Fibrin monomers evaluation during hospitalization for COVID-19 is a predictive marker of in-hospital mortality.

Background: Coagulopathy is one of the main triggers of severity and worsening of Coronavirus disease 2019 (COVID-19) particularly in critically ill patients. D-dimer has been widely used to detect COVID-19 coagulation disorders and has been correlated with outcomes such as disease severity and in-hospital mortality. Involvement of other fibrin degradation products, particularly fibrin monomers (FM), remains an ongoing question. Methods: We performed a monocentric study of adult patients with COVID-19, who were admitted either in the medical ward (MW) or in the intensive care unit (ICU) and who had FM measurements performed on them during the first wave of COVID-19 outbreak. We analyzed the positivity of FM levels (FM > 7 µg/mL) to assess the ability of FM monitoring during the first days of hospitalization to predict COVID-19 outcomes. Results: In our cohort, 935 FM measurements were performed in 246 patients during their first 9 days of hospitalization. During patient follow-up, the FM levels were higher in patients admitted directly to the ICU than in those admitted to the MW. Moreover, we observed significantly increased levels of FM in patients when the data were stratified for in-hospital mortality. At hospital admission, only 27 (11%) patients displayed a positive value for FM; this subgroup did not differ from other patients in terms of severity (indicated by ICU referral at admission) or in-hospital mortality. When analyzing FM positivity in the first 9 days of hospitalization, we found that 37% of patients had positive FM at least once during hospitalization and these patients had increased in-hospital mortality (p = 0.001). Thus, we used non-adjusted Kaplan-Meier curves for in-hospital mortality according to FM positivity during hospitalization and we observed a statistically significant difference for in-hospital mortality (hazard ratio = 1.48, 95% CI: 1.25-1.76, p < 0.001). However, we compared the AUC of FM positivity associated with a ratio of D-dimer >70% and found that this combined receiver operating characteristic (ROC) curve was superior to the FM positivity ROC curve alone. Conclusion: Monitoring of FM positivity in hospitalized patients with COVID-19 could be a reliable and helpful tool to predict the worsening condition and mortality of COVID-19.

Safety of coronavirus disease 2019 vaccines in 213 adult patients with sickle cell disease.

Given the lack of information about safety of the COVID-19 vaccines for sickle cell disease (SCD) patients, we sought to determine whether COVID-19 vaccine was associated with subsequent hospital admission for vaso-occlusive events (VOEs). We included 402 patients with SCD, including 88 regularly transfused. As of July 31, 2021, 213 (53.0%) of them had received a least one dose of COVID vaccine (Pfizer 93.0%). We showed similar risk of hospital admission for a VOE among vaccinated patients (whether transfused or not) and among a control group of non-vaccinated patients matched for age, sex and genotype.

Impact of the COVID-19 pandemic on the care of rare and undiagnosed diseases patients in France: a longitudinal population-based study.

BACKGROUND: Preliminary data suggest that COVID-19 pandemic has generated a switch from face-to-face to remote care for individuals with chronic diseases. However, few data are available for rare and undiagnosed diseases (RUDs). We aimed to assess the impact of the COVID-19 pandemic on the activities of the French reference network for RUDs in 2020. RESULTS: In this longitudinal retrospective study, we extracted and analyzed the data of the French national registry for RUDs collected between Jan 1, 2019 and Dec 31, 2020. We compared the annual longitudinal evolution of face-to-face and remote care activities between 2019 and 2020 focusing on adult and pediatric patients. Compared to 2019, rare diseases (RD) care activities showed a decrease in 2020 (- 12%) which occurred mostly during the first lockdown (- 45%) but did not catch up completely. This decrease was mainly in face-to-face care activities. Telehealth activities showed a 9-fold increase during the first lockdown and was able to cover for one third of the decrease in RD activities. Finally, the total number of patients receiving care was lower in 2020(- 9%) with a drastic decrease of cases with newly confirmed diagnosis (- 47%). CONCLUSION: Although telehealth was quickly introduced during the COVID-19 pandemic, RUD patient care was strongly affected in France with a decline in the number of patients treated and new patients recruited. This is likely to result in delays in patient diagnosis and care over the next few years.

The French Covid-19 vaccination policy did not solve vaccination inequities: a nationwide study on 64.5 million people.

BACKGROUND: To encourage Covid-19 vaccination, France introduced during the Summer 2021 a 'Sanitary Pass', which morphed into a 'Vaccine Pass' in early 2022. While the sanitary pass led to an increase in Covid-19 vaccination rates, spatial heterogeneities in vaccination rates remained. To identify potential determinants of these heterogeneities and evaluate the French sanitary and vaccine passes' efficacies in reducing them, we used a data-driven approach on exhaustive nationwide data, gathering 141 socio-economic, political and geographic indicators. METHODS: We considered the association between vaccination rates and each indicator at different time points: before the sanitary pass announcement (week 2021-W27), before the sanitary pass came into force (week 2021-W31) and 1 month after (week 2021-W35) and the equivalent dates for the vaccine pass (weeks 2021-W49, 2022-W03 and 2022-W07). RESULTS: The indicators most associated with vaccination rates were the share of local income coming from unemployment benefits, overcrowded households rate, immigrants rate and vote for an 'anti-establishment' candidate at the 2017 Presidential election. These associations increase over time. Consequently, living in a district below the median of such indicator decreases the probability to be vaccinated by about 30% at the end of the studied period, and this probability gradually decreases by deciles of these indicators. CONCLUSIONS: Our analysis reveals that factors related to poverty, immigration and trust in the government are strong determinants of vaccination rate, and that vaccination inequities tended to increase after the introduction of the French sanitary and vaccination passes.

Spatio-temporal mixture process estimation to detect dynamical changes in population.

Population monitoring is a challenge in many areas such as public health and ecology. We propose a method to model and monitor population distributions over space and time, in order to build an alert system for spatio-temporal data changes. Assuming that mixture models can correctly model populations, we propose a new version of the Expectation-Maximization (EM) algorithm to better estimate the number of clusters and their parameters at the same time. This algorithm is compared to existing methods on several simulated datasets. We then combine the algorithm with a temporal statistical model, allowing for the detection of dynamical changes in population distributions, and call the result a spatio-temporal mixture process (STMP). We test STMPs on synthetic data, and consider several different behaviors of the distributions, to fit this process. Finally, we validate STMPs on a real data set of positive diagnosed patients to coronavirus disease 2019. We show that our pipeline correctly models evolving real data and detects epidemic changes.

Cardiometabolic Disorders and the Risk of Critical COVID-19 as Compared to Influenza Pneumonia.

We aimed to compare the influence of cardiometabolic disorders on the incidence of severe COVID-19 vs. non-COVID pneumonia. We included all consecutive patients admitted with SARS-CoV-2-positive pneumonia between 12 March 2020 and 1 April 2020 and compared them to patients with influenza pneumonia hospitalized between December 2017 and December 2019 at the same tertiary hospital in Paris. Patients with COVID-19 were significantly younger and more frequently male. In the analysis adjusted for age and sex, patients with COVID-19 were more likely to be obese (adjOR: 2.25; 95% CI 1.24-4.09; p = 0.0076) and receive diuretics (adjOR: 2.13; 95% CI 1.12-4.03; p = 0.021) but were less likely to be smokers (adjOR: 0.40; 95% CI 0.24-0.64; p = 0.0002), have COPD (adjOR: 0.25; 95% CI 0.11-0.56; p = 0.0008), or have a previous or active cancer diagnosis (adjOR: 0.54, 95% CI 0.32-0.91; p = 0.020). The rate of ICU admission was significantly higher in patients with COVID-19 (32.4% vs. 5.2% p < 0.0001). Obesity was significantly associated with the risk of direct ICU admission in patients with COVID-19 but not in patients with influenza pneumonia. Likewise, pre-existing hypertension was significantly associated with mortality in patients with COVID-19 but not in patients with influenza pneumonia. Cardiometabolic disorders differentially influenced the risk of presenting with severe COVID-19 or influenza pneumonia.

Low-income neighbourhood was a key determinant of severe COVID-19 incidence during the first wave of the epidemic in Paris.

BACKGROUND: Previous studies have demonstrated that socioeconomic factors are associated with COVID-19 incidence. In this study, we analysed a broad range of socioeconomic indicators in relation to hospitalised cases in the Paris area. METHODS: We extracted 303 socioeconomic indicators from French census data for 855 residential units in Paris and assessed their association with COVID-19 hospitalisation risk. FINDINGS: The indicators most associated with hospitalisation risk were the third decile of population income (OR=9.10, 95% CI 4.98 to 18.39), followed by the primary residence rate (OR=5.87, 95% CI 3.46 to 10.61), rate of active workers in unskilled occupations (OR=5.04, 95% CI 3.03 to 8.85) and rate of women over 15 years old with no diploma (OR=5.04, 95% CI 3.03 to 8.85). Of note, population demographics were considerably less associated with hospitalisation risk. Among these indicators, the rate of women aged between 45 and 59 years (OR=2.17, 95% CI 1.40 to 3.44) exhibited the greatest level of association, whereas population density was not associated. Overall, 86% of COVID-19 hospitalised cases occurred within the 45% most deprived areas. INTERPRETATION: Studying a broad range of socioeconomic indicators using census data and hospitalisation data as a readily available and large resource can provide real-time indirect information on populations with a high incidence of COVID-19.

Differential association between inflammatory cytokines and multiorgan dysfunction in COVID-19 patients with obesity.

To investigate the mechanisms underlying the SARS-CoV-2 infection severity observed in patients with obesity, we performed a prospective study of 51 patients evaluating the impact of multiple immune parameters during 2 weeks after admission, on vital organs' functions according to body mass index (BMI) categories. High-dimensional flow cytometric characterization of immune cell subsets was performed at admission, 30 systemic cytokines/chemokines levels were sequentially measured, thirteen endothelial markers were determined at admission and at the zenith of the cytokines. Computed tomography scans on admission were quantified for lung damage and hepatic steatosis (n = 23). Abnormal BMI (> 25) observed in 72.6% of patients, was associated with a higher rate of intensive care unit hospitalization (p = 0.044). SARS-CoV-2 RNAaemia, peripheral immune cell subsets and cytokines/chemokines were similar among BMI groups. A significant association between inflammatory cytokines and liver, renal, and endothelial dysfunctions was observed only in patients with obesity (BMI > 30). In contrast, early signs of lung damage (ground-glass opacity) correlated with Th1/M1/inflammatory cytokines only in normal weight patients. Later lesions of pulmonary consolidation correlated with BMI but were independent of cytokine levels. Our study reveals distinct physiopathological mechanisms associated with SARS-CoV-2 infection in patients with obesity that may have important clinical implications.

Proteinuria and Clinical Outcomes in Hospitalized COVID-19 Patients: A Retrospective Single-Center Study.

BACKGROUND AND OBJECTIVES: Kidney involvement is frequent among patients with coronavirus disease 2019 (COVID-19), and occurrence of AKI is associated with higher mortality in this population. The objective of this study was to describe occurrence and significance of proteinuria in this setting. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS : We conducted a single-center retrospective study to describe the characteristic features of proteinuria measured within 48 hours following admission among patients with COVID-19 admitted in a tertiary care hospital in France, and to evaluate its association with initiation of dialysis, intensive care unit admission, and death. RESULTS: Among 200 patients with available data, urine protein-creatinine ratio at admission was ≥1 g/g for 84 (42%), although kidney function was normal in most patients, with a median serum creatinine of 0.94 mg/dl (interquartile range, 0.75-1.21). Median urine albumin-creatinine ratio was 110 mg/g (interquartile range, 50-410), with a urine albumin-protein ratio <50% in 92% of patients. Urine retinol binding protein concentrations, available for 85 patients, were ≥0.03 mg/mmol in 62% of patients. Urine protein-creatinine ratio ≥1 g/g was associated with initiation of dialysis (odds ratio, 4.87; 95% confidence interval, 2.03 to 13.0; P<0.001), admission to the intensive care unit (odds ratio, 3.55; 95% confidence interval, 1.93 to 6.71; P<0.001), and death (odds ratio, 3.56; 95% confidence interval, 1.90 to 6.54; P<0.001). CONCLUSIONS: Proteinuria is very frequent among patients admitted for COVID-19 and may precede AKI. Low levels of albuminuria suggest a predominant tubular origin, confirmed by the elevated levels of urine retinol binding protein. Urine protein-creatinine ratio ≥1 g/g at admission is strongly associated with poor kidney and patient outcome.

Observational study of haloperidol in hospitalized patients with COVID-19.

BACKGROUND: Haloperidol, a widely used antipsychotic, has been suggested as potentially useful for patients with COVID-19 on the grounds of its in-vitro antiviral effects against SARS-CoV-2, possibly through sigma-1 receptor antagonist effect. METHODS: We examined the associations of haloperidol use with intubation or death and time to discharge home among adult patients hospitalized for COVID-19 at Assistance Publique-Hôpitaux de Paris (AP-HP) Greater Paris University hospitals. Study baseline was defined as the date of hospital admission. The primary endpoint was a composite of intubation or death and the secondary endpoint was discharge home among survivors in time-to-event analyses. In the primary analyses, we compared these two outcomes between patients receiving and not receiving haloperidol using univariate Cox regression models in matched analytic samples based on patient characteristics and other psychotropic medications. Sensitivity analyses included propensity score analyses with inverse probability weighting and multivariable Cox regression models. RESULTS: Of 15,121 adult inpatients with a positive COVID-19 PT-PCR test, 39 patients (0.03%) received haloperidol within the first 48 hours of admission. Over a mean follow-up of 13.8 days (SD = 17.9), 2,024 patients (13.4%) had a primary end-point event and 10,179 patients (77.6%) were discharged home at the time of study end on May 1st. The primary endpoint occurred in 9 patients (23.1%) who received haloperidol and 2,015 patients (13.4%) who did not. The secondary endpoint of discharge home occurred in 16 patients (61.5%) who received haloperidol and 9,907 patients (85.8%) who did not. There were no significant associations between haloperidol use and the primary (HR, 0.80; 95% CI, 0.39 to 1.62, p = 0.531) and secondary (HR, 1.30; 95% CI, 0.74 to 2.28, p = 0.355) endpoints. Results were similar in multiple sensitivity analyses. CONCLUSION: Findings from this multicenter observational study suggest that haloperidol use prescribed at a mean dose of 4.5 mg per day (SD = 5.2) for a mean duration of 8.4 days (SD = 7.2) may not be associated with risk of intubation or death, or with time to discharge home, among adult patients hospitalized for COVID-19.

Observational Study of Chlorpromazine in Hospitalized Patients with COVID-19.

INTRODUCTION: Chlorpromazine has been suggested as being potentially useful in patients with coronavirus disease 2019 (COVID-19) on the grounds of its potential antiviral and anti-inflammatory effects. OBJECTIVE: The aim of this study was to examine the association between chlorpromazine use and mortality among adult patients hospitalized for COVID-19. METHODS: We conducted an observational, multicenter, retrospective study at Assistance Publique-Hôpitaux de Paris (AP-HP) Greater Paris University hospitals. Study baseline was defined as the date of first prescription of chlorpromazine during hospitalization for COVID-19. The primary endpoint was death. Among patients who had not been hospitalized in intensive care units (ICUs), we compared this endpoint between those who received chlorpromazine and those who did not, in time-to-event analyses adjusted for patient characteristics, clinical markers of disease severity, and other psychotropic medications. The primary analysis used a Cox regression model with inverse probability weighting. Multiple sensitivity analyses were performed. RESULTS: Of the 14,340 adult inpatients hospitalized outside ICUs for COVID-19, 55 patients (0.4%) received chlorpromazine. Over a mean follow-up of 14.3 days (standard deviation [SD] 18.2), death occurred in 13 patients (23.6%) who received chlorpromazine and 1289 patients (9.0%) who did not. In the primary analysis, there was no significant association between chlorpromazine use and mortality (hazard ratio [HR] 2.01, 95% confidence interval [CI] 0.75-5.40; p = 0.163). Sensitivity analyses included a Cox regression in a 1:5 ratio matched analytic sample that showed a similar result (HR 1.67, 95% CI 0.91-3.06; p = 0.100) and a multivariable Cox regression that indicated a significant positive association (HR 3.10, 95% CI 1.31-7.34; p = 0.010). CONCLUSION: Our results suggest that chlorpromazine prescribed at a mean daily dose of 70.8 mg (SD 65.3) was not associated with reduced mortality.

Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study.

A prior meta-analysis showed that antidepressant use in major depressive disorder was associated with reduced plasma levels of several pro-inflammatory mediators, which have been associated with severe COVID-19. Recent studies also suggest that several antidepressants may inhibit acid sphingomyelinase activity, which may prevent the infection of epithelial cells with SARS-CoV-2, and that the SSRI fluoxetine may exert in-vitro antiviral effects on SARS-CoV-2. We examined the potential usefulness of antidepressant use in patients hospitalized for COVID-19 in an observational multicenter retrospective cohort study conducted at AP-HP Greater Paris University hospitals. Of 7230 adults hospitalized for COVID-19, 345 patients (4.8%) received an antidepressant within 48 h of hospital admission. The primary endpoint was a composite of intubation or death. We compared this endpoint between patients who received antidepressants and those who did not in time-to-event analyses adjusted for patient characteristics, clinical and biological markers of disease severity, and other psychotropic medications. The primary analysis was a multivariable Cox model with inverse probability weighting. This analysis showed a significant association between antidepressant use and reduced risk of intubation or death (HR, 0.56; 95% CI, 0.43-0.73, p < 0.001). This association remained significant in multiple sensitivity analyses. Exploratory analyses suggest that this association was also significant for SSRI and non-SSRI antidepressants, and for fluoxetine, paroxetine, escitalopram, venlafaxine, and mirtazapine (all p < 0.05). These results suggest that antidepressant use could be associated with lower risk of death or intubation in patients hospitalized for COVID-19. Double-blind controlled randomized clinical trials of antidepressant medications for COVID-19 are needed.

Obesity Doubles Mortality in Patients Hospitalized for Severe Acute Respiratory Syndrome Coronavirus 2 in Paris Hospitals, France: A Cohort Study on 5,795 Patients.

OBJECTIVE: Preliminary data from different cohorts of small sample size or with short follow-up indicate poorer prognosis in people with obesity compared with other patients. This study aims to precisely describe the strength of association between obesity in patients hospitalized with coronavirus disease 2019 (COVID-19) and mortality and to clarify the risk according to usual cardiometabolic risk factors in a large cohort. METHODS: This is a prospective cohort study including 5,795 patients aged 18 to 79 years hospitalized from February 1 to April 30, 2020, in the Paris area, with confirmed infection by severe acute respiratory syndrome coronavirus 2. Adjusted regression models were used to estimate the odds ratios (ORs) and 95% CIs for the mortality rate at 30 days across BMI classes, without and with imputation for missing BMI values. RESULTS: Eight hundred ninety-one deaths had occurred at 30 days. Mortality was significantly raised in people with obesity, with the following ORs for BMI of 30 to 35 kg/m2 , 35 to 40 kg/m2 , and >40 kg/m2 : 1.89 (95% CI: 1.45-2.47), 2.79 (95% CI: 1.95-3.97), and 2.55 (95% CI: 1.62-3.95), respectively (18.5-25 kg/m2 was used as the reference class). This increase holds for all age classes. CONCLUSIONS: Obesity doubles mortality in patients hospitalized with COVID-19.