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Group IIA secreted phospholipase A2 is associated with the pathobiology leading to COVID-19 mortality.
Snider, JM, You, JK, Wang, X, Snider, AJ, Hallmark, B, Zec, MM, Seeds, MC, Sergeant, S, Johnstone, L, Wang, Q, et al
The Journal of clinical investigation. 2021;(19)
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Abstract
There is an urgent need to identify the cellular and molecular mechanisms responsible for severe COVID-19 that results in death. We initially performed both untargeted and targeted lipidomics as well as focused biochemical analyses of 127 plasma samples and found elevated metabolites associated with secreted phospholipase A2 (sPLA2) activity and mitochondrial dysfunction in patients with severe COVID-19. Deceased COVID-19 patients had higher levels of circulating, catalytically active sPLA2 group IIA (sPLA2-IIA), with a median value that was 9.6-fold higher than that for patients with mild disease and 5.0-fold higher than the median value for survivors of severe COVID-19. Elevated sPLA2-IIA levels paralleled several indices of COVID-19 disease severity (e.g., kidney dysfunction, hypoxia, multiple organ dysfunction). A decision tree generated by machine learning identified sPLA2-IIA levels as a central node in the stratification of patients who died from COVID-19. Random forest analysis and least absolute shrinkage and selection operator-based (LASSO-based) regression analysis additionally identified sPLA2-IIA and blood urea nitrogen (BUN) as the key variables among 80 clinical indices in predicting COVID-19 mortality. The combined PLA-BUN index performed significantly better than did either one alone. An independent cohort (n = 154) confirmed higher plasma sPLA2-IIA levels in deceased patients compared with levels in plasma from patients with severe or mild COVID-19, with the PLA-BUN index-based decision tree satisfactorily stratifying patients with mild, severe, or fatal COVID-19. With clinically tested inhibitors available, this study identifies sPLA2-IIA as a therapeutic target to reduce COVID-19 mortality.
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Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study.
Menni, C, Klaser, K, May, A, Polidori, L, Capdevila, J, Louca, P, Sudre, CH, Nguyen, LH, Drew, DA, Merino, J, et al
The Lancet. Infectious diseases. 2021;(7):939-949
Abstract
BACKGROUND The Pfizer-BioNTech (BNT162b2) and the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccines have shown excellent safety and efficacy in phase 3 trials. We aimed to investigate the safety and effectiveness of these vaccines in a UK community setting. METHODS In this prospective observational study, we examined the proportion and probability of self-reported systemic and local side-effects within 8 days of vaccination in individuals using the COVID Symptom Study app who received one or two doses of the BNT162b2 vaccine or one dose of the ChAdOx1 nCoV-19 vaccine. We also compared infection rates in a subset of vaccinated individuals subsequently tested for SARS-CoV-2 with PCR or lateral flow tests with infection rates in unvaccinated controls. All analyses were adjusted by age (≤55 years vs >55 years), sex, health-care worker status (binary variable), obesity (BMI <30 kg/m2vs ≥30 kg/m2), and comorbidities (binary variable, with or without comorbidities). FINDINGS Between Dec 8, and March 10, 2021, 627 383 individuals reported being vaccinated with 655 590 doses: 282 103 received one dose of BNT162b2, of whom 28 207 received a second dose, and 345 280 received one dose of ChAdOx1 nCoV-19. Systemic side-effects were reported by 13·5% (38 155 of 282 103) of individuals after the first dose of BNT162b2, by 22·0% (6216 of 28 207) after the second dose of BNT162b2, and by 33·7% (116 473 of 345 280) after the first dose of ChAdOx1 nCoV-19. Local side-effects were reported by 71·9% (150 023 of 208 767) of individuals after the first dose of BNT162b2, by 68·5% (9025 of 13 179) after the second dose of BNT162b2, and by 58·7% (104 282 of 177 655) after the first dose of ChAdOx1 nCoV-19. Systemic side-effects were more common (1·6 times after the first dose of ChAdOx1 nCoV-19 and 2·9 times after the first dose of BNT162b2) among individuals with previous SARS-CoV-2 infection than among those without known past infection. Local effects were similarly higher in individuals previously infected than in those without known past infection (1·4 times after the first dose of ChAdOx1 nCoV-19 and 1·2 times after the first dose of BNT162b2). 3106 of 103 622 vaccinated individuals and 50 340 of 464 356 unvaccinated controls tested positive for SARS-CoV-2 infection. Significant reductions in infection risk were seen starting at 12 days after the first dose, reaching 60% (95% CI 49-68) for ChAdOx1 nCoV-19 and 69% (66-72) for BNT162b2 at 21-44 days and 72% (63-79) for BNT162b2 after 45-59 days. INTERPRETATION Systemic and local side-effects after BNT162b2 and ChAdOx1 nCoV-19 vaccination occur at frequencies lower than reported in phase 3 trials. Both vaccines decrease the risk of SARS-CoV-2 infection after 12 days. FUNDING ZOE Global, National Institute for Health Research, Chronic Disease Research Foundation, National Institutes of Health, UK Medical Research Council, Wellcome Trust, UK Research and Innovation, American Gastroenterological Association.
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Metabolic Signatures Associated with Severity in Hospitalized COVID-19 Patients.
Marín-Corral, J, Rodríguez-Morató, J, Gomez-Gomez, A, Pascual-Guardia, S, Muñoz-Bermúdez, R, Salazar-Degracia, A, Pérez-Terán, P, Restrepo, MI, Khymenets, O, Haro, N, et al
International journal of molecular sciences. 2021;(9)
Abstract
The clinical evolution of COVID-19 pneumonia is poorly understood. Identifying the metabolic pathways that are altered early with viral infection and their association with disease severity is crucial to understand COVID-19 pathophysiology, and guide clinical decisions. This study aimed at assessing the critical metabolic pathways altered with disease severity in hospitalized COVID-19 patients. Forty-nine hospitalized patients with COVID-19 pneumonia were enrolled in a prospective, observational, single-center study in Barcelona, Spain. Demographic, clinical, and analytical data at admission were registered. Plasma samples were collected within the first 48 h following hospitalization. Patients were stratified based on the severity of their evolution as moderate (N = 13), severe (N = 10), or critical (N = 26). A panel of 221 biomarkers was measured by targeted metabolomics in order to evaluate metabolic changes associated with subsequent disease severity. Our results show that obesity, respiratory rate, blood pressure, and oxygen saturation, as well as some analytical parameters and radiological findings, were all associated with disease severity. Additionally, ceramide metabolism, tryptophan degradation, and reductions in several metabolic reactions involving nicotinamide adenine nucleotide (NAD) at inclusion were significantly associated with respiratory severity and correlated with inflammation. In summary, assessment of the metabolomic profile of COVID-19 patients could assist in disease severity stratification and even in guiding clinical decisions.
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Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19.
Zuo, T, Liu, Q, Zhang, F, Lui, GC, Tso, EY, Yeoh, YK, Chen, Z, Boon, SS, Chan, FK, Chan, PK, et al
Gut. 2021;(2):276-284
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Abstract
OBJECTIVE Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in faeces of patients with COVID-19, the activity and infectivity of the virus in the GI tract during disease course is largely unknown. We investigated temporal transcriptional activity of SARS-CoV-2 and its association with longitudinal faecal microbiome alterations in patients with COVID-19. DESIGN We performed RNA shotgun metagenomics sequencing on serial faecal viral extractions from 15 hospitalised patients with COVID-19. Sequencing coverage of the SARS-CoV-2 genome was quantified. We assessed faecal microbiome composition and microbiome functionality in association with signatures of faecal SARS-CoV-2 infectivity. RESULTS Seven (46.7%) of 15 patients with COVID-19 had stool positivity for SARS-CoV-2 by viral RNA metagenomic sequencing. Even in the absence of GI manifestations, all seven patients showed strikingly higher coverage (p=0.0261) and density (p=0.0094) of the 3' vs 5' end of SARS-CoV-2 genome in their faecal viral metagenome profile. Faecal viral metagenome of three patients continued to display active viral infection signature (higher 3' vs 5' end coverage) up to 6 days after clearance of SARS-CoV-2 from respiratory samples. Faecal samples with signature of high SARS-CoV-2 infectivity had higher abundances of bacterial species Collinsella aerofaciens, Collinsella tanakaei, Streptococcus infantis, Morganella morganii, and higher functional capacity for nucleotide de novo biosynthesis, amino acid biosynthesis and glycolysis, whereas faecal samples with signature of low-to-none SARS-CoV-2 infectivity had higher abundances of short-chain fatty acid producing bacteria, Parabacteroides merdae, Bacteroides stercoris, Alistipes onderdonkii and Lachnospiraceae bacterium 1_1_57FAA. CONCLUSION This pilot study provides evidence for active and prolonged 'quiescent' GI infection even in the absence of GI manifestations and after recovery from respiratory infection of SARS-CoV-2. Gut microbiota of patients with active SARS-CoV-2 GI infection was characterised by enrichment of opportunistic pathogens, loss of salutary bacteria and increased functional capacity for nucleotide and amino acid biosynthesis and carbohydrate metabolism.
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Is There a Crucial Link Between Vitamin D Status and Inflammatory Response in Patients With COVID-19?
Saponaro, F, Franzini, M, Okoye, C, Antognoli, R, Campi, B, Scalese, M, Neri, T, Carrozzi, L, Monzani, F, Zucchi, R, et al
Frontiers in immunology. 2021;:745713
Abstract
BACKGROUND Hypovitaminosis D has been suggested to play a possible role in coronavirus disease 2019 (COVID-19) infection. METHODS The aim of this study is to analyze the relationship between vitamin D status and a biochemical panel of inflammatory markers in a cohort of patients with COVID-19. A secondary endpoint was to evaluate the correlation between 25OHD levels and the severity of the disease. Ninety-three consecutive patients with COVID-19-related pneumonia were evaluated from March to May 2020 in two hospital units in Pisa, in whom biochemical inflammatory markers, 25OHD levels, P/F ratio at nadir during hospitalization, and complete clinical data were available. RESULTS Sixty-five percent of patients presented hypovitaminosis D (25OHD ≤ 20 ng/ml) and showed significantly higher IL-6 [20.8 (10.9-45.6) vs. 12.9 (8.7-21.1) pg/ml, p = 0.02], CRP [10.7 (4.2-19.2) vs. 5.9 (1.6-8.1) mg/dl, p = 0.003], TNF-α [8.9 (6.0-14.8) vs. 4.4 (1.5-10.6) pg/ml, p = 0.01], D-dimer [0.53 (0.25-0.72) vs. 0.22 (0.17-0.35) mg/l, p = 0.002], and IL-10 [3.7 (1.8-6.9) vs. 2.3 (0.5-5.8) pg/ml, p = 0.03]. A significant inverse correlation was found between 25OHD and all these markers, even adjusted for age and sex. Hypovitaminosis D was prevalent in patients with severe ARDS, compared with the other groups (75% vs. 68% vs. 55%, p < 0.001), and 25OHD levels were lower in non-survivor patients. CONCLUSIONS The relationship between 25OHD levels and inflammatory markers suggests that vitamin D status needs to be taken into account in the management of these patients. If vitamin D is a marker of poor prognosis or a possible risk factor with beneficial effects from supplementation, this still needs to be elucidated.
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People living with type 1 diabetes point of view in COVID-19 times (COVIDT1 study): Disease impact, health system pitfalls and lessons for the future.
Tejera-Perez, C, Moreno-Pérez, Ó, Rios, J, Reyes-García, R
Diabetes research and clinical practice. 2021;:108547
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AIMS: To analyse the effects of confinement among people with type 1 diabetes (T1D) and their caregivers over the course of the COVID-19 crisis and to evaluate contemporary changes in medical assistance and patient preferences. METHODS An observational cross-sectional study designed as a self-reported web-based survey was conducted over the course of the COVID-19 pandemic. RESULTS A total of 769 subjects participated in the survey (603 people with T1D and 166 caregivers). Changes in glycaemic control were reported in 66% of cases, weight gain in 40.4% of cases and decreased exercise levels in 65.4% of cases. Of the cohort, 53% maintained contact with the healthcare team, and 23% received specific information related to COVID-19. Emotional support was requested by 17% of respondents. Regarding telemedicine, 97.9% agreed with its use with the following preferences regarding the future: telephone call (84.5%), video-call (60.6%) and platform devices (39.7%). CONCLUSIONS Over the course of the COVID-19 pandemic, at least two-thirds of people with T1D underwent changes in the management of their condition. Almost all participants agreed with the concept of telemedicine, favouring telephone and video calls as their preferred means of communication.
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COVID-19 Disease Severity and Death in Relation to Vitamin D Status among SARS-CoV-2-Positive UAE Residents.
AlSafar, H, Grant, WB, Hijazi, R, Uddin, M, Alkaabi, N, Tay, G, Mahboub, B, Al Anouti, F
Nutrients. 2021;(5)
Abstract
Insufficient blood levels of the neurohormone vitamin D are associated with increased risk of COVID-19 severity and mortality. Despite the global rollout of vaccinations and promising preliminary results, the focus remains on additional preventive measures to manage COVID-19. Results conflict on vitamin D's plausible role in preventing and treating COVID-19. We examined the relation between vitamin D status and COVID-19 severity and mortality among the multiethnic population of the United Arab Emirates. Our observational study used data for 522 participants who tested positive for SARS-CoV-2 at one of the main hospitals in Abu Dhabi and Dubai. Only 464 of those patients were included for data analysis. Demographic and clinical data were retrospectively analyzed. Serum samples immediately drawn at the first hospital visit were used to measure serum 25-hydroxyvitamin D [25(OH)D] concentrations through automated electrochemiluminescence. Levels < 12 ng/mL were significantly associated with higher risk of severe COVID-19 infection and of death. Age was the only other independent risk factor, whereas comorbidities and smoking did not contribute to the outcomes upon adjustment. Sex of patients was not an important predictor for severity or death. Our study is the first conducted in the UAE to measure 25(OH)D levels in SARS-CoV-2-positive patients and confirm the association of levels < 12 ng/mL with COVID-19 severity and mortality.
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Diabetes Increases Severe COVID-19 Outcomes Primarily in Younger Adults.
Diedisheim, M, Dancoisne, E, Gautier, JF, Larger, E, Cosson, E, Fève, B, Chanson, P, Czernichow, S, Tatulashvili, S, Raffin-Sanson, ML, et al
The Journal of clinical endocrinology and metabolism. 2021;(9):e3364-e3368
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CONTEXT Diabetes is reported as a risk factor for severe coronavirus disease 2019 (COVID-19), but whether this risk is similar in all categories of age remains unclear. OBJECTIVE To investigate the risk of severe COVID-19 outcomes in hospitalized patients with and without diabetes according to age categories. DESIGN SETTING AND PARTICIPANTS We conducted a retrospective observational cohort study of 6314 consecutive patients hospitalized for COVID-19 between February and 30 June 2020 in the Paris metropolitan area, France; follow-up was recorded until 30 September 2020. MAIN OUTCOME MEASURE(S): The main outcome was a composite outcome of mortality and orotracheal intubation in subjects with diabetes compared with subjects without diabetes, after adjustment for confounding variables and according to age categories. RESULTS Diabetes was recorded in 39% of subjects. Main outcome was higher in patients with diabetes, independently of confounding variables (hazard ratio [HR] 1.13 [1.03-1.24]) and increased with age in individuals without diabetes, from 23% for those <50 to 35% for those >80 years but reached a plateau after 70 years in those with diabetes. In direct comparison between patients with and without diabetes, diabetes-associated risk was inversely proportional to age, highest in <50 years and similar after 70 years. Similarly, mortality was higher in patients with diabetes (26%) than in those without diabetes (22%, P < 0.001), but adjusted HR for diabetes was significant only in patients younger than age 50 years (HR 1.81 [1.14-2.87]). CONCLUSIONS Diabetes should be considered as an independent risk factor for the severity of COVID-19 in young adults more so than in older adults, especially for individuals younger than 70 years.
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The impact of chest CT body composition parameters on clinical outcomes in COVID-19 patients.
Besutti, G, Pellegrini, M, Ottone, M, Cantini, M, Milic, J, Bonelli, E, Dolci, G, Cassone, G, Ligabue, G, Spaggiari, L, et al
PloS one. 2021;(5):e0251768
Abstract
We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality.
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Umbilical cord clamping and skin-to-skin contact in deliveries from women positive for SARS-CoV-2: a prospective observational study.
Mejía Jiménez, I, Salvador López, R, García Rosas, E, Rodriguez de la Torre, I, Montes García, J, de la Cruz Conty, ML, Martínez Pérez, O, ,
BJOG : an international journal of obstetrics and gynaecology. 2021;(5):908-915
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OBJECTIVE To demonstrate that delayed cord clamping (DCC) is safe in mothers with confirmed SARS-CoV-2 infection. DESIGN, SETTING AND PARTICIPANTS Prospective observational study involving epidemiological information from 403 pregnant women with SARS-CoV-2 between 1 March and 31 May 2020. Data were collected from 70 centres that participate in the Spanish Registry of COVID-19. METHODS Patients' information was collected from their medical chart. MAIN OUTCOMES AND MEASURES The rate of perinatal transmission of SARS-CoV-2 and development of the infection in neonates within 14 days postpartum. RESULTS The early cord clamping (ECC) group consisted of 231 infants (57.3%) and the DCC group consisted of 172 infants (42.7%). Five positive newborns (1.7% of total tests performed) were identified with the nasopharyngeal PCR tests performed in the first 12 hours postpartum, two from the ECC group (1.7%) and three from the DCC group (3.6%). No significant differences between groups were found regarding neonatal tests for SARS-CoV-2. No confirmed cases of vertical transmission were detected. The percentage of mothers who made skin-to-skin contact within the first 24 hours after delivery was significantly higher in the DCC group (84.3% versus 45.9%). Breastfeeding in the immediate postpartum period was also significantly higher in the DCC group (77.3% versus 50.2%). CONCLUSIONS The results of our study show no differences in perinatal outcomes when performing ECC or DCC, and skin-to-skin contact, or breastfeeding. TWEETABLE ABSTRACT This study demonstrates that delayed cord clamping is safe in mothers with confirmed SARS-CoV-2 infection.