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BackgroundRespiratory syncytial virus (RSV) infection has been associated with the subsequent development of recurrent wheezing and asthma, although the mechanisms involved are still unknown. We investigate the role of epigenetics in the respiratory morbidity after infection by comparing methylation patterns from children who develop recurrent wheezing (RW-RSV), subsequent asthma (AS-RVS), and those experiencing complete recovery (CR-RSV).MethodsProspective, observational study of infants aged < 2 years with RSV respiratory infection admitted to hospital and followed-up after discharge for at least three years. According to their clinical course, patients were categorized into subgroups: RW-RSV (n = 36), AS-RSV (n = 9), and CR-RSV (n = 32). The DNA genome-wide methylation pattern was analyzed in whole blood samples, collected during the acute phase of the infection, using the Illumina Infinium Methylation EPIC BeadChip (850K CpG sites). Differences in methylation were determined through a linear regression model adjusted for age, gender and cell composition.ResultsPatients who developed respiratory sequelae showed a statistically significant higher proportion of NK and CD8T cells (inferred through a deconvolution approach) than those with complete recovery. We identified 5,097 significant differentially methylated positions (DMPs) when comparing RW-RSV and AS-RVS together against CR-RSV. Methylation profiles affect several genes involved in airway inflammation processes. The most significant DMPs were found to be hypomethylated in cases and therefore generally leading to overexpression of affected genes. The lead CpG position (cg24509398) falls at the gene body of EYA3 (P-value = 2.77×10-10), a tyrosine phosphatase connected with pulmonary vascular remodeling, a key process in the asthma pathology. Logistic regression analysis resulted in a diagnostic epigenetic signature of 3-DMPs (involving genes ZNF2698, LOC102723354 and RPL15/NKIRAS1) that allows to efficiently differentiate sequelae cases from CR-RSV patients (AUC = 1.00). Enrichment pathway analysis reveals the role of the cell cycle checkpoint (FDR P-value = 4.71×10-2), DNA damage (FDP-value = 2.53×10-2), and DNA integrity checkpoint (FDR P-value = 2.56×10-2) in differentiating sequelae from CR-RSV patients.ConclusionsEpigenetic mechanisms might play a fundamental role in the long-term sequelae after RSV infection, contributing to explain the different phenotypes observed.

Spain is one of the countries most severely affected by the SARS-CoV-2 pandemic, with almost 190,000 cases as of April 18, 2020. As healthcare workers (HCW) are one of the groups hardest hit by the infection, it is important to know the seroprevalence of antibodies against SARS-CoV-2 in pediatric departments. We performed 175 immunoglobulin (Ig)M and IgG immunochromatographic rapid tests in the personnel working at the Pediatric Department of the Hospital Clínico Universitario of Santiago de Compostela (Spain), including pediatricians, residents, nurses, and other staff, on days 31–33 since the lockdown started. Seven out of the 175 tests were positive, including four for IgM and three for IgG, leading to a seroprevalence of 4.0% (95% CI: 1.1–6.9%). Only one of them had symptoms at the time of testing (sore throat). All seropositive cases yielded negative RT-PCR of the upper and lower respiratory tract. This is the first SARS-CoV-2 serological survey among HCWs reported in Spain. Notwithstanding the test limitations, our results reveal that personal protection policy and lockdown measures have been effective to limit population exposure. The low seroprevalence rate poses a significant challenge for the next strategic steps of pandemic control.

BackgroundEmerging evidence indicates a potential role for monocytes in COVID-19 immunopathology. We investigated two soluble markers of monocyte activation, sCD14 and sCD163, in COVID-19 patients, with the aim of characterizing their potential role in monocyte-macrophage disease immunopathology. To the best of our knowledge, this is the first study of its kind.MethodsFifty-nine SARS-Cov-2 positive hospitalized patients, classified according to ICU or non-ICU admission requirement, were prospectively recruited and analyzed by ELISA for levels of sCD14 and sCD163, along with other laboratory parameters, and compared to a healthy control group.ResultssCD14 and sCD163 levels were significantly higher among COVID-19 patients, independently of ICU admission requirement, compared to the control group. We found a significant correlation between sCD14 levels and other inflammatory markers, particularly Interleukin-6, in the non-ICU patients group. sCD163 showed a moderate positive correlation with the time lapsed from admission to sampling, independently of severity group. Treatment with corticoids showed an interference with sCD14 levels, whereas hydroxychloroquine and tocilizumab did not.ConclusionsMonocyte-macrophage activation markers are increased and correlate with other inflammatory markers in SARS-Cov-2 infection, in association to hospital admission. These data suggest a preponderant role for monocyte-macrophage activation in the development of immunopathology of COVID-19 patients.