Timing and Predictors of Loss of Infectivity Among Healthcare Workers With Mild Primary and Recurrent COVID-19: A Prospective Observational Cohort Study.

BACKGROUND: There is a need to understand the duration of infectivity of primary and recurrent coronavirus disease 2019 (COVID-19) and identify predictors of loss of infectivity. METHODS: Prospective observational cohort study with serial viral culture, rapid antigen detection test (RADT) and reverse transcription polymerase chain reaction (RT-PCR) on nasopharyngeal specimens of healthcare workers with COVID-19. The primary outcome was viral culture positivity as indicative of infectivity. Predictors of loss of infectivity were determined using multivariate regression model. The performance of the US Centers for Disease Control and Prevention (CDC) criteria (fever resolution, symptom improvement, and negative RADT) to predict loss of infectivity was also investigated. RESULTS: In total, 121 participants (91 female [79.3%]; average age, 40 years) were enrolled. Most (n = 107, 88.4%) had received ≥3 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine doses, and 20 (16.5%) had COVID-19 previously. Viral culture positivity decreased from 71.9% (87/121) on day 5 of infection to 18.2% (22/121) on day 10. Participants with recurrent COVID-19 had a lower likelihood of infectivity than those with primary COVID-19 at each follow-up (day 5 odds ratio [OR], 0.14; P < .001]; day 7 OR, 0.04; P = .003]) and were all non-infective by day 10 (P = .02). Independent predictors of infectivity included prior COVID-19 (adjusted OR [aOR] on day 5, 0.005; P = .003), an RT-PCR cycle threshold [Ct] value <23 (aOR on day 5, 22.75; P < .001) but not symptom improvement or RADT result.The CDC criteria would identify 36% (24/67) of all non-infectious individuals on day 7. However, 17% (5/29) of those meeting all the criteria had a positive viral culture. CONCLUSIONS: Infectivity of recurrent COVID-19 is shorter than primary infections. Loss of infectivity algorithms could be optimized.

Pseudo-outbreak of haemodiafiltration dialysis fluid contamination: results of a detailed epidemiologic investigation.

Background: Compliance with dialysis fluid ultrapurity standards is a paramount for online modalities. More than 200 dialysis fluid samples have been analyzed monthly for years in our two dialysis units, with compliant microbiological results until mid-2020. Aim: In mid-2020, an unusual occurrence (30%) of contaminated dialysis fluids in dialysis units led us to investigate to determine the source. Methods: Microbiological methods for aquaphilic bacteria culturing and endotoxin detection in dialysis fluids were routinely performed on a monthly basis for all dialysis machines. As the contamination appeared randomly and almost simultaneously in our two units without any routine change or febrile syndrome, we searched for a common cause. Supplier's sampling kits as well as microbiological laboratory procedures were scrupulously investigated. Findings: 21 out of 30 sampling bags filled with sterile water brought back numerous fungi and bacteria. Laboratory's investigation, through the negative control tests performed routinely, exonerated the lab. All batches of bags analyzed later showed variable levels of contamination according to their transport/storage mode or date of manufacturing. Analyses performed by the supplier - methods complying with the medical device's standards but different from those recommended for dialysis fluids purity - remained negative. Conclusion: Our investigation revealed that the contamination of our sampling kits came presumably from the manufacturer's supplying chain. Such false-positive results findings, created serious safety issues and disturbed clinical activities since positive machines were quarantined. Furthermore, it raised a serious concern about manufacturing, microbiological checking and shipping methods for the medical device industry that deserve further attention.

On-demand, hospital-based, severe acute respiratory coronavirus virus 2 (SARS-CoV-2) genomic epidemiology to support nosocomial outbreak investigations: A prospective molecular epidemiology study.

Objectives: We evaluated the added value of infection control-guided, on demand, and locally performed severe acute respiratory coronavirus virus 2 (SARS-CoV-2) genomic sequencing to support outbreak investigation and control in acute-care settings. Design and setting: This 18-month prospective molecular epidemiology study was conducted at a tertiary-care hospital in Montreal, Canada. When nosocomial transmission was suspected by local infection control, viral genomic sequencing was performed locally for all putative outbreak cases. Molecular and conventional epidemiology data were correlated on a just-in-time basis to improve understanding of coronavirus disease 2019 (COVID-19) transmission and reinforce or adapt control measures. Results: Between April 2020 and October 2021, 6 outbreaks including 59 nosocomial infections (per the epidemiological definition) were investigated. Genomic data supported 7 distinct transmission clusters involving 6 patients and 26 healthcare workers. We identified multiple distinct modes of transmission, which led to reinforcement and adaptation of infection control measures. Molecular epidemiology data also refuted (n = 14) suspected transmission events in favor of community acquired but institutionally clustered cases. Conclusion: SARS-CoV-2 genomic sequencing can refute or strengthen transmission hypotheses from conventional nosocomial epidemiological investigations, and guide implementation of setting-specific control strategies. Our study represents a template for prospective, on site, outbreak-focused SARS-CoV-2 sequencing. This approach may become increasingly relevant in a COVID-19 endemic state where systematic sequencing within centralized surveillance programs is not available. Trial registration: clinicaltrials.gov identifier: NCT05411562.

Erratum: Is your ice machine really clean? Uncovering the presence of opportunistic pathogens in hospital ice machines - CORRIGENDUM.

[This corrects the article DOI: 10.1017/ash.2022.76.].

Symptomatology during previous SARS-CoV-2 infection and serostatus before vaccination influence the immunogenicity of BNT162b2 COVID-19 mRNA vaccine.

Public health vaccination recommendations for COVID-19 primary series and boosters in previously infected individuals differ worldwide. As infection with SARS-CoV-2 is often asymptomatic, it remains to be determined if vaccine immunogenicity is comparable in all previously infected subjects. This study presents detailed immunological evidence to clarify the requirements for one- or two-dose primary vaccination series for naturally primed individuals. The main objective was to evaluate the immune response to COVID-19 mRNA vaccination to establish the most appropriate vaccination regimen to induce robust immune responses in individuals with prior SARS-CoV-2 infection. The main outcome measure was a functional immunity score (zero to three) before and after vaccination, based on anti-RBD IgG levels, serum capacity to neutralize live virus and IFN-γ secretion capacity in response to SARS-CoV-2 peptide pools. One point was attributed for each of these three functional assays with response above the positivity threshold. The immunity score was compared based on subjects' symptoms at diagnosis and/or serostatus prior to vaccination. None of the naïve participants (n=14) showed a maximal immunity score of three following one dose of vaccine compared to 84% of the previously infected participants (n=55). All recovered individuals who did not have an immunity score of three were seronegative prior to vaccination, and 67% had not reported symptoms resulting from their initial infection. Following one dose of vaccine, their immune responses were comparable to naïve individuals, with significantly weaker responses than individuals who were symptomatic during infection. These results indicate that the absence of symptoms during initial infection and negative serostatus prior to vaccination predict the strength of immune responses to COVID-19 mRNA vaccine. Altogether, these findings highlight the importance of administering the complete two-dose primary regimen and following boosters of mRNA vaccines to individuals who experienced asymptomatic SARS-CoV-2 infection.

The REinfection in COVID-19 Estimation of Risk (RECOVER) study: Reinfection and serology dynamics in a cohort of Canadian healthcare workers.

BACKGROUND: Understanding the immune response to natural infection by SARS-CoV-2 is key to pandemic management, especially in the current context of emerging variants. Uncertainty remains regarding the efficacy and duration of natural immunity against reinfection. METHODS: We conducted an observational prospective cohort study in Canadian healthcare workers (HCWs) with a history of PCR-confirmed SARS-CoV-2 infection to (i) measure the average incidence rate of reinfection and (ii) describe the serological immune response to the primary infection. RESULTS: Our cohort comprised 569 HCWs; median duration of individual follow-up was 371 days. We detected six cases of reinfection in absence of vaccination between August 21, 2020, and March 1, 2022, for a reinfection incidence rate of 4.0 per 100 person-years. Median duration of seropositivity was 415 days in symptomatics at primary infection compared with 213 days in asymptomatics (p < 0.0001). Other characteristics associated with prolonged seropositivity for IgG against the spike protein included age over 55 years, obesity, and non-Caucasian ethnicity. CONCLUSIONS: Among unvaccinated healthcare workers, reinfection with SARS-CoV-2 following a primary infection remained rare.

Infectivity of healthcare workers diagnosed with coronavirus disease 2019 (COVID-19) approximately 2 weeks after onset of symptoms: A cross-sectional study.

We performed viral culture of respiratory specimens in 118 severe acute respiratory coronavirus virus 2 (SARS-CoV-2)-infected healthcare workers (HCWs), ∼2 weeks after symptom onset. Only 1 HCW (0.8%) had a positive culture. No factors for prolonged viral shedding were identified. Infectivity is resolved in nearly all HCWs ∼2 weeks after symptom onset.

SARS-CoV-2 seroprevalence in health care workers from 10 hospitals in Quebec, Canada: a cross-sectional study.

BACKGROUND: The COVID-19 pandemic has disproportionately affected health care workers. We sought to estimate SARS-CoV-2 seroprevalence among hospital health care workers in Quebec, Canada, after the first wave of the pandemic and to explore factors associated with SARS-CoV-2 seropositivity. METHODS: Between July 6 and Sept. 24, 2020, we enrolled health care workers from 10 hospitals, including 8 from a region with a high incidence of COVID-19 (the Montréal area) and 2 from low-incidence regions of Quebec. Eligible health care workers were physicians, nurses, orderlies and cleaning staff working in 4 types of care units (emergency department, intensive care unit, COVID-19 inpatient unit and non-COVID-19 inpatient unit). Participants completed a questionnaire and underwent SARS-CoV-2 serology testing. We identified factors independently associated with higher seroprevalence. RESULTS: Among 2056 enrolled health care workers, 241 (11.7%) had positive SARS-CoV-2 serology. Of these, 171 (71.0%) had been previously diagnosed with COVID-19. Seroprevalence varied among hospitals, from 2.4% to 3.7% in low-incidence regions to 17.9% to 32.0% in hospitals with outbreaks involving 5 or more health care workers. Higher seroprevalence was associated with working in a hospital where outbreaks occurred (adjusted prevalence ratio 4.16, 95% confidence interval [CI] 2.63-6.57), being a nurse or nursing assistant (adjusted prevalence ratio 1.34, 95% CI 1.03-1.74) or an orderly (adjusted prevalence ratio 1.49, 95% CI 1.12-1.97), and Black or Hispanic ethnicity (adjusted prevalence ratio 1.41, 95% CI 1.13-1.76). Lower seroprevalence was associated with working in the intensive care unit (adjusted prevalence ratio 0.47, 95% CI 0.30-0.71) or the emergency department (adjusted prevalence ratio 0.61, 95% CI 0.39-0.98). INTERPRETATION: Health care workers in Quebec hospitals were at high risk of SARS-CoV-2 infection, particularly in outbreak settings. More work is needed to better understand SARS-CoV-2 transmission dynamics in health care settings.

Analysis of an IncR Plasmid Carrying blaNDM-1 Linked to an Azithromycin Resistance Region in Enterobacter hormaechei Involved in an Outbreak in Quebec.

In the context of a recent rise in prevalence of NDM-encoding carbapenemase-producing Enterobacterales (CPE) in the province of QC, Canada, the genetic environment of blaNDM-1 was investigated. Three NDM-producing clinical isolates of Enterobacter hormaechei recovered from hospitalized patients involved in a putative outbreak were further characterized by whole-genome sequencing (WGS). Two isolates were confirmed by pulsed-field gel electrophoresis and WGS to be closely related. In addition to a ∼128 kb IncFII conjugative multidrug-resistance (MDR) plasmid, these isolates possessed a ∼45 kb mobilizable IncR MDR plasmid containing 2 MDR regions: a complex class 1 integron harboring blaNDM-1 and 7 other AMR genes, and the IS26-mph(A)-mrx-mphR(A)-IS6100 azithromycin resistance unit. The predicted antimicrobial resistance (AMR) genes correlated with the antimicrobial susceptibility testing results. The multidrug-resistant phenotype in addition to the presence of two important mobile genetic elements, suggest a potent role as a reservoir of antibiotic resistance for such a small IncR plasmid. IMPORTANCE Analyzing the genetic environment of clinically relevant MDR genes can provide information on the way in which such genes are maintained and disseminated. Understanding this phenomenon is of interest for clinicians as it can also provide insight on where these genes might have been sourced, possibly supporting outbreak investigations.

Targeted caspofungin prophylaxis for invasive aspergillosis in high-risk liver transplant recipients, a single-center experience.

BACKGROUND: Invasive aspergillosis (IA) is a rare but highly lethal complication after orthotopic liver transplantation (OLT). Targeted antifungal prophylaxis has been proposed as a strategy to prevent IA among orthotopic liver transplant recipient (OLTr), but limited data are available to support its efficacy. METHOD: We conducted a single-center, retrospective, before and after cohort study, comparing IA incidences among OLTr who did not receive antifungal prophylaxis after transplantation (cohort 1) to OLTr who received targeted antifungal prophylaxis after liver transplantation (cohort 2). Patients in cohort 2 received caspofungin prophylaxis if they presented one of the following risk factors: retransplantation, acute liver failure, dialysis, or Aspergillus colonization prior to transplantation. The primary outcome was IA at 90 days after transplantation. RESULTS: A total of 391 OLTr were included in the study; 181 patients in the cohort 1 (no prophylaxis) and 210 patients in the cohort 2 (targeted prophylaxis). Among patients in cohort 2, 19% (40/ 210) were considered at high risk for IA and 85% (34/40) of those received caspofungin prophylaxis. The incidence of IA at 90 days was 3.3% (6/ 181) and 0.5% (1/ 210), in cohort 1 and 2, respectively (OR 0.14; 95%CI 0.01-0.83; P = .03). Ninety-day mortality was similar among the two cohorts (3.9% (7/181) and 2.4% (5/210) in cohort 1 and 2, respectively (OR 0.61; 95% 0.18-1.93; P = .40)). The 90-day mortality among the OLTs with IA was 71% (5/7). CONCLUSION: Targeted caspofungin prophylaxis was associated with lower rate of IA.

Adoption of infection prevention and control practices by healthcare workers in Québec: A qualitative study.

OBJECTIVE: To describe barriers and facilitators to the adoption of recommended infection prevention and control (IPC) practices among healthcare workers (HCWs). METHODS: A qualitative research design was used. Individual semistructured interviews with HCWs and observations of clinical practices were conducted from February to May 2018 in 8 care units of 2 large tertiary-care hospitals in Montreal (Québec, Canada). RESULTS: We interviewed 13 managers, 4 nurses, 2 physicians, 3 housekeepers, and 2 medical laboratory technologists. We conducted 7 observations by following IPC nurses (n = 3), nurses (n = 2), or patient attendants (n = 2) in their work routines. Barriers to IPC adoption were related to the context of care, workplace environment issues, and communication issues. The main facilitator of the IPC adoption by HCWs was the "development of an IPC culture or safety culture." The "IPC culture" relied upon leadership support by managers committed to IPC, shared belief in the importance of IPC measures to limit healthcare-associated infections (HAIs), collaboration and good communication among staff, as well as proactivity and ownership of IPC measures (ie, development of local solutions to reduce HAIs and "working together" toward common goals). CONCLUSIONS: Adoption of recommended IPC measures by HCWs is strongly influenced by the "IPC culture." The IPC culture was not uniform within hospital and differences in IPC culture were identified between care units.

Hiding in plain sight: A case of fever, rash, and jaundice.

A 25-year-old man presented to the emergency department with a 3-day history of fever, anorexia, jaundice, and a generalized skin eruption. His liver function tests showed marked cholestatic and cytolytic abnormalities without liver insufficiency. A liver biopsy was performed, and morphology with routine stains was considered non-specific. Because of the dermatological findings, the non-specific biopsy morphology, and the absence of an identified infectious etiology, a diagnosis of Kawasaki disease was presumed. However, additional colorations on liver biopsy with Warthin-Starry stain revealed multiple thin and coiled microorganisms compatible with spirochetes. His serology for leptospirosis was found to be positive for IgM, supporting the diagnosis of acute leptospirosis with liver involvement. Our case illustrates the diagnostic challenge of leptospirosis and highlights the utility of conventional laboratory tests to confirm the diagnosis. Exceptionally, Warthin-Starry stain allowed the identification of leptospires in liver biopsy and confirmed liver involvement of systemic leptospirosis.

Un homme de 25 ans a consulté à l'urgence parce qu'il faisait de la fièvre depuis trois jours, de l'anorexie, un ictère et une éruption cutanée généralisée. Les tests de fonction hépatique ont révélé des anomalies cholestatiques et cytolytiques marquées, sans insuffisance hépatique. La coloration standard de la biopsie hépatique a révélé une morphologie cellulaire considérée comme non spécifique. Compte tenu des observations dermatologiques, de la morphologie non spécifique de la biopsie et de l'absence d'étiologie infectieuse établie, un diagnostic de maladie de Kawasaki a été présumé. Cependant, l'ajout d'une coloration de Warthin-Starry a révélé de multiples microorganismes minces et torsadés compatibles avec des spirochètes. La sérologie pour la leptospirose s'est avérée positive pour les anticorps IgM, appuyant un diagnostic de leptospirose aiguë avec atteinte hépatique. Ce cas illustre les difficultés diagnostiques de la leptospirose et fait ressortir l'utilité des tests de laboratoire traditionnels pour confirmer le diagnostic. Exceptionnellement, la coloration de Warthin­Starry a permis d'observer des leptospires à la biopsie hépatique et confirmé la leptospirose systémique avec atteinte hépatique.

Plesiomonas shigelloides: An Unusual Cause of Septic Abortion.

Plesiomonas shigelloides, the only oxidase-positive Enterobacteriaceae, is an inhabitant of freshwater and estuary ecosystems. We report the first possible case of Plesiomonas shigelloides-induced septic abortion. This 24-year-old female was successfully treated by dilatation and curettage as well as antimicrobial therapy.

New Delhi metallo-ß-lactamase-producing Enterobacteriaceae, United States.

We characterized 9 New Delhi metallo-ß-lactamase-producing Enterobacteriaceae (5 Klebsiella pneumoniae, 2 Escherichia coli, 1 Enterobacter cloacae, 1 Salmonella enterica serovar Senftenberg) isolates identified in the United States and cultured from 8 patients in 5 states during April 2009-March 2011. Isolates were resistant to ß-lactams, fluoroquinolones, and aminoglycosides, demonstrated MICs ≤1 µg/mL of colistin and polymyxin, and yielded positive metallo-ß-lactamase screening results. Eight isolates had blaNDM-1, and 1 isolate had a novel allele (blaNDM-6). All 8 patients had recently been in India or Pakistan, where 6 received inpatient health care. Plasmids carrying blaNDM frequently carried AmpC or extended spectrum ß-lactamase genes. Two K. pneumoniae isolates and a K. pneumoniae isolate from Sweden shared incompatibility group A/C plasmids with indistinguishable restriction patterns and a common blaNDM fragment; all 3 were multilocus sequence type 14. Restriction profiles of the remaining New Delhi metallo-ß-lactamase plasmids, including 2 from the same patient, were diverse.

A call for action: managing the emergence of multidrug-resistant Enterobacteriaceae in the acute care settings.

PURPOSE OF REVIEW: Multidrug-resistant (MDR) Enterobacteriaceae are an emerging and a major concern for the medical community. Reported rates of MDR Enterobacteriaceae are increasing, and infections with these organisms are no longer limited to those associated with healthcare in the severely ill or infirm. Community-acquired infections are now described. The purpose of this review is to provide the readers with an up to date picture of MDR Enterobacteriaceae and to highlight the infection prevention practices that will impede the spread of this public health threat. RECENT FINDINGS: The epidemiology of MDR Enterobacteriaceae is rapidly evolving. Among the various MDR Gram-negatives, carbapenemase-producing organisms have been some of the most concerning. Descriptions of the global spread of carbapenemase-producing Enterobacteriaceae, and emerging epidemiology including the findings of the New Delhi metallo beta-lactamase (NDM) in water and other environmental sources, have forced reconsideration of prevention strategies. Similarly, food-borne outbreaks of extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae have also caused public health experts to rethink approaches to control their spread. Finally, several articles published in the past year address the challenges and contemporary strategies to combat the MDR Enterobacteriaceae. SUMMARY: The speed with which the newest resistance genes have disseminated among the different Gram-negative species and around the world is such that it is now considered a global public health crisis. Proposed infection prevention and control practices related to MDR Enterobacteriaceae are primarily 'bundled' and based on clinical case reports derived from outbreak-like situations, on expert opinion and understanding about other Gram-negatives.