RESUMEN
COVID-19 might lead to multi-organ failure and, in some cases, to death. The COVID-19 severity is associated with a "cytokine storm." Danger-associated molecular patterns (DAMPs) are proinflammatory molecules that can activate pattern recognition receptors, such as toll-like receptors (TLRs). DAMPs and TLRs have not received much attention in COVID-19 but can explain some of the gender-, weight- and age-dependent effects. In females and males, TLRs are differentially expressed, likely contributing to higher COVID-19 severity in males. DAMPs and cytokines associated with COVID-19 mortality are elevated in obese and elderly individuals, which might explain the higher risk for severer COVID-19 in these groups. Adenosine signaling inhibits the TLR/NF-κB pathway and, through this, decreases inflammation and DAMPs' effects. As vaccines will not be effective in all susceptible individuals and as new vaccine-resistant SARS-CoV-2 mutants might develop, it remains mandatory to find means to dampen COVID-19 disease severity, especially in high-risk groups. We propose that the regulation of DAMPs via adenosine signaling enhancement might be an effective way to lower the severity of COVID-19 and prevent multiple organ failure in the absence of severe side effects.
Asunto(s)
Alarminas/inmunología , COVID-19/fisiopatología , Mediadores de Inflamación/inmunología , Adenosina/metabolismo , Alarminas/antagonistas & inhibidores , Animales , COVID-19/complicaciones , COVID-19/inmunología , COVID-19/terapia , Humanos , Inflamación/prevención & control , Mediadores de Inflamación/antagonistas & inhibidores , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/prevención & control , Gravedad del Paciente , Transducción de Señal , Receptores Toll-Like/antagonistas & inhibidores , Receptores Toll-Like/inmunologíaAsunto(s)
Antiinflamatorios/uso terapéutico , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/prevención & control , Dexametasona/uso terapéutico , Inmunosupresores/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Alarminas/antagonistas & inhibidores , Alarminas/genética , Alarminas/inmunología , Betacoronavirus/inmunología , COVID-19 , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/patología , Síndrome de Liberación de Citoquinas/virología , Esquema de Medicación , Humanos , Inmunidad Innata/efectos de los fármacos , Pandemias , Neumonía Viral/inmunología , Neumonía Viral/patología , Neumonía Viral/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptores de Glucocorticoides/antagonistas & inhibidores , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/inmunología , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
COVID-19 is a pandemic disease caused by the new coronavirus SARS-CoV-2 that mostly affects the respiratory system. The consequent inflammation is not able to clear viruses. The persistent excessive inflammatory response can build up a clinical picture that is very difficult to manage and potentially fatal. Modulating the immune response plays a key role in fighting the disease. One of the main defence systems is the activation of neutrophils that release neutrophil extracellular traps (NETs) under the stimulus of autophagy. Various molecules can induce NETosis and autophagy; some potent activators are damage-associated molecular patterns (DAMPs) and, in particular, the high-mobility group box 1 (HMGB1). This molecule is released by damaged lung cells and can induce a robust innate immunity response. The increase in HMGB1 and NETosis could lead to sustained inflammation due to SARS-CoV-2 infection. Therefore, blocking these molecules might be useful in COVID-19 treatment and should be further studied in the context of targeted therapy.