ABSTRACT
Background: The mechanisms driving SARS-CoV-2 susceptibility remain poorly understood, especially the factors determining why unvaccinated individuals remain uninfected despite high-risk exposures. Objective: to understand lipid and metabolite profiles related with COVID-19 susceptibility and disease progression. Methods: we collected samples from an exceptional group of unvaccinated healthcare workers heavily exposed to SARS-CoV-2 but not infected (‘non-susceptible’) and subjects who became infected during the follow-up (‘susceptible’), including non-hospitalized and hospitalized patients with different disease severity providing samples at early disease stages. Then, we analyzed their plasma metabolomic profiles using mass spectrometry coupled with liquid and gas chromatography. Results:we show specific lipids profiles and metabolites that could explain SARS-CoV-2 susceptibility and COVID-19 severity. More importantly, non-susceptible individuals show a unique lipidomic pattern characterized by the upregulation of most lipids, especially ceramides and sphingomyelin, which could be interpreted as markers of low susceptibility to SARS-CoV-2 infection. Conclusion: this study strengthens the findings of other researchers about the importance of studying lipid profiles as relevant markers of SARS-CoV-2 pathogenesis.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
Pneumonia is a frequent manifestation of COVID-19 in hospitalized children. Methods The study involved 80 hospitals in the 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 characteristics of SARS-CoV-2-associated CAP with CAP due to other viral etiologies from 2012 to 2019. Results In total, 151 children with SARS-CoV-2-associated CAP and 138 with other viral CAP included. Main clinical features of SARS-CoV-2-associated CAP were cough 117/151(77%), fever 115/151(76%) and dyspnea 63/151(46%); 22/151(15%) patients were admitted to a pediatric intensive care unit (PICU), and 5/151(3%) patients died. Lymphopenia was found in 63/147(43%) patients. Chest X-ray revealed condensation (64/151[42%]) and other infiltrates (87/151[58%]). Compared with CAP from other viral pathogens, COVID-19 patients were older (8 vs.1 year; odds ratio [OR] 1.42 [95% confidence interval, CI 1.23;1.42]), with lower CRP levels (23 vs.48 mg/L; OR 1 [95%CI 0.99;1]), less wheezing (17 vs.53%; OR 0.18 [95%CI 0.11;0.31]) and greater need of mechanical ventilation, MV (7 vs.0.7%, OR 10.8 [95%CI 1.3;85). Patients with non-SARS-CoV-2-associated CAP had a greater need for oxygen therapy (77 vs.44%, OR 0.24 [95%CI 0.14;0.40]). There were no differences in the use of 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.
Subject(s)
Communication Disorders , Dyspnea , Pneumonia , COVID-19ABSTRACT
Epidemics caused by microbial organisms are part of the natural phenomena of increasing biological complexity. The heterogeneity and constant variability of hosts, in terms of age, immunological status, family structure, lifestyle, work activities, social and leisure habits, daily division of time, and other demographic characteristics make it extremely difficult to predict the evolution of epidemics. Such prediction is, however, critical for implementing intervention measures in due time and with appropriate intensity. General conclusions should be precluded, given that local parameters dominate the flow of local epidemics. Membrane computing models allows us to reproduce the objects (viruses, hosts) and their interactions (stochastic but also with defined probabilities) with an unprecedented level of detail. Our LOIMOS model helps reproduce the demographics and social aspects of a hypothetical town of 10,320 inhabitants in an average European country where COVID-19 is imported from the outside. The above-mentioned characteristics of hosts and their lifestyle are minutely considered. The dynamics of the epidemics are reproduced and include the effects on viral transmission of innate and acquired immunity at various ages. The model predicts the consequences of delaying the adoption of non-pharmaceutical interventions (between 15 and 45 days after the first reported cases) and the effect of those interventions on infection and mortality rates (reducing transmission by 20%, 50%, and 80%) in immunological response groups. The lockdown for the elderly population as a single intervention appears to be effective. This modelling exercise exemplifies the application of membrane computing for designing appropriate interventions in epidemic situations.
Subject(s)
COVID-19ABSTRACT
The standard RT-PCR assay for COVID-19 is laborious and time-consuming, limiting the availability of testing. Rapid antigen-detection tests are faster and less expensive; however, the reliability of these tests must be validated before they can be used widely. The objective of this study was to determine the reliability of the PanbioTM COVID-19 Ag Rapid Test Device (PanbioRT) (Abbott) for SARS-CoV-2 in nasopharyngeal swab specimens. This was a prospective multicenter study in ten Spanish university hospitals of patients from hospital units with clinical symptoms or epidemiological criteria for COVID-19. Patients whose onset of symptoms or exposure was more than 7 days earlier were excluded. Two nasopharyngeal exudate samples were taken to perform the PanbioRT and a diagnostic RT-PCR test. Among the 958 patients studied, 359 (37.5%) were positive by RT-PCR and 325 (33.9%) were also positive by the PanbioRT. Agreement was 95.7% (kappa score: 0.90). All 34 false-negative PanbioRT results were in symptomatic patients, with 23.5% of them at 6-7 days since the onset of symptoms and 58.8% presenting CT >30 values for RT-PCR, indicating a low viral load. Overall sensitivity and specificity for the PanbioRT were 90.5% and 98.8%, respectively. The PanbioRT provides good clinical performance as a point-of-care test, with even more reliable results for patients with a shorter clinical course of the disease or a higher viral load. While this study has had a direct impact on the national diagnostic strategy for COVID-19 in Spain, the results must be interpreted based on the local epidemiological context.
Subject(s)
COVID-19ABSTRACT
Since its emergence, in December 2019, COVID-19 has resulted in more than 12 million people infected and has killed more than 570000. Hypoxemia has been identified as one of the main clinical manifestations of this disease, especially in severe cases. We have previously reported that in critically ill COVID-19 patients there is a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, which, together with mature monocytes and segmented neutrophils, comprise the vast majority of blood cells in these patients. Such an immature myeloid profile may be the result of a physiological response known as emergency myelopoiesis. In the present study, we performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α (HIF1α) mRNA and its transcriptionally regulated genes. HIF1α is a master transcription factor involved in the cellular response to hypoxia. We herein report that these cellular subsets express high levels of HIF1α mRNA and several of their transcriptional targets, including those related to inflammation, such as CXCL8, CXCR1, CXCR2, and CXCR4; those potentially involved in virus sensing, such as TLR2 and TLR4; and those related to metabolism, such as SLC2A3, PFKFB3, PGK1, GAPDH and SOD2. The up-regulation and participation of HIF1α in relevant events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy.
Subject(s)
Hypoxia , Hallucinations , COVID-19 , InflammationABSTRACT
Importance: The actual demand on SARS-CoV-2 diagnosis is a current challenge for clinical laboratories. Sample pooling may help to ameliorate workload in clinical laboratories. Objective: to evaluate the efficacy of sample pooling compared to the individual analysis for the diagnosis of CoVID-19, by using different commercial platforms for nucleic acid extraction and amplification. Design and settings: observational, prospective, multicentre study across 9 Spanish clinical microbiology laboratories including SARS-CoV-2 RNA testing performed in April 2020, during the first three days after acceptance to participate. Participants and Methods: 3519 naso-oro-pharyngeal samples received at the participating laboratories were processed individually and in pools (351 pools) according to the existing methodology in each of the centres. Results: We found that 253 pools (2519 samples) were negative, and 99 pools (990 samples) were positive; with 241 positive samples (6.85%), our pooling strategy would have saved 2167 PCR tests. For 29 pools (made out of 290 samples) we found discordant results when compared to their correspondent individual samples: in 24/29 pools (30 samples), minor discordances were found; for five pools (5 samples), we found major discordances. Sensitivity, specificity, positive and negative predictive values for pooling were 97.93%, 100%, 100% and 99.85% respectively; accuracy was 99.86% and kappa concordant coefficient was 0.988. As a result of the sample dilution effect of pooling, a loss of 2-3 Cts was observed for E, N or RdRP genes. Conclusion: we show a high efficiency of pooling strategies for SARS-CoV-2 RNA testing, across different RNA extraction and amplification platforms, with excellent performance in terms of sensitivity, specificity, and positive and negative predictive values. We believe that our results may help clinical laboratories to respond to the actual demand and clinical need on SARS-CoV-2 testing, especially for the screening of low prevalence populations.
Subject(s)
COVID-19ABSTRACT
SARS-CoV-2, the etiological agent causing COVID-19, has infected more than 8.7 million people with over 461000 deaths worldwide since its emergence in December 2019. Factors for severe disease, such as diabetes, hypertension and obesity have been identified however, the precise pathogenesis is poorly understood. In order to understand its pathophysiology and to develop effective therapeutic strategies, it is essential to define the prevailing immune cellular subsets. We performed circulating immune cells scRNAseq from five critically ill COVID-19 patients. Immature myeloid populations, such as promyelocytes-myelocytes, metamyelocytes, band neutrophils, monocytoid precursors and activated monocytes predominated. Trajectory with pseudotime analysis supported the finding of immature cell states. Gene ontology showed myeloid cell activation in immune response, DNA and RNA processing, defense response to virus and response to type 1 interferon. Lymphoid lineage was scarce. Our results uncover a transcriptomic profiles related to immature myeloid lineages and suggest the potential induction of trained immunity.