Comparison of pneumonia features in children caused by SARS-CoV-2 and other viral respiratory pathogens.

BACKGROUND: Pneumonia is a frequent manifestation of coronavirus disease 2019 (COVID-19) in hospitalized children. METHODS: The study involved 80 hospitals in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spanish Pediatric National Cohort. Participants were children <18 years, hospitalized with SARS-CoV-2 community-acquired pneumonia (CAP). We compared the clinical and radiological characteristics of SARS-CoV-2-associated CAP with CAP due to other viral etiologies from ValsDance (retrospective) cohort. RESULTS: In total, 151 children with SARS-CoV-2-associated CAP and 138 with other viral CAP were included. Main clinical features of SARS-CoV-2-associated CAP were cough, fever, or dyspnea. Lymphopenia was found in 43% patients and 15% required admission to the pediatric intensive care unit (PICU). Chest X-ray revealed condensation (42%) and other infiltrates (58%). Compared with CAP from other viral pathogens, COVID-19 patients were older, with lower C-reactive protein (CRP) levels, less wheezing, and greater need of mechanical ventilation (MV). There were no differences in the use of continuous positive airway pressure (CPAP) or HVF, or PICU admission between groups. CONCLUSION: SARS-CoV-2-associated CAP in children presents differently to other virus-associated CAP: children are older and rarely have wheezing or high CRP levels; they need less oxygen but more CPAP or MV. However, several features overlap and differentiating the etiology may be difficult. The overall prognosis is good.

RNA SARS-CoV-2 Persistence in the Lung of Severe COVID-19 Patients: A Case Series of Autopsies.

The exact role of viral replication in patients with severe COVID-19 has not been extensively studied, and it has only been possible to demonstrate the presence of replicative virus for more than 3 months in a few cases using different techniques. Our objective was to study the presence of RNA SARS-CoV-2 in autopsy samples of patients who died from COVID-19 long after the onset of symptoms. Secondary superimposed pulmonary infections present in these patients were also studied. We present an autopsy series of 27 COVID-19 patients with long disease duration, where pulmonary and extrapulmonary samples were obtained. In addition to histopathological analysis, viral genomic RNA (gRNA) and viral subgenomic RNA (sgRNA) were detected using RT-PCR and in situ hybridization, and viral protein was detected using immunohistochemistry. This series includes 26 adults with a median duration of 39 days from onset of symptoms to death (ranging 9-108 days), 92% of them subjected to immunomodulatory therapy, and an infant patient. We detected gRNA in the lung of all but one patient, including those with longer disease duration. SgRNA was detected in 11 out of 17 patients (64.7%) with illness duration up to 6 weeks and in 3 out of 9 patients (33.3%) with more than 6 weeks of disease progression. Viral protein was detected using immunohistochemistry and viral mRNA was detected using in situ hybridization in 3 out of 4 adult patients with illness duration of <2 weeks, but in none of the 23 adult patients with an illness duration of >2 weeks. A remarkable result was the detection of viral protein, gRNA and sgRNA in the lung cells of the pediatric patient after 95 days of illness. Additional pulmonary infections included: 9 acute bronchopneumonia, 2 aspergillosis, 2 cytomegalovirus, and 1 BK virus infection. These results suggest that in severe COVID-19, SARS-CoV-2 could persist for longer periods than expected, especially in immunocompromised populations, contributing to the persistence of chronic lung lesions. Additional infections contribute to the fatal course of the disease.

Viruses and Mycoplasma pneumoniae are the main etiological agents of community-acquired pneumonia in hospitalized pediatric patients in Spain.

OBJECTIVES: To describe the etiology of community-acquired pneumonia (CAP) in hospitalized children in Spain and analyze the predictors of the etiology. HYPOTHESIS: The different etiological groups of pediatric CAP are associated with different clinical, radiographic, and analytical data. DESIGN: Observational, multicenter, and prospective study. PATIENT SELECTION: This study included children aged 1 month to 17 years with CAP, who were hospitalized between April 2012 and May 2019. METHODS: An extensive microbiological workup was performed. The clinical, radiographic, and analytical parameters were analyzed for three etiological groups. RESULTS: Among the 495 children included, at least one causative pathogen was identified in 262 (52.9%): pathogenic viruses in 155/262 (59.2%); atypical bacteria (AB), mainly Mycoplasma pneumonia, in 84/262 (32.1%); and typical bacteria (TyB) in 40/262 (15.3%). Consolidation was observed in 89/138 (64.5%) patients with viral CAP, 74/84 (88.1%) with CAP caused by AB, and 40/40 (100%) with CAP caused by TyB. Para-pneumonic pleural effusion (PPE) was observed in 112/495 (22.6%) patients, of which 61/112 (54.5%) presented a likely causative pathogen: viruses in 12/61 (19.7%); AB in 23/61 (37.7%); and TyB in 26/61 (42.6%). Viral etiology was significantly frequent in young patients and in those with low oxygen saturation, wheezing, no consolidation, and high lymphocyte counts. CAP patients with AB as the etiological agent had a significantly longer and less serious course as compared to those with other causative pathogens. CONCLUSIONS: Viruses and M. pneumoniae are the main causes of pediatric CAP in Spain. Wheezing, young age, and no consolidation on radiographs are indicative of viral etiology. Viruses and AB can also cause PPE. Since only a few cases can be directly attributed to TyB, the indications for antibiotics must be carefully considered in each patient.

Simulating the efficacy of vaccines on the epidemiological dynamics of SARS-CoV-2 in a membrane computing model.

Membrane computing is a natural computing procedure inspired in the compartmental structure of living cells. This approach allows mimicking the complex structure of biological processes, and, when applied to transmissible diseases, can simulate a virtual 'epidemic' based on interactions between elements within the computational model according to established conditions. General and focused vaccination strategies for controlling SARS-Cov-2 epidemics have been simulated for 2.3 years from the emergence of the epidemic in a hypothetical town of 10320 inhabitants in a country with mean European demographics where COVID-19 is imported. The age and immunological-response groups of the hosts and their lifestyles were minutely examined. The duration of natural, acquired immunity influenced the results; the shorter the duration, the more endemic the process, resulting in higher mortality, particularly among elderly individuals. During epidemic valleys between waves, the proportion of infected patients belonging to symptomatic groups (mostly elderly) increased in the total population, a population that largely benefits from standard double vaccination, particularly with boosters. There was no clear difference when comparing booster shots provided at 4 or 6 months after standard double-dose vaccination. Vaccines even of moderate efficacy (short-term protection) were effective in decreasing the number of symptomatic cases. Generalized vaccination of the entire population (all ages) added little benefit to overall mortality rates, and this situation also applied for generalized lockdowns. Elderly-only vaccination and lockdowns, even without general interventions directed to reduce population transmission, is sufficient for dramatically reducing mortality.

Smoking may increase the risk of hospitalization due to influenza.

BACKGROUND: Smoking may facilitate influenza virus infections and their severity. The objective was to investigate the risk of hospitalization due to influenza in Spanish smokers and ex-smokers. METHODS: We carried out a multicentre, case-control study in 2011. Cases [patients ≥ 18 years hospitalized > 24 h with real time polymerase chain reaction (RT-PCR)-confirmed influenza] were selected from 29 Spanish hospitals. For each case, we selected an outpatient aged ≥ 18 years with RT-PCR-confirmed influenza matched by age (±5 years), date of hospitalization of the case (±10 days) and province of residence. We collected epidemiological variables, comorbidities and the smoking history. The risk of hospitalization due to smoking was determined by the adjusted odds ratio (aOR) using logistic regression. RESULTS: We studied 471 hospitalized cases and 476 outpatient cases. Hospitalized cases had a higher frequency of influenza risk factors compared with outpatient cases. Hospitalized cases had a higher frequency of smoking (30.9% vs. 17.1%) and being ex-smokers (29.3% vs. 25.3%). Current smoking (aOR = 2.18, 95% CI: 1.23-3.87) and being an ex-smoker (aOR = 1.73, 95% CI: 1.07-2.82) were associated with the risk of hospitalization. CONCLUSIONS: Smoking may increase the risk of hospitalization in smokers and ex-smokers when infected by the influenza virus. Smoking prevention could reduce hospitalizations. Influenza vaccination is recommended for smokers.

Pandemic influenza A (H1N1) infection in pregnant and nonpregnant women in Spain (2009-2010).

The present study aimed to compare the main features of infection with pandemic influenza A virus in pregnant and nonpregnant women admitted to hospitals in Spain during the first waves of the 2009-2010 influenza pandemic. This was a prospective (November 2009 to June 2010), multicenter observational study. All cases were women of reproductive age who had not been vaccinated against seasonal or pandemic influenza A. Influenza infection was confirmed by reverse transcription-polymerase chain reaction (RT-PCR). The sociodemographic and clinical data of all cases were reviewed. A total of 219 inpatients, including 49 pregnant women and 170 nonpregnant women, were enrolled in the study upon admission to participating hospitals. The most substantially different symptoms between the groups were respiratory distress and unilobar consolidation, both of which were more frequent among nonpregnant women. Antibiotics and systemic corticosteroids were more frequently used in nonpregnant women; however, there were no differences in the rates of treatment with antivirals. Our findings indicated that the compared with nonpregnant women, pregnant women in this study did not have significantly different symptoms and were not at increased risk of complications from pandemic influenza virus infection.

Different prognosis in hospitalized patients with influenza one season after the pandemic H1N1 influenza of 2009-2010 in Spain.

BACKGROUND: The present report compares prognosis in hospitalized cases with the H1N1 pandemic virus in two seasons. METHODS: Two series of hospitalized patients with laboratory-confirmed H1N1 pandemic influenza have been compared: 813 in the season 2009-2010 and 707 in the season 2010-2011. A detailed history of variables preceding hospital admission and during hospitalization was obtained by interview and clinical charts. A combined endpoint of death admission to intensive care was used as outcome due to the low number of deaths. Logistic regression was applied in the analysis for adverse outcome. RESULTS: Patients of the second season had different characteristics than in the first one (older, more underlying conditions, more malfunctioning organs and more symptoms). Patients with H1N1 pandemic virus when hospitalized were more frequently directly admitted to ICU during the 2010-2011 season than in the previous season (RR=2·10; 95% confidence intervals CI, 1·55-2·85), as a consequence of a higher presence of sepsis and respiratory distress. These patients also showed during hospitalization a higher risk of ICU admission or death (RR=3·22, 95% CI, 2·15-4·83). After adjusting for the differences in risk factors of adverse outcome, patients in the second season showed a higher risk of ICU admission and/or in-hospital death odds ratio (OR=3·77, 95% CI, 2·30-6·18). CONCLUSION: Hospitalized patients with H1N1 pandemic influenza during the second season were more severely affected at hospital admission and showed a worse prognosis than in previous season, independently of the differences found at hospital admission.

The neglected intrinsic resistome of bacterial pathogens.

Bacteria with intrinsic resistance to antibiotics are a worrisome health problem. It is widely believed that intrinsic antibiotic resistance of bacterial pathogens is mainly the consequence of cellular impermeability and activity of efflux pumps. However, the analysis of transposon-tagged Pseudomonas aeruginosa mutants presented in this article shows that this phenotype emerges from the action of numerous proteins from all functional categories. Mutations in some genes make P. aeruginosa more susceptible to antibiotics and thereby represent new targets. Mutations in other genes make P. aeruginosa more resistant and therefore define novel mechanisms for mutation-driven acquisition of antibiotic resistance, opening a new research field based in the prediction of resistance before it emerges in clinical environments. Antibiotics are not just weapons against bacterial competitors, but also natural signalling molecules. Our results demonstrate that antibiotic resistance genes are not merely protective shields and offer a more comprehensive view of the role of antibiotic resistance genes in the clinic and in nature.