RESUMEN
Coronavirus disease 2019 (COVID-19) has emerged as a serious threat to global health. The disregulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) cell signaling pathway observed in patients with COVID-19 has attracted attention for the possible use of specific inhibitors of this pathway for the treatment of the disease. Here, we review emerging data on the involvement of the PI3K/Akt/mTOR pathway in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the clinical studies investigating its tailored inhibition in COVID-19. Current in silico, in vitro, and in vivo data convergently support a role for the PI3K/Akt/mTOR pathway in COVID-19 and suggest the use of specific inhibitors of this pathway that, by a combined mechanism entailing downregulation of excessive inflammatory reactions, cell protection, and antiviral effects, could ameliorate the course of COVID-19.
Asunto(s)
Antivirales/farmacología , Tratamiento Farmacológico de COVID-19 , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Animales , COVID-19/metabolismo , HumanosRESUMEN
The SARS-CoV-2 virus, first reported in December 2019 in China, is the causative agent of the current COVID-19 pandemic that, at the time of writing (1 November 2020) has infected almost 43 million people and caused the death of more than 1 million people. The spectrum of clinical manifestations observed during COVID-19 infection varies from asymptomatic to critical life-threatening clinical conditions. Emerging evidence shows that COVID-19 affects far more organs than just the respiratory system, including the heart, kidneys, blood vessels, liver, as well as the central nervous system (CNS) and the peripheral nervous system (PNS). It is also becoming clear that the neurological and psychological disturbances that occur during the acute phase of the infection may persist well beyond the recovery. The aim of this review is to propel further this emerging and relevant field of research related to the pathophysiology of neurological manifestation of COVID-19 infection (Neuro-COVID). We will summarize the PNS and CNS symptoms experienced by people with COVID-19 both during infection and in the recovery phase. Diagnostic and pharmacological findings in this field of study are strongly warranted to address the neurological and psychological symptoms of COVID-19.
RESUMEN
The severe acute respiratory syndrome coronavirus 2 (SARSCoV2) is a novel ß coronavirus that is the etiological agent of the pandemic coronavirus disease 2019 (COVID19) that at the time of writing (June 16, 2020) has infected almost 6 million people with some 450,000 deaths. These numbers are still rising daily. Most (some 80%) cases of COVID19 infection are asymptomatic, a substantial number of cases (15%) require hospitalization and an additional fraction of patients (5%) need recovery in intensive care units. Mortality for COVID19 infection appears to occur globally between 0.1 and 0.5% of infected patients although the frequency of lethality is significantly augmented in the elderly and in patients with other comorbidities. The development of acute respiratory distress syndrome and episodes of thromboembolism that may lead to disseminated intravascular coagulation (DIC) represent the primary causes of lethality during COVID19 infection. Increasing evidence suggests that thrombotic diathesis is due to multiple derangements of the coagulation system including marked elevation of Ddimer that correlate negatively with survival. We propose here that the thromboembolic events and eventually the development of DIC provoked by SARSCoV2 infection may represent a secondary antiphospholipid antibody syndrome (APS). We will apply both Baconian inductivism and Cartesian deductivism to prove that secondary APS is likely responsible for coagulopathy during the course of COVID19 infection. Diagnostic and therapeutic implications of this are also discussed.
Asunto(s)
Síndrome Antifosfolípido/patología , Infecciones por Coronavirus/patología , Coagulación Intravascular Diseminada/patología , Neumonía Viral/patología , Tromboembolia/patología , Trombosis/patología , Síndrome Antifosfolípido/inmunología , Antivirales/uso terapéutico , Betacoronavirus , Coagulación Sanguínea/fisiología , COVID-19 , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/inmunología , Coagulación Intravascular Diseminada/inmunología , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Humanos , Pandemias , Fosfolípidos/inmunología , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/inmunología , SARS-CoV-2 , Tromboembolia/inmunologíaRESUMEN
The outbreak of the 2019 coronavirus disease (named, COVID19), caused by the novel SARSCoV2 virus, represents a worldwide severe threat to public health. It is of the utmost importance to characterize the immune responses against the SARSCoV2 and the mechanisms of hyperinflammation, in order to design better therapeutic strategies for COVID19. In the present study, a transcriptomic analysis was performed to profile the immune signatures in lung and the bronchoalveolar lavage fluid samples from COVID19 patients and controls. Our data concordantly revealed increased humoral responses to infection. The elucidation of the host responses to SARSCoV2 infection may further improve our understanding of COVID19 pathogenesis and suggest better therapeutic strategies.