Evaluating the serological status of COVID-19 patients using an indirect immunofluorescent assay, France.

An indirect in-house immunofluorescent assay was developed in order to assess the serological status of COVID-19 patients in Marseille, France. Performance of IFA was compared to a commercial ELISA IgG kit. We tested 888 RT-qPCR-confirmed COVID-19 patients (1302 serum samples) and 350 controls including 200 sera collected before the pandemic, 64 sera known to be associated with nonspecific serological interference, 36 sera from non-coronavirus pneumonia and 50 sera from patient with other common coronavirus to elicit false-positive serology. Incorporating an inactivated clinical SARS-CoV-2 isolate as the antigen, the specificity of the assay was measured as 100% for IgA titre ≥ 1:200, 98.6% for IgM titre ≥ 1:200 and 96.3% for IgG titre ≥ 1:100 after testing a series of negative controls. IFA presented substantial agreement (86%) with ELISA EUROIMMUN SARS-CoV-2 IgG kit (Cohen's Kappa = 0.61). The presence of antibodies was then measured at 3% before a 5-day evolution up to 47% after more than 15 days of evolution. We observed that the rates of seropositivity as well as the titre of specific antibodies were both significantly higher in patients with a poor clinical outcome than in patients with a favourable evolution. These data, which have to be integrated into the ongoing understanding of the immunological phase of the infection, suggest that detection anti-SARS-CoV-2 antibodies is useful as a marker associated with COVID-19 severity. The IFA assay reported here is useful for monitoring SARS-CoV-2 exposure at the individual and population levels.

The value of specialist care-infectious disease specialist referrals-why and for whom? A retrospective cohort study in a French tertiary hospital.

This study evaluated the impact of infectious disease (ID) specialist referrals on outcomes in a tertiary hospital in France. This study tackled methodological constraints (selection bias, endogeneity) using instrumental variables (IV) methods in order to obtain a quasi-experimental design. In addition, we investigated whether certain characteristics of patients have a bearing on the impact of the intervention. We used the payments database and ID department files to obtain data for adults admitted with an ID diagnosis in the North Hospital, Marseille from 2012 to 2014. Comparable cohorts were obtained using coarsened exact matching and analysed using IV models. Mortality, readmissions, cost (payer perspective) and length of stay (LoS) were analysed. We recorded 15,393 (85.97%) stays, of which 2,159 (14.03%) benefited from IDP consultations. The intervention was seen to significantly lower the risk of inpatient mortality (marginal effect (M.E) = -19.06%) and cost of stay (average treatment effect (ATE) = - €5,573.39). The intervention group was seen to have a longer LoS (ATE = +4.95 days). The intervention conferred a higher reduction in mortality and cost for stays that experienced ICU care (mortality: odds ratio (OR) =0.09, M.E cost = -8,328.84 €) or had a higher severity of illness (mortality: OR=0.35, M.E cost = -1,331.92 €) and for patients aged between 50 and 65 years (mortality: OR=0.28, M.E cost = -874.78 €). This study shows that ID referrals are associated with lower risk of inpatient mortality and cost of stay, especially when targeted to certain subgroups.

Dramatic reduction in Clostridium difficile ribotype 027-associated mortality with early fecal transplantation by the nasogastric route: a preliminary report.

Clostridium difficile ribotype 027 (CD027)-associated diarrhea preferentially affects elderly patients and causes a high mortality rate. Fecal microbiota transplantation has become an alternative treatment for recurrent C. difficile infections. An outbreak of CD027 infections has occurred in Marseille since March 2013. From March to November 2013, we treated patients using only antibiotics or fecal microbiota transplantation after at least three relapses. Beginning in November 2013, we performed early transplantation using a nasogastric tube during the first week of infection, in combination with antibiotic treatment. Sixty-one patients with a mean age of 84 years were hospitalized, including 42 patients treated only with antibiotics, three with tardive transplantation, and 16 with early transplantation. The patients were comparable in clinical involvement. The global mortality rate was 3/16 (18.75 %) among the patients treated by early transplantation and 29/45 (64.4 %) among the patients only treated by antibiotics or by tardive transplantation (p < 0.01). Among these 45 patients, 23 (51 %) died at day 31, including 17 who died at day 7. Early fecal transplantation was associated with a significantly reduced mortality rate, with only one patient dead at day 31 (6.25 %). In a Cox model, early transplantation was the only independent predictor of survival (hazard ratio 0.18, 95 % confidence interval 0.05-0.61, p = 0.006). Six of the 16 patients (37.5 %) needed a second transplantation before symptom resolution. Early fecal microbiota transplantation in combination with antibiotics should be the first-line treatment for CD027 infections.

The gut microbiota of a patient with resistant tuberculosis is more comprehensively studied by culturomics than by metagenomics.

Gut microbiota consists of 10(10) bacteria per gram of stool. Many antibiotic regimens induce a reduction in both the diversity and the abundance of the gut flora. We analyzed one stool sample collected from a patient treated for drug-resistant Mycobacterium tuberculosis and who ultimately died from pneumonia due to a Streptococcus pneumoniae 10 months later. We performed microscopic observation, used 70 culture conditions (microbial culturomics) with identification by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) and 16S rRNA amplification and sequencing, pyrosequencing, and 18S rRNA amplification and clone sequencing. Electron and optical microscopic observations revealed the presence of yeast, but no bacterial species were observed. By culture, only 39 bacterial species were identified, including one new species, as well as three species that have not been previously observed in the human gut. The pyrosequencing showed only 18 phylotypes, detecting a lower number of bacterial species than the culture techniques. Only two phylotypes overlapped with culturomics. In contrast, an amount of chloroplasts was found. Additionally, specific molecular eukaryote detection found three fungal species. We recovered, for the first time, more cultivable than non-cultivable bacterial species in a patient with a low bacterial load in the gut, demonstrating the depth bias of pyrosequencing. We propose that the desertification of gut microbiota in this patient is a reflection of the total body microbiota and may have contributed to the invasive infection of S. pneumoniae. This finding suggests that caution should be applied when treating patients with broad-spectrum antibiotics, and preventive measures should be taken in order to avoid invasive infection.

Hajj pilgrims knowledge about Middle East respiratory syndrome coronavirus, August to September 2013.

In preparation for Hajj 2013, 360 French pilgrims were interviewed regarding their knowledge about Middle East respiratory syndrome (MERS). Respondents were aged 20­85 years, male-female ratio was 1.05:1;64.7% were aware of the MERS situation in Saudi Arabia; 35.3% knew about the Saudi Ministry of Health recommendations for at-risk pilgrims to postpone participation in the 2013 Hajj. None of 179 at-risk individuals(49.9%) decided to cancel their Hajj participation even after advice during consultation.

The viral etiology of an influenza-like illness during the 2009 pandemic.

Many viruses are known to cause influenza-like illness (ILI); however, in nearly 50% of patients, the etiologic agent remains unknown. The distribution of viruses in patients with ILI was investigated during the 2009 A/H1N1 influenza pandemic (A/H1N1p). From June 2009 to January 2010, 660 patients with suspected influenza were questioned and examined, and nasal swabs were collected. All patient samples were tested for influenza virus, and 286 negative nasal swabs were tested further for 18 other respiratory viruses using real-time RT-PCR. Two waves of ILI were observed in the epidemic curve (weeks 35-42 and 42-49). At least eight viruses co-circulated during this period: human rhinovirus (HRV) (58), parainfluenza 1-4 viruses (PIV) (9), human Coronavirus (hCoV) OC43 (9), enterovirus (5), adenovirus (AdV) (4), and human metapneumovirus (hMPV) (2); however, 204 samples remained negative for all viruses tested. ILI symptoms, according to the Centers for Disease Control and Prevention criteria for ILI definition, were reported in 75% of cases. These patients had positive swabs for A/H1N1p, HRV, hCoV-OC43, PIV, AdV, and hMPV without significant difference with non-ILI patients. This study found that many respiratory viruses circulated during this period and that the A/H1N1p did not impact on the kinetics of other respiratory viruses. The proportion of non-documented cases remains high. ILI could not distinguish A/H1N1p infection from that due to other respiratory viruses. However, in multivariate anlaysis, cough, chills, hyperemia, and dyspnea were associated significantly with influenza virus versus other respiratory viruses.

2012 outbreak of acute haemorrhagic conjunctivitis in Indian Ocean Islands: identification of Coxsackievirus A24 in a returned traveller.

In May 2012, a Coxsackievirus A24 haemorrhagic conjunctivitis was diagnosed in Marseille, France, in a traveller returning from the Comoros Islands. This case allowed identification of the cause of an ongoing outbreak of haemorrhagic conjunctivitis in Indian Ocean Islands, illustrating that returning travellers may serve as sentinels for infectious diseases outbreaks in tropical areas where laboratory investigation is limited.

Measles among healthcare workers: a potential for nosocomial outbreaks.

We report here 14 cases of measles among healthcare workers (HCWs) in Public Hospitals of Marseilles, France that occurred between April and November 2010. All cases but one were under 30 years of age. Following the identification of these cases, we checked the immune status among 154 HCWs who volunteered to take part in the study and showed that 93% and 88% were immune against measles and mumps respectively. HCWs non-immunised against measles were all under 30 years of age.

Imported extensively drug-resistant Mycobacterium tuberculosis Beijing genotype, Marseilles, France, 2011.

Multidrug- (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) are reported to gradually spread across European countries with low TB prevalence including France. Some isolates may even accumulate traits of resistance in addition to the XDR profile, as a result of therapeutic mismanagement. We report here the first case of XDR TB in Marseilles and discuss the potential effectiveness of sulfamide treatment in such cases.

Disinfection of gloved hands during routine care.

Healthcare-associated infections are a major issue in public health. After several decades of hand hygiene programmes, it is time to admit that we have failed to achieve our goal. One of the reasons is the overuse of gloves, which is in part justified by the nature of the nursing care. Several experimental studies supported the effectiveness of disinfecting gloves, but evidence for routine feasibility and effectiveness is lacking. The aim of this study was to evaluate the effectiveness of alcohol-based disinfection of gloves during nursing care. Swabs were taken from the most contaminated part of both hands at different times: T0 (before wearing gloves), T10 (after 10 minutes of nursing care) from both gloves, T10A (just after the gloves were disinfected for 30 seconds with bedside disposable hydroalcoholic solution) and when possible at T20 and T20A. After 10 minutes of nursing care, gloves were contaminated in 72.5% of cases. After alcohol-based disinfection, gloves became free of microorganism in 79.3% of cases. Alcohol-based disinfection of gloves during routine care is effective and appears to be a reasonable alternative to current recommendations.

Three-year hand hygiene monitoring and impact of real-time reminders on compliance.

BACKGROUND: Hand hygiene remains both the major strategy and an ongoing challenge for infection control. The main issues in the sustainability of hand hygiene automatic monitoring are healthcare worker (HCW) turnover rates and declining participation. AIM: To assess hand hygiene compliance and the impact of real-time reminders over three years. METHODS: HCW compliance was observed for the use of alcohol-based hand rubs (AHR) on room entry and exit. Linear multi-level mixed models with time autocorrelations were performed to analyse the repeated measurements of daily room compliance and the effect of reminders over eight quarters (24 months). FINDINGS: In all, 111 HCWs were observed and 525,576 activities were identified in the database. There was an improvement in compliance both on room entry and exit over two years, and the rooms which had activated reminders had better performance than the rooms which did not have activated reminders. CONCLUSIONS: This study showed the benefit of using real-time reminders; even 20% of rooms with an activated reminder improved overall hand hygiene compliance. A randomized real-time reminder setting may be a potential solution in reducing user fatigue and enhancing HCW self-awareness.

COVID-19 outbreak and healthcare worker behavioural change toward hand hygiene practices.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has affected healthcare workers (HCWs) in their clinical practice. HCWs were challenged with new guidelines and practices to protect themselves from occupational risks. AIM: To determine whether hand hygiene behaviour by real-time measurement was related to the dynamic of the epidemic, and the type of patient being cared for in France. METHODS: This study used an automated hand hygiene recording system to measure HCW hand hygiene on entry to and exit from patient rooms throughout the COVID-19 pandemic. The correlation between hand hygiene compliance and COVID-19 epidemiological data was analysed. Analysis of variance was performed to compare compliance rate during the different periods of the epidemic. FINDINGS: HCW hand hygiene rate on room entry decreased over time; on room exit, it increased by 13.73% during the first wave of COVID-19, decreased by 9.87% during the post-lockdown period, then rebounded by 2.82% during the second wave of the epidemic. Hand hygiene during patient care and hand hygiene on room exit had a positive relationship with the local COVID-19 epidemic; conversely, hand hygiene on room entry did not depend on the trend of the epidemic, nor on nursing of COVID-19 patients, and it decreased over time. CONCLUSION: HCWs modified their behaviours to face the risk propensity of the pandemic. However, to improve the poor compliance at room entry, reducing confusion between the hand hygiene recommendation and glove recommendation may be necessary; disinfection of gloving hands might solve this issue.

Critical reappraisal of remdesivir investigational trials in COVID-19.

During disease outbreaks, the pharmaceutical industry generally puts a lot of effort into promoting clinical trials studying their new drugs. We review evidence of the ten most recent reports on remdesivir. We conclude that it is far too premature to identify remdesivir as a curative or life-saving intervention during the COVID-19 pandemic.

Remdesivir investigational trials in COVID-19: a critical reappraisal.

During outbreak of emerging disease, the most important aim is to discover an effective drug to save life. Consequently, a lot of effort are generally made by the industry to promote clinical trials with new drugs. Here we review evidence of the 8 most recent reports including 3 randomized controlled trials on the clinical efficacy of remdesivir in treating COVID-19 patient. We conclude that it is far too premature to identify remdesivir as a curative or life-saving intervention.

Peripherally inserted central catheters: a hidden emerging cause of infection outbreaks.

In our institution, between January 2010 and December 2017, 15 140 peripherally inserted central catheters (PICCs) were inserted in 12 314 patients. Using time-series analysis to evaluate the annual historical trend (AHT), we observed a significant increase in bloodstream infections (BSIs; AHT = 24; p < 0.001) and associated deaths (AHT = 3; p 0.02) in patient with PICCs. The risk of experiencing a BSI was significantly higher in patients with PICCs (odds ratio = 9.6; 95% confidence interval, 9.08-10.18; p < 0.001). To reduce PICC-related BSIs and their related mortality, it is important to limit the overuse of PICCs and to implement a 'no PICC' policy by limiting the insertion of PICCs to situations without other available options.

Clinical efficacy of chloroquine derivatives in COVID-19 infection: comparative meta-analysis between the big data and the real world.

In the context of the current coronavirus disease 2019 (COVID-19) pandemic, we conducted a meta-analysis on the effects of chloroquine derivatives in patients, based on unpublished and published reports available publicly on the internet as of 27 May 2020. The keywords 'hydroxychloroquine', 'chloroquine', 'coronavirus', 'COVID-19' and 'SARS-Cov-2' were used in the PubMed, Google Scholar and Google search engines without any restrictions as to date or language. Twenty studies were identified involving 105 040 patients (19 270 treated patients) from nine countries (Brazil, China, France, Iran, Saudi Arabia, South Korea, Spain and the USA). Big data observational studies were associated with conflict of interest, lack of treatment dosage and duration, and absence of favourable outcome. Clinical studies were associated with favourable outcomes and details on therapy. Among clinical studies, three of four randomized controlled trials reported a significant favourable effect. Among clinical studies, a significant favourable summary effect was observed for duration of cough (OR 0.19, p 0.00003), duration of fever (OR 0.11, p 0.039), clinical cure (OR 0.21, p 0.0495), death (OR 0.32, p 4.1 × 10-6) and viral shedding (OR 0.43, p 0.031). A trend for a favourable effect was noted for the outcome 'death and/or intensive care unit transfer' (OR 0.29, p 0.069) with a point estimate remarkably similar to that observed for death (∼0.3). In conclusion, a meta-analysis of publicly available clinical reports demonstrates that chloroquine derivatives are effective to improve clinical and virological outcomes, but, more importantly, they reduce mortality by a factor of 3 in patients with COVID-19. Big data are lacking basic treatment definitions and are linked to conflict of interest. The retraction of the only big data study associated with a significantly deleterious effect the day after (June 5, 2020) the acceptance of the present work (June 4, 2020) confirms the relevance of this work.

Healthcare workers' attitudes towards hand-hygiene monitoring technology.

BACKGROUND: Automated radio-frequency identification (RFID)-based hand-hygiene monitoring technology was implemented in an infectious disease department to study healthcare workers' (HCWs') practices and to improve hand hygiene. AIM: To assess HCWs' attitudes towards this innovative monitoring device in order to anticipate resistance to change and facilitate future implementation. METHODS: In-depth interviews and an ethnographic approach. FINDINGS: From the perspective of HCWs, while they recognize the usefulness of RFID technology to prevent the transmission of infections to patients, they expressed concerns about risks related to RFID electromagnetic waves, as well as control by their superiors. Overall, HCWs' opinions oscillated between positive feelings characterized by enthusiasm for the possibility of changing their practices using technologies and research, and negative feelings marked by strong criticisms of these technologies and research. These criticisms included blaming hand-hygiene monitoring technology for decontextualizing HCWs' practices. They perceived the technologies through the prism of the local and national contexts in which they are embedded. From their point of view, technologies are primarily in the best interests of the project team. Thus, they affirm and maintain the different interests and objectives between themselves and the project team, crystallizing a conflict of professional norms and values between these two groups. The forms of resistance taken by HCWs were practical as well as oral. CONCLUSION: Innovative technologies should be developed to address HCWs' attitudes surrounding RFIDs. It is crucial to inform HCWs about the nature of these technologies, although some criticisms about monitoring systems are based on more structural causes.