RESUMEN
Mounting evidence suggests that the gut-to-lung axis is critical during respiratory viral infections. We herein hypothesized that disruption of gut homeostasis during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may associate with early disease outcomes. To address this question, we took advantage of the Syrian hamster model. Our data confirmed that this model recapitulates some hallmark features of the human disease in the lungs. We further showed that SARS-CoV-2 infection associated with mild intestinal inflammation, relative alteration in intestinal barrier property and liver inflammation and altered lipid metabolism. These changes occurred concomitantly with an alteration of the gut microbiota composition over the course of infection, notably characterized by a higher relative abundance of deleterious bacterial taxa such as Enterobacteriaceae and Desulfovibrionaceae. Conversely, several members of the Ruminococcaceae and Lachnospiraceae families, including bacteria known to produce the fermentative products short-chain fatty acids (SCFAs), had a reduced relative proportion compared to non-infected controls. Accordingly, infection led to a transient decrease in systemic SCFA amounts. SCFA supplementation during infection had no effect on clinical and inflammatory parameters. Lastly, a strong correlation between some gut microbiota taxa and clinical and inflammation indices of SARS-CoV-2 infection severity was evidenced. Collectively, alteration of the gut microbiota correlates with disease severity in hamsters making this experimental model valuable for the design of interventional, gut microbiota-targeted, approaches for the control of COVID-19.Abbreviations: SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; COVID-19, coronavirus disease 2019; SCFAs, short-chain fatty acids; dpi, day post-infection; RT-PCR, reverse transcription polymerase chain reaction; IL, interleukin. ACE2, angiotensin converting enzyme 2; TMPRSS2, transmembrane serine protease 2.
Asunto(s)
COVID-19/microbiología , COVID-19/fisiopatología , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Mesocricetus , Animales , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/metabolismo , COVID-19/patología , Cricetinae , Ácidos Grasos Volátiles/administración & dosificación , Ácidos Grasos Volátiles/metabolismo , Humanos , Masculino , SARS-CoV-2/fisiología , Índice de Severidad de la Enfermedad , Tratamiento Farmacológico de COVID-19RESUMEN
BACKGROUND: Although human airway epithelial cells are the main target of respiratory syncytial virus (RSV), it also infects immune cells, such as macrophages and B cells. Whether T cells are permissive to RSV infection is unknown. We sought to analyze the permissiveness of CD4+ T cells to RSV infection. METHODS: CD4+ and CD8+ T cells from cord blood, healthy young children, and adults were challenged by RSV or cocultured with infected HEp-2 cells. Infection, phenotype, and cytokine production by T cells were analyzed by flow cytometry or enzyme-linked immunosorbent assay. Expression of RSV antigens by circulating CD4+ T cells from infected children was analyzed by flow cytometry, and disease severity was defined by standard criteria. RESULTS: CD4+ and CD8+ T cells were productively infected by RSV. Infection decreased interleukin 2 and interferon γ production as well as the expression of CD25 and Ki-67 by activated CD4+ T cells. Respiratory syncytial virus antigens were detected in circulating CD4+ and CD8+ T cells during severe RSV infection of young children. Interestingly, the frequency of CD4+ RSV+ T cells positively correlated with disease severity. CONCLUSIONS: Respiratory syncytial virus infects CD4+ and CD8+ T cells and compromises T-cell function. The frequency of circulating CD4+ RSV+ T cells might represent a novel marker of severe infection.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Infecciones por Virus Sincitial Respiratorio/inmunología , Adulto , Biomarcadores/sangre , Linfocitos T CD4-Positivos/virología , Linfocitos T CD8-positivos/virología , Línea Celular , Femenino , Sangre Fetal/citología , Citometría de Flujo , Humanos , Lactante , Recién Nacido , Interferón gamma/inmunología , Interleucina-2/inmunología , Masculino , Virus Sincitial Respiratorio HumanoRESUMEN
Few studies show patient outcomes over time in chronic obstructive pulmonary disease (COPD). In the present study, we monitored forced expiratory volume in the first second (FEV1) and other manifestations of the disease over 3 years in 133 COPD patients (69 percent males, age = 65 ± 9 years, FEV1 = 59 ± 25 percent) evaluated at baseline. During follow-up, 15 patients (11 percent) died and 23 (17 percent) dropped out. Measurements for 95 (72 percent) COPD patients alive after 3 years were analyzed. FEV1, body mass index (BMI), 6-min walking distance (6MWD), Medical Research Council scale (MRC), Saint Georges Respiratory Questionnaire (SGRQ), Charlson Comorbidity index, and BODE index were obtained at baseline and after 3 years. At baseline, 17 patients (18 percent) presented mild, 39 percent moderate, 19 percent severe, and 24 percent very severe COPD. Predicted FEV1 percent and BMI did not change over the period (P > 0.05). FEV1 in liters [1.25 (0.96-1.72) vs 1.26 (0.88-1.60) L; P < 0.001], 6MWD (438 ± 86 vs 412 ± 100 m; P < 0.001), MRC [1 (1-2) vs 2 (1-3); P = 0.002], Charlson index [3 (3-4) vs4 (3-5); P = 0.009], BODE index (2.2 ± 1.8 vs 2.6 ± 2.3; P = 0.008), and total SGRQ (42 ± 19 vs 44 ± 19 percent; P = 0.041) worsened after 3 years compared to baseline measurements. These data show that COPD patients deteriorated during the 3-year follow-up despite the fact that they had only minor modifications in airway obstruction and body composition. They support the need for comprehensive patient assessment to better identify disease progression.