Half a Century of Research on Membrane-Containing Bacteriophages: Bringing New Concepts to Modern Virology

Half a century of research on membrane-containing phages has had a major impact on virology, providing new insights into virus diversity, evolution and ecological importance. The recent revolutionary technical advances in imaging, sequencing and lipid analysis have significantly boosted the depth and volume of knowledge on these viruses. This has resulted in new concepts of virus assembly, understanding of virion stability and dynamics, and the description of novel processes for viral genome packaging and membrane-driven genome delivery to the host. The detailed analyses of such processes have given novel insights into DNA transport across the protein-rich lipid bilayer and the transformation of spherical membrane structures into tubular nanotubes, resulting in the description of unexpectedly dynamic functions of the membrane structures. Membrane-containing phages have provided a framework for understanding virus evolution. The original observation on membrane-containing bacteriophage PRD1 and human pathogenic adenovirus has been fundamental in delineating the concept of “viral lineages”, postulating that the fold of the major capsid protein can be used as an evolutionary fingerprint to trace long-distance evolutionary relationships that are unrecognizable from the primary sequences. This has brought the early evolutionary paths of certain eukaryotic, bacterial, and archaeal viruses together, and potentially enables the reorganization of the nearly immeasurable virus population (~1 × 1031) on Earth into a reasonably low number of groups representing different architectural principles. In addition, the research on membrane-containing phages can support the development of novel tools and strategies for human therapy and crop protection

Mental Well-being of Healthcare Workers in 2 Hospital Districts During the First Wave Ofthe Covid-19 Pandemic in Finland a Cross-sectional Study

Peer reviewe

SOURCES OF HEALTHCARE WORKERS' COVID-19 INFECTIONS AND RELATED SAFETY GUIDELINES

Objectives: To evaluate the effectiveness of safety guidelines in the workplace, the authors analyzed the work-related exposure to SARS-CoV-2 and the source of COVID-19 infections among healthcare workers (HCWs), together with the use of personal protective equipment (PPE). Material and Methods: A cross-sectional prospective study was conducted in tertiary hospitals in the Uusimaa region, Finland, with 1072 volunteers being enrolled in the study from among the HCWs at the Helsinki University Hospital. Overall, 866 (80.8%) HCWs (including 588 nurses, 170 doctors, and 108 laboratory and medical imaging nurses) completed the questionnaire by July 15, 2020, with 52% of the participants taking care of COVID-19 patients. The participants answered a structured questionnaire regarding their use of PPE, the ability to follow safety guidelines, exposure to COVID-19, and the source of potential COVID-19 infections. The participants with COVID-19 symptoms were tested with the SARS-CoV-2 real-time polymerase chain reaction method. All infected participants were contacted, and their answers were confirmed regarding COVID-19 exposure. Results: In total, 41 (4.7%) participants tested positive for SARS-CoV-2, with 22 (53.6%) of infections being confirmed or likely occupational, and 12 (29.3%) originating from colleagues. In 14 cases (63.6%), occupational infections occurred while using a surgical mask, and all infections originating from patients occurred while using a surgical mask or no mask at all. No occupational infections were found while using an FFP2/3 respirator and following aerosol precautions. The combined odds ratio for working at an intensive care unit, an emergency department, or a ward was 3.4 (95% CI: 1.2-9.2, p = 0.016). Conclusions: A high infection rate was found among HCWs despite safety guidelines. Based on these findings, the authors recommend the use of FFP2/3 respirators in all patient contacts with confirmed or suspected COVID-19, along with the use of universal masking, also in personnel rooms.Peer reviewe

"As protective gear began to run low, guidance on protection became looser" - Healthcare workers' perspectives on infection prevention and control during the COVID-19 pandemic

ObjectivesThe COVID-19 pandemic has posed several risk factors to healthcare workers' (HCWs') emotional distress. The purpose of the study was to enhance understanding of the experiences and feelings of HCWs during the COVID-19 pandemic, with specific reference to infection prevention and control (IPC) practices and guidance, focusing on the quality and availability of personal protective equipment (PPE), guidelines, and management. With a qualitative approach, we aimed to enable a wider narrative; to gain a more detailed understanding related to PPE use and identify experiences that can be overlooked in forced-choice questionnaires. MethodsAn online questionnaire was conducted among HCWs of the City of Helsinki and Helsinki University Hospital between 12.6.2020 and 5.4.2021. Altogether 1,580 HCWs participated in the study, from whom 579 shared 1,666 free-text responses. These responses were analyzed qualitatively, and the results were combined with statistical data on the participants' working conditions and backgrounds. ResultsWe identified problems in PPE availability and changing guidelines as factors causing the most distress in the participants. Regarding availability, running out of masks and respirators emerged as the most worrying issue, and inadequate PPE was associated with the excessive workload (OR 1.51, CI 95% 1.01-2.25). The results also highlight the importance of transparent and clear communication regarding IPC instructions and guidance, and clear IPC guidance was associated with better levels of reported recovery from work (OR 1.51, CI 95% 1.06-2.14). ConclusionsOur study highlights the importance of adequate PPE provision, transparent communication, clear guidance, and supportive supervisory work in this ongoing pandemic and potential new ones. We suggest more rigorous preparation, with crisis communication planning and emergency storage of PPE.Peer reviewe

Aerosol Generation During Otologic Surgery

Objective To assess whether aerosol generation occurs during otologic surgery, to define which instruments are aerosol generating, and to identify factors that enhance safety in protection against airborne pathogens, such as severe acute respiratory syndrome coronavirus 2. Study Design An observational prospective study on aerosol measurements during otologic operations recorded between August and December 2020. Setting Aerosol generation was measured with an Optical Particle Sizer as part of otologic operations with anesthesia. Particles with a size range of 0.3 to 10 mu m were quantified. Aerosol generation was measured during otologic operations to analyze aerosols during drilling in transcanal and transmastoid operations and when using the following instruments: bipolar electrocautery, laser, suction, and cold instruments. Coughing is known to produce significant concentration of aerosols and is commonly used as a reference for high-risk aerosol generation. Thus, the operating room background concentration and coughing were chosen as reference values. Patients Thirteen otologic operations were included. The average drilling time per surgery was 27.00 minutes (range, 2.00-71.80 min). Intervention Different rotation speeds during drilling and other instruments were used. Main Outcome Measures Aerosol concentrations during operations were recorded and compared with background and cough aerosol concentrations. Results Total aerosol concentrations during drilling were significantly higher than background (p < 0.0001, d = 2.02) or coughing (p < 0.0001, d = 0.50). A higher drilling rotation speed was associated with higher particle concentration (p = 0.037, eta(2) = 0.01). Aerosol generation during bipolar electrocautery, drilling, and laser was significantly higher than with cold instruments or suction (p < 0.0001, eta(2) = 0.04). Conclusion High aerosol generation is observed during otologic surgery when drill, laser, or bipolar electrocautery is used. Aerosol generation can be reduced by using cold instruments instead of electric and keeping the suction on during aerosol-generating procedures. If drilling is required, lower rotation speeds are recommended. These measures may help reduce the spread of airborne pathogens during otologic surgery.Peer reviewe

Työolot perusterveydenhuollossa ja erikoissairaanhoidossa covid-19 pandemian aikana

Objectives: The COVID-19 pandemic has globally affected healthcare workers’ (HCWs) health and wellbeing. Most studies on COVID-19 have focused on tertiary healthcare. The aim of this study was to increase the knowledge on the effects of the pandemic on working conditions in tertiary and primary healthcare. Material and Methods: The comparative cross-sectional study consisted of an online questionnaire sent to HCWs of the City of Helsinki (primary healthcare) and Helsinki University Hospital (tertiary healthcare). Altogether 1580 HCWs with direct patient contact participated in the study: 895 from tertiary and 685 from primary healthcare. Statistical analysis used SPSS 25 from IBM. The tests used were the χ2 test, Fisher’s exact test, and binary logistic regression analysis. Results: Primary HCWs were less likely to treat COVID-19 patients (OR = 0.45, 95% CI: 0.37–0.56). However, both groups reported a similar number of COVID-19 infections, primary HCWs 4.9% and tertiary HCWs 5.0%, and work-related quarantine was significantly more prevalent (OR = 1.96, 95% CI: 1.38–2.79) among primary HCWs. In addition, work-related wellbeing was poorer among primary HCWs than tertiary HCWs in terms of feeling more stressed at work (OR = 3.20, 95% CI: 2.55–4.02), not recovering from work (OR = 0.49, 95% CI: 0.39–0.62), reported mental wellbeing below normal levels (OR: 1.59, 95% CI: 1.26–2.00), and increased working hours (OR = 1.63, 95% CI: 1.25–2.12). Conclusions: The study demonstrates how the pandemic has affected the wellbeing and working conditions of not only tertiary but also less studied primary HCWs. The authors’ findings suggest that the challenges identified during the COVID-19 pandemic in the health and wellbeing of healthcare workers are even greater in primary care than in tertiary care.Peer reviewe

ICTV Virus Taxonomy Profile: Finnlakeviridae

Finnlakeviridae is a family of icosahedral, internal membrane-containing bacterial viruses with circular, single-stranded DNA genomes. The family includes the genus, Finnlakevirus, with the species, Flavobacterium virus FLiP. Flavobacterium phage FLiP was isolated with its Gram-negative host bacterium from a boreal freshwater habitat in Central Finland in 2010. It is the first described single-stranded DNA virus with an internal membrane and shares minimal sequence similarity with other known viruses. The virion organization (pseudo T=21 dextro) and major capsid protein fold (double-beta-barrel) resemble those of Pseudoalteromonas phage PM2 (family Corticoviridae), which has a double-stranded DNA genome. A similar major capsid protein fold is also found in other double-stranded DNA viruses in the kingdom Bamfordvirae.Non peer reviewe

Blood and saliva SARS-CoV-2 antibody levels in self-collected dried spot samples

We examined the usefulness of dried spot blood and saliva samples in SARS-CoV-2 antibody analyses. We analyzed 1231 self-collected dried spot blood and saliva samples from healthcare workers. Participants filled in a questionnaire on their COVID-19 exposures, infections, and vaccinations. Anti-SARS-CoV-2 IgG, IgA, and IgM levels were determined from both samples using the GSP/DELFIA method. The level of exposure was the strongest determinant of all blood antibody classes and saliva IgG, increasing as follows: (1) no exposure (healthy, non-vaccinated), (2) exposed, (3) former COVID-19 infection, (4) one vaccination, (5) two vaccinations, and (6) vaccination and former infection. While the blood IgG assay had a 99.5% sensitivity and 75.3% specificity to distinguish participants with two vaccinations from all other types of exposure, the corresponding percentages for saliva IgG were 85.3% and 65.7%. Both blood and saliva IgG-seropositivity proportions followed similar trends to the exposures reported in the questionnaires. Self-collected dry blood and saliva spot samples combined with the GSP/DELFIA technique comprise a valuable tool to investigate an individual's immune response to SARS-CoV-2 exposure or vaccination. Saliva IgG has high potential to monitor vaccination response wane, since the sample is non-invasive and easy to collect.Peer reviewe

Biodistribution Analysis of Oncolytic Adenoviruses in Patient Autopsy Samples Reveals Vascular Transduction of Noninjected Tumors and Tissues

In clinical trials with oncolytic adenoviruses, there has been no mortality associated with treatment vectors. Likewise, in the Advanced Therapy Access Program (ATAP), where 290 patients were treated with 10 different viruses, no vector-related mortality was observed. However, as the patient population who received adenovirus treatments in ATAP represented heavily pretreated patients, often with very advanced disease, some patients died relatively soon after receiving their virus treatment mandating autopsy to investigate cause of death. Eleven such autopsies were performed and confirmed disease progression as the cause of death in each case. The regulatory requirement for investigating the safety of advanced therapy medical products presented a unique opportunity to study tissue samples collected as a routine part of the autopsies. Oncolytic adenoviral DNA was recovered in a wide range of tissues, including injected and noninjected tumors and various normal tissues, demonstrating the ability of the vector to disseminate through the vascular route. Furthermore, we recovered and cultured viable virus from samples of noninjected brain metastases of an intravenously treated patient, confirming that oncolytic adenovirus can reach tumors through the intravascular route. Data presented here give mechanistic insight into mode of action and biodistribution of oncolytic adenoviruses in cancer patients.Peer reviewe