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Abstract Background Understanding factors associated with antimicrobial resistance (AMR) distribution across populations is a necessary step in planning mitigation measures. While associations between AMR and socioeconomic-status (SES), including employment and education have been increasingly recognized in low- and middle-income settings, connections are less clear in high-income countries where SES remains an important influence on other health outcomes. Methods We explored the relationship between SES and AMR in Calgary, Canada using spatially-resolved wastewater-based surveillance of resistomes detected by metagenomics across eight socio-economically diverse urban neighborhoods. Resistomes were established by shotgun-sequencing of wastewater pellets, and qPCR of targeted-AMR genes. SES status was established using 2021 Canadian census data. Conducting this comparison during the height of COVID-related international travel restrictions (Dec. 2020–Oct. 2021) allowed the hypotheses linking SES and AMR to be assessed with limited confounding. These were compared with sewage metagenomes from 244 cities around the world, linked with Human Development Index (HDI). Results Wastewater metagenomes from Calgary’s socioeconomically diverse neighborhoods exhibit highly similar resistomes, with no quantitative differences (p > 0.05), low Bray-Curtis dissimilarity, and no significant correlations with SES. By comparison, dissimilarity is observed between globally-sourced resistomes (p

Abstract Background Haemophilus influenzae is prevalent within the airways of persons with cystic fibrosis (pwCF). H. influenzae is often associated with pulmonary exacerbations (PEx) in pediatric cohorts, but in adults, studies have yielded conflicting reports around the impact(s) on clinical outcomes such as lung function decline. Accordingly, we sought to discern the prevalence, natural history, and clinical impact of H. influenzae in adult pwCF. Methods This single-centre retrospective cohort study reviewed all adult pwCF with H. influenzae sputum cultures between 2002 and 2016. From this cohort, persistently infected subjects (defined as: ≥2 samples with the same pulsotype and > 50% sputum culture-positive for H. influenzae in each year) were matched (1:2) to controls without H. influenzae. Demographic and clinical status (baseline health or during periods of PEx) were obtained at each visit that H. influenzae was cultured. Yearly biobank isolates were typed using pulsed-field gel electrophoresis (PFGE) to assess relatedness. Results Over the study period, 30% (n = 70/240) of pwCF were culture positive for H. influenzae, of which 38 (54%) were culture-positive on multiple occasions and 12 (17%) had persistent infection. One hundred and thirty-seven isolates underwent PFGE, with 94 unique pulsotypes identified. Two (1.5%) were serotype f with the rest non-typeable (98.5%). H. influenzae isolation was associated with an increased risk of PEx (RR = 1.61 [1.14–2.27], p = 0.006), however, this association was lost when we excluded those who irregularly produced sputum (i.e. only during a PEx). Annual lung function decline did not differ across cohorts. Conclusions Isolation of H. influenzae was common amongst adult pwCF but often transient. H. influenzae infection was not associated with acute PEx or chronic lung function decline.

Abstract Background Clostridioides difficile infection (CDI) is associated with considerable morbidity and mortality in hospitalized patients, especially among older adults. Probiotics have been evaluated to prevent hospital-acquired (HA) CDI in patients who are receiving systemic antibiotics, but the implementation of timely probiotic administration remains a challenge. We evaluated methods for effective probiotic implementation across a large health region as part of a study to assess the real-world effectiveness of a probiotic to prevent HA-CDI (Prevent CDI-55 +). Methods We used a stepped-wedge cluster-randomized controlled trial across four acute-care adult hospitals (n = 2,490 beds) to implement the use of the probiotic Bio-K + ® (Lactobacillus acidophilus CL1285®, L. casei LBC80R® and L. rhamnosus CLR2®; Laval, Quebec, Canada) in patients 55 years and older receiving systemic antimicrobials. The multifaceted probiotic implementation strategy included electronic clinical decision support, local site champions, and both health care provider and patient educational interventions. Focus groups were conducted during study implementation to identify ongoing barriers and facilitators to probiotic implementation, guiding needed adaptations of the implementation strategy. Focus groups were thematically analyzed using the Theoretical Domains Framework and the Consolidated Framework of Implementation Research. Results A total of 340 education sessions with over 1,800 key partners and participants occurred before and during implementation in each of the four hospitals. Site champions were identified for each included hospital, and both electronic clinical decision support and printed educational resources were available to health care providers and patients. A total of 15 individuals participated in 2 focus group and 7 interviews. Key barriers identified from the focus groups resulted in adaptation of the electronic clinical decision support and the addition of nursing education related to probiotic administration. As a result of modifying implementation strategies for identified behaviour change barriers, probiotic adherence rates were from 66.7 to 75.8% at 72 h of starting antibiotic therapy across the four participating acute care hospitals. Conclusions Use of a barrier-targeted multifaceted approach, including electronic clinical decision support, education, focus groups to guide the adaptation of the implementation plan, and local site champions, resulted in a high probiotic adherence rate in the Prevent CDI-55 + study.

RationaleChronic infection with Stenotrophomonas maltophilia in persons with cystic fibrosis (pwCF) has been linked to an increased risk of pulmonary exacerbations and lung function decline. We sought to establish whether baseline sputum microbiome associates with risk of S. maltophilia incident infection and persistence in pwCF.MethodspwCF experiencing incident S. maltophilia infections attending the Calgary Adult CF Clinic from 2010–2018 were compared with S. maltophilia-negative sex, age (+/−2 years), and birth-cohort-matched controls. Infection outcomes were classified as persistent (when the pathogen was recovered in ≥50% of cultures in the subsequent year) or transient. We assessed microbial communities from prospectively biobanked sputum using V3-V4 16S ribosomal RNA (rRNA) gene sequencing, in the year preceding (Pre) (n = 57), at (At) (n = 22), and after (Post) (n = 31) incident infection. We verified relative abundance data using S. maltophilia-specific qPCR and 16S rRNA-targeted qPCR to assess bioburden. Strains were typed using pulse-field gel electrophoresis.ResultsTwenty-five pwCF with incident S. maltophilia (56% female, median 29 years, median FEV1 61%) with 33 total episodes were compared with 56 uninfected pwCF controls. Demographics and clinical characteristics were similar between cohorts. Among those with incident S. maltophilia infection, sputum communities did not cluster based on infection timeline (Pre, At, Post). Communities differed between the infection cohort and controls (n = 56) based on Shannon Diversity Index (SDI, p = 0.04) and clustered based on Aitchison distance (PERMANOVA, p = 0.01) prior to infection. At the time of incident S. maltophilia isolation, communities did not differ in SDI but clustered based on Aitchison distance (PERMANOVA, p = 0.03) in those that ultimately developed persistent infection versus those that were transient. S. maltophilia abundance within sputum was increased in samples from patients (Pre) relative to controls, measuring both relative (p = 0.004) and absolute (p = 0.001). Furthermore, S. maltophilia abundance was increased in sputum at incident infection in those who ultimately developed persistent infection relative to those with transient infection, measured relatively (p = 0.04) or absolute (p = 0.04), respectively.ConclusionMicrobial community composition of CF sputum associates with S. maltophilia infection acquisition as well as infection outcome. Our study suggests sputum microbiome may serve as a surrogate for identifying infection risk and persistence risk.

Abstract Objective: To describe antimicrobial usage (AMU) trends before and during the coronavirus disease 2019 (COVID-19) pandemic, between COVID-19 and non-COVID-19 wards, and if there was any association with a COVID-19 order set. Design: Quasi-experimental retrospective interrupted time series analysis of AMU rates with a contemporaneous comparison of COVID-19 versus non-COVID-19 control wards. Analysis using incidence rate ratios (IRR) was conducted using a Poisson regression generalized linear model. Setting: Five COVID-19 and 4 comparable non-COVID-19 wards and 6 intensive care units (ICUs) at 4 hospitals during pandemic waves 1–4. Participants: All inpatients receiving systemic antimicrobials. Intervention: The COVID-19 checkbox antimicrobial order set was implemented in March 2020, to be used only if considered clinically indicated with modification in August 2021. Main Outcome(s) and Measure(s): The primary outcome was a change in AMU rates (defined daily dose per 100 patient days per month) comparing pre- versus peri-pandemic periods and COVID-19 versus control non-COVID-19 wards. Secondary outcomes included antifungal usage rate in ICUs and assessing AMUs following implementation and modification of a COVID-19 order set. Results: Significantly greater rates of AMU (IRR[95%CI]) were observed on COVID-19 wards versus non-COVID-19 wards during waves 1–4 for all systemic antimicrobials (1.76[1.71–1.81], 1.10[1.07–1.13], 1.48[1.43–1.53], and 1.06[1.03–1.09]); for azithromycin (11.76[9.80–14.23], 10.96[9.49–12.74], 12.41[10.73–14.45], and 4.88[4.31–5.55]); and for ceftriaxone (2.39[2.16–2.65], 3.64[3.29–4.03], 2.94[2.67–3.23], and 1.62[1.49–1.76]). Conclusions: We observed significantly increased AMU rates of all systemic agents during the first 4 waves of the pandemic and on COVID-19 wards compared with control wards for azithromycin and ceftriaxone. These agents saw a twofold reduction following order-set removal, suggesting that the clinical decision-support tool order set, as utilized, had influenced prescribing behavior.

Abstract Background Risk factors for nosocomial COVID-19 outbreaks continue to evolve. The aim of this study was to investigate a multi-ward nosocomial outbreak of COVID-19 between 1st September and 15th November 2020, occurring in a setting without vaccination for any healthcare workers or patients. Methods Outbreak report and retrospective, matched case–control study using incidence density sampling in three cardiac wards in an 1100-bed tertiary teaching hospital in Calgary, Alberta, Canada. Patients were confirmed/probable COVID-19 cases and contemporaneous control patients without COVID-19. COVID-19 outbreak definitions were based on Public Health guidelines. Clinical and environmental specimens were tested by RT-PCR and as applicable quantitative viral cultures and whole genome sequencing were conducted. Controls were inpatients on the cardiac wards during the study period confirmed to be without COVID-19, matched to outbreak cases by time of symptom onset dates, age within ± 15 years and were admitted in hospital for at least 2 days. Demographics, Braden Score, baseline medications, laboratory measures, co-morbidities, and hospitalization characteristics were collected on cases and controls. Univariate and multivariate conditional logistical regression was used to identify independent risk factors for nosocomial COVID-19. Results The outbreak involved 42 healthcare workers and 39 patients. The strongest independent risk factor for nosocomial COVID-19 (IRR 3.21, 95% CI 1.47–7.02) was exposure in a multi-bedded room. Of 45 strains successfully sequenced, 44 (97.8%) were B.1.128 and differed from the most common circulating community lineages. SARS-CoV-2 positive cultures were detected in 56.7% (34/60) of clinical and environmental specimens. The multidisciplinary outbreak team observed eleven contributing events to transmission during the outbreak. Conclusions Transmission routes of SARS-CoV-2 in hospital outbreaks are complex; however multi-bedded rooms play a significant role in the transmission of SARS-CoV-2.

Abstract Haemophilus influenzae is a Gram-negative pathobiont, frequently recovered from the airways of persons with cystic fibrosis (pwCF). Previous studies of H. influenzae infection dynamics and transmission in CF predominantly used molecular methods, lacking resolution. In this retrospective cohort study, representative yearly H. influenzae isolates from all pwCF attending the Calgary Adult CF Clinic with H. influenzae positive sputum cultures between 2002 and 2016 were typed by pulsed-field gel electrophoresis. Isolates with shared pulsotypes common to ≥ 2 pwCF were sequenced by Illumina MiSeq. Phylogenetic and pangenomic analyses were used to assess genetic relatedness within shared pulsotypes, and epidemiological investigations were performed to assess potential for healthcare associated transmission. H. influenzae infection was observed to be common (33% of patients followed) and dynamic in pwCF. Most infected pwCF exhibited serial infections with new pulsotypes (75% of pwCF with ≥ 2 positive cultures), with up to four distinct pulsotypes identified from individual patients. Prolonged infection by a single pulsotype was only rarely observed. Intra-patient genetic diversity was observed at the single-nucleotide polymorphism and gene content levels. Seven shared pulsotypes encompassing 39% of pwCF with H. influenzae infection were identified, but there was no evidence, within our sampling scheme, of direct patient-to-patient infection transmission.

IntroductionStenotrophomonas maltophilia is an opportunistic pathogen infecting persons with cystic fibrosis (pwCF) and portends a worse prognosis. Studies of S. maltophilia infection dynamics have been limited by cohort size and follow-up. We investigated the natural history, transmission potential, and evolution of S. maltophilia in a large Canadian cohort of 321 pwCF over a 37-year period.MethodsOne-hundred sixty-two isolates from 74 pwCF (23%) were typed by pulsed-field gel electrophoresis, and shared pulsotypes underwent whole-genome sequencing.ResultsS. maltophilia was recovered at least once in 82 pwCF (25.5%). Sixty-four pwCF were infected by unique pulsotypes, but shared pulsotypes were observed between 10 pwCF. In chronic carriage, longer time periods between positive sputum cultures increased the likelihood that subsequent isolates were unrelated. Isolates from individual pwCF were largely clonal, with differences in gene content being the primary source of genetic diversity objectified by gene content differences. Disproportionate progression of CF lung disease was not observed amongst those infected with multiple strains over time (versus a single) or amongst those with shared clones (versus strains only infecting one patient). We did not observe evidence of patient-to-patient transmission despite relatedness between isolates. Twenty-four genes with ≥ 2 mutations accumulated over time were identified across 42 sequenced isolates from all 11 pwCF with ≥ 2 sequenced isolates, suggesting a potential role for these genes in adaptation of S. maltophilia to the CF lung.DiscussionGenomic analyses suggested common, indirect sources as the origins of S. maltophilia infections in the clinic population. The information derived from a genomics-based understanding of the natural history of S. maltophilia infection within CF provides unique insight into its potential for in-host evolution.

Abstract Antimicrobial resistance is a complex One Health issue that exists in both human and veterinary medicine. To mitigate this ever-growing problem, efforts have been made to develop guidelines for appropriate antimicrobial use (AMU) across sectors. In veterinary medicine, there are notable literature gaps for proper AMU in minor species. We conducted a structured narrative review covering the years of July 2006 – July 2021 to find antimicrobial treatments for common bacterial infections in exotic (birds, rodents, reptiles, and others), small flock (chickens, turkeys, and other fowl), and backyard small ruminant (sheep and goats) species. We retrieved a total of 4728 articles, of which 21 articles met the criteria for our review. Studies were grouped according to species, syndrome, and body system affected. Other data extracted included the bacterial pathogen(s), treatment (active ingredient), and geographical origin. Body systems reported included: intra-oral (n = 4), gastrointestinal (n = 1), respiratory (n = 2), reproductive (n = 1), skin (n = 3), aural (n = 1), ocular (n = 4), and other/multisystem (n = 5). By species, our search resulted in: rabbit (n = 5), rat (n = 2), guinea pig (n = 1), chinchilla (n = 1), guinea pig and chinchilla (n = 1), avian species (n = 1), psittacine birds (n = 2), loris and lorikeets (n = 1), turtles (n = 2), lizards (n = 1), goats (n = 2) and sheep (n = 2). The results of our findings identified a distinct gap in consistent antimicrobial treatment information for commonly encountered bacterial conditions within these species. There is a persisting need for clinical trials that focus on antibacterial treatment to strengthen the evidence base for AMU within exotic, small flock, and backyard small ruminant species.

Staphylococcus aureus sequence type (ST) 398 is a lineage affecting both humans and livestock worldwide. However, the mechanisms underlying its clonal evolution are still not clearly elucidated. We applied whole-genome sequencing (WGS) typing to 45 S. aureus strains from China and Canada between 2005 and 2014, in order to gain insight into their evolutionary pathway. Based on WGS phylogenetic analysis, 42 isolates were assigned to the human-associated clade (I/II-GOI) and 3 isolates to livestock-associated clade (IIa). Phylogeny of ϕSa3 sequences revealed five phage groups (Groups 1–5), with Group 1 carrying ϕSa3-Group 1 (ϕSa3-G1), Group 2 carrying ϕSa3-G2, Group 3 carrying ϕSa3-G3, Group 4 carrying ϕSa3-G4 and Group 5 lacking ϕSa3. ϕSa3-G1 was only found in strains that accounted for the most ancestral human clade I, while ϕSa3-G2, ϕSa3-G3 and ϕSa3-G4 were found restricted to sublineages within clade II-GOI. Some isolates of clade II-GOI were also found to be ϕSa3-negative or resistant to methicillin which are unusual characteristics for human-adapted isolates. This study demonstrated a strong association between phylogenetic grouping and phage type, suggesting an important role of ϕSa3 prophage in the evolution of human-adapted ST398 subclones. In addition, our results suggest that this subclone slowly began to adapt to animal hosts by losing ϕSa3 and acquiring methicillin resistance, which was observed in some strains of human-associated clade II-GOI, an intermediate human to livestock transmission clade.

Abstract Determining the viral load and infectivity of SARS-CoV-2 in macroscopic respiratory droplets, bioaerosols, and other bodily fluids and secretions is important for identifying transmission modes, assessing risks and informing public health guidelines. Here we show that viral load of SARS-CoV-2 Ribonucleic Acid (RNA) in participants’ naso-pharyngeal (NP) swabs positively correlated with RNA viral load they emitted in both droplets >10 $$\upmu \hbox {m}$$ μ m and bioaerosols

Abstract To explore the potential modes of Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) transmission, we collected 535 diverse clinical and environmental samples from 75 infected hospitalized and community patients. Infectious SARS-CoV-2 with quantitative burdens varying from 5 plaque-forming units/mL (PFU/mL) up to 1.0 × 106 PFU/mL was detected in 151/459 (33%) of the specimens assayed and up to 1.3 × 106 PFU/mL on fomites with confirmation by plaque morphology, PCR, immunohistochemistry, and/or sequencing. Infectious virus in clinical and associated environmental samples correlated with time since symptom onset with no detection after 7–8 days in immunocompetent hosts and with N-gene based Ct values ≤ 25 significantly predictive of yielding plaques in culture. SARS-CoV-2 isolated from patient respiratory tract samples caused illness in a hamster model with a minimum infectious dose of ≤ 14 PFU. Together, our findings offer compelling evidence that large respiratory droplet and contact (direct and indirect i.e., fomites) are important modes of SARS-CoV-2 transmission.

Abstract Background Pneumonia from SARS-CoV-2 is difficult to distinguish from other viral and bacterial etiologies. Broad-spectrum antimicrobials are frequently prescribed to patients hospitalized with COVID-19 which potentially acts as a catalyst for the development of antimicrobial resistance (AMR). Objectives We conducted a systematic review and meta-analysis during the first 18 months of the pandemic to quantify the prevalence and types of resistant co-infecting organisms in patients with COVID-19 and explore differences across hospital and geographic settings. Methods We searched MEDLINE, Embase, Web of Science (BioSIS), and Scopus from November 1, 2019 to May 28, 2021 to identify relevant articles pertaining to resistant co-infections in patients with laboratory confirmed SARS-CoV-2. Patient- and study-level analyses were conducted. We calculated pooled prevalence estimates of co-infection with resistant bacterial or fungal organisms using random effects models. Stratified meta-analysis by hospital and geographic setting was also performed to elucidate any differences. Results Of 1331 articles identified, 38 met inclusion criteria. A total of 1959 unique isolates were identified with 29% (569) resistant organisms identified. Co-infection with resistant bacterial or fungal organisms ranged from 0.2 to 100% among included studies. Pooled prevalence of co-infection with resistant bacterial and fungal organisms was 24% (95% CI 8–40%; n = 25 studies: I2 = 99%) and 0.3% (95% CI 0.1–0.6%; n = 8 studies: I2 = 78%), respectively. Among multi-drug resistant organisms, methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and multi-drug resistant Candida auris were most commonly reported. Stratified analyses found higher proportions of AMR outside of Europe and in ICU settings, though these results were not statistically significant. Patient-level analysis demonstrated > 50% (n = 58) mortality, whereby all but 6 patients were infected with a resistant organism. Conclusions During the first 18 months of the pandemic, AMR prevalence was high in COVID-19 patients and varied by hospital and geography although there was substantial heterogeneity. Given the variation in patient populations within these studies, clinical settings, practice patterns, and definitions of AMR, further research is warranted to quantify AMR in COVID-19 patients to improve surveillance programs, infection prevention and control practices and antimicrobial stewardship programs globally.

Abstract Background Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is completed through reverse transcriptase-PCR (RT-PCR) from either oropharyngeal or nasopharyngeal swabs, critically important for diagnostics but also from an infection control lens. Recent studies have suggested that COVID-19 patients can demonstrate prolonged viral shedding with immunosuppression as a key risk factor. Case presentation We present a case of an immunocompromised patient with SARS-CoV-2 infection demonstrating prolonged infectious viral shedding for 189 days with virus cultivability and clinical relapse with an identical strain based on whole genome sequencing, requiring a multi-modal therapeutic approach. We correlated clinical parameters, PCR cycle thresholds and viral culture until eventual resolution. Conclusions We successfully demonstrate resolution of viral shedding, administration of COVID-19 vaccination and maintenance of viral clearance. This case highlights implications in the immunosuppressed patient towards infection prevention and control that should consider those with prolonged viral shedding and may require ancillary testing to fully elucidate viral activity. Furthermore, this case raises several stimulating questions around complex COVID-19 patients around the role of steroids, effect of antiviral therapies in absence of B-cells, role for vaccination and the requirement of a multi-modal approach to eventually have successful clearance of the virus.

Introduction: Remotely Piloted Aircraft Systems (RPAS) can access patients inaccessible to traditional rescue. Just-in-time remote telementoring (RTM) of naïve users to self-care could potentially address challenges in salvaging exsanguination in remote environments. Methods: An exsanguination self-application task was established in a wilderness location. Three volunteers-initiated distress calls to prompt RPAS precision delivered STOP-THE-BLEED kits, after which a remote mentor directed the volunteers how to self-care. Results: Limited connectivity prevented video, however each volunteer delivered images and initiated conversation with the mentor pre-RPAS arrival. Thereafter, all subjects were able to unpack and deploy hemorrhage control adjuncts under verbal direction, and to simulate self-application. All subjects were able to successfully apply wound-clamps, tourniquets, and pack wounds although one had insufficient pressure. Discussion: RPASs can deliver supplies long before human rescuers, and communication connectivity might allow remote mentoring in device application. Further development of technology and self-care paradigms for exsanguination are encouraged.

We examined the effect of an antimicrobial stewardship program (ASP), procalcitonin testing and rapid blood-culture identification on hospital mortality in a prospective quality improvement project in critically ill septic adults. Secondarily, we have reported antimicrobial guideline concordance, acceptance of ASP interventions, and antimicrobial and health-resource utilization.

Background: SARS-CoV-2 transmission has been reported to be associated with close contact with infected individuals. However, the mechanistic pathway for transmission in close contact settings is unclear. Our objective was to identify, appraise and summarise the evidence from studies assessing the role of close contact in SARS-CoV-2 transmission. Methods: This review is part of an Open Evidence Review on Transmission Dynamics of SARS-CoV-2. We conduct ongoing searches using WHO Covid-19 Database, LitCovid, medRxiv, PubMed and Google Scholar; assess study quality based on the QUADAS-2 criteria and report important findings on an ongoing basis. Results: We included 278 studies: 258 primary studies and 20 systematic reviews. The settings for primary studies were predominantly in home/quarantine facilities (39.5%) and acute care hospitals (12%). The overall reporting quality of the studies was low-to-moderate. There was significant heterogeneity in design and methodology. The frequency of attack rates (PCR testing) varied between 2.1-75%; attack rates were highest in prison and wedding venues, and in households. The frequency of secondary attack rates was 0.3-100% with rates highest in home/quarantine settings. Three studies showed no transmission if the index case was a recurrent infection. Viral culture was performed in four studies of which three found replication-competent virus; culture results were negative where index cases had recurrent infections. Eighteen studies performed genomic sequencing with phylogenetic analysis – the completeness of genomic similarity ranged from 77-100%. Findings from systematic reviews showed that children were significantly less likely to transmit SARS-CoV-2 and household contact was associated with a significantly increased risk of infection. Conclusions: The evidence from published studies demonstrates that SARS-CoV-2 can be transmitted in close contact settings. The risk of transmission is greater in household contacts. There was a wide variation in methodology. Standardized guidelines for reporting transmission in close contact settings should be developed.

Abstract COVID-19 has impacted human life globally and threatens to overwhelm health-care resources. Infection rates are rapidly rising almost everywhere, and new approaches are required to both prevent transmission, but to also monitor and rescue infected and at-risk patients from severe complications. Point-of-care lung ultrasound has received intense attention as a cost-effective technology that can aid early diagnosis, triage, and longitudinal follow-up of lung health. Detecting pleural abnormalities in previously healthy lungs reveal the beginning of lung inflammation eventually requiring mechanical ventilation with sensitivities superior to chest radiographs or oxygen saturation monitoring. Using a paradigm first developed for space-medicine known as Remotely Telementored Self-Performed Ultrasound (RTSPUS), motivated patients with portable smartphone support ultrasound probes can be guided completely remotely by a remote lung imaging expert to longitudinally follow the health of their own lungs. Ultrasound probes can be couriered or even delivered by drone and can be easily sterilized or dedicated to one or a commonly exposed cohort of individuals. Using medical outreach supported by remote vital signs monitoring and lung ultrasound health surveillance would allow clinicians to follow and virtually lay hands upon many at-risk paucisymptomatic patients. Our initial experiences with such patients are presented, and we believe present a paradigm for an evolution in rich home-monitoring of the many patients expected to become infected and who threaten to overwhelm resources if they must all be assessed in person by at-risk care providers.

Congenital infections with SARS-CoV-2 are uncommon. We describe two confirmed congenital SARS-CoV-2 infections using descriptive, epidemiologic and standard laboratory methods and in one case, viral culture. Clinical data were obtained from health records. Nasopharyngeal (NP) specimens, cord blood and placentas when available were tested by reverse transcriptase real-time PCR (RT-PCR). Electron microscopy and histopathological examination with immunostaining for SARS-CoV-2 was conducted on the placentas. For Case 1, placenta, umbilical cord, and cord blood were cultured for SARS-CoV-2 on Vero cells. This neonate was born at 30 weeks, 2 days gestation by vaginal delivery. RT-PCR tests were positive for SARS-CoV-2 from NP swabs and cord blood; NP swab from the mother and placental tissue were positive for SARS-CoV-2. Placental tissue yielded viral plaques with typical morphology for SARS-CoV-2 at 2.8 × 102 pfu/mL confirmed by anti-spike protein immunostaining. Placental examination revealed chronic histiocytic intervillositis with trophoblast necrosis and perivillous fibrin deposition in a subchorionic distribution. Case 2 was born at 36 weeks, 4 days gestation. RT-PCR tests from the mother and infant were all positive for SARS-CoV-2, but placental pathology was normal. Case 1 may be the first described congenital case with SARS-CoV-2 cultivated directly from placental tissue.

Background: SARS-CoV-2 transmission has been reported to be associated with close contact with infected individuals. However, the mechanistic pathway for transmission in close contact settings is unclear. Our objective was to identify, appraise and summarise the evidence from studies assessing the role of close contact in SARS-CoV-2 transmission. Methods: This review is part of an Open Evidence Review on Transmission Dynamics of SARS-CoV-2. We conduct ongoing searches using WHO Covid-19 Database, LitCovid, medRxiv, PubMed and Google Scholar; assess study quality based on the QUADAS-2 criteria and report important findings on an ongoing basis. Results: We included 278 studies: 258 primary studies and 20 systematic reviews. The settings for primary studies were predominantly in home/quarantine facilities (39.5%) and acute care hospitals (12%). The overall reporting quality of the studies was low-to-moderate. There was significant heterogeneity in design and methodology. The frequency of attack rates (PCR testing) varied between 2.1-75%; attack rates were highest in prison and wedding venues, and in households. The frequency of secondary attack rates was 0.3-100% with rates highest in home/quarantine settings. Three studies showed no transmission if the index case was a recurrent infection. Viral culture was performed in four studies of which three found replication-competent virus; culture results were negative where index cases had recurrent infections. Eighteen studies performed genomic sequencing with phylogenetic analysis – the completeness of genomic similarity ranged from 77-100%. Findings from systematic reviews showed that children were significantly less likely to transmit SARS-CoV-2 and household contact was associated with a significantly increased risk of infection. Conclusions: The evidence from published studies demonstrates that SARS-CoV-2 can be transmitted in close contact settings. The risk of transmission is greater in household contacts. There was a wide variation in methodology. Standardized guidelines for reporting transmission in close contact settings should be developed.

Background: Treatments for COVID-19, including steroids, might exacerbate Strongyloides disease in patients with coinfection. We aimed to systematically review clinical and laboratory features of SARS-CoV-2 and Strongyloides coinfection, investigate possible interventions, assess outcomes, and identify research gaps requiring further attention. Methods: We searched two electronic databases, LitCOVID and WHO, up to August 2022, including SARS-CoV-2 and Strongyloides coinfection studies. We adapted the World Health Organization—Uppsala Monitoring Centre (WHO-UMC) system for standardized case causality assessment to evaluate if using corticosteroids or other immunosuppressive drugs in COVID-19 patients determined acute manifestations of strongyloidiasis. Results: We included 16 studies reporting 25 cases of Strongyloides and SARS-CoV-2 coinfection: 4 with hyperinfection syndrome; 2 with disseminated strongyloidiasis; 3 with cutaneous reactivation of strongyloidiasis; 3 with isolated digestive symptoms; and 2 with solely eosinophilia, without clinical manifestations. Eleven patients were asymptomatic regarding strongyloidiasis. Eosinopenia or normal eosinophil count was reported in 58.3% of patients with Strongyloides reactivation. Steroids were given to 18/21 (85.7%) cases. A total of 4 patients (19.1%) received tocilizumab and/or Anakirna in addition to steroids. Moreover, 2 patients (9.5%) did not receive any COVID-19 treatment. The causal relationship between Strongyloides reactivation and COVID-19 treatments was considered certain (4% of cases), probable (20% of patients), and possible (20% of patients). For 8% of cases, it was considered unlikely that COVID-19 treatment was associated with strongyloidiasis reactivations; the relationship between the Strongyloides infection and administration of COVID-19 treatment was unassessable/unclassifiable in 48% of cases. Of 13 assessable cases, 11 (84.6%) were considered to be causally associated with Strongyloides, ranging from certain to possible. Conclusions: Further research is needed to assess the frequency and risk of Strongyloides reactivation in SARS-CoV-2 infection. Our limited data using causality assessment supports recommendations that clinicians should screen and treat for Strongyloides infection in patients with coinfection who receive immunosuppressive COVID-19 therapies. In addition, the male gender and older age (over 50 years) may be predisposing factors for Strongyloides reactivation. Standardized guidelines should be developed for reporting future research.

Introduction Despite the availability of various pressure injury (PI) prevention strategies (e.g., risk identification, use of pressure re-distribution surfaces, frequent repositioning), they persist as a significant issue for healthcare systems worldwide. Continuous pressure imaging (CPI) is a novel technology that could be integrated within a comprehensive approach to the prevention of PIs. We studied the perceptions of healthcare providers and patients/families to identify facilitators and barriers to the use of this technology. Methods Hospitalized patients/family members from a randomized controlled trial assessing the efficacy of CPI in preventing PIs completed a survey after 72 hours (or upon discharge from hospital) of CPI monitoring. They were asked questions about prior and current experience with CPI technology. For healthcare providers, perceptions on the use of the device and its impact on care were explored through a survey distributed by email or hard copies. Results A total of 125 healthcare providers and 525 patients/family members completed the surveys. Of the healthcare providers, 95% either agreed/strongly agreed that the CPI technology was easy to use and 65% stated that the device improved how they provided pressure relief for patients. Identified issues with the device were cost, the fitting of the mattress cover, and the fixation of the patients/families on the device. Over a quarter of the patient/family respondents agreed/strongly agreed that the device influenced how pressure relief was provided. This response was statistically associated with whether the monitor was turned on (intervention arm; 52.7%) or off (control arm; 4.2%). Discussion and conclusion CPI technology was positively perceived by healthcare providers. Most patients/families felt it influenced care when the CPI monitor was turned on. Concerns raised around cost and the ease of use of these devices by healthcare providers may affect the decisions of healthcare system administrators to adopt and implement this technology.

Background: Modes of transmission of SARS-CoV-2 are of key public health importance. SARS-CoV-2 has been detected in the feces of some COVID-19 patients, suggesting the possibility that the virus could, in addition to droplet and fomite transmission, be transmitted via the orofecal route. Methods: This review is part of an Open Evidence Review on Transmission Dynamics of COVID-19. We conduct ongoing searches using WHO COVID-19 Database, LitCovid, medRxiv, and Google Scholar; assess study quality based on five criteria and report important findings. Where necessary, authors are contacted for further details on the content of their articles. Results: We include searches up until 20 December 2020. We included 110 relevant studies: 76 primary observational studies or reports, and 35 reviews (one cohort study also included a review) examining the potential role of orofecal transmission of SARS-CoV-2. Of the observational studies, 37 were done in China. A total of 48 studies (n=9,081 patients) reported single cases, case series or cohort data on individuals with COVID-19 diagnosis or their contacts and 46 (96%) detected binary RT-PCR with 535 out of 1358 samples positive for SARS-CoV-2 (average 39.4%). The results suggest a long duration of fecal shedding, often recorded after respiratory samples tested negative, and symptoms of gastrointestinal disease were reported in several studies. Twenty-nine studies reported finding SARS-CoV-2 RNA in wastewater, river water or toilet areas. Six studies attempted viral culture from COVID-19 patients’ fecal samples: culture was successful in 3 of 6 studies, and one study demonstrated invasion of the virus into intestinal epithelial cells. Conclusions: Varied observational and mechanistic evidence suggests SARS-CoV-2 can infect and be shed from the gastrointestinal tract, including some data demonstrating viral culture in fecal samples. To fully assess these risks, quantitative data on infectious virus in these settings and infectious dose are needed.

Current limitations in the understanding and control of antimicrobial resistance (AMR) in Canada are described through a comprehensive review focusing on: (1) treatment optimization; (2) surveillance of antimicrobial use and AMR; and (3) prevention of transmission of AMR. Without addressing gaps in identified areas, sustained progress in AMR mitigation is unlikely. Expert opinions and perspectives contributed to prioritizing identified gaps. Using Canada as an example, this review emphasizes the importance and necessity of a One Health approach for understanding and mitigating AMR. Specifically, antimicrobial use in human, animal, crop, and environmental sectors cannot be regarded as independent; therefore, a One Health approach is needed in AMR research and understanding, current surveillance efforts, and policy. Discussions regarding addressing described knowledge gaps are separated into four categories: (1) further research; (2) increased capacity/resources; (3) increased prescriber/end-user knowledge; and (4) policy development/enforcement. This review highlights the research and increased capacity and resources to generate new knowledge and implement recommendations needed to address all identified gaps, including economic, social, and environmental considerations. More prescriber/end-user knowledge and policy development/enforcement are needed, but must be informed by realistic recommendations, with input from all relevant stakeholders. For most knowledge gaps, important next steps are uncertain. In conclusion, identified knowledge gaps underlined the need for AMR policy decisions to be considered in a One Health framework, while highlighting critical needs to achieve realistic and meaningful progress.

Background: Maritime and river travel may be associated with respiratory viral spread via infected passengers and/or crew and potentially through other transmission routes. The transmission models of SARS-CoV-2 associated with cruise ship travel are based on transmission dynamics of other respiratory viruses. We aimed to provide a summary and evaluation of relevant data on SARS-CoV-2 transmission aboard cruise ships, report policy implications, and highlight research gaps. Methods: We searched four electronic databases (up to 26 May 2022) and included studies on SARS-CoV-2 transmission aboard cruise ships. The quality of the studies was assessed based on five criteria, and relevant findings were reported. Results: We included 23 papers on onboard SARS-CoV-2 transmission (with 15 reports on different aspects of the outbreak on Diamond Princess and nine reports on other international cruises), 2 environmental studies, and 1 systematic review. Three articles presented data on both international cruises and the Diamond Princess. The quality of evidence from most studies was low to very low. Index case definitions were heterogeneous. The proportion of traced contacts ranged from 0.19 to 100%. Studies that followed up >80% of passengers and crew reported attack rates (AR) up to 59%. The presence of a distinct dose–response relationship was demonstrated by findings of increased ARs in multi-person cabins. Two studies performed viral cultures with eight positive results. Genomic sequencing and phylogenetic analyses were performed in individuals from three cruises. Two environmental studies reported PCR-positive samples (cycle threshold range 26.21–39.00). In one study, no infectious virus was isolated from any of the 76 environmental samples. Conclusion: Our review suggests that crowding and multiple persons per cabin were associated with an increased risk of transmission on cruise ships. Variations in design, methodology, and case ascertainment limit comparisons across studies and quantification of transmission risk. Standardized guidelines for conducting and reporting studies on cruise ships of acute respiratory infection transmission should be developed.

Background: SARS-CoV-2 RNA has been detected in fomites which suggests the virus could be transmitted via inanimate objects. However, there is uncertainty about the mechanistic pathway for such transmissions. Our objective was to identify, appraise and summarise the evidence from primary studies and systematic reviews assessing the role of fomites in transmission. Methods: This review is part of an Open Evidence Review on Transmission Dynamics of SARS-CoV-2. We conduct ongoing searches using WHO Covid-19 Database, LitCovid, medRxiv, and Google Scholar; assess study quality based on five criteria and report important findings on an ongoing basis. Results: We found 64 studies: 63 primary studies and one systematic review (n=35). The settings for primary studies were predominantly in hospitals (69.8%) including general wards, ICU and SARS-CoV-2 isolation wards. There were variations in the study designs including timing of sample collection, hygiene procedures, ventilation settings and cycle threshold. The overall quality of reporting was low to moderate. The frequency of positive SARS-CoV-2 tests across 51 studies (using RT-PCR) ranged from 0.5% to 75%. Cycle threshold values ranged from 20.8 to 44.1. Viral concentrations were reported in 17 studies; however, discrepancies in the methods for estimation prevented comparison. Eleven studies (17.5%) attempted viral culture, but none found a cytopathic effect. Results of the systematic review showed that healthcare settings were most frequently tested (25/35, 71.4%), but laboratories reported the highest frequency of contaminated surfaces (20.5%, 17/83). Conclusions: The majority of studies report identification of SARS-CoV-2 RNA on inanimate surfaces; however, there is a lack of evidence demonstrating the recovery of viable virus. Lack of positive viral cultures suggests that the risk of transmission of SARS-CoV-2 through fomites is low. Heterogeneity in study designs and methodology prevents comparisons of findings across studies. Standardized guidelines for conducting and reporting research on fomite transmission is warranted.

Background: SARS-CoV-2 RNA has been detected in fomites which suggests the virus could be transmitted via inanimate objects. However, there is uncertainty about the mechanistic pathway for such transmissions. Our objective was to identify, appraise and summarise the evidence from primary studies and systematic reviews assessing the role of fomites in transmission. Methods: This review is part of an Open Evidence Review on Transmission Dynamics of SARS-CoV-2. We conduct ongoing searches using WHO Covid-19 Database, LitCovid, medRxiv, and Google Scholar; assess study quality based on five criteria and report important findings on an ongoing basis. Results: We found 64 studies: 63 primary studies and one systematic review (n=35). The settings for primary studies were predominantly in hospitals (69.8%) including general wards, ICU and SARS-CoV-2 isolation wards. There were variations in the study designs including timing of sample collection, hygiene procedures, ventilation settings and cycle threshold. The overall quality of reporting was low to moderate. The frequency of positive SARS-CoV-2 tests across 51 studies (using RT-PCR) ranged from 0.5% to 75%. Cycle threshold values ranged from 20.8 to 44.1. Viral concentrations were reported in 17 studies; however, discrepancies in the methods for estimation prevented comparison. Eleven studies (17.5%) attempted viral culture, but none found a cytopathic effect. Results of the systematic review showed that healthcare settings were most frequently tested (25/35, 71.4%), but laboratories reported the highest frequency of contaminated surfaces (20.5%, 17/83). Conclusions: The majority of studies report identification of SARS-CoV-2 RNA on inanimate surfaces; however, there is a lack of evidence demonstrating the recovery of viable virus. Lack of positive viral cultures suggests that the risk of transmission of SARS-CoV-2 through fomites is low. Heterogeneity in study designs and methodology prevents comparisons of findings across studies. Standardized guidelines for conducting and reporting research on fomite transmission is warranted.

Despite initially being described in North America, Staphylococcus aureus (SA) sequence type ST59 is the most commonly isolated sequence type in Eastern Asia. The origins and evolution of this strain type remains unclear and therefore we gathered a collection of ST59 isolates from Canada and mainland China for a detailed genetic analysis of the lineage. Bayesian inference phylogenomic analysis of our isolates, along with previously published ST59 sequences indicated that the lineage could be divided into 6 distinct subgroups (WGS-1 thorough 6), each having distinct molecular characteristics. Analysis also demonstrated the concurrent but separate evolution of North American and East Asian lineages, as well as the extensive diversification of the East Asian lineage. The presence of a mobile element structure (MES) was found to be the major difference between these two continental lineages, absent in all North American isolates, and present in all East Asian ones. Other mobile genetic elements, such as the Immune Evasion Complex (IEC), Panton Valentine Leukocidin (PVL), and Staphylococcal Cassette Chromosome mec (SCCmec), showed significant variability within each sub-group and likely represents local selective pressures rather than major characteristics defining the groups. Our analysis also demonstrated the existence of a more ancient ST59 sub-lineage from North America, which was MES negative and contained some of the earliest reported ST59 isolates. Combined with the existence of a MES negative isolate from Taiwan, predicted to have appeared prior to diversification of the East Asian lineages, these results hint at the possibility of a North American origin for the lineage, which gained hold in Eastern Asia following acquisition of MES, and subsequently diversified.

The timely detection of Methicillin-resistant Staphylococcus aureus (MRSA) is crucial for antimicrobial therapy and a key factor to limit the hospital spread of MRSA. Currently available commercial MRSA detection assays target the 3′ end of the orfX gene and the right extremity of Staphylococcal Cassette Chromosome mec (SCCmec). These assays suffer from both false positive due to SCC-like elements that lack mecA and false negative results due to the inability to detect new or variant SCCmec cassettes with the existing primers. We developed a novel MRSA detection scheme, designed to circumvent issues present in the existing commercial assays. Our assay demonstrated specificity and accuracy, capable of detecting prototypic strains of SCCmec types I-XIII [C(t) values ranged 8.58–26.29]. Previous false positive isolates (N = 19) by Xpert MRSA nasal assay were accurately classified with our assay. Further validation with 218 randomly selected clinical isolates (73 MRSA, 75 MSSA, 43 MR-CoNS, and 27 MS-CoNS) confirmed its feasibility and practicality. Testing assay performance with 88 direct clinical swabs from 33 patients showed that the assay was 96.6% in agreement with clinical culture results. Our novel MRSA detection assay targets both the S. aureus specific sequence and the mecA/mecC genes simultaneously to overcome the false positive and false negative deficits of currently available commercial assays. The results validate our assay and confirmed its feasibility and practicality. The assay is not affected by SCCmec types and only needs modification if new mec homologs emerge and establishes a new platform for other emerging SCCmec types.

Escherichia coli is frequently isolated from the respiratory secretions of cystic fibrosis (CF) patients yet is not considered a classical CF pathogen. Accordingly, little is known about the natural history of this organism in the CF airways, as well as the potential for patient-to-patient transmission. Patients attending the Calgary Adult CF Clinic (CACFC) between January 1983 and December 2016 with at least one E. coli-positive sputum culture were identified by retrospective review. Annual E. coli isolates from the CACFC biobank from each patient were typed by pulsed-field gel electrophoresis (PFGE) and isolates belonging to shared pulsotypes were sequenced. Single nucleotide polymorphism (SNP) and phylogenetic analysis were used to investigate the natural history of E. coli infection and identify potential transmission events. Forty-five patients with E. coli-positive sputum cultures were identified. Most patients had a single infection episode with a single pulsotype, while replacement of an initial pulsotype with a second was observed in three patients. Twenty-four had E. coli recovered from their sputum more than once and 18 patients had persistent infections (E. coli carriage >6 months with ≥3 positive cultures). Shared pulsotypes corresponded to known extraintestinal pathogenic E. coli strains: ST-131, ST-73, and ST-1193. Phylogenetic relationships and SNP distances among isolates within shared pulsotypes were consistent with independent acquisition of E. coli by individual patients. Most recent common ancestor date estimates of isolates between patients were inconsistent with patient-to-patient transmission. E. coli infection in CF is a dynamic process that appears to be characterized by independent acquisition within our patient population and carriage of unique sets of strains over time by individual patients.

Abstract Background Antimicrobial use in food-producing animals selects for antimicrobial resistance that can be transmitted to humans via food or other transmission routes. The World Health Organization (WHO) in 2005 ranked the medical importance of antimicrobials used in humans. In late 2017, to preserve the effectiveness of medically important antimicrobials for humans, WHO released guidelines on use of antimicrobials in food-producing animals that incorporated the latest WHO rankings. Methods WHO commissioned systematic reviews and literature reviews, and convened a Guideline Development Group (GDG) of external experts free of unacceptable conflicts-of-interest. The GDG assessed the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, and formulated recommendations using a structured evidence-to-decision approach that considered the balance of benefits and harms, feasibility, resource implications, and impact on equity. The resulting guidelines were peer-reviewed by an independent External Review Group and approved by the WHO Guidelines Review Committee. Results These guidelines recommend reductions in the overall use of medically important antimicrobials in food-producing animals, including complete restriction of use of antimicrobials for growth promotion and for disease prevention (i.e., in healthy animals considered at risk of infection). These guidelines also recommend that antimicrobials identified as critically important for humans not be used in food-producing animals for treatment or disease control unless susceptibility testing demonstrates the drug to be the only treatment option. Conclusions To preserve the effectiveness of medically important antimicrobials, veterinarians, farmers, regulatory agencies, and all other stakeholders are urged to adopt these recommendations and work towards implementation of these guidelines.

An increasing number of severe infections caused by Staphylococcus aureus ST398 strains has been observed. However, it has not been elucidated whether all ST398 strains are equally virulent. We collected 13 strains from China and Canada to test in a Caenorhabditis elegans infection model and compared their whole genome sequences (WGS) to explore potential insights into their virulence. All isolates belonged to ST398-methicillin-susceptible S. aureus (MSSA) with variant spa types (t034, t571, t1451, t1250). Pulsed field gel electrophoresis (PFGE) and WGS analyses showed that the 13 isolates clustered into 3 genomic types (Types A-C). WGS and prophage phylogenetic analyses also revealed that the strains could be divided into 3 phage groups (Groups 1–3), which correlated with high-, moderate-, and low-nematocidal activities, with mean killing rates of 94, 67, and 40%, respectively. Group 1 carried ϕSa3-Group 1 (ϕSa3-G1), Group 2 carried ϕSa3-G2, and Group 3 lacked ϕSa3. Interestingly, strain GD1706 (that genetically clustered within Type C) and strain GD487 (within Type B) both carried ϕSa3-G1 like phages and killed 92% of the nematodes, similar to the Type A strains carrying ϕSa3-G1. This study demonstrated that different ST398 sub-lineages possess variable virulence capacities, depending on the presence or absence, as well as the structure of the prophage ϕSa3 that carries virulence factors.IMPORTANCESince first being reported in the early 2000s, Staphylococcus aureus ST398 has not only become recognized as a frequent colonizing strain in economically important livestock animals, but has also proven to be a concern for infection in humans and, in particular, has been linked to higher rates of severe invasive human infections. We collected ST398 strains from China and Canada to test in a worm (Caenorhabditis elegans) infection model and compared their whole genome sequences to gain insight into pathogenesis. We have shown that different ST398 sub-strains differ in their virulence potential based on the presence or absence and structure of prophage ϕSa3, which carries important virulence factors. Our observations suggest that ST398 strains are relatively heterogeneous from a clinical perspective, and more studies are needed to differentiate between virulent and non-virulent ST398 strains to determine the true global spread of relevant sub-strains.

The genomic comparison of virulent (TW20), moderately virulent (CMRSA6/CMRSA3), and avirulent (M92) strains from a genetically closely-related MRSA ST239 sub-lineage revealed striking similarities in their genomes and antibiotic resistance profiles, despite differences in virulence and pathogenicity. The main differences were in the spa gene (coding for staphylococcal protein A), lpl genes (coding for lipoprotein-like membrane proteins), cta genes (genes involved in heme synthesis), and the dfrG gene (coding for a trimethoprim-resistant dihydrofolate reductase), as well as variations in the presence or content of some prophages and plasmids, which could explain the virulence differences of these strains. TW20 was positive for all genetic traits tested, compared to CMRSA6, CMRSA3, and M92. The major components differing among these strains included spa and lpl with TW20 carrying both whereas CMRSA6/CMRSA3 carry spa identical to TW20 but have a disrupted lpl. M92 is devoid of both these traits. Considering the role played by these components in innate immunity and virulence, it is predicted that since TW20 has both the components intact and functional, these traits contribute to its pathogenesis. However, CMRSA6/CMRSA3 are missing one of these components, hence their intermediately virulent nature. On the contrary, M92 is completely devoid of both the spa and lpl genes and is avirulent. Mobile genetic elements play a potential role in virulence. TW20 carries three prophages (ϕSa6, ϕSa3, and ϕSPβ-like), a pathogenicity island and two plasmids. CMRSA6, CMRSA3, and M92 contain variations in one or more of these components. The virulence associated genes in these components include staphylokinase, entertoxins, antibiotic/antiseptic/heavy metal resistance and bacterial persistence. Additionally, there are many hypothetical proteins (present with variations among strains) with unknown function in these mobile elements which could be making an important contribution in the virulence of these strains. The above mentioned repertoire of virulence components in TW20 likely contributes to its increased virulence, while the absence and/or modification of one or more of these components in CMRSA6/CMRSA3 and M92 likely affects the virulence of the strains.

Background: SARS-CoV-2 transmission has been reported to be associated with close contact with infected individuals. However, the mechanistic pathway for transmission in close contact settings is unclear. Our objective was to identify, appraise and summarise the evidence from studies assessing the role of close contact in SARS-CoV-2 transmission. Methods: This review is part of an Open Evidence Review on Transmission Dynamics of SARS-CoV-2. We conduct ongoing searches using WHO Covid-19 Database, LitCovid, medRxiv, PubMed and Google Scholar; assess study quality based on the QUADAS-2 criteria and report important findings on an ongoing basis. Results: We included 278 studies: 258 primary studies and 20 systematic reviews. The settings for primary studies were predominantly in home/quarantine facilities (39.5%) and acute care hospitals (12%). The overall reporting quality of the studies was low-to-moderate. There was significant heterogeneity in design and methodology. The frequency of attack rates (PCR testing) varied between 2.1-75%; attack rates were highest in prison and wedding venues, and in households. The frequency of secondary attack rates was 0.3-100% with rates highest in home/quarantine settings. Three studies showed no transmission if the index case was a recurrent infection. Viral culture was performed in four studies of which three found replication-competent virus; culture results were negative where index cases had recurrent infections. Eighteen studies performed genomic sequencing with phylogenetic analysis – the completeness of genomic similarity ranged from 77-100%. Findings from systematic reviews showed that children were significantly less likely to transmit SARS-CoV-2 and household contact was associated with a significantly increased risk of infection. Conclusions: The evidence from published studies demonstrates that SARS-CoV-2 can be transmitted in close contact settings. The risk of transmission is greater in household contacts. There was a wide variation in methodology. Standardized guidelines for reporting transmission in close contact settings should be developed.

Background: Airborne transmission is the spread of an infectious agent caused by the dissemination of droplet nuclei (aerosols) that remain infectious when suspended in the air. We carried out a systematic review to identify, appraise and summarise the evidence from studies of the role of airborne transmission of SARS-CoV-2. Methods: We searched LitCovid, MedRxiv, Google Scholar and the WHO Covid-19 database from 1 February 2020 to 30 May 2022 and included studies on airborne transmission. Data were dual extracted, and we assessed quality using a modified QUADAS 2 risk of bias tool. Results: We included 128 primary studies and 29 reviews on airborne SARS-CoV-2. Of the 128 primary studies, 105 (82%) reported data on RT-PCR from air samples, 28 (22%) report cycle threshold values and 36 (28%) copies per sample volume. All primary studies were observational. The research often lacked standard methods, standard sampling sizes and reporting items. We found 69 descriptions of different air samplers deployed. Of the 80 in-hospital studies that reported binary RT-PCR tests, 362/3079 air samples from 75 studies conducted in hospital ward environments were positive (median 8%, IQR=0 to 23%); 23 studies reported 74/703 RT-PCR positive air samples in the ICU setting (median 17%, IQR=0% to 38%) Thirty-eight studies reported potential air transmission in the outdoors or in the community. Twenty-six studies attempted viral culture, none of which definitively demonstrated that replication-competent SARS-CoV-2 could be recovered in the air. Conclusion: SARS-CoV-2 RNA is detectable intermittently in the air in various settings. Standardized guidelines for conducting and reporting research on airborne transmission are needed. The lack of recoverable viral culture of SARS-CoV-2 from air samples prevents firm conclusions about the definitive role of airborne transmission in SARS-CoV-2.

Background: SARS-CoV-2 transmission has been reported to be associated with close contact with infected individuals. However, the mechanistic pathway for transmission in close contact settings is unclear. Our objective was to identify, appraise and summarise the evidence from studies assessing the role of close contact in SARS-CoV-2 transmission. Methods: This review is part of an Open Evidence Review on Transmission Dynamics of SARS-CoV-2. We conduct ongoing searches using WHO Covid-19 Database, LitCovid, medRxiv, PubMed and Google Scholar; assess study quality based on the QUADAS-2 criteria and report important findings on an ongoing basis. Results: We included 278 studies: 258 primary studies and 20 systematic reviews. The settings for primary studies were predominantly in home/quarantine facilities (39.5%) and acute care hospitals (12%). The overall reporting quality of the studies was low-to-moderate. There was significant heterogeneity in design and methodology. The frequency of attack rates (PCR testing) varied between 2.1-75%; attack rates were highest in prison and wedding venues, and in households. The frequency of secondary attack rates was 0.3-100% with rates highest in home/quarantine settings. Three studies showed no transmission if the index case was a recurrent infection. Viral culture was performed in four studies of which three found replication-competent virus; culture results were negative where index cases had recurrent infections. Eighteen studies performed genomic sequencing with phylogenetic analysis – the completeness of genomic similarity ranged from 77-100%. Findings from systematic reviews showed that children were significantly less likely to transmit SARS-CoV-2 and household contact was associated with a significantly increased risk of infection. Conclusions: The evidence from published studies demonstrates that SARS-CoV-2 can be transmitted in close contact settings. The risk of transmission is greater in household contacts. There was a wide variation in methodology. Standardized guidelines for reporting transmission in close contact settings should be developed.

Background: Modes of transmission of SARS-CoV-2 are of key public health importance. SARS-CoV-2 has been detected in the feces of some COVID-19 patients, suggesting the possibility that the virus could, in addition to droplet and fomite transmission, be transmitted via the orofecal route. Methods: This review is part of an Open Evidence Review on Transmission Dynamics of COVID-19. We conduct ongoing searches using WHO COVID-19 Database, LitCovid, medRxiv, and Google Scholar; assess study quality based on five criteria and report important findings. Where necessary, authors are contacted for further details on the content of their articles. Results: We include searches up until 20 December 2020. We included 110 relevant studies: 76 primary observational studies or reports, and 35 reviews (one cohort study also included a review) examining the potential role of orofecal transmission of SARS-CoV-2. Of the observational studies, 37 were done in China. A total of 48 studies (n=9,081 patients) reported single cases, case series or cohort data on individuals with COVID-19 diagnosis or their contacts and 46 (96%) detected binary RT-PCR with 535 out of 1358 samples positive for SARS-CoV-2 (average 39.4%). The results suggest a long duration of fecal shedding, often recorded after respiratory samples tested negative, and symptoms of gastrointestinal disease were reported in several studies. Twenty-nine studies reported finding SARS-CoV-2 RNA in wastewater, river water or toilet areas. Six studies attempted viral culture from COVID-19 patients’ fecal samples: culture was successful in 3 of 6 studies, and one study demonstrated invasion of the virus into intestinal epithelial cells. Conclusions: Varied observational and mechanistic evidence suggests SARS-CoV-2 can infect and be shed from the gastrointestinal tract, including some data demonstrating viral culture in fecal samples. To fully assess these risks, quantitative data on infectious virus in these settings and infectious dose are needed.

Background: Airborne transmission is the spread of an infectious agent caused by the dissemination of droplet nuclei (aerosols) that remain infectious when suspended in the air. We carried out a systematic review to identify, appraise and summarise the evidence from studies of the role of airborne transmission of SARS-CoV-2. Methods: We searched LitCovid, MedRxiv, Google Scholar and the WHO Covid-19 database from 1 February to 20 December 2020 and included studies on airborne transmission. Data were dual extracted and we assessed quality using a modified QUADAS 2 risk of bias tool. Results: We included 67 primary studies and 22 reviews on airborne SARS-CoV-2. Of the 67 primary studies, 53 (79%) reported data on RT-PCR from air samples, 12 (18%) report cycle threshold values and 18 (127%) copies per sample volume. All primary studies were observational and of low quality. The research often lacked standard methods, standard sampling sizes and reporting items. We found 36 descriptions of different air samplers deployed. Of the 42 studies conducted in-hospital that reported binary RT-PCR tests, 24 (57%) reported positive results for SARs-CoV-2 (142 positives out of 1,403 samples: average 10.1%, range 0% to 100%). There was no pattern between the type of hospital setting (ICU versus non-ICU) and RT-PCR positivity. Seventeen studies reported potential air transmission in the outdoors or in the community, of which seven performed RT-PCR sampling, and two studies reported weak positive RNA samples for 2 or more genes (5 of 125 samples positive: average 4.0%). Ten studies attempted viral culture with no serial passage. Conclusion: SARS-CoV-2 RNA is detected intermittently in the air in various settings. Standardized guidelines for conducting and reporting research on airborne transmission are needed. The lack of recoverable viral culture samples of SARS-CoV-2 prevents firm conclusions from being drawn about airborne transmission.

Background: SARS-CoV-2 transmission has been reported to be associated with close contact with infected individuals. However, the mechanistic pathway for transmission in close contact settings is unclear. Our objective was to identify, appraise and summarise the evidence from studies assessing the role of close contact in SARS-CoV-2 transmission. Methods: This review is part of an Open Evidence Review on Transmission Dynamics of SARS-CoV-2. We conduct ongoing searches using WHO Covid-19 Database, LitCovid, medRxiv, PubMed and Google Scholar; assess study quality based on the QUADAS-2 criteria and report important findings on an ongoing basis. Results: We included 181 studies: 171 primary studies and 10 systematic reviews. The settings for primary studies were predominantly in home/quarantine facilities (31.6%) and acute care hospitals (15.2%). The overall reporting quality of the studies was low to moderate. There was significant heterogeneity in design and methodology. The frequency of attack rates (PCR testing) was 3.5-75%; attack rates were highest in prison and wedding venues, and in households. The frequency of secondary attack rates was 0.3-100% with rates highest in home/quarantine settings. Three studies showed no transmission if index cases had recurrent infection. Viral culture was performed in three studies of which two found viable virus; culture results were negative where index cases had recurrent infections. Ten studies performed genomic sequencing with phylogenetic analysis – the completeness of genomic similarity ranged from 81-100%. Findings from systematic reviews showed that children were significantly less likely to transmit SARS-CoV-2 and household contact was associated with a significantly increased risk of infection. Conclusions: The evidence from published studies demonstrates that SARS-CoV-2 can be transmitted via close contact settings. The risk of transmission is greater in household contacts. There was wide variation in methodology. Standardized guidelines for reporting transmission in close contact settings should be developed to improve the quality reporting.

Background: Airborne transmission is the spread of an infectious agent caused by the dissemination of droplet nuclei (aerosols) that remain infectious when suspended in the air. We carried out a systematic review to identify, appraise and summarise the evidence from studies of the role of airborne transmission of SARS-CoV-2. Methods: We searched LitCovid, MedRxiv, Google Scholar and the WHO Covid-19 database from 1 February to 20 December 2020 and included studies on airborne transmission. Data were dual extracted and we assessed quality using a modified QUADAS 2 risk of bias tool. Results: We included 67 primary studies and 22 reviews on airborne SARS-CoV-2. Of the 67 primary studies, 53 (79%) reported data on RT-PCR air samples, 12 report cycle threshold values and 18 copies per sample volume. All primary studies were observational and of low quality. The research often lacked standard methods, standard sampling sizes and reporting items. We found 36 descriptions of different air samplers deployed. Of the 42 studies conducted in-hospital that reported binary RT-PCR tests, 24 (57%) reported positive results for SARs-CoV-2 (142 positives out of 1,403 samples: average 10.1%, range 0% to 100%). There was no pattern between the type of hospital setting (ICU versus non-ICU) and RT-PCR positivity. Seventeen studies reported potential air transmission in the outdoors or in the community. Seven performed RT-PCR sampling, of which two studies report weak positive RNA samples for 2 or more genes (5 of 125 samples positive: average 4.0%). Ten studies attempted viral culture with no serial passage for viral culture. Conclusion: SARS-CoV-2 RNA is detected intermittently in the air in various settings. Standardized guidelines for conducting and reporting research on airborne transmission are needed. The lack of recoverable viral culture samples of SARS-CoV-2 prevents firm conclusions over airborne transmission.

Background: Mode of transmission of SARS-CoV-2 is of key public health importance. SARS-CoV-2 has been detected in the feces of some COVID-19 patients, suggesting the possibility that the virus could, in addition to droplet and fomite transmission, be transmitted via the orofecal route. Methods: This review is part of an Open Evidence Review on Transmission Dynamics of COVID-19. We conduct ongoing searches using WHO COVID-19 Database, LitCovid, medRxiv, and Google Scholar; assess study quality based on five criteria and report important findings on an ongoing basis. Where necessary, authors are contacted for further details on the content of their articles. Results: We include searches up until 20 December 2020. We included 110 relevant studies: 76 primary observational studies or reports, and 35 reviews (one cohort study also included a review) examining the potential role of orofecal transmission of SARS-CoV-2. Of the observational studies, 37 were done in China. A total of 48 studies (n=9,081 patients) reported single cases, case series or cohort data on individuals with COVID-19 diagnosis or their contacts and 46 (96%) detected binary RT-PCR with 535 out of 1358 samples positive for SARs-CoV-2 (average 39.4%). The results suggest a long duration of fecal shedding, often recorded after respiratory samples tested negative, and symptoms of gastrointestinal disease were reported in several studies. Twenty-nine studies reported finding SARS-CoV-2 RNA in wastewater, river water or toilet areas. Six studies attempted viral culture from COVID-19 patients’ fecal samples: culture was successful in 3 of 6 studies, and one study demonstrated invasion of the virus into the intestinal epithelial cells. Conclusions: Varied observational and mechanistic evidence suggests SARS-CoV-2 can infect and be shed from the gastrointestinal tract, including some data demonstrating viral culture in fecal samples. Future studies should test this hypothesis rigorously to allow the development of appropriate public health measures.