Diabetes and the risk of cardiovascular events and all-cause mortality among older adults: an individual participant data analysis of five prospective studies.

BACKGROUND: Guidelines and studies provide conflicting information on whether type 2 diabetes (T2D) should be considered a coronary heart disease risk (CHD) equivalent in older adults. METHODS: We synthesized participant-level data on 82,723 individuals aged ≥65 years from five prospective studies in two-stage meta-analyses. We estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of T2D (presence versus absence) on a primary composite outcome defined as cardiovascular events or all-cause mortality. Secondary outcomes were the components of the composite. We evaluated CHD risk equivalence by comparing outcomes between individuals with T2D but no CHD versus CHD but no T2D. RESULTS: The median age of participants was 71 years, 20% had T2D and 17% had CHD at baseline. A total of 29,474 participants (36%) experienced the composite outcome. Baseline T2D was associated with higher risk of cardiovascular events or all-cause mortality versus no T2D (HR 1.44, 95% CI [1.40-1.49]). The association was weaker in individuals aged ≥75 years versus 65-74 years (HR 1.32 [1.19-1.46] vs. 1.56 [1.50-1.62]; p-value for interaction = .032). Compared to individuals with CHD but no T2D, individuals with T2D but no CHD had a similar risk of the composite outcome (HR 0.95 [0.85-1.07]), but a lower risk of cardiovascular events (HR 0.76 [0.59-0.98]). CONCLUSIONS: T2D was associated with increased risk of cardiovascular events and all-cause mortality in older adults, but T2D without CHD conferred lower risk of cardiovascular events compared to CHD without T2D. Our results suggest that T2D should not be considered a CHD risk equivalent in older adults.

[Do we all suffer from imposter syndrome?] / Souffrons-nous toutes et tous d'un syndrome d'imposture?

Imposture syndrome is widespread among physicians and medical students. It is defined as a psychological experience in which people doubt their own skills and achievements despite proven successes and thus have an unfounded fear of being found out. This can have serious consequences, such as anxiety and/or depressive disorders, and can lead to burn-out. The Clance scale is a self-assessment tool used to measure the level of imposture experienced and, when appropriate, to assess the suffering caused. The aim of this article is to help recognise this syndrome, which is one way of preventing it.

Le syndrome d'imposture est largement répandu chez les médecins et les étudiant-e-s en médecine. Il est défini comme une expérience psychologique où l'individu, malgré des succès démontrés, doute de ses compétences et réussites et, ainsi, éprouve une crainte infondée d'être démasqué. D'importantes conséquences comme des troubles anxieux et/ou dépressifs associés à un burnout peuvent en découler. L'échelle de Clance est un outil d'autoévaluation permettant de mesurer le niveau d'imposture ressenti et, le cas échéant, d'en évaluer la souffrance engendrée. Le but de cet article est d'aider à reconnaître ce syndrome, ce qui constitue l'un des axes de sa prévention.

How ambient temperature affects mood: an ecological momentary assessment study in Switzerland.

BACKGROUND: Recent research has suggested that an increase in temperature can negatively affect mental health and increase hospitalization for mental illness. It is not clear, however, what factors or mechanisms mediate this association. We aimed to (1) investigate the associations between ambient temperatures and bad daily mood, and (2) identify variables affecting the strength of these associations (modifiers) including the time, the day of the week and the year of the mood rating, socio-demographic characteristics, sleep quality, psychiatric disorders and the personality trait neuroticism in the community. METHODS: Data stemmed from the second follow-up evaluation of CoLaus|PsyCoLaus, a prospective cohort study conducted in the general population of Lausanne (Switzerland). The 906 participants rated their mood level four times a day during seven days using a cell phone app. Mixed-effects logistic regression was used to determine the association between daily maximum temperature and mood level. Participant ID was inserted as a random effect in the model, whereas the time of the day, the day of the week and the year were inserted as fixed effects. Models were controlled for several confounders (socio-demographic characteristics, sleep quality, weather parameters and air pollutants). Stratified analyses were conducted based on socio-demographic characteristics, sleep quality, presence of psychiatric disorders or a high neuroticism. RESULTS: Overall, the probability of having a bad mood for the entire day decreased by 7.0% (OR: 0.93: 95% CI 0.88, 0.99) for each 5 °C increase in maximum temperature. A smaller and less precise effect (-3%; OR: 0.97: 95% CI 0.91, 1.03) was found when controlling for sunshine duration. A higher association was found in participants with bipolar disorder (-23%; OR: 0.77: 95% CI 0.51, 1.17) and in participants with a high neuroticism (-13%; OR: 0.87 95% CI 0.80, 0.95), whereas the association was reversed for participants with anxiety (20%; OR: 1.20: 95% CI 0.90, 1.59), depression (18%; OR: 1.18 95% CI 0.94, 1.48) and schizophrenia (193%; OR: 2.93 95% CI 1.17, 7.73). CONCLUSIONS: According to our findings, rising temperatures may positively affect mood in the general population. However, individuals with certain psychiatric disorders, such as anxiety, depression, and schizophrenia, may exhibit altered responses to heat, which may explain their increased morbidity when exposed to high temperatures. This suggests that tailored public health policies are required to protect this vulnerable population.

Association between Mediterranean Diet and Type 2 Diabetes: Multiple Cross-Sectional Analyses.

AIM: To assess whether the Mediterranean diet (MD) is associated with lower levels of type 2 diabetes (T2D) in a non-Mediterranean population. METHODS: Cross-sectional analysis of follow-ups 1 (FU1, 2009-2012, n = 4398, 45.7% men, 57.7 ± 10.5 years), 2 (FU2, 2014-2017, n = 3154, 45.0% men, 61.7 ± 9.9 years), and 3 (FU3, 2018-2021, n = 2394, 45.2% men, 65.0 ± 9.6 years) of the Colaus|PsyCoLaus study (Lausanne, Switzerland). Two MD scores (Trichopoulou, noted MD1, and Sofi, noted MD2) were calculated using participants' dietary data. T2D was defined as a fasting plasma glucose ≥7 mmol/L and/or the presence of an antidiabetic drug treatment. RESULTS: Participants with the highest MD adherence had a higher educational level, a lower BMI, were less frequent smokers, presented less frequently with hypertension, and were more frequent alcohol consumers. After multivariable adjustment, no differences were found between participants with and without T2D regarding MD scores: 3.93 ± 0.07 vs. 3.97 ± 0.02; 4.08 ± 0.10 vs. 3.98 ± 0.03, and 3.83 ± 0.11 vs. 3.97 ± 0.03, respectively, for the MD1 score in FU1, FU2, and FU3. In addition, no association was found between adherence to MD and T2D: odds ratio (and 95% confidence interval) for medium and high relative to low adherence to MD1: 0.87 (0.68-1.10) and 0.89 (0.64-1.24) in FU1, 1.04 (0.76-1.42) and 1.07 (0.68-1.67) in FU2, and 0.73 (0.53-1.03) and 0.61 (0.37-1.02) in FU3, respectively. Corresponding results for MD2 were 0.90 (0.70-1.15) and 1.03 (0.69-1.53) in FU1, 1.16 (0.82-1.63) and 1.40 (0.81-2.41) in FU2, and 0.93 (0.65-1.34) and 0.55 (0.28-1.08) in FU3. CONCLUSION: We found no association between Mediterranean diet adherence and T2D in a non-Mediterranean population.

Objective polysomnography-based sleep features and major depressive disorder subtypes in the general population.

Insomnia and its opposite hypersomnia are part of the diagnostic criteria for major depressive disorder (MDD). However, no study has investigated whether the postulated sleep alterations in clinical subtypes of MDD are reflected in polysomnography (PSG)-derived objective sleep measures. The objective of this study was to establish associations between the melancholic, atypical and unspecified subtypes of MDD and objective PSG-based sleep features. This cross-sectional analysis included 1820 community-dwelling individuals who underwent PSG and a semi-structured psychiatric interview to elicit diagnostic criteria for MDD and its subtypes. Adjusted robust linear regression was used to assess associations between MDD subtypes and PSG-derived objective sleep measures. Current melancholic MDD was significantly associated with decreased absolute delta power and sleep efficiency and with increased wake after sleep onset. Remitted unspecified MDD was significantly associated with increased rapid eye movements density. No other significant associations were identified. Our findings reflect that some PSG-based sleep features differed in MDD subtypes compared with no MDD. The largest number of significant differences were observed for current melancholic MDD, whereas only rapid eye movements density could represent a risk factor for MDD as it was the only sleep measure that was also associated with MDD in remitted participants.

Cardiovascular disease and type 2 diabetes in older adults: a combined protocol for an individual participant data analysis for risk prediction and a network meta-analysis of novel anti-diabetic drugs.

Introduction: Older and multimorbid adults with type 2 diabetes (T2D) are at high risk of cardiovascular disease (CVD) and chronic kidney disease (CKD). Estimating risk and preventing CVD is a challenge in this population notably because it is underrepresented in clinical trials. Our study aims to (1) assess if T2D and haemoglobin A1c (HbA1c) are associated with the risk of CVD events and mortality in older adults, (2) develop a risk score for CVD events and mortality for older adults with T2D, (3) evaluate the comparative efficacy and safety of novel antidiabetics. Methods and analysis: For Aim 1, we will analyse individual participant data on individuals aged ≥65 years from five cohort studies: the Optimising Therapy to Prevent Avoidable Hospital Admissions in Multimorbid Older People study; the Cohorte Lausannoise study; the Health, Aging and Body Composition study; the Health and Retirement Study; and the Survey of Health, Ageing and Retirement in Europe. We will fit flexible parametric survival models (FPSM) to assess the association of T2D and HbA1c with CVD events and mortality. For Aim 2, we will use data on individuals aged ≥65 years with T2D from the same cohorts to develop risk prediction models for CVD events and mortality using FPSM. We will assess model performance, perform internal-external cross validation, and derive a point-based risk score. For Aim 3, we will systematically search randomized controlled trials of novel antidiabetics. Network meta-analysis will be used to determine comparative efficacy in terms of CVD, CKD, and retinopathy outcomes, and safety of these drugs. Confidence in results will be judged using the CINeMA tool. Ethics and dissemination: Aims 1 and 2 were approved by the local ethics committee (Kantonale Ethikkommission Bern); no approval is required for Aim 3. Results will be published in peer-reviewed journals and presented in scientific conferences.

Prevalence of atrial fibrillation : The Swiss population-based CoLaus|PsyCoLaus study.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia worldwide and is associated with increased morbi-mortality. The prevalence of AF in the Western world is increasing; however, reports on the prevalence of AF in the past decade are scarce, and whether the prevalence of AF increased during the last decade in Switzerland remains uncertain. Therefore, using data from a Swiss population-based sample, we aimed to assess the point prevalence of AF from 2014 to 2017 and to investigate determinants of AF. METHODS: A cross-sectional analysis of 4616 Caucasian participants aged 45-86 years (55% women) from a population-based sample was designed to explore the point prevalence and determinants of cardiovascular risk factors in the population of Lausanne, Switzerland. AF was assessed using electrocardiography (ECG) between 2014 and 2017. RESULTS: Overall, the point prevalence of AF was 0.9% (95% confidence interval [95% CI]: 0.7-1.2%) and the combined AF + atrial flutter (AFL) point prevalence was 1.1% (95% CI: 8.4-1.5%). The point prevalence of AF was higher among men (81% vs. 19% in women) and increased with age, reaching 3.1% in participants aged ≥ 80. In multivariable analysis, male gender (odds ratio and 95% CI: 4.98 [1.01-24.6]) and increasing age (2.86 [1.40-5.87] per decade) were associated with AF. CONCLUSION: The point prevalence of AF and of AF + AFL, assessed between 2014 and 2017 in the city of Lausanne (Switzerland), was low but increased with age and in men.

[Teaching and learning during attending rounds in internal medicine: an anthropological study]. / Enseigner et apprendre lors des grandes visites en médecine interne hospitalière : Une étude anthropologique.

This anthropological research aims to highlight the educational approaches in action during attending rounds. The goal is to understand how specific learning domains, professional socialization and learning environments are influenced by the different ways of conducting attending rounds. Two formats of rounds were noted: the IN format, when the patient case is presented in the patient room, and the OUT format. Six educational approaches were identified. The attending round format has an impact on the approaches used. The latter contribute to the development, to varying degrees, of knowledge, skills and attitudes. Attending rounds remain a space for "top-down" transmission and supervision, even though some approaches involve learner initiatives and peer group logic.

Notre recherche anthropologique vise à mettre en lumière les approches pédagogiques à l'œuvre durant les grandes visites. Comment les domaines d'apprentissages visés, la socialisation professionnelle et l'environnement d'apprentissage sont-ils influencés par les différentes manières de les conduire ? Deux formes de visites sont retrouvées : la forme IN (le cas est présenté au lit du patient) et la forme OUT. Six approches pédagogiques ont été identifiées. La forme de grande visite influence les approches pédagogiques mobilisées. Celles-ci contribuent à développer, à des degrés variables, des savoirs, savoir-faire et savoir-être. Les grandes visites restent un espace de transmission « top-down ¼ et de surveillance, même si certaines approches encouragent les initiatives des apprenants ainsi que les logiques de groupes de pairs.

Investigating acceptability of a training programme in precision medicine for frontline healthcare professionals: a mixed methods study.

BACKGROUND: Precision Medicine offers tailored prevention, diagnosis, treatment and management to patients that considers genomics, lifestyle and environmental factors. If implementation of Precision Medicine is to advance, effective, focused upskilling of frontline healthcare professionals through quality continuing professional development is needed. This study reports on an evidence-based approach to needs assessment to investigate the current level of knowledge of Precision Medicine, acceptable content for training, the perceived potential of a more precision approach to patient care and motivation to participate in a training programme among pharmacists, advanced practice nurses and general practitioners. Investigating perceived needs can avoid a top-down approach and support a design that is fit for purpose to targeted professions. METHODS: This study reports on 2 focus groups (n = 12) delivered in French and German with equal professional participation of the targeted professions. The research objectives were investigated in two phases. During the first phase, a literature review and expert consultations were conducted to develop a definition of PM, patient cases and content for training. In a second phase, these investigations were further explored using focus groups to investigate acceptable learning objectives, the potential of PM to relevant professions and motivation of participants. Quantitative investigations using rating scales and visual analogues were incorporated. The focus groups were audio recorded, transcribed by intelligent verbatim and translated to English. NVivo was used for data analysis and interpretation following a hybrid approach using the Framework Method and thematic analysis. The analytical framework, Implementation Science, was applied to organise and present research data. RESULTS: Precision Medicine is considered a new topic area, largely unfamiliar to frontline healthcare professionals.. There was acceptance of a more precision approach to care among all participants with perceived positive implications for patients. Valuable insight was gathered on acceptable content and form for training. All participants expressed concerns on readiness within their professions which included an insufficient system infrastructure, a lack of time to attend needed training, a lack of clarity for use in practice and the time needed to build a support network. CONCLUSIONS: A precision approach to patient care is on the horizon for health care professionals not only in hospital settings but also at the community level. Our results conclude that an adaptable and flexible training programme in PM is timely, contextually relevant and conducive to the needs of targeted health professions for successful implementation. A training programme in PM will require support across sectors and stakeholders, supporting insurance models, educated patients and integrated care supported by innovative technology. Implementation Science outcomes are a useful strategy towards design of an effective training programme that can have measurable impact in practice.

Effect of acute iron infusion on insulin secretion: A randomized, double-blind, placebo-controlled trial.

Background: Chronic exposure to high iron levels increases diabetes risk partly by inducing oxidative stress, but the consequences of acute iron administration on beta cells are unknown. We tested whether the acute administration of iron for the correction of iron deficiency influenced insulin secretion and the production of reactive oxygen species. Methods: Single-center, double-blinded, randomized controlled trial conducted between June 2017 and March 2020. 32 women aged 18 to 47 years, displaying symptomatic iron deficiency without anaemia, were recruited from a community setting and randomly allocated (1:1) to a single infusion of 1000 mg intravenous ferric carboxymaltose (iron) or saline (placebo). The primary outcome was the between group mean difference from baseline to day 28 in first and second phase insulin secretion, assessed by a two-step hyperglycaemic clamp. All analyses were performed by intention to treat. This trial was registered in ClinicalTrials.gov NCT03191201. Findings: Iron infusion did not affect first and second phase insulin release. For first phase, the between group mean difference from baseline to day 28 was 0 µU × 10 min/mL [95% CI, -22 to 22, P = 0.99]. For second phase, it was -5 µUx10min/mL [95% CI, -161 to 151; P = 0.95] at the first plateau of the clamp and -249 µUx10min/mL [95% CI, -635 to 137; P = 0.20] at the second plateau. Iron infusion increased serum ascorbyl/ascorbate ratio, a marker of plasma oxidative stress, at day 14, with restoration of normal ratio at day 28 relative to placebo. Finally, high-sensitive C-reactive protein levels remained similar among groups. Interpretation: In iron deficient women without anaemia, intravenous administration of 1000 mg of iron in a single sitting did not impair glucose-induced insulin secretion despite a transient increase in the levels of circulating reactive oxygen species. Funding: The Swiss National Science Foundation, University of Lausanne and Leenaards, Raymond-Berger and Placide Nicod Foundations.

The association between objective sleep duration and diet. The CoLaus|HypnoLaus study.

BACKGROUND AND AIMS: Sleep deprivation is frequently associated with an unhealthy diet. So far, most studies used reported sleep duration. We assessed the associations between objectively measured sleep duration and dietary intake. METHODS: Cross-sectional study conducted between 2009 and 2013 on 1910 participants (49.5% women, 58.3 ± 11.0 years) living in Lausanne, Switzerland. Total sleep time (TST) was assessed using polysomnography and categorized into <7, 7-9 and >9 hours/day. Total energy, macro and micronutrients intake, dietary adequacy scores and compliance to Swiss dietary recommendations were assessed. RESULTS: There were 60.6%, 37.2% and 2.2% of the participants in the categories <7, 7-9 and >9 h/day, respectively. Body mass index was higher in the >9 h/d sleep category. After multivariate adjustment, significant (p < 0.05) differences were found between sleep categories regarding total carbohydrates (46.6 ± 8.6, 46.0 ± 8.8 and 48.1 ± 8.0% of total energy intake for <7, 7-9 and >9 h/day, respectively), mono and disaccharides (22.7 ± 8.0, 22.4 ± 8.3 and 25.2 ± 8.8), and total fat (33.9 ± 6.4, 34.7 ± 6.9 and 34.2 ± 5.8). No association was found for total energy intake, other nutrients, dietary adequacy scores, dietary patterns or compliance to dietary guidelines. The differences in mono and disaccharides were found in women and the differences in total fat in men, although sex-diet intake interactions were not significant. Sensitivity analyses excluding participants with sleep apnea, using quartiles of TST or subjective sleep duration yielded similar conclusions. CONCLUSION: Little if no associations were found between objectively measured TST and dietary intake in a Swiss general adult population. The associations with total carbohydrate, mono and disaccharide and total fat intake deserve further investigation.

Association between nocturnal heart rate variability and incident cardiovascular disease events: The HypnoLaus population-based study.

BACKGROUND: Although heart rate variability (HRV) is widely used to assess cardiac autonomic function, few studies have specifically investigated nocturnal HRV. OBJECTIVE: The purpose of this study was to assess the association between nocturnal HRV and cardiovascular disease (CVD) incidence over 4 years in a population-based sample. METHODS: A total of 1784 participants (48.2% men; 58 ± 11 years) from the HypnoLaus population-based cohort free of CVD at baseline were included. Polysomnography-based electrocardiograms were exported to analyze time- and frequency-domain HRV, Poincaré plots indices, detrended fluctuation analysis, acceleration capacity (AC) and deceleration capacity (DC), entropy, heart rate fragmentation (HRF), and heart rate turbulence. Multivariable-adjusted Cox regression analysis was used to assess the association between HRV indices and incident CVD events. RESULTS: Sixty-seven participants (3.8%) developed CVD over mean follow-up of 4.1 ± 1.1 years. In a fully adjusted model, AC (hazard ratio per 1-SD increase; 95% confidence interval: 1.59; 1.17-2.16; P = .004), DC (0.63; 0.47-0.84; P = .002), and HRF (1.41; 1.11-1.78; P = .005) were the only HRV metrics significantly associated with incident CVD events after controlling for false discovery rate. CONCLUSION: Nocturnal novel HRV parameters such as AC, DC, and HRF are better predictors of CVD events than time and frequency traditional HRV parameters. These findings suggest a form of dysautonomia and fragmented rhythms, but further experimental studies are needed to delineate the underlying physiological mechanisms of these novel HRV parameters.

Prevalence and factors associated with chronic use of levothyroxine: A cohort study.

IMPORTANCE: Levothyroxine prescriptions are rising worldwide. However, there are few data on factors associated with chronic use. OBJECTIVE: To assess the prevalence of chronic levothyroxine use, its rank among other chronic drugs and factors associated with chronic use. To assess the proportion of users outside the therapeutic range of thyroid-stimulating hormone (TSH). DESIGN: Cohort study (CoLaus|PsyCoLaus) with recruitment from 2003 to 2006. Follow-ups occurred 5 and 10 years after baseline. PARTICIPANTS: A random sample of Lausanne (Switzerland) inhabitants aged 35-75 years. MAIN OUTCOMES: We evaluated the prevalence of chronic levothyroxine use and we then ranked it among the other most used chronic drugs. The ranking was compared to data from health insurance across the country. We assessed the association between each factor and chronic levothyroxine use in multivariable logistic regression models. The proportion of chronic levothyroxine users outside the usual TSH therapeutic range was assessed. RESULTS: 4,334 participants were included in the analysis (mean±SD age 62.8±10.4 years, 54.9% women). 166 (3.8%) participants were chronic levothyroxine users. Levothyroxine was the second most prescribed chronic drug after aspirin in the cohort (8.2%) and the third most prescribed when using Swiss-wide insurance data. In multivariable analysis, chronic levothyroxine use was associated with increasing age [odds ratio 1.03, 95% confidence interval 1.01-1.05 per 1-year increase]; female sex [11.87 (5.24-26.89)]; BMI [1.06 (1.02-1.09) per 1-kg/m2 increase]; number of concomitant drugs [1.22 (1.16-1.29) per 1-drug increase]; and family history of thyroid pathologies [2.18 (1.37-3.48)]. Among chronic levothyroxine users with thyroid hormones assessment (n = 157), 42 (27%) were outside the TSH therapeutic range (17% overtreated and 10% undertreated). CONCLUSIONS: In this population-based study, levothyroxine ranked second among chronic drugs. Age, female sex, BMI, number of drugs and family history of thyroid pathologies were associated with chronic levothyroxine use. More than one in four chronic users were over- or undertreated.

[Strategy diagnostic and therapeutic of an hypophosphatemia]. / Stratégie diagnostique et thérapeutique d'une hypophosphatémie.

Hypophosphatemia is an electrolyte disorder frequently faced in inpatient and outpatient practice. Associated symptoms are very variable but are often nonspecific. The consequence is that it might be overlooked. Yet, when severe, hypophosphatemia is associated with a significant morbi-mortality and, therefore, needs to be identified and treated appropriately. Treatment goes from identifying the cause to substitution according to whether it is symptomatic or not and its severity. Mild to moderate hypophosphatemia needs substitution only when symptomatic which will be administrated orally, while severe hypophosphatemia requires an intravenous substitution. We review here situations at risk of hypophosphatemia, its clinical manifestations and its management in terms of diagnostic and treatment.

L'hypophosphatémie est un désordre électrolytique fréquemment rencontré, tant en milieu hospitalier qu'ambulatoire. Sa symptomatologie est très variable et souvent aspécifique. De ce fait, elle peut parfois être manquée. Pourtant, lorsque sévère, elle est grevée d'une morbimortalité non négligeable. Le traitement passe par l'identification de sa cause, puis une substitution en fonction de la présentation clinique et de sa sévérité. Une hypophosphatémie légère à modérée nécessite une supplémentation en cas de symptômes et sera administrée par voie orale, tandis qu'une hypophosphatémie sévère justifie une supplémentation intraveineuse. Cet article intègre un rappel du métabolisme du phosphate, les situations associées à un risque d'hypophosphatémie, ses manifestations cliniques et sa gestion tant sur le plan diagnostique que thérapeutique.

The cytokines HGF and CXCL13 predict the severity and the mortality in COVID-19 patients.

The objective of the present study was to identify biological signatures of severe coronavirus disease 2019 (COVID-19) predictive of admission in the intensive care unit (ICU). Over 170 immunological markers were investigated in a 'discovery' cohort (n = 98 patients) of the Lausanne University Hospital (LUH-1). Here we report that 13 out of 49 cytokines were significantly associated with ICU admission in the three cohorts (P < 0.05 to P < 0.001), while cellular immunological markers lacked power in discriminating between ICU and non-ICU patients. The cytokine results were confirmed in two 'validation' cohorts, i.e. the French COVID-19 Study (FCS; n = 62) and a second LUH-2 cohort (n = 47). The combination of hepatocyte growth factor (HGF) and C-X-C motif chemokine ligand 13 (CXCL13) was the best predictor of ICU admission (positive and negative predictive values ranging from 81.8% to 93.1% and 85.2% to 94.4% in the 3 cohorts) and occurrence of death during patient follow-up (8.8 fold higher likelihood of death when both cytokines were increased). Of note, HGF is a pleiotropic cytokine with anti-inflammatory properties playing a fundamental role in lung tissue repair, and CXCL13, a pro-inflammatory chemokine associated with pulmonary fibrosis and regulating the maturation of B cell response. Up-regulation of HGF reflects the most powerful counter-regulatory mechanism of the host immune response to antagonize the pro-inflammatory cytokines including CXCL13 and to prevent lung fibrosis in COVID-19 patients.