AIMS:We examined the predictive value of soluble levels of triggering receptor expressed on myeloid cells 1 (sTREM-1) for incident cardiovascular disease (CVD). METHODS:The main analysis was conducted in an observational prospective cohort. Adjudicated CVD events included coronary heart disease, stroke, heart failure and peripheral artery disease. sTREM-1 measures were centralized using a protocol optimized for Meso Scale Discovery technology. RESULTS:Among 9097 CVD-free participants (39% females, mean age 59.6±6.3 years), median sTREM-1 concentration was 193.41 pg/mL (IQR= 158.13 to 241.54) at baseline (2008 to 2012). Over 10.1 years of median follow-up (IQR= 9.2 to 12.0), 444 participants experienced 479 CVD events. Higher sTREM-1 concentrations were associated with higher risk of CVD in multivariable Cox proportional hazard model (HR 200-290 vs. <200pg/ml= 4.25;95% CI:3.20 to 5.63 and HR >290 vs. <200pg/ml=10.40;95% CI:7.72 to 14.02). Results were consistent across CVD subtypes. Adding sTREM-1 to SCORE2-SCORE2 OP improved the Harell-C index (C-index 0.79 vs. 0.71; bootstrapped C index difference: 0.084; 95% CI: 0.083 to 0.085) overall including among individuals at low to moderate 10-year risk of CHD or stroke, and reclassification: categorical NRI: 0.34; 95% CI: 0.28 to 0.40. Findings were similar with other recommended risk scores. CONCLUSIONS:In this prospective study, higher circulating sTREM-1 levels were independently associated with incident CVD. Addition of sTREM-1 to established risk scores was associated with improvements in discrimination and reclassification metrics, supporting its potential relevance as a candidate biomarker for further evaluation in primary prevention.

Healthcare workers (HCW) have been at the frontline during the COVID-19 pandemic, with an increased risk of infection, particularly due to the emergence of the omicron variant. This study aims to assess risk factors for omicron acquisition among vaccinated HCW, comparing hybrid immunity (previous infection and vaccination) to vaccine-induced immunity alone. We took advantage of the COVID-HOP prospective cohort, which includes vaccinated HCW followed over several months, collecting detailed data on demographic characteristics, comorbidities, and professional and personal exposures to COVID-19. We analyzed factors associated with omicron acquisition after January 2022, with a focus on immunization scheme (hybrid or vaccine-induced immunity). Out of 698 HCW analyzed, 298 acquired the omicron variant. In the multivariable analysis (taking into account comorbidities, professional/personal exposure and lifestyle), the two independent factors associated with an increased risk of infection were: younger age (P = 0.005) and immunization scheme (OR associated with vaccine-induced immunity alone: 2.43 [95% Confidence Interval: 1.64-3.60]) with hybrid immunity as reference). HCW with hybrid immunity have a reduced risk of acquiring omicron compared to those with vaccine-induced immunity alone. These findings emphasize the importance of a combined vaccination strategy to better protect HCW against emerging variants, and to vaccine HCW who experienced previous COVID-19 episodes.

A diet high in n-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) (C20:5 n-3), is cardioprotective. PUFAs integrate into membrane phospholipids, altering membrane protein function. We investigated the effects of various PUFAs on the anti-atherogenic cholesterol efflux pathways from cholesterol-loaded human THP-1 macrophages. Cells were supplemented (or not: standard cells) with 70 μM EPA, 50 μM arachidonic acid (AA) (C20:4 n-6) or 15 μM docosahexaenoic acid (DHA) (C22:6 n-3) for an extended duration to simulate a dietary strategy. EPA led to a 13 % decrease in ABCA1-mediated cholesterol efflux and to a 17 % decrease in SR-BI/ABCG1-mediated cholesterol efflux without affecting the expression of efflux proteins, while AA and DHA showed no impact. Compared to standard cells, EPA cells exhibited higher EPA levels along with reduced AA levels. EPA cells showed increased amounts of triglycerides and cholesteryl esters (CE) without a change in the acetylated LDL uptake. EPA did not influence the phenotype of macrophages according to surface markers and released cytokines. The incorporation of EPA did not disrupt efflux in macrophages loaded with free cholesterol. Conversely, EPA decreased CE hydrolysis from lipid droplets by 22 %. The diminished cholesterol efflux was not related to triglyceride accumulation or to variations in apo E secretion. EPA reduced the expression of carboxylesterase 1 (CES1) protein by 17 % without affecting the expression of neutral cholesterol ester hydrolase 1 (NCEH1). In conclusion, the membrane incorporation of EPA hinders the cholesterol efflux pathways in THP-1 foam cells likely by impairing the CE hydrolysis mediated by carboxylesterase 1.

Despite the progress of anti-cancer treatment, the prognosis of many patients with solid tumors is still dismal. Reliable noninvasive biomarkers are needed to predict patient survival and therapy response. Here, we propose a Humoral Complementomics approach: a work-up of assays to comprehensively evaluate complement proteins, activation fragments, and autoantibodies targeting complement proteins in plasma, which we correlated with the intratumoral complement activation, and/or local production, focusing on localized and metastatic clear cell renal cell carcinoma (ccRCC). In two prospective ccRCC cohorts, plasma C2, C5, Factor D and properdin were elevated compared to healthy controls, reflecting an inflammatory phenotype that correlated with plasma calprotectin levels but did not associate with CRP or with patient prognosis. Conversely, autoantibodies against the complement C3 and the reduced form of FH (a tumor neo-epitope reported in lung cancer) correlated with a favorable outcome. Our findings pointed to a specific group of patients with elevated plasma C4d and C1s-C1INH complexes, indicating the initiation of the classical pathway, along with elevated Ba and Bb, indicating alternative pathway activation. Boostrapped Lasso regularized Cox regression revealed that the most predictive complement biomarkers were elevated plasma C4d and Bb levels at the time of surgery, which correlated with poor prognosis. In conclusion, we propose Humoral Complementomics as an unbiased approach to study the global state of the complement system in any pathological plasma sample and disease context. Its implementation for ccRCC revealed that elevated C4d and Bb in plasma are promising prognostic biomarkers, correlating with shorter progression-free survival.

We present a case of a 48-year-old woman with a fortuitous discovery of macrocytic anemia and thrombocytopenia. Serum folate and vitamin B12 levels were normal. However, due to the presence of indirect signs of cobalamin deficiency, such as elevated homocysteine and methylmalonic acid, and signs of dyserythropoiesis on the bone marrow aspirate, pernicious anemia was suspected. Vitamin B12 dosage was repeated finding fluctuating but always normal results. Anti-intrinsic factor antibodies were present at a very high level, explaining the fluctuations and the interference found on the assay using competitive binding chemiluminescence (CBLA). Serum vitamin B12 dosage by electrochemiluminescence, a method described as not interfering with intrinsic factor antibodies, showed a collapsed vitamin B12 level. Measurement of vitamin B12 with CBLA after adsorption of immunoglobulins in the sample using protein G SepharoseTM, confirmed the interference of the cobalamin assay with autoantibodies. This case illustrates the difficulties regarding the analysis and standardization of the vitamin B12 assay for the diagnosis of pernicious anemia.

Thrombosis is a hallmark of severe COVID-19. Alpha-1-antitrypsin (AAT), an inflammation-inducible serpin with anti-inflammatory, tissue protective and anticoagulant properties may be involved in severe COVID-19 pathophysiology including thrombosis onset. In this study, we examined AAT ability to predict occurrence of thrombosis and in-hospital mortality during COVID-19. To do so, we performed a monocentric cross-sectional study of 137 hospitalized patients with COVID-19 of whom 56 (41%) were critically ill and 33 (22.4%) suffered from thrombosis during hospitalization. We measured AAT and IL-6 plasma levels in all patients and phenotyped AAT in a subset of patients with or without thrombosis paired for age, sex and COVID-19 severity. We observed that AAT levels at admission were higher in both non-survivors and thrombosis patients than in survivors and non-thrombosis patients. AAT: IL-6 ratio was lower in non-survivors and thrombosis patients. In a logistic regression multivariable analysis model adjusted on age, BMI and D-dimer levels, a higher AAT: IL-6 was a protective factor of both in-hospital mortality (Odds ratio, OR: 0.07 95%CI [0.02-0.25], p < 0.001) and thrombosis (OR 0.36 95%CI [0.14 -0.82], p 1/4 0.02). AAT phenotyping did not show a higher proportion of AAT abnormal variants in thrombosis patients.Our findings suggest an insufficient production of AAT regarding inflammation intensity during severe COVID-19. AAT appeared as a powerful predictive marker of severity, mortality and thrombosis mirroring the imbalance between harmful inflammation and protective counter-balancing mechanism in COVID-19. Restoring the balance between AAT and inflammation could offer therapeutic opportunities in severe COVID-19. (c) 2022 Published by Elsevier B.V.

Abstract Background Cardiac troponin I (cTnI) as measured by high-sensitive assays has been related to incident cardiovascular disease events (CVD) in the community. With the advent of ultra-sensitive assays, it is now possible to detect troponin I at very low concentration, far below the classical threshold of 1.9 pg/mL. However, the clinical relevance of these low concentrations for predicting CVD is largely unknown. Purpose To examine the association of cTnI as low as 0.013 pg/mL with incident cardiovascular disease events (CVDs) in the primary prevention setting. Methods cTnI was analyzed in the baseline plasma (2008–2012) of CVD free volunteers from the Paris Prospective Study III using for the first time a novel ultra-sensitive immunoassay (Simoa Troponin-I 2.0 Kit, Quanterix, Lexington) with a limit of detection (LOD) of 0.013 pg/mL. Incident CVD hospitalizations for coronary heart disease, stroke, arrhythmias, venous thromboembolism, arterial aneurysms and heart failure were validated by critical review of the hospital records. Hazard ratios were estimated per log-transformed standard deviation (SD) increase of cTnI in Cox models using age as the time scale. The added value (gain in discriminatory capacity) of cTnI for CVD risk prediction was examined by calculating the Harell's C-index boostraped difference of the SCORE 2 risk model with and without cTnI. Results There were 9503 CVD free participants (40% women) aged 59.6 (6.3) years at baseline. cTnI was detected in 99.6% of the participants (median value = 0.63 pg/mL, interquartile range [IQR] 0.39–1.09). After a median follow-up of 8.34 years (IQR, 8.0–10.07), 516 participants suffered 612 events. In fully-adjusted analysis, higher cTnI (per 1 SD increase of log cTnI) was significantly associated with CVD events combined (n=516, HR= 1.21; 1.06; 1.39). In univariate Cox analysis and compared to each single established risk factor, cTnI had the highest discrimination capacity for incident CVD events (C-index=0.6349) (Figure 1). Adding log cTnI to the SCORE 2 algorithm increased significantly albeit moderately discriminatory capacity (C-index 0.698 vs. 0.685; boostraped C index difference: 0.0135 (95% CI: 0.0131; 0.0138)). Conclusion cTnI concentrations as measured by a novel ultra-sensitive immunoassay is associated with a significant increased risk of incident CVD events in the primary prevention setting. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): ANR: French National Research AgencyEurope: Horizon 2020

BACKGROUND:Carmat bioprosthetic total artificial heart (Aeson; A-TAH) is a pulsatile and autoregulated device. The aim of this study is to evaluate level of hemolysis potential acquired von Willebrand syndrome after A-TAH implantation.METHODS:We examined the presence of hemolysis and acquired von Willebrand syndrome in adult patients receiving A-TAH support (n=10) during their whole clinical follow-up in comparison with control subjects and adult patients receiving Heartmate II or Heartmate III support. We also performed a fluid structure interaction model coupled with computational fluid dynamics simulation to evaluate the A-TAH resulting shear stress and its distribution in the blood volume.RESULTS:The cumulative duration of A-TAH support was 2087 days. A-TAH implantation did not affect plasma free hemoglobin over time, and there was no association between plasma free hemoglobin and cardiac output or beat rate. For VWF (von Willebrand factor) evaluation, A-TAH implantation did not modify multimers profile of VWF in contrast to Heartmate II and Heartmate III. Furthermore, fluid structure interaction coupled with computational fluid dynamics showed a gradually increase of blood damage according to increase of cardiac output (P<0.01), however, the blood volume fraction that endured significant shear stresses was always inferior to 0.03% of the volume for both ventricles in all regimens tested. An inverse association between cardiac output, beat rate, and high-molecular weight multimers ratio was found.CONCLUSIONS:We demonstrated that A-TAH does not cause hemolysis or AWVS. However, relationship between HMWM and cardiac output depending flow confirms relevance of VWF as a biological sensor of blood flow, even in normal range.

Background:To examine the association of ultrasensitive cTnI (cardiac troponin I) with incident cardiovascular disease events (CVDs) in the primary prevention setting. Methods:cTnI was analyzed in the baseline plasma (2008-2012) of CVD-free volunteers from the Paris Prospective Study III using a novel ultrasensitive immunoassay (Simoa Troponin-I 2.0 Kit, Quanterix, Lexington) with a limit of detection of 0.013 pg/mL. Incident CVD hospitalizations (coronary heart disease, stroke, cardiac arrhythmias, deep venous thrombosis or pulmonary embolism, heart failure, or arterial aneurysm) were validated by critical review of the hospital records. Hazard ratios were estimated per log-transformed SD increase of cTnI in Cox models using age as the time scale. Results:The study population includes 9503 participants (40% women) aged 59.6 (6.3) years. cTnI was detected in 99.6% of the participants (median value=0.63 pg/mL, interquartile range, 0.39-1.09). After a median follow-up of 8.34 years (interquartile range, 8.0-10.07), 516 participants suffered 612 events. In fully adjusted analysis, higher cTnI (per 1 SD increase of log cTnI) was significantly associated with CVD events combined (hazard ratio, 1.18 [1.08-1.30]). Among all single risk factors, cTnI had the highest discrimination capacity for incident CVD events (C index=0.6349). Adding log cTnI to the SCORE 2 (Systematic Coronary Risk Evaluation) risk improved moderately discriminatory capacity (C index 0.698 versus 0.685; bootstrapped C index difference: 0.0135 [95% CI, 0.0131-0.0138]), and reclassification of the participants (categorical net reclassification index, 0.0628 [95% CI, 0.023-0.102]). Findings were consistent using the US pooled cohort risk equation. Conclusions:Ultrasensitive cTnI is an independent marker of CVD events in the primary prevention setting.

Objectives: Risk of reinfection with SARS-CoV-2 among health-care workers (HCWs) is unknown. We assessed the incidence rate of SARS-CoV-2 reinfection in the real-life setting of a longitudinal observational cohort of HCWs from the Hopital Europeen Georges Pompidou, Assistance Publique-Hopitaux de Paris, France, during the first and second waves of COVID-19 epidemic. Methods: From March to December 2020, HCWs were subjected to molecular and serology testing of SARS-CoV-2. Reinfection was defined as a positive test result during the first wave, either by serology or PCR, followed by a positive PCR during the second wave. Evolution of COVID-19 status of HWCs was assessed by a Sankey diagram. Results: A total of 7765 tests (4579 PCR and 3186 serology) were carried out and 4168 HCWs had at least one test result during the follow-up period with a positivity rate of 15.9%. No case of reinfection during the second wave could be observed among 102 positive HCWs of the first wave, nor among 175 HCWs found positive by PCR during the second wave who were negative during the first wave. Conclusions: SARS-CoV-2 reinfection was not observed among HCWs, suggesting a protective immunity against reinfection that lasts at least 8 months post infection.

Background: SARS-CoV-2 induces a humoral response with seroconversion occurring within the first weeks after COVID-19 disease. Those antibodies exert a neutralizing activity against SARS-CoV-2, whose evolution overtime after COVID-19 is however unknown.Methods: In this monocentric prospective study, sera of 107 patients hospitalized with COVID-19 were collected at 3 months and 6 months post-infection. We performed quantitative neutralization experiments on top of high-throughput serological assays evaluating anti-Spike (S) and anti-Nucleocapsid (NP) IgG.Findings: Levels of sero-neutralization decreased significantly over study time, as well as IgG rates. After 6 months, 2.8% of the patients had a negative serological status for both anti-S and anti-NP IgG. However, all sera had a persistent and effective neutralizing effect on SARS-CoV-2 neutralizing assays. IgG levels correlated with sero-neutralization and this correlation was stronger for anti-S than for anti-NP antibodies. The level of sero-neutralization quantified at 6 months correlated with markers of initial severity, notably admission in intensive care units and the need for mechanical invasive ventilation.Interpretation: Decrease of IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity in our patients. Those results are encouraging and in favor of sustained humoral response for at least 6 months in patients previously hospitalized for COVID-19, which will have to be considered in global deployment of vaccination strategy.Trial Registration: The French Covid cohort (NCT04262921)Funding Statement: The French COVID cohort is funding by the REACTing (REsearch & ACtion emergING infectious diseases) consortium and by a grant of the French Ministry of Health (PHRC n°20-0424).Outside the submitted work, JSH is supported by AP-HP, INSERM, the French National Research Agency (NADHeart ANR-17-CE17-0015-02, PACIFIC ANR-18-CE14-0032-01, CORRECT_LMNA ANR-19-CE17-0013-02), the ERA-Net-CVD (ANR-16-ECVD-0011-03, Clarify project), Fédération Française de Cardiologie, the Fondation pour la Recherche Médicale, and by a grant from the Leducq Foundation (18CVD05), and is coordinating a French PIA Project (2018-PSPC-07, PACIFIC-preserved, BPIFrance) and a University Research Federation against heart failure (FHU2019, PREVENT_Heart Failure). JG reports personal fees from ViiV Healthcare, Gilead Science, Janssen Cilag, and research grants from Gilead Sciences, MSD and ViiV Healthcare, outside the submitted work.Declaration of Interests: Authors have nothing to disclose. There are no relationships with industry.Ethics Approval Statement: The French Covid cohort (NCT04262921) is a prospective multi-center observational cohort sponsored by Inserm which was authorized by the French Ethics Committee CPP Ile-de-France VI (ID RCB:2020-A00256-33).

Leber's hereditary optic neuropathy (LHON) is the most common disorder due to mitochondrial DNA mutations and complex I deficiency. It is characterized by an acute vision loss, generally in young adults, with a higher penetrance in males. How complex I dysfunction induces the peculiar LHON clinical presentation remains an unanswered question. To gain an insight into this question, we carried out a non-targeted metabolomic investigation using the plasma of 18 LHON patients, during the chronic phase of the disease, comparing them to 18 healthy controls. A total of 500 metabolites were screened of which 156 were accurately detected. A supervised Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) highlighted a robust model for disease prediction with a Q2 (cum) of 55.5%, with a reliable performance during the permutation test (cross-validation analysis of variance, P-value = 5.02284e-05) and a good prediction of a test set (P = 0.05). This model highlighted 10 metabolites with variable importance in the projection (VIP) > 0.8. Univariate analyses revealed nine discriminating metabolites, six of which were the same as those found in the Orthogonal Projections to Latent Structures Discriminant Analysis model. In total, the 13 discriminating metabolites identified underlining dietary metabolites (nicotinamide, taurine, choline, 1-methylhistidine and hippurate), mitochondrial energetic substrates (acetoacetate, glutamate and fumarate) and purine metabolism (inosine). The decreased concentration of taurine and nicotinamide (vitamin B3) suggest interesting therapeutic targets, given their neuroprotective roles that have already been demonstrated for retinal ganglion cells. Our results show a reliable predictive metabolomic signature in the plasma of LHON patients and highlighted taurine and nicotinamide deficiencies.

Background. Humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs within the first weeks after coronavirus disease 2019 (COVID-19). Those antibodies exert a neutralizing activity against SARS-CoV-2, whose evolution over time after COVID-19 as well as efficiency against novel variants are poorly characterized. Methods. In this prospective study, sera of 107 patients hospitalized with COVID-19 were collected at 3 and 6 months postinfection. We performed quantitative neutralization experiments on top of high-throughput serological assays evaluating anti-spike (S) and anti-nucleocapsid (NP) immunoglobulin G (IgG). Results. Levels of seroneutralization and IgG rates against the ancestral strain decreased significantly over time. After 6 months, 2.8% of the patients had a negative serological status for both anti-S and anti-NP IgG. However, all sera had a persistent and effective neutralizing effect against SARS-CoV-2. IgG levels correlated with seroneutralization, and this correlation was stronger for anti-S than for anti-NP antibodies. The level of seroneutralization quantified at 6 months correlated with markers of initial severity, notably admission to intensive care units and the need for mechanical invasive ventilation. In addition, sera collected at 6 months were tested against multiple SARS-CoV-2 variants and showed efficient neutralizing effects against the D614G, B.1.1.7, and P.1 variants but significantly weaker activity against the B.1.351 variant. Conclusions. Decrease in IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Our results indicate a sustained humoral response against the ancestral strain and the D614G, B.1.1.7, and P.1 variants for at least 6 months in patients previously hospitalized for COVID-19. A weaker protection was, however, observed for the B.1.351 variant.

Objective: The mechanisms underlying the association between low number of masticatory units and cardiovascular disease remain unclear. Under a nutritional framework, we hypothesized that poor masticatory capacity could represent an early sign of elevated cardiovascular disease risk as evaluated by circulating markers of systemic inflammation and cardiomyocyte stress or damage. Approach and Results: In this cross-sectional analysis of the Paris Prospective Study III, a community-based observational study, 4837 adults aged 50 to 75 without cardiovascular disease history underwent a full-mouth clinical examination and plasma NTproBNP (N-terminal natriuretic propeptide), hs-CRP (high-sensitivity C-reactive protein), IL-6 (interleukin-6), hs-TNI (high-sensitivity troponin I) were measured using highly sensitive technics. Poor masticatory capacity was defined as <5 functional masticatory units, that is, pairs of opposing natural or prosthetically replaced posterior teeth. In linear regression analysis accounting for sociodemographic factors, cardiovascular disease risk factors, gingival inflammation, and body mass index, poor masticatory capacity was significantly associated with lower levels of NTproBNP (β=−0.11, P =0.045). The significant association between poor masticatory capacity and higher IL-6 in multivariable analysis was confounded by body mass index. There was no association between functional masticatory units and hs-TNI even in unadjusted analysis. Conclusions: The present findings support a nutritional pathway whereby diet alterations and the resulting abdominal obesity associated with poor masticatory capacity may contribute to the higher level of IL-6 and to the lower level of NTproBNP, respectively.

Poor oral health has been linked to coronary heart disease (CHD). Clustering clinical oral conditions routinely recorded in adults may identify their CHD risk profile. Participants from the Paris Prospective Study 3 received, between 2008 and 2012, a baseline routine full-mouth clinical examination and an extensive physical examination and were thereafter followed up every 2 y until September 2020. Three axes defined oral health conditions: 1) healthy, missing, filled, and decayed teeth; 2) masticatory capacity denoted by functional masticatory units; and 3) gingival inflammation and dental plaque. Hierarchical cluster analysis was performed with multivariate Cox proportional hazards regression models and adjusted for age, sex, smoking, body mass index, education, deprivation (EPICES score; Evaluation of Deprivation and Inequalities in Health Examination Centres), hypertension, type 2 diabetes, LDL and HDL serum cholesterol (low- and high-density lipoprotein), triglycerides, lipid-lowering medications, NT-proBNP and IL-6 serum level. A sample of 5,294 participants (age, 50 to 75 y; 37.10% women) were included in the study. Cluster analysis identified 3,688 (69.66%) participants with optimal oral health and preserved masticatory capacity (cluster 1), 1,356 (25.61%) with moderate oral health and moderately impaired masticatory capacity (cluster 2), and 250 (4.72%) with poor oral health and severely impaired masticatory capacity (cluster 3). After a median follow-up of 8.32 y (interquartile range, 8.00 to 10.05), 128 nonfatal incident CHD events occurred. As compared with cluster 1, the risk of CHD progressively increased from cluster 2 (hazard ratio, 1.45; 95% CI, 0.98 to 2.15) to cluster 3 (hazard ratio, 2.47; 95% CI, 1.34 to 4.57; P < 0.05 for trend). To conclude, middle-aged individuals with poor oral health and severely impaired masticatory capacity have more than twice the risk of incident CHD than those with optimal oral health and preserved masticatory capacity (ClinicalTrials.gov NCT00741728).

A high intake in polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) (C20:5 n-3), is cardioprotective. Dietary PUFAs incorporate into membrane phospholipids, which may modify the function of membrane proteins. We investigated the consequences of the membrane incorporation of several PUFAs on the key antiatherogenic ABCA1-mediated cholesterol efflux pathway. Human THP-1 macrophages were incubated with EPA, arachidonic acid (AA) (C20:4 n-6) or docosahexaenoic acid (DHA) (C22:6 n-3) for a long time to mimic a chronic exposure. EPA 70 μM, but not AA 50 μM or DHA 15 μM, increased ABCA1-mediated cholesterol efflux to apolipoprotein (apo) AI by 28% without altering aqueous diffusion. No variation in ABCA1 expression or localization was observed after EPA treatment. EPA incorporation did not affect the phenotype of THP-1 macrophages. The membrane phospholipids composition of EPA cells displayed higher levels of both EPA and its elongation product docosapentaenoic acid, which was associated with drastic lower levels of AA. Treatment by EPA increased the ATPase activity of the transporter, likely through a PKA-dependent mechanism. Eicosanoids were not involved in the stimulated ABCA1-mediated cholesterol efflux from EPA-enriched macrophages. In addition, EPA supplementation increased the apo AI binding capacity from macrophages by 38%. Moreover, the increased apo AI binding in EPA-enriched macrophages can be competed. In conclusion, EPA membrane incorporation increased ABCA1 functionality in cholesterol-normal human THP-1 macrophages, likely through a combination of different mechanisms. This beneficial in vitro effect may partly contribute to the cardioprotective effect of a diet enriched with EPA highlighted by several recent clinical trials.

Background: Coronavirus disease 2019 (COVID-19) has been associated with cardiovascular complications and coagulation disorders. Objectives: To explore clinical and biological parameters of COVID-19 patients with hospitalization criteria that could predict referral to intensive care unit (ICU). Methods: Analyzing the clinical and biological profiles of COVID-19 patients at admission. Results: Among 99 consecutive patients that fulfilled criteria for hospitalization, 48 were hospitalized in the medicine department, 21 were first admitted to the medicine ward department and referred later to ICU, and 30 were directly admitted to ICU from the emergency department. At admission, patients requiring ICU were more likely to have lymphopenia, decreased SpO2, a D-dimer level above 1,000 ng/mL, and a higher high-sensitivity cardiac troponin (Hs-cTnI) level. A receiver operating characteristic curve analysis identified Hs-cTnI above 9.75 pg/mL as the best predictive criteria for ICU referral [area under the curve (AUC), 86.4; 95% CI, 76.6–96.2]. This cutoff for Hs-cTnI was confirmed in univariate [odds ratio (OR), 22.8; 95% CI, 6.0–116.2] and multivariate analysis after adjustment for D-dimer level (adjusted OR, 20.85; 95% CI, 4.76–128.4). Transthoracic echocardiography parameters subsequently measured in 72 patients showed an increased right ventricular (RV) afterload correlated with Hs-cTnI (r = 0.42, p = 0.010) and D-dimer (r = 0.18, p = 0.047). Conclusion: Hs-cTnI appears to be the best relevant predictive factor for referring COVID-19 patients to ICU. This result associated with the correlation of D-dimer with RV dilatation probably reflects a myocardial injury due to an increased RV wall tension. This reinforces the hypothesis of a COVID-19-associated microvascular thrombosis inducing a higher RV afterload.

Facing the ongoing pandemic caused by SARS-CoV-2, there is an urgent need for serological assays identifying individuals with on-going infection as well as past coronavirus infectious disease 2019 (COVID-19). We herein evaluated the analytical performances of the CE IVD-labeled Abbott SARS-CoV-2 IgG assay (Des Plaines, IL, USA) carried out with the automated Abbott Architect™ i2000 platform at Hôpital Européen Georges Pompidou, Paris, France, using serum sample panels obtained from health-workers with COVID-19 history confirmed by positive nucleic acid amplification-based diagnosis and from patients randomly selected for whom serum samples were collected before the COVID-19 epidemic. The Abbott SARS-CoV-2 IgG assay showed sensitivity of 94 % and specificity of 100 %, demonstrating high analytical performances allowing convenient management of suspected on-going and past-infections. In addition, the SARS-CoV-2 IgG positivity rates were compared in COVID-19 positive and COVID-19 free areas from our hospital. Thus, the frequency of SARS-CoV-2-specific IgG was around 10-fold higher in COVID-19 areas than COVID-19 free areas (75 % versus 8%; P < 0.001). Interestingly, several inpatients hospitalized in COVID-19 free areas suffering from a wide range of unexplained clinical features including cardiac, vascular, renal, metabolic and infectious disorders, were unexpectedly found seropositive for SARS-CoV-2 IgG by systematic routine serology, suggesting possible causal involvement of SARS-CoV-2 infection. Taken together, these observations highlight the potential interest of SARS-CoV-2-specific serology in the context of COVID-19 epidemic, especially to assess past SARS-CoV-2 infection as well as possible unexpected COVID-19-associated disorders.