RESUMEN
It has been suggested that some individuals may present genetic susceptibility to SARS-CoV-2 infection, with particular research interest in variants of the ACE2 and TMPRSS2 genes, involved in viral penetration into cells, in different populations and geographic regions, although insufficient information is currently available. This study addresses the apparently reasonable hypothesis that variants of these genes may modulate viral infectivity, making some individuals more vulnerable than others. Through whole-exome sequencing, the frequency of exonic variants of the ACE2, TMPRSS2, and Furin genes was analyzed in relation to presence or absence of SARS-CoV-2 infection in a familial multiple sclerosis cohort including 120 individuals from Madrid. The ACE2 gene showed a low level of polymorphism, and none variant was significantly associated with SARS-CoV-2 infection. These variants have previously been detected in Italy. While TMPRSS2 is highly polymorphic, the variants found do not coincide with those described in other studies, with the exception of rs75603675, which may be associated with SARS-CoV-2 infection. The synonymous variants rs61735792 and rs61735794 showed a significant association with infection. Despite the limited number of patients with SARS-CoV-2 infection, some variants, especially in TMPRSS2, may be associated with COVID-19.
Asunto(s)
Enzima Convertidora de Angiotensina 2/genética , COVID-19/genética , Furina/genética , Esclerosis Múltiple/genética , Receptores Virales/genética , Serina Endopeptidasas/genética , Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/metabolismo , COVID-19/virología , Estudios de Cohortes , Furina/metabolismo , Expresión Génica , Predisposición Genética a la Enfermedad , Interacciones Huésped-Patógeno/genética , Humanos , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/virología , Polimorfismo Genético , Unión Proteica , Receptores Virales/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidad , Serina Endopeptidasas/metabolismo , España , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , Encuestas y Cuestionarios , Internalización del Virus , Secuenciación del ExomaRESUMEN
We aimed to evaluate the frequency and mortality of COVID-19 in patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD). We conducted an observational case series. We enrolled 204 patients, 15.2% of whom were diagnosed with COVID-19, and 41.9% of patients with the infection died. Patients with AD were older than patients with FTD (80.36±8.77 versus 72.00±8.35 years old) and had a higher prevalence of arterial hypertension (55.8% versus 26.3%). COVID-19 occurred in 7.3% of patients living at home, but 72.0% of those living at care homes. Living in care facilities and diagnosis of AD were independently associated with a higher probability of death. We found that living in care homes is the most relevant factor for an increased risk of COVID-19 infection and death, with AD patients exhibiting a higher risk than those with FTD.
Asunto(s)
Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/mortalidad , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/mortalidad , Demencia Frontotemporal/complicaciones , Demencia Frontotemporal/mortalidad , Neumonía Viral/complicaciones , Neumonía Viral/mortalidad , Factores de Edad , Anciano , Anciano de 80 o más Años , COVID-19 , Femenino , Humanos , Hipertensión/complicaciones , Vida Independiente , Masculino , Casas de Salud , Pandemias , Prevalencia , Factores de RiesgoRESUMEN
BACKGROUND: Management of disease-modifying therapies in Multiple Sclerosis (MS) during the COVID-19 pandemic is a controversial issue. Alemtuzumab is an immunosuppressive drug that induces lymphocytes depletion. In this study, we aimed to evaluate the frequency and severity of COVID-19 in a case series of patients treated with alemtuzumab in our center. METHODS: Ten patients with a diagnosis of relapsing-remitting MS were phoned and asked about symptoms suggestive and COVID-19 using a semi-structured questionnaire. RESULTS: The mean age was 43.7 ± 9.65 years old, and 8 (80%) were females. The mean time since disease diagnosis was 17.30 ± 8.59 years, and all were patients with relapsing-remitting MS. Mean time from the last dose of Alemtuzumab was 9.80 ± 6.64 months, and last lymphocyte count was 760 ± 231 / µL. Two patients (20%) developed symptoms highly suggestive of COVID-19. Disease duration was 2 and 7 days. None patient required hospital admission. Patients with COVID-19 symptoms had longer clinical course of MS. Conversely, we did not find statistically significant differences regarding age, EDSS, last lymphocyte count, and months since the last dose of alemtuzumab administered between patients having or not symptoms of COVID-19. CONCLUSIONS: Our data suggest that patients receiving alemtuzumab showed very mild symptoms of COVID-19. We speculate that immune reconstitution induced by treatment may induce positive changes in the immune system in the defense against SARS-CoV2. Further research about alemtuzumab and their role in COVID-infection is necessary to confirm these preliminary findings.