a metal transporter. This is the first report of a ZIP protein having a crucial role in Plasmodium liver-stage development, as well as the first metal ion transporter identified in Plasmodium pre-erythrocytic stages. Because of the drastic dependence on iron of Plasmodium growth, ZIPCO and related proteins might constitute attractive drug targets to fight against malaria.