Pre-Hospital Management of Patients with COVID-19 and the Impact on Hospitalization.

Background and Objectives: During the COVID-19 pandemic, patient care was mainly organized around the hospital. Pre-hospital care has, to our knowledge, never been evaluated. We aimed to study the impact of pre-hospital pathways on hospitalization during the last part of the pandemic. Materials and Methods: This was a monocentric, retrospective analysis of prospectively collected medical records. Data from patients admitted to our institute between 1 February and 7 March 2022 were analyzed. The primary outcomes were defined as the number of hospitalizations, resuscitations, and deaths at the time of interview and in the subsequent 30 days. The main explanatory variables were times from onset of symptoms to care, age, gender, News2 score, comorbidities, and pre-hospital pathways and their duration. Results: Three pre-hospital pathways were identified: a pathway in which the patient consults a general practitioner for a test (PHP1); a pathway in which the patient consults for care (PHP2); and no pre-hospital pathway and direct admission to hospital (PHP3). Factors independently associated with outcome (hospitalization) were being male (OR 95% CI; 2.21 (1.01-4.84), p = 0,04), News2 score (OR 95% CI; 2.04 (1.65-2.51), p < 0.001), obesity (OR 95% CI; 3.45 (1.48-8.09), p = 0.005), D-dimers > 0.5 µg/mL (OR 95% CI; 3.45 (1.47-8.12), p = 0.005), and prolonged time from symptoms to hospital care (PHP duration) (OR 95% CI; 1.07 (1.01-1.14), p = 0.03). All things being equal, patients with a "PHP2" pre-hospital pathway had a higher probability of hospitalization compared to those with a "PHP3" pre-hospital pathway (OR 95% CI; 4.31 (1.48-12.55), p = 0.007). Conclusions: Along with recognized risk factors such as gender, News 2 score, and obesity, the patient's pre-hospital pathway is an important risk factor associated with hospitalization.

Endogenous Ethanol and Triglyceride Production by Gut Pichia kudriavzevii, Candida albicans and Candida glabrata Yeasts in Non-Alcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH) increases with fructose consumption and metabolic syndrome and has been recently linked with endogenous ethanol production, notably by high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn). Candida yeasts are the main causes of auto-brewery syndromes but have been neglected in NASH. Here, the fecal ethanol and microbial content of 10 cases and 10 controls were compared. Ethanol was measured by gas chromatography-mass spectrometry. Species identification was performed by MALDI-TOF MS, and triglyceride production was assessed by a colorimetric enzymatic assay. The fecal ethanol concentration was four times higher in patients with NASH (median [interquartile range]: 0.13 [0.05-1.43] vs. 0.034 [0.008-0.57], p = 0.037). Yeasts were isolated from almost all cases but not from controls (9/10 vs. 0/10, p = 0.0001). Pichia kudriavzevii was the most frequent (four patients), while Candida glabrata, Candida albicans, and Galactomyces geotrichum were identified in two cases each. The concentration of ethanol produced by yeasts was 10 times higher than that produced by bacteria (median, 3.36 [0.49-5.60] vs. 0.32 [0.009-0.43], p = 0.0029). Using a 10% D-fructose restricted medium, we showed that NASH-associated yeasts transformed fructose in ethanol. Unexpectedly, yeasts isolated from NASH patients produced a substantial amount of triglycerides. Pichia kudriavzevii strains produced the maximal ethanol and triglyceride levels in vitro. Our preliminary human descriptive and in vitro experimental results suggest that yeasts have been neglected. In addition to K. pneumoniae, gut Pichia and Candida yeasts could be linked with NASH pathophysiology in a species- and strain-specific manner through fructose-dependent endogenous alcohol and triglyceride production.

Long-Term Persistence of Olfactory and Gustatory Disorders in COVID-19 Patients.

Smell and taste disorders are frequent symptoms during acute COVID-19 and may persist long after the resolution of the initial phase. This study aims to estimate the proportion and risk factors for smell and/or taste disorders at the onset of symptoms and their persistence after more than 6 months of follow-up in COVID-19 patients. We analyzed a prospective cohort of COVID-19 patients admitted to our institute in Marseille, France in early 2020. After being discharged from the hospital, patients with smell and/or taste disorders were contacted for a telephone interview. Logistic regression analysis was performed to determine the risk factors for smell and/or taste disorders. A total of 3,737 patients were included, of whom 1,676 reported smell and/or taste disorders at the onset of symptoms. Taste and/or smell disorders were independently associated with being younger and female, a lower likelihood of suffering from diabetes, cardiovascular diseases and cancer, a longer delay between the onset of symptoms and consultation, and non-severe forms of COVID-19 at admission. Of the 605 patients with smell and/or taste disorders who were followed-up, 154 (25.5%) reported the persistence of symptoms for more than 6 months. At the time of follow-up, being female, having a chronic respiratory disease and using angiotensin-converting enzyme inhibitors (ACEis) were factors independently associated with the persistence of smell and/or taste disorders. In conclusion, the long-term persistence of olfactory and gustative disorders is frequent among COVID-19 patients, notably affecting female patients and patients who suffered from chronic respiratory diseases before infection. The role of ACEis needs to be further evaluated in larger numbers of patients.

Evaluation of pain susceptibility by taking blood pressure in patients with infections: A prospective comparative study.

ABSTRACT: Pain sensitization leading to polyalgia can be observed during infectious diseases. The blood pressure cuff-evoked pain threshold (BPCEPT) has been used in previous studies as a screening tool for fibromyalgia.We aimed to use the BPCEPT as a screening test for detecting pain sensitization in patients suffering from infectious diseases. We also investigated whether specific factors were associated with pain sensitization.We performed a prospective comparative study including all patients of our infectious diseases center in a 1-year period. We created a positive control group of patients suffering from fibromyalgia and a negative control group of "apparently healthy" patients consulting for vaccination.The blood pressure (BP) cuff was inflated until the patient signaled that they experienced pain, and this pressure value was noted.A total of 2355 patients were included. The positive control group had significantly lower values of the BPCEPT than all other groups. Among hospitalized patients with infectious diseases, a low BPCEPT was significantly associated with high temperature (P < .0001), older age (P = .002), being a woman (P = .004), high serum glutamic-oxaloacetic transaminase (P = .007), and high C reactive protein levels (P = .02). Moreover, in multivariate analysis, respiratory infection, meningitis, urinary tract infection, febrile neutropenia, and Q fever were independently associated with a low BPCEPT. A significant negative dynamic correlation between the BPCEPT and temperature was also observed (P < .001).We demonstrated for the first time in a large sample of patients that the BPCEPT method can be used to detect pain susceptibility. We observed a significant dynamic correlation between pain sensitization and temperature. Additionally, pain sensitization was associated with some diseases, suggesting that they trigger pain sensitivity.

Expression of ACE2, Soluble ACE2, Angiotensin I, Angiotensin II and Angiotensin-(1-7) Is Modulated in COVID-19 Patients.

The etiological agent of COVID-19 SARS-CoV-2, is primarily a pulmonary-tropic coronavirus. Infection of alveolar pneumocytes by SARS-CoV-2 requires virus binding to the angiotensin I converting enzyme 2 (ACE2) monocarboxypeptidase. ACE2, present on the surface of many cell types, is known to be a regulator of blood pressure homeostasis through its ability to catalyze the proteolysis of Angiotensin II (Ang II) into Angiotensin-(1-7) [Ang-(1-7)]. We therefore hypothesized that SARS-CoV-2 could trigger variations of ACE2 expression and Ang II plasma concentration in SARS-CoV-2-infected patients. We report here, that circulating blood cells from COVID-19 patients express less ACE2 mRNA than cells from healthy volunteers. At the level of circulating cells, this ACE2 gene dysregulation mainly affects the monocytes, which also show a lower expression of membrane ACE2 protein. Moreover, soluble ACE2 (sACE2) plasma concentrations are lower in prolonged viral shedders than in healthy controls, while the concentration of sACE2 returns to normal levels in short viral shedders. In the plasma of prolonged viral shedders, we also found higher concentrations of Ang II and angiotensin I (Ang I). On the other hand, the plasma levels of Ang-(1-7) remains almost stable in prolonged viral shedders but seems insufficient to prevent the adverse effects of Ang II accumulation. Altogether, these data evidence that the SARS-CoV-2 may affect the expression of blood pressure regulators with possible harmful consequences on COVID-19 outcome.

Respiratory Syncytial Virus Infection: Its Propensity for Bacterial Coinfection and Related Mortality in Elderly Adults.

Respiratory syncytial virus (RSV) is an increasingly recognized cause of acute respiratory infection (ARI) in adults. We compared the crude in-hospital mortality of patients with RSV infection alone with that of patients with RSV-bacterial coinfection. Overall, 12 144 hospitalized patients with ARI were screened for RSV detection by polymerase chain reaction between February 2014 and April 2019. In total, 701 (5.8%) had a positive RSV result, including 85 (12.1%) with bacterial coinfection. RSV-bacterial coinfection was associated with an increase in crude in-hospital mortality in patients >65 years old (hazard ratio, 2.94; 95% CI, 1.30-6.60; P = .010). Optimized prevention and management strategies to reduce this burden are needed.

Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study.

BACKGROUND: We need an effective treatment to cure COVID-19 patients and to decrease virus carriage duration. METHODS: We conducted an uncontrolled, non-comparative, observational study in a cohort of 80 relatively mildly infected inpatients treated with a combination of hydroxychloroquine and azithromycin over a period of at least three days, with three main measurements: clinical outcome, contagiousness as assessed by PCR and culture, and length of stay in infectious disease unit (IDU). RESULTS: All patients improved clinically except one 86 year-old patient who died, and one 74 year-old patient still in intensive care. A rapid fall of nasopharyngeal viral load was noted, with 83% negative at Day7, and 93% at Day8. Virus cultures from patient respiratory samples were negative in 97.5% of patients at Day5. Consequently patients were able to be rapidly discharged from IDU with a mean length of stay of five days. CONCLUSION: We believe there is urgency to evaluate the effectiveness of this potentially-life saving therapeutic strategy at a larger scale, both to treat and cure patients at an early stage before irreversible severe respiratory complications take hold and to decrease duration of carriage and avoid the spread of the disease. Furthermore, the cost of treatment is negligible.

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.

BACKGROUND: Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the effect of hydroxychloroquine on respiratory viral loads. PATIENTS AND METHODS: French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point. RESULTS: Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported in the litterature for untreated patients. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination. CONCLUSION: Despite its small sample size, our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.

Early mortality attributable to PICC-lines in 4 public hospitals of Marseille from 2010 to 2016 (Revised V3).

INTRODUCTION: Peripherally inserted central catheters (PICC-line) are devices inserted through peripheral venous access. In our institution, this technology has been rapidly adopted by physicians in their routine practice. Bacteremia on catheters remains an important public health issue in France. However, the mortality attributable to bacteremia on PICC-line remains poorly evaluated in France and in the literature in general. We report in our study an exhaustive inventory of bacteremia on PICC-line and their 30 days mortality, over a 7 years period. MATERIAL AND METHODS: From January 2010 to December 2016, we retrospectively matched PICC-line registers of the radiology department, blood culture records of the microbiology laboratory and medical records from the Hospital Information Systems. RESULTS: The 11,334 hospital stays during which a PICC-line was inserted were included over a period of 7 years. Among them, 258 episodes of PICC-line-associated bacteremia were recorded, resulting in a prevalence of 2.27%. Hematology units: 20/324 (6.17%), oncology units: 55/1375 (4%) and hepato-gastro-enterology units: 42/1142 (3.66%) had the highest prevalence of PICC-line related bacteremia. The correlation analysis, when adjusted by exposure and year, shows that the unit profile explains 72% of the variability in the rate of bacteremia with a P = .023. Early bacteremia, occurring within 21 days of insertion, represented 75% of cases. The crude death ratio at 30 days, among patients PICC-line associated bacteremia was 57/11 334 (0.50%). The overall 30-day mortality of patients with PICC-line with and without bacteremia was 1369/11334 (12.07%). On day 30, mortality of patients with bacteremia associated PICC-line was 57/258 or 22.09% of cases, compared to a mortality rate of 1311/11076, or 11.83% in the control group (P < .05, RR 2.066 [1.54-2.75]). Kaplan-Meier survival analysis revealed a statistically significant excess mortality between patients with PICC-line associated bacteremia and PICC-line carriers without bacteremia (P < .0007, hazard ratio 1.89 [1307-2709]). CONCLUSION: Patients with PICC-line associated bacteremia have a significant excess mortality. The implementation of a PICC-line should remain the last resort after a careful assessment of the benefit/risk ratio by a senior doctor.

Thromboses in tuberculosis are linked to antiphosphatidylethanolamine antibodies levels: A cross-sectional study.

Venous thromboses have been associated with tuberculosis, but the relationship with circulating anticoagulant has not been studied yet. In a cohort of 48 patients with tuberculosis, 22.9% of them presented with venous thromboses significantly associated with dose dependent level of antiphosphophatidyl-ethanolamine antibodies.

No difference in congenital anomalies prevalence irrespective of insemination methods and freezing procedure: cohort study over fourteen years of an ART population in the south of France.

PURPOSE: A retrospective cohort study was conducted to evaluate and compare the prevalence of congenital anomalies in babies and fetuses conceived after four procedures of assisted reproduction technologies (ART). METHODS: The prevalence of congenital anomalies was compared retrospectively between 2750 babies and fetuses conceived between 2001 and 2014 in vitro fertilization with standard insemination (IVF), IVF with intracytoplasmic sperm injection (ICSI), IVF with frozen embryo transfer (FET-IVF), and ICSI with frozen embryo transfer (FET-ICSI). Congenital anomalies were described according to European Surveillance of Congenital Anomalies (EUROCAT) classification. The parental backgrounds, biologic parameters, obstetric parameters, and perinatal outcomes were compared between babies and fetuses with and without congenital anomalies. Data were analyzed by the generalized estimating equation. RESULTS: Between 2001 and 2014, a total of 2477 evolutionary pregnancies were notified. Among these pregnancies, 2379 were included in the analysis. One hundred thirty-four babies and fetuses had a congenital anomaly (4.9%). The major prevalences found among the recorded anomalies were congenital heart defects, chromosomal anomalies, and urinary defects. However, the risk of congenital anomalies in babies and fetuses conceived after FET was not increased compared with babies and fetuses conceived after fresh embryo transfer, even when adjusted for confounding factors (p = 0.40). CONCLUSIONS: There is no increased risk of congenital anomalies in babies and fetuses conceived by fresh versus frozen embryo transfer after in vitro fertilization with and without micromanipulation. Indeed, distribution of congenital anomalies found in our population is consistent with the high prevalence of congenital heart defects, chromosomal anomalies, and urinary defects that have been found by other authors in children conceived by infertile couples when compared to children conceived spontaneously.