An appeal for strengthening genomic pathogen surveillance to improve pandemic preparedness and infection prevention: the German perspective.

The SARS-CoV-2 pandemic has highlighted the importance of viable infection surveillance and the relevant infrastructure. From a German perspective, an integral part of this infrastructure, genomic pathogen sequencing, was at best fragmentary and stretched to its limits due to the lack or inefficient use of equipment, human resources, data management and coordination. The experience in other countries has shown that the rate of sequenced positive samples and linkage of genomic and epidemiological data (person, place, time) represent important factors for a successful application of genomic pathogen surveillance. Planning, establishing and consistently supporting adequate structures for genomic pathogen surveillance will be crucial to identify and combat future pandemics as well as other challenges in infectious diseases such as multi-drug resistant bacteria and healthcare-associated infections. Therefore, the authors propose a multifaceted and coordinated process for the definition of procedural, legal and technical standards for comprehensive genomic pathogen surveillance in Germany, covering the areas of genomic sequencing, data collection and data linkage, as well as target pathogens. A comparative analysis of the structures established in Germany and in other countries is applied. This proposal aims to better tackle epi- and pandemics to come and take action from the "lessons learned" from the SARS-CoV-2 pandemic.

[Establishment of genomic pathogen surveillance to strengthen pandemic preparedness and infection prevention in Germany]. / Etablierung der Genomischen Erreger-Surveillance zur Stärkung des Pandemie- und Infektionsschutzes in Deutschland.

The SARS-CoV­2 pandemic has shown a deficit of essential epidemiological infrastructure, especially with regard to genomic pathogen surveillance in Germany. In order to prepare for future pandemics, the authors consider it urgently necessary to remedy this existing deficit by establishing an efficient infrastructure for genomic pathogen surveillance. Such a network can build on structures, processes, and interactions that have already been initiated regionally and further optimize them. It will be able to respond to current and future challenges with a high degree of adaptability.The aim of this paper is to address the urgency and to outline proposed measures for establishing an efficient, adaptable, and responsive genomic pathogen surveillance network, taking into account external framework conditions and internal standards. The proposed measures are based on global and country-specific best practices and strategy papers. Specific next steps to achieve an integrated genomic pathogen surveillance include linking epidemiological data with pathogen genomic data; sharing and coordinating existing resources; making surveillance data available to relevant decision-makers, the public health service, and the scientific community; and engaging all stakeholders. The establishment of a genomic pathogen surveillance network is essential for the continuous, stable, active surveillance of the infection situation in Germany, both during pandemic phases and beyond.

Inhibition of p38 signaling curtails the SARS-CoV-2 induced inflammatory response but retains the IFN-dependent antiviral defense of the lung epithelial barrier.

SARS-CoV-2 is the causative agent of the immune response-driven disease COVID-19 for which new antiviral and anti-inflammatory treatments are urgently needed to reduce recovery time, risk of death and long COVID development. Here, we demonstrate that the immunoregulatory kinase p38 MAPK is activated during viral entry, mediated by the viral spike protein, and drives the harmful virus-induced inflammatory responses. Using primary human lung explants and lung epithelial organoids, we demonstrate that targeting p38 signal transduction with the selective and clinically pre-evaluated inhibitors PH-797804 and VX-702 markedly reduced the expression of the pro-inflammatory cytokines IL6, CXCL8, CXCL10 and TNF-α during infection, while viral replication and the interferon-mediated antiviral response of the lung epithelial barrier were largely maintained. Furthermore, our results reveal a high level of drug synergism of both p38 inhibitors in co-treatments with the nucleoside analogs Remdesivir and Molnupiravir to suppress viral replication of the SARS-CoV-2 variants of concern, revealing an exciting and novel mode of synergistic action of p38 inhibition. These results open new avenues for the improvement of the current treatment strategies for COVID-19.

Outbreak of MRSA in a Gynecology/Obstetrics Department during the COVID-19 Pandemic: A Cautionary Tale.

Since March 2020, the COVID-19 pandemic forced hospitals worldwide to intensify their infection control measures to prevent health care-associated transmission of SARS-CoV-2. The correct use of personal protective equipment, especially the application of masks, was quickly identified as priority to reduce transmission with this pathogen. Here, we report a nosocomial cluster of methicillin-resistant Staphylococcus aureus (MRSA) that occurred during the COVID-19 pandemic in a gynecology/obstetrics department, despite these intensified contact precautions. Five MRSA originating from clinical samples after surgical intervention led to an outbreak investigation. Firstly, this included environmental sampling of the operation theatre (OT) and, secondly, a point prevalence screening of patients and health care workers (HCW). All detected MRSA were subjected to whole genome sequencing (WGS) and isolate relatedness was determined using core genome multilocus sequence typing (cgMLST). WGS revealed one MRSA cluster with genetically closely related five patient and two HCW isolates differing in a single cgMLST allele at maximum. The outbreak was terminated after implementation of infection control bundle strategies. Although contact precaution measures, which are also part of MRSA prevention bundle strategies, were intensified during the COVID-19 pandemic, this MRSA outbreak could take place. This illustrates the importance of adherence to classical infection prevention strategies.

Outbreak of MRSA in a Gynecology/Obstetrics Department during the COVID-19 Pandemic: A Cautionary Tale

Since March 2020, the COVID-19 pandemic forced hospitals worldwide to intensify their infection control measures to prevent health care-associated transmission of SARS-CoV-2. The correct use of personal protective equipment, especially the application of masks, was quickly identified as priority to reduce transmission with this pathogen. Here, we report a nosocomial cluster of methicillin-resistant Staphylococcus aureus (MRSA) that occurred during the COVID-19 pandemic in a gynecology/obstetrics department, despite these intensified contact precautions. Five MRSA originating from clinical samples after surgical intervention led to an outbreak investigation. Firstly, this included environmental sampling of the operation theatre (OT) and, secondly, a point prevalence screening of patients and health care workers (HCW). All detected MRSA were subjected to whole genome sequencing (WGS) and isolate relatedness was determined using core genome multilocus sequence typing (cgMLST). WGS revealed one MRSA cluster with genetically closely related five patient and two HCW isolates differing in a single cgMLST allele at maximum. The outbreak was terminated after implementation of infection control bundle strategies. Although contact precaution measures, which are also part of MRSA prevention bundle strategies, were intensified during the COVID-19 pandemic, this MRSA outbreak could take place. This illustrates the importance of adherence to classical infection prevention strategies.

Surgeons' non-transparent facemasks challenge the physician-patient relationship in the orthopedic outpatient clinic of a tertiary university hospital during the COVID-19 pandemic: a prospective cohort study of 285 patients.

Background and purpose - Facemasks play a role in preventing the respiratory spread of SARS-CoV-2, but their impact on the physician-patient relationship in the orthopedic outpatient clinic is unclear. We investigated whether the type of surgeons' facemask impacts patients' perception of the physician-patient relationship, influences their understanding of what the surgeon said, or affects their perceived empathy. Patients and methods - All patients with an appointment in the orthopedic outpatient clinic of a tertiary university hospital during the 2-week study period were included. During consultations, all surgeons wore a non-transparent (first study week) or transparent facemask (second study week). Results of 285 of 407 eligible patients were available for analysis. The doctor-patient relationship was evaluated using the standardized Patient Reactions Assessment (PRA) and a 10-point Likert-scale questionnaire ranging from 0 (strongly disagree) to 10 (strongly agree). Results - A non-transparent facemask led to more restrictions in the physician-patient communication and a worse understanding of what the surgeon said. Patients' understanding improved with a transparent facemask with greatest improvements reported by patients aged 65 years and older (non-transparent: 6 [IQR 5-10] vs. transparent: 10 [IQR 9-10], p < 0.001) and by patients with a self-reported hearing impairment (non-transparent: 7 [IQR 3-7] vs. transparent: 9 [IQR 9-10], p < 0.001). The median PRA score was higher when surgeons wore a transparent facemask (p= 0.003). Interpretation - Surgeons' non-transparent facemasks pose a new communication barrier that can negatively affect the physician-patient relationship. While emotional factors like affectivity and empathy seem to be less affected overall, the physician-patient communication and patients' understanding of what the surgeon said seem to be negatively affected.

Decontamination of disposable respirators for reuse in a pandemic employing in-situ-generated peracetic acid.

BACKGROUND: During shortages of filtering face pieces (FFP) in a pandemic, it is necessary to implement a method for safe reuse or extended use. Our aim was to develop a simple, inexpensive and ecological method for decontamination of disposable FFPs that preserves filtration efficiency and material integrity. MATERIAL AND METHODS: Contamination of FFPs (3M Aura 9320+) with SARS-CoV-2 (1.15 × 104 PFUs), Enterococcus faecium (>106 CFUs), and physiological nasopharyngeal flora was performed prior to decontamination by submersion in a solution of 6 % acetic acid and 6 % hydrogen peroxide (6%AA/6%HP solution) over 30 minutes. Material integrity was assessed by testing the filtering efficiency, loss of fit and employing electron microscopy. RESULTS AND DISCUSSION: Decontamination with the 6%AA/6%HP solution resulted in the complete elimination of SARS-CoV-2, E. faecium and physiological nasopharyngeal flora. Material characterization post-treatment showed neither critical material degradation, loss of fit or reduction of filtration efficiency. Electron microscopy revealed no damage to the fibers, and the rubber bands' elasticity was not affected by the decontamination procedure. No concerning residuals of the decontamination procedure were found. CONCLUSION: The simple application and widespread availability of 6%AA/6%HP solution for decontaminating disposable FFPs make this solution globally viable, including developing and third world countries.

First Reported Nosocomial Outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 in a Pediatric Dialysis Unit.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was initially detected in China in December 2019. Currently, in Germany >140 000 cases of COVID-19 are confirmed. Here we report a nosocomial outbreak of SARS-CoV-2 infections in the pediatric dialysis unit of the University Hospital Münster (UHM). METHODS: Single-step real-time reverse-transcription polymerase chain reaction (rRT-PCR) from nasopharyngeal swabs was used to diagnose the index patient and identify infected contacts. Epidemiological links were analyzed by patient interviews and medical record reviews. In addition, each contact was assessed for exposure to the index case and monitored for clinical symptoms. Cycle threshold (Ct) values of all positive test results were compared between symptomatic and asymptomatic cases. RESULTS: Forty-eight cases were involved in this nosocomial outbreak. Nine contact cases developed laboratory-confirmed COVID-19 infections. Two SARS-CoV-2-positive cases remained clinically asymptomatic. Eleven cases reported flulike symptoms without positive results. Ct values were significantly lower in cases presenting typical COVID-19 symptoms, suggesting high viral shedding (P = .007). CONCLUSIONS: Person-to-person transmission was at the heart of a hospital outbreak of SARS-CoV-2 between healthcare workers (HCWs) and patients in the pediatric dialysis unit at UHM. Semiquantitative rRT-PCR results suggest that individuals with high viral load pose a risk to spread SARS-CoV-2 in the hospital setting. Our epidemiological observation highlights the need to develop strategies to trace and monitor SARS-CoV-2-infected HCWs to prevent COVID-19 outbreaks in the hospital setting.

A nosocomial cluster of vancomycin resistant enterococci among COVID-19 patients in an intensive care unit.

BACKGROUND: Currently, hospitals have been forced to divert substantial resources to cope with the ongoing coronavirus disease 2019 (COVID-19) pandemic. It is unclear if this situation will affect long-standing infection prevention practices and impact on healthcare associated infections. Here, we report a nosocomial cluster of vancomycin-resistant enterococci (VRE) that occurred on a COVID-19 dedicated intensive care unit (ICU) despite intensified contact precautions during the current pandemic. Whole genome sequence-based typing (WGS) was used to investigate genetic relatedness of VRE isolates collected from COVID-19 and non-COVID-19 patients during the outbreak and to compare them to environmental VRE samples. METHODS: Five VRE isolated from patients (three clinical and two screening samples) as well as 11 VRE and six vancomycin susceptible Enterococcus faecium (E. faecium) samples from environmental sites underwent WGS during the outbreak investigation. Isolate relatedness was determined using core genome multilocus sequence typing (cgMLST). RESULTS: WGS revealed two genotypic distinct VRE clusters with genetically closely related patient and environmental isolates. The cluster was terminated by enhanced infection control bundle strategies. CONCLUSIONS: Our results illustrate the importance of continued adherence to infection prevention and control measures during the COVID-19 pandemic to prevent VRE transmission and healthcare associated infections.

Healthcare-Associated SARS-CoV-2 Transmission-Experiences from a German University Hospital.

During the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, healthcare systems worldwide have to prevent nosocomial SARS-CoV-2 transmission while maintaining duty of care. In our study, we characterize the transmission dynamic of SARS-CoV-2 in inpatients and healthcare workers (HCWs) at the University Hospital Münster (UHM) in northwest Germany. We identified 27 cases of healthcare-associated SARS-CoV-2 infections (4 inpatients and 23 HCWs) who had contact with patients and/or HCWs without the use of adequate PPE. The contacts of these index cases were followed up for SARS-CoV-2 infection after unprotected exposure and a quantitative measure of probability of becoming infected, the attack rate, was calculated. In addition, transmission was evaluated in the context of infection control measures established during the pandemic and we compared the epidemiological data of all index cases, including symptoms and Ct values of virology test results. The overall attack rate in the hospital setting was 1.3% (inpatients 0.9%, HCWs 1.6%). However, during an outbreak, the attack rate was 25.5% (inpatients 20.0%, HCWs 29.6%). For both scenarios, HCWs had a higher attack rate illustrating their role in healthcare-associated SARS-CoV-2 transmission. Taken together, our experiences demonstrate how infection control measures can minimize the transmission of SARS-CoV-2 in the healthcare setting.